TY  - JOUR
A1  - Ferreira, Manuel A.
A1  - Gamazon, Eric R.
A1  - Al-Ejeh, Fares
A1  - Aittomäki, Kristiina
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arason, Adalgeir
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Arun, Banu K.
A1  - Asseryanis, Ella
A1  - Azzollini, Jacopo
A1  - Balmaña, Judith
A1  - Barnes, Daniel R.
A1  - Barrowdale, Daniel
A1  - Beckmann, Matthias W.
A1  - Behrens, Sabine
A1  - Benitez, Javier
A1  - Bermisheva, Marina
A1  - Bialkowska, Katarzyna
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Bolla, Manjeet K.
A1  - Borg, Ake
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Broeks, Annegien
A1  - Burwinkel, Barbara
A1  - Caldés, Trinidad
A1  - Caligo, Maria A.
A1  - Campa, Daniele
A1  - Campbell, Ian
A1  - Canzian, Federico
A1  - Carter, Jonathan
A1  - Carter, Brian D.
A1  - Castelao, Jose E.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Christiansen, Hans
A1  - Chung, Wendy K.
A1  - Claes, Kathleen B. M.
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Cox, Angela
A1  - Cross, Simon S.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - de la Hoya, Miguel
A1  - Dennis, Joe
A1  - Devilee, Peter
A1  - Diez, Orland
A1  - Dörk, Thilo
A1  - Dunning, Alison M.
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ejlertsen, Bent
A1  - Ellberg, Carolina
A1  - Engel, Christoph
A1  - Eriksson, Mikael
A1  - Fasching, Peter A.
A1  - Fletcher, Olivia
A1  - Flyger, Henrik
A1  - Friedman, Eitan
A1  - Frost, Debra
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Ganz, Patricia A.
A1  - Gapstur, Susan M.
A1  - Garber, Judy
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Glendon, Gord
A1  - Godwin, Andrew K.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - González-Neira, Anna
A1  - Greene, Mark H.
A1  - Gronwald, Jacek
A1  - Guenél, Pascal
A1  - Haimann, Christopher A.
A1  - Hall, Per
A1  - Hamann, Ute
A1  - He, Wei
A1  - Heyworth, Jane
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hoover, Robert N.
A1  - Hopper, John L.
A1  - Hulick, Peter J.
A1  - Humphreys, Keith
A1  - Imyanitov, Evgeny N.
A1  - Isaacs, Claudine
A1  - Jakimovska, Milena
A1  - Jakubowska, Anna
A1  - James, Paul A.
A1  - Janavicius, Ramunas
A1  - Jankowitz, Rachel C.
A1  - John, Esther M.
A1  - Johnson, Nichola
A1  - Joseph, Vijai
A1  - Karlan, Beth Y.
A1  - Khusnutdinova, Elza
A1  - Kiiski, Johanna I.
A1  - Ko, Yon-Dschun
A1  - Jones, Michael E.
A1  - Konstantopoulou, Irene
A1  - Kristensen, Vessela N.
A1  - Laitman, Yael
A1  - Lambrechts, Diether
A1  - Lazaro, Conxi
A1  - Leslie, Goska
A1  - Lester, Jenny
A1  - Lesueur, Fabienne
A1  - Lindström, Sara
A1  - Long, Jirong
A1  - Loud, Jennifer T.
A1  - Lubiński, Jan
A1  - Makalic, Enes
A1  - Mannermaa, Arto
A1  - Manoochehri, Mehdi
A1  - Margolin, Sara
A1  - Maurer, Tabea
A1  - Mavroudis, Dimitrios
A1  - McGuffog, Lesley
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Michailidou, Kyriaki
A1  - Miller, Austin
A1  - Montagna, Marco
A1  - Moreno, Fernando
A1  - Moserle, Lidia
A1  - Mulligan, Anna Marie
A1  - Nathanson, Katherine L.
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Nevelsteen, Ines
A1  - Nielsen, Finn C.
A1  - Nikitina-Zake, Liene
A1  - Nussbaum, Robert L.
A1  - Offit, Kenneth
A1  - Olah, Edith
A1  - Olopade, Olufunmilayo I.
A1  - Olsson, Håkan
A1  - Osorio, Ana
A1  - Papp, Janos
A1  - Park-Simon, Tjoung-Won
A1  - Parsons, Michael T.
A1  - Pedersen, Inge Sokilde
A1  - Peixoto, Ana
A1  - Peterlongo, Paolo
A1  - Pharaoh, Paul D. P.
A1  - Plaseska-Karanfilska, Dijana
A1  - Poppe, Bruce
A1  - Presneau, Nadege
A1  - Radice, Paolo
A1  - Rantala, Johanna
A1  - Rennert, Gad
A1  - Risch, Harvey A.
A1  - Saloustros, Emmanouil
A1  - Sanden, Kristin
A1  - Sawyer, Elinor J.
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Sharma, Priyanka
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Singer, Christian F.
A1  - Soucy, Penny
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Spurdle, Amanda B.
A1  - Stone, Jennifer
A1  - Swerdlow, Anthony J.
A1  - Tapper, William J.
A1  - Taylor, Jack A.
A1  - Teixeira, Manuel R.
A1  - Terry, Mary Beth
A1  - Teulé, Alex
A1  - Thomassen, Mads
A1  - Thöne, Kathrin
A1  - Thull, Darcy L.
A1  - Tischkowitz, Marc
A1  - Toland, Amanda E.
A1  - Torres, Diana
A1  - Truong, Thérèse
A1  - Tung, Nadine
A1  - Vachon, Celine M.
A1  - van Asperen, Christi J.
A1  - van den Ouweland, Ans M. W.
A1  - van Rensburg, Elizabeth J.
A1  - Vega, Ana
A1  - Viel, Alexandra
A1  - Wang, Qin
A1  - Wappenschmidt, Barbara
A1  - Weitzel, Jeffrey N.
A1  - Wendt, Camilla
A1  - Winqvist, Robert
A1  - Yang, Xiaohong R.
A1  - Yannoukakos, Drakoulis
A1  - Ziogas, Argyrios
A1  - Kraft, Peter
A1  - Antoniou, Antonis C.
A1  - Zheng, Wei
A1  - Easton, Douglas F.
A1  - Milne, Roger L.
A1  - Beesley, Jonathan
A1  - Chenevix-Trench, Georgia
T1  - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
JF  - Nature Communications
N2  - Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
KW  - cancer
KW  - genetics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228024
VL  - 10
ER  - 
TY  - JOUR
A1  - Fan, Sook-Ha
A1  - Ebner, Patrick
A1  - Reichert, Sebstian
A1  - Hertlein, Tobias
A1  - Zabel, Susanne
A1  - Lankapalli, Aditya Kumar
A1  - Nieselt, Kay
A1  - Ohlsen, Knut
A1  - Götz, Friedrich
T1  - MpsAB is important for Staphylococcus aureus virulence and growth at atmospheric CO2 levels
JF  - Nature Communications
N2  - The mechanisms behind carbon dioxide (CO2) dependency in non-autotrophic bacterial isolates are unclear. Here we show that the Staphylococcus aureus mpsAB operon, known to play a role in membrane potential generation, is crucial for growth at atmospheric CO2 levels. The genes mpsAB can complement an Escherichia coli carbonic anhydrase (CA) mutant, and CA from E. coli can complement the S. aureus delta-mpsABC mutant. In comparison with the wild type, S. aureus mps mutants produce less hemolytic toxin and are less virulent in animal models of infection. Homologs of mpsA and mpsB are widespread among bacteria and are often found adjacent to each other on the genome. We propose that MpsAB represents a dissolved inorganic carbon transporter, or bicarbonate concentrating system, possibly acting as a sodium bicarbonate cotransporter.
KW  - bacterial physiology
KW  - bacteriology
KW  - pathogens
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227624
VL  - 10
ER  - 
TY  - JOUR
A1  - El-Mesery, Mohamed
A1  - Rosenthal, Tina
A1  - Rauert-Wunderlich, Hilka
A1  - Schreder, Martin
A1  - Stühmer, Thorsten
A1  - Leich, Ellen
A1  - Schlosser, Andreas
A1  - Ehrenschwender, Martin
A1  - Wajant, Harald
A1  - Siegmund, Daniela
T1  - The NEDD8-activating enzyme inhibitor MLN4924 sensitizes a TNFR1+ subgroup of multiple myeloma cells for TNF-induced cell death
JF  - Cell Death & Disease
N2  - The NEDD8-activating enzyme (NAE) inhibitor MLN4924 inhibits cullin-RING ubiquitin ligase complexes including the SKP1-cullin-F-box E3 ligase βTrCP. MLN4924 therefore inhibits also the βTrCP-dependent activation of the classical and the alternative NFĸB pathway. In this work, we found that a subgroup of multiple myeloma cell lines (e.g., RPMI-8226, MM.1S, KMS-12BM) and about half of the primary myeloma samples tested are sensitized to TNF-induced cell death by MLN4924. This correlated with MLN4924-mediated inhibition of TNF-induced activation of the classical NFκB pathway and reduced the efficacy of TNF-induced TNFR1 signaling complex formation. Interestingly, binding studies revealed a straightforward correlation between cell surface TNFR1 expression in multiple myeloma cell lines and their sensitivity for MLN4924/TNF-induced cell death. The cell surface expression levels of TNFR1 in the investigated MM cell lines largely correlated with TNFR1 mRNA expression. This suggests that the variable levels of cell surface expression of TNFR1 in myeloma cell lines are decisive for TNF/MLN4924 sensitivity. Indeed, introduction of TNFR1 into TNFR1-negative TNF/MLN4924-resistant KMS-11BM cells, was sufficient to sensitize this cell line for TNF/MLN4924-induced cell death. Thus, MLN4924 might be especially effective in myeloma patients with TNFR1+ myeloma cells and a TNFhigh tumor microenvironment.
KW  - cancer therapy
KW  - tumour-necrosis factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226666
VL  - 10
ER  - 
TY  - JOUR
A1  - Dörk, Thilo
A1  - Peterlongo, Peter
A1  - Mannermaa, Arto
A1  - Bolla, Manjeet K.
A1  - Wang, Qin
A1  - Dennis, Joe
A1  - Ahearn, Thomas
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Augustinsson, Annelie
A1  - Beane Freeman, Laura E.
A1  - Beckmann, Matthias W.
A1  - Beeghly-Fadiel, Alicia
A1  - Behrens, Sabine
A1  - Bermisheva, Marina
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Burwinkel, Barbara
A1  - Canzian, Federico
A1  - Chan, Tsun L.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Choi, Ji-Yeob
A1  - Christiansen, Hans
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - dos-Santos-Silva, Isabel
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ekici, Arif B.
A1  - Eriksson, Mikael
A1  - Evans, D. Gareth
A1  - Fasching, Peter A.
A1  - Figueroa, Jonine
A1  - Flyger, Henrik
A1  - Fritschi, Lin
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Gao, Chi
A1  - Gapstur, Susan M.
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - Guenél, Pascal
A1  - Haeberle, Lothar
A1  - Haimann, Christopher A.
A1  - Håkansson, Niclas
A1  - Hall, Per
A1  - Hamann, Ute
A1  - Hartman, Mikael
A1  - Hauke, Jan
A1  - Hein, Alexander
A1  - Hillemanns, Peter
A1  - Hogervorst, Frans B. L.
A1  - Hooning, Maartje J.
A1  - Hopper, John L.
A1  - Howell, Tony
A1  - Huo, Dezheng
A1  - Ito, Hidemi
A1  - Iwasaki, Motoki
A1  - Jakubowska, Anna
A1  - Janni, Wolfgang
A1  - John, Esther M.
A1  - Jung, Audrey
A1  - Kaaks, Rudolf
A1  - Kang, Daehee
A1  - Kapoor, Pooja Middha
A1  - Khusnutdinova, Elza
A1  - Kim, Sung-Won
A1  - Kitahara, Cari M.
A1  - Koutros, Stella
A1  - Kraft, Peter
A1  - Kristensen, Vessela N.
A1  - Kwong, Ava
A1  - Lambrechts, Diether
A1  - Le Marchand, Loic
A1  - Li, Jingmei
A1  - Lindström, Sara
A1  - Linet, Martha
A1  - Lo, Wing-Yee
A1  - Long, Jirong
A1  - Lophatananon, Artitaya
A1  - Lubiński, Jan
A1  - Manoochehri, Mehdi
A1  - Manoukian, Siranoush
A1  - Margolin, Sara
A1  - Martinez, Elena
A1  - Matsuo, Keitaro
A1  - Mavroudis, Dimitris
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Milne, Roger L.
A1  - Mohd Taib, Nur Aishah
A1  - Muir, Kenneth
A1  - Mulligan, Anna Marie
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Neven, Patrick
A1  - Newman, William G.
A1  - Offit, Kenneth
A1  - Olopade, Olufunmilayo I.
A1  - Olshan, Andrew F.
A1  - Olson, Janet E.
A1  - Olsson, Håkan
A1  - Park, Sue K.
A1  - Park-Simon, Tjoung-Won
A1  - Peto, Julian
A1  - Plaseska-Karanfilska, Dijana
A1  - Pohl-Rescigno, Esther
A1  - Presneau, Nadege
A1  - Rack, Brigitte
A1  - Radice, Paolo
A1  - Rashid, Muhammad U.
A1  - Rennert, Gad
A1  - Rennert, Hedy S.
A1  - Romero, Atocha
A1  - Ruebner, Matthias
A1  - Saloustros, Emmanouil
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Schneider, Michael O.
A1  - Schoemaker, Minouk J.
A1  - Scott, Christopher
A1  - Shen, Chen-Yang
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Slager, Susan
A1  - Smichkoska, Snezhana
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Stone, Jennifer
A1  - Surowy, Harald
A1  - Swerdlow, Anthony J.
A1  - Tamimi, Rulla M.
A1  - Tapper, William J.
A1  - Teo, Soo H.
A1  - Terry, Mary Beth
A1  - Toland, Amanda E.
A1  - Tollenaar, Rob A. E. M.
A1  - Torres, Diana
A1  - Torres-Mejía, Gabriela
A1  - Troester, Melissa A.
A1  - Truong, Thérèse
A1  - Tsugane, Shoichiro
A1  - Untch, Michael
A1  - Vachon, Celine M.
A1  - van den Ouweland, Ans M. W.
A1  - van Veen, Elke M.
A1  - Vijai, Joseph
A1  - Wendt, Camilla
A1  - Wolk, Alicja
A1  - Yu, Jyh-Cherng
A1  - Zheng, Wei
A1  - Ziogas, Argyrios
A1  - Ziv, Elad
A1  - Dunnig, Alison
A1  - Pharaoh, Paul D. P.
A1  - Schindler, Detlev
A1  - Devilee, Peter
A1  - Easton, Douglas F.
T1  - Two truncating variants in FANCC and breast cancer risk
JF  - Scientific Reports
N2  - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
KW  - oncology
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838
VL  - 9
ER  - 
TY  - JOUR
A1  - Dietrich, Thomas
A1  - Krug, Ralf
A1  - Krastl, Gabriel
A1  - Tomson, Philip L.
T1  - Restoring the unrestorable! Developing coronal tooth tissue with a minimally invasive surgical extrusion technique
JF  - British Dental Journal
N2  - Surgical extrusion is a recognised treatment option for teeth that have insufficient coronal tooth structure remaining due to deep caries, resorption or traumatic injury. However, the technique has not been widely adopted, arguably because extraction of a severely compromised tooth may be difficult to achieve in a gentle and predictable way. In this paper, we present our novel approach to surgical extrusion and subsequent management of teeth using a vertical extraction system (Benex), which has become the method of choice in the authors' practice for many teeth that would otherwise be deemed unrestorable. We describe the clinical procedure in detail and discuss the advantages and disadvantages compared to alternative approaches, including surgical crown lengthening and orthodontic extrusion.
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225333
VL  - 226
ER  - 
TY  - JOUR
A1  - Diehl-Schmid, Janine
A1  - Licata, Abigail
A1  - Goldhardt, Oliver
A1  - Förstl, Hans
A1  - Yakushew, Igor
A1  - Otto, Markus
A1  - Anderl-Straub, Sarah
A1  - Beer, Ambros
A1  - Ludolph, Albert Christian
A1  - Landwehrmeyer, Georg Bernhard
A1  - Levin, Johannes
A1  - Danek, Adrian
A1  - Fliessbach, Klaus
A1  - Spottke, Annika
A1  - Fassbender, Klaus
A1  - Lyros, Epameinondas
A1  - Prudlo, Johannes
A1  - Krause, Bernd Joachim
A1  - Volk, Alexander
A1  - Edbauer, Dieter
A1  - Schroeter, Matthias Leopold
A1  - Drzezga, Alexander
A1  - Kornhuber, Johannes
A1  - Lauer, Martin
A1  - Grimmer, Timo
T1  - FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations
JF  - Translational Psychiatry
N2  - C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.
KW  - diagnostic markers
KW  - psychiatric disorders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225308
VL  - 9
ER  - 
TY  - JOUR
A1  - Dekker, Annelot M.
A1  - Diekstra, Frank P.
A1  - Pulit, Sara L.
A1  - Tazelaar, Gijs H. P.
A1  - van der Spek, Rick A.
A1  - van Rheenen, Wouter
A1  - van Eijk, Kristel R.
A1  - Calvo, Andrea
A1  - Brunetti, Maura
A1  - Van Damme, Philip
A1  - Robberecht, Wim
A1  - Hardiman, Orla
A1  - McLaughlin, Russell
A1  - Chiò, Adriano
A1  - Sendtner, Michael
A1  - Ludolph, Albert C.
A1  - Weishaupt, Jochen H.
A1  - Pardina, Jesus S. Mora
A1  - van den Berg, Leonard H.
A1  - Veldink, Jan H.
T1  - Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis
JF  - Scientific Reports
N2  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. In this largest exome-wide study of rare variants in ALS to date, we performed single-variant association testing, gene-based burden, and exome-wide individual set-unique burden (ISUB) testing to identify single or aggregated rare variation that modifies disease risk. In single-variant testing no variants reached exome-wide significance, likely due to limited statistical power. Gene-based burden testing of rare non-synonymous and loss-of-function variants showed NEK1 as the top associated gene. ISUB analysis did not show an increased exome-wide burden of deleterious variants in patients, possibly suggesting a more region-specific role for rare variation. Complete summary statistics are released publicly. This study did not implicate new risk loci, emphasizing the immediate need for future large-scale collaborations in ALS that will expand available sample sizes, increase genome coverage, and improve our ability to detect rare variants associated to ALS.
KW  - amyotrophic lateral sclerosis
KW  - genome-wide association studies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223686
VL  - 9
ER  - 
TY  - JOUR
A1  - Dammert, Marcel A.
A1  - Brägelmann, Johannes
A1  - Olsen, Rachelle R.
A1  - Böhm, Stefanie
A1  - Monhasery, Niloufar
A1  - Whitney, Christopher P.
A1  - Chalishazar, Milind D.
A1  - Tumbrink, Hannah L.
A1  - Guthrie, Matthew R.
A1  - Klein, Sebastian
A1  - Ireland, Abbie S.
A1  - Ryan, Jeremy
A1  - Schmitt, Anna
A1  - Marx, Annika
A1  - Ozretić, Luka
A1  - Castiglione, Roberta
A1  - Lorenz, Carina
A1  - Jachimowicz, Ron D.
A1  - Wolf, Elmar
A1  - Thomas, Roman K.
A1  - Poirier, John T.
A1  - Büttner, Reinhard
A1  - Sen, Triparna
A1  - Byers, Lauren A.
A1  - Reinhardt, H. Christian
A1  - Letai, Anthony
A1  - Oliver, Trudy G.
A1  - Sos, Martin L.
T1  - MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer
JF  - Nature Communications
N2  - MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.
KW  - genetic engineering
KW  - oncogenes
KW  - small-cell lung cancer
KW  - targeted therapies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223569
VL  - 10
ER  - 
TY  - JOUR
A1  - Steuer Costa, Wagner
A1  - Van der Auwera, Petrus
A1  - Glock, Caspar
A1  - Liewald, Jana F.
A1  - Bach, Maximilian
A1  - Schüler, Christina
A1  - Wabnig, Sebastian
A1  - Oranth, Alexandra
A1  - Masurat, Florentin
A1  - Bringmann, Henrik
A1  - Schoofs, Liliane
A1  - Stelzer, Ernst H. K.
A1  - Fischer, Sabine C.
A1  - Gottschalk, Alexander
T1  - A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics
JF  - Nature Communications
N2  - Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.
KW  - Cellular neuroscience
KW  - Neural circuits
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223273
VL  - 10
ER  - 
TY  - JOUR
A1  - Annunziata, Ida
A1  - van de Vlekkert, Diantha
A1  - Wolf, Elmar
A1  - Finkelstein, David
A1  - Neale, Geoffrey
A1  - Machado, Eda
A1  - Mosca, Rosario
A1  - Campos, Yvan
A1  - Tillman, Heather
A1  - Roussel, Martine F.
A1  - Weesner, Jason Andrew
A1  - Fremuth, Leigh Ellen
A1  - Qiu, Xiaohui
A1  - Han, Min-Joon
A1  - Grosveld, Gerard C.
A1  - d'Azzo, Alessandra
T1  - MYC competes with MiT/TFE in regulating lysosomal biogenesis and autophagy through an epigenetic rheostat
JF  - Nature Communications
N2  - Coordinated regulation of the lysosomal and autophagic systems ensures basal catabolism and normal cell physiology, and failure of either system causes disease. Here we describe an epigenetic rheostat orchestrated by c-MYC and histone deacetylases that inhibits lysosomal and autophagic biogenesis by concomitantly repressing the expression of the transcription factors MiT/TFE and FOXH1, and that of lysosomal and autophagy genes. Inhibition of histone deacetylases abates c-MYC binding to the promoters of lysosomal and autophagy genes, granting promoter occupancy to the MiT/TFE members, TFEB and TFE3, and/or the autophagy regulator FOXH1. In pluripotent stem cells and cancer, suppression of lysosomal and autophagic function is directly downstream of c-MYC overexpression and may represent a hallmark of malignant transformation. We propose that, by determining the fate of these catabolic systems, this hierarchical switch regulates the adaptive response of cells to pathological and physiological cues that could be exploited therapeutically.
KW  - autophagy
KW  - cancer
KW  - cancer metabolism
KW  - cell biology
KW  - mechanisms of disease
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221189
VL  - 10
ER  - 
TY  - JOUR
A1  - Al-Zaben, Naim
A1  - Medyukhina, Anna
A1  - Dietrich, Stefanie
A1  - Marolda, Alessandra
A1  - Hünniger, Kerstin
A1  - Kurzai, Oliver
A1  - Figge, Marc Thilo
T1  - Automated tracking of label-free cells with enhanced recognition of whole tracks
JF  - Scientific Reports
N2  - Migration and interactions of immune cells are routinely studied by time-lapse microscopy of in vitro migration and confrontation assays. To objectively quantify the dynamic behavior of cells, software tools for automated cell tracking can be applied. However, many existing tracking algorithms recognize only rather short fragments of a whole cell track and rely on cell staining to enhance cell segmentation. While our previously developed segmentation approach enables tracking of label-free cells, it still suffers from frequently recognizing only short track fragments. In this study, we identify sources of track fragmentation and provide solutions to obtain longer cell tracks. This is achieved by improving the detection of low-contrast cells and by optimizing the value of the gap size parameter, which defines the number of missing cell positions between track fragments that is accepted for still connecting them into one track. We find that the enhanced track recognition increases the average length of cell tracks up to 2.2-fold. Recognizing cell tracks as a whole will enable studying and quantifying more complex patterns of cell behavior, e.g. switches in migration mode or dependence of the phagocytosis efficiency on the number and type of preceding interactions. Such quantitative analyses will improve our understanding of how immune cells interact and function in health and disease.
KW  - image processing
KW  - software
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221093
VL  - 9
ER  - 
TY  - JOUR
A1  - Albrecht, Franziska
A1  - Mueller, Karsten
A1  - Ballarini, Tommaso
A1  - Lampe, Leonie
A1  - Diehl-Schmid, Janine
A1  - Fassbender, Klaus
A1  - Fliessbach, Klaus
A1  - Jahn, Holger
A1  - Jech, Robert
A1  - Kassubek, Jan
A1  - Kornhuber, Johannes
A1  - Landwehrmeyer, Bernhard
A1  - Lauer, Martin
A1  - Ludolph, Albert C.
A1  - Lyros, Epameinondas
A1  - Prudlo, Johannes
A1  - Schneider, Anja
A1  - Synofzik, Matthis
A1  - Wiltfang, Jens
A1  - Danek, Adrian
A1  - Otto, Markus
A1  - Schroeter, Matthias L.
T1  - Unraveling corticobasal syndrome and alien limb syndrome with structural brain imaging
JF  - Cortex
N2  - Alien limb phenomenon is a rare syndrome associated with a feeling of non-belonging and disowning toward one's limb. In contrast, anarchic limb phenomenon leads to involuntary but goal-directed movements. Alien/anarchic limb phenomena are frequent in corticobasal syndrome (CBS), an atypical parkinsonian syndrome characterized by rigidity, akinesia, dystonia, cortical sensory deficit, and apraxia. The structure function relationship of alien/anarchic limb was investigated in multi centric structural magnetic resonance imaging (MRI) data. Whole-group and single subject comparisons were made in 25 CBS and eight CBS-alien/anarchic limb patients versus controls. Support vector machine was used to see if CBS with and without alien/anarchic limb could be distinguished by structural MRI patterns. Whole-group comparison of CBS versus controls revealed asymmetric frontotemporal atrophy. CBS with alien/anarchic limb syndrome versus controls showed frontoparietal atrophy including the supplementary motor area contralateral to the side of the affected limb. Exploratory analysis identified frontotemporal regions encompassing the pre-/and postcentral gyrus as compromised in CBS with alien limb syndrome. Classification of CBS patients yielded accuracies of 79%. CBS-alien/anarchic limb syndrome was differentiated from CBS patients with an accuracy of 81%. Predictive differences were found in the cingulate gyrus spreading to frontomedian cortex, postcentral gyrus, and temporoparietoocipital regions. We present the first MRI-based group analysis on CBS-alien/anarchic limb. Results pave the way for individual clinical syndrome prediction and allow understanding the underlying neurocognitive architecture. (C) 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
KW  - Alien limb syndrome
KW  - Anarchic limb syndrome
KW  - Corticobasal syndrome
KW  - Diagnosis prediction
KW  - Support vector machine
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221040
VL  - 117
ER  - 
TY  - JOUR
T1  - Search for Multimessenger Sources of Gravitational Waves and High-energy Neutrinos with Advanced LIGO during Its First Observing Run, ANTARES, and IceCube
JF  - The Astrophysical Journal
N2  - Astrophysical sources of gravitational waves, such as binary neutron star and black hole mergers or core-collapse supernovae, can drive relativistic outflows, giving rise to non-thermal high-energy emission. High-energy neutrinos are signatures of such outflows. The detection of gravitational waves and high-energy neutrinos from common sources could help establish the connection between the dynamics of the progenitor and the properties of the outflow. We searched for associated emission of gravitational waves and high-energy neutrinos from astrophysical transients with minimal assumptions using data from Advanced LIGO from its first observing run O1, and data from the Antares and IceCube neutrino observatories from the same time period. We focused on candidate events whose astrophysical origins could not be determined from a single messenger. We found no significant coincident candidate, which we used to constrain the rate density of astrophysical sources dependent on their gravitational-wave and neutrino emission processes.
KW  - gravitational waves
KW  - neutrinos
KW  - Electromagnetic signals
KW  - Events GW150914
KW  - ray
KW  - emission
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-360189
VL  - 870
IS  - 2
PB  - The American Astronomical Society
ER  - 
TY  - JOUR
A1  - Albert, A.
A1  - André, M.
A1  - Anghinolfi, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Aublin, J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martít, J.
A1  - Basa, S.
A1  - Belhorma, B.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Boumaaza, J
A1  - Bourret, S.
A1  - Bouwhuis, M. C.
A1  - Brânzas, H.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chabab, M.
A1  - Cherkaoui El Moursli, R.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coelho, J. A. B.
A1  - Coleiro, A.
A1  - Colomer, M
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Díaz, A. F.
A1  - Deschamps, A.
A1  - Distefano, C.
A1  - Di Palma, I.
A1  - Domi, A.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - El Khayati, N.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Ettahiri, A.
A1  - Fassi, F.
A1  - Felis, I.
A1  - Fermani, P.
A1  - Ferrara, G.
A1  - Fusco, L. A.
A1  - Gay, P.
A1  - Glotin, H.
A1  - Grégoire, T.
A1  - Gracia Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A. J.
A1  - Hello, Y.
A1  - Hernández-Rey, J. J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Illuminati, G.
A1  - de Jong, M.
A1  - Jongen, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Khan-Chowdhury, N. R.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Levi, G.
A1  - Lotze, M.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J. A.
A1  - Mele, R.
A1  - Melis, K.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Navas, S.
A1  - Nezri, E.
A1  - Nuñez, A.
A1  - Organokov, M.
A1  - Pavalas, G. E.
A1  - Pellegrino, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Quinn, L.
A1  - Racca, C.
A1  - Randazzo, N.
A1  - Riccobene, G.
A1  - Sánchez-Losa, A.
A1  - Saldaña, M.
A1  - Salvadori, I.
A1  - Samtleben, D. F. E.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schüssler, F.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Taiuti, M.
A1  - Tayalati, Y.
A1  - Trovato, A.
A1  - Vallage, B.
A1  - Van Elewyck, V.
A1  - Versari, F.
A1  - Vivolo, D.
A1  - Wilms, J.
A1  - Zaborov, D.
A1  - Zornoza, J. D.
A1  - Zúñiga, J.
T1  - The cosmic ray shadow of the Moon observed with the ANTARES neutrino telescope
JF  - European Physical Journal C
N2  - One of the main objectives of the ANTARES telescope is the search for point- like neutrino sources. Both the pointing accuracy and the angular resolution of the detector are important in this context and a reliableway to evaluate this performance is needed. In order to measure the pointing accuracy of the detector, one possibility is to study the shadow of the Moon, i. e. the deficit of the atmospheric muon flux from the direction of the Moon induced by the absorption of cosmic rays. Analysing the data taken between 2007 and 2016, theMoon shadow is observed with 3.5s statistical significance. The detector angular resolution for downwardgoing muons is 0.73. +/- 0.14.. The resulting pointing performance is consistent with the expectations. An independent check of the telescope pointing accuracy is realised with the data collected by a shower array detector onboard of a ship temporarily moving around the ANTARES location.
KW  - Atmospheric muons
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227802
VL  - 78
ER  - 
TY  - JOUR
T1  - Measuring the atmospheric neutrino oscillation parameters and constraining the 3+1 neutrino model with ten years of ANTARES data
JF  - Journal of High Energy Physics
N2  - The ANTARES neutrino telescope has an energy threshold of a few tens of GeV. This allows to study the phenomenon of atmospheric muon neutrino disappearance due to neutrino oscillations. In a similar way, constraints on the 3+1 neutrino model, which foresees the existence of one sterile neutrino, can be inferred. Using data collected by the ANTARES neutrino telescope from 2007 to 2016, a new measurement of m 2 and (23) has been performed which is consistent with world best-fit values and constraints on the 3+1 neutrino model have been derived.
KW  - Neutrino Detectors and Telescopes (experiments)
KW  - Oscillation
KW  - Matter
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227791
VL  - 113
IS  - 6
ER  - 
TY  - JOUR
A1  - Alacevich, Massimo
A1  - Carloni Calame, Carlo M.
A1  - Chiesa, Mauro
A1  - Montagna, Guido
A1  - Nicrosini, Oreste
A1  - Piccinini, Fulvio
T1  - Muon-electron scattering at NLO
JF  - Journal of High Energy Physics
N2  - We consider the process of muon-electron elastic scattering, which has been proposed as an ideal framework to measure the running of the electromagnetic coupling constant at space-like momenta and determine the leading-order hadronic contribution to the muon g-2 (MUonE experiment). We compute the next-to-leading (NLO) contributions due to QED and purely weak corrections and implement them into a fully differential Monte Carlo event generator, which is available for first experimental studies. We show representative phenomenological results of interest for the MUonE experiment and examine in detail the impact of the various sources of radiative corrections under different selection criteria, in order to study the dependence of the NLO contributions on the applied cuts. The study represents the first step towards the realisation of a high-precision Monte Carlo code necessary for data analysis.
KW  - NLO Computations
KW  - Anomalous magnetic-moment
KW  - Radiative-corrections
KW  - Reduction
KW  - G-2
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227777
VL  - 155
IS  - 2
ER  - 
TY  - JOUR
A1  - Aktas, Bertal H.
A1  - Upcin, Berin
A1  - Henke, Erik
A1  - Padmasekar, Manju
A1  - Qin, Xuebin
A1  - Ergün, Süleyman
T1  - The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells
JF  - Stem Cells International
N2  - Pluripotent stem cells give rise to reproductively enabled offsprings by generating progressively lineage-restricted multipotent stem cells that would differentiate into lineage-committed stem and progenitor cells. These lineage-committed stem and progenitor cells give rise to all adult tissues and organs. Adult stem and progenitor cells are generated as part of the developmental program and play critical roles in tissue and organ maintenance and/or regeneration. The ability of pluripotent stem cells to self-renew, maintain pluripotency, and differentiate into a multicellular organism is highly dependent on sensing and integrating extracellular and extraorganismal cues. Proteins perform and integrate almost all cellular functions including signal transduction, regulation of gene expression, metabolism, and cell division and death. Therefore, maintenance of an appropriate mix of correctly folded proteins, a pristine proteome, is essential for proper stem cell function. The stem cells' proteome must be pristine because unfolded, misfolded, or otherwise damaged proteins would interfere with unlimited self-renewal, maintenance of pluripotency, differentiation into downstream lineages, and consequently with the development of properly functioning tissue and organs. Understanding how various stem cells generate and maintain a pristine proteome is therefore essential for exploiting their potential in regenerative medicine and possibly for the discovery of novel approaches for maintaining, propagating, and differentiating pluripotent, multipotent, and adult stem cells as well as induced pluripotent stem cells. In this review, we will summarize cellular networks used by various stem cells for generation and maintenance of a pristine proteome. We will also explore the coordination of these networks with one another and their integration with the gene regulatory and signaling networks.
KW  - Endoplasmic-Reticulum Stress
KW  - Heme-regulated inhibitor
KW  - Human Muse Cells
KW  - Transcription factor NRF1
KW  - ER-Stress
KW  - Hematopoietic Stem
KW  - Quality-control
KW  - Messenger-RNAs
KW  - Neural Differentiation
KW  - Translation Initiation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227769
ER  - 
TY  - JOUR
T1  - Sensitivity of the KM3NeT/ARCA neutrino telescope to point-like neutrino sources
JF  - Astroparticle Physics
N2  - KM3NeT will be a network of deep-sea neutrino telescopes in the Mediterranean Sea. The KM3NeT/ARCA detector, to be installed at the Capo Passero site (Italy), is optimised for the detection of high-energy neutrinos of cosmic origin. Thanks to its geographical location on the Northern hemisphere, KM3NeT/ARCA can observe upgoing neutrinos from most of the Galactic Plane, including the Galactic Centre. Given its effective area and excellent pointing resolution, KM3NeT/ARCA will measure or significantly constrain the neutrino flux from potential astrophysical neutrino sources. At the same time, it will test flux predictions based on gamma-ray measurements and the assumption that the gamma-ray flux is of hadronic origin. Assuming this scenario, discovery potentials and sensitivities for a selected list of Galactic sources and to generic point sources with an E-2 spectrum are presented. These spectra are assumed to be time independent. The results indicate that an observation with 3 sigma significance is possible in about six years of operation for the most intense sources, such as Supernovae Remnants RX J1713.7-3946 and Vela Jr. If no signal will be found during this time, the fraction of the gamma-ray flux coming from hadronic processes can be constrained to be below 50% for these two objects. (C) 2019 The Authors. Published by Elsevier B.V.
KW  - Astrophysical neutrino sources
KW  - Cherenkov underwater neutrino telescope
KW  - KM3NeT
KW  - Remnant RX J1713.7-3946
KW  - Particle-acceleration
KW  - Galactic sources
KW  - Cosmic-rays
KW  - Supernova
KW  - Radiation
KW  - Icecube
KW  - Shell
KW  - TEV
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227759
VL  - 111
ER  - 
TY  - JOUR
A1  - Abt, Raimond
A1  - Erdmenger, Johanna
A1  - Gerbershagen, Marius
A1  - Melby-Thompson, Charles M.
A1  - Northe, Christian
T1  - Holographic subregion complexity from kinematic space
JF  - Journal of High Energy Physics
N2  - We consider the computation of volumes contained in a spatial slice of AdS(3) in terms of observables in a dual CFT. Our main tool is kinematic space, defined either from the bulk perspective as the space of oriented bulk geodesics, or from the CFT perspective as the space of entangling intervals. We give an explicit formula for the volume of a general region in a spatial slice of AdS(3) as an integral over kinematic space. For the region lying below a geodesic, we show how to write this volume purely in terms of entangling entropies in the dual CFT. This expression is perhaps most interesting in light of the complexity = volume proposal, which posits that complexity of holographic quantum states is computed by bulk volumes. An extension of this idea proposes that the holographic subregion complexity of an interval, defined as the volume under its Ryu-Takayanagi surface, is a measure of the complexity of the corresponding reduced density matrix. If this is true, our results give an explicit relationship between entanglement and subregion complexity in CFT, at least in the vacuum. We further extend many of our results to conical defect and BTZ black hole geometries.
KW  - AdS-CFT Correspondence
KW  - Gauge-gravity correspondence
KW  - Black Holes in String Theory
KW  - Black-hole
KW  - Entanglement
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227711
VL  - 1
IS  - 12
ER  - 
TY  - JOUR
A1  - Abimannan, Nagarajan
A1  - Sumathi, G.
A1  - Krishnarajasekhar, O. R.
A1  - Sinha, Bhanu
A1  - Krishnan, Padma
T1  - Clonal Clusters and Virulence Factors of Methicillin-Resistant \(Staphylococcus\) \(Aureus\): Evidence for Community-Acquired Methicillin-Resistant \(Staphylococcus\) \(Aureus\) Infiltration into Hospital Settings in Chennai, South India
JF  - Indian Journal of Medical Microbiology
N2  - Background and Objective: Staphylococcus aureus is one of the major pathogens of nosocomial infections as wells as community-acquired (CA) infections worldwide. So far, large-scale comprehensive molecular and epidemiological characterisation of S. aureus from very diverse settings has not been carried out in India. The objective of this study is to evaluate the molecular, epidemiological and virulence characteristics of S. aureus in both community and hospital settings in Chennai, southern India. Methods: S. aureus isolates were obtained from four different groups (a) healthy individuals from closed community settings, (b) inpatients from hospitals, (c) outpatients from hospitals, representing isolates of hospital-community interface and (d) HIV-infected patients to define isolates associated with the immunocompromised. Antibiotic susceptibility testing, multiplex polymerase chain reactions for detection of virulence and resistance determinants, molecular typing including Staphylococcal cassette chromosome mec (SCCmec) and agr typing, were carried out. Sequencing-based typing was done using spa and multilocus sequence typing (MLST) methods. Clonal complexes (CC) of hospital and CA methicillin-resistant S. aureus (MRSA) were identified and compared for virulence and resistance. 

Results and Conclusion: A total of 769 isolates of S. aureus isolates were studied. The prevalence of MRSA was found to be 7.17%, 81.67%, 58.33% and 22.85% for groups a, b, c and d, respectively. Of the four SCCmec types (I, III, IV and V) detected, SCCmec V was found to be predominant. Panton-Valentine leucocidin toxin genes were detected among MRSA isolates harbouring SCCmec IV and V. A total of 78 spa types were detected, t657 being the most prevalent. 13 MLST types belonging to 9 CC were detected. CC1 (ST-772, ST-1) and CC8 (ST238, ST368 and ST1208) were found to be predominant among MRSA. CA-MRSA isolates with SCCmec IV and V were isolated from all study groups including hospitalised patients and were found to be similar by molecular tools. This shows that CA MRSA has probably infiltrated into the hospital settings.
KW  - Community-acquired methicillin-resistant Staphylococcus aureus
KW  - HIV
KW  - hospital-acquired methicillin-resistant Staphylococcus aureus
KW  - innate immune evasions
KW  - MLST
KW  - microbial surface component recognising adhesive matrix molecules
KW  - spa typing
KW  - ST 772
KW  - Inducible Clindamycin Resistance
KW  - Valentine Leukocidin Genes
KW  - Multiplex PCR
KW  - Nasal Carriage
KW  - Colonization
KW  - Prevalence
KW  - Emergence
KW  - Skin
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226963
VL  - 37
IS  - 3
ER  - 
TY  - JOUR
A1  - Coelho, Luis Pedro
A1  - Alves, Renato
A1  - Monteiro, Paulo
A1  - Huerta-Cepas, Jaime
A1  - Freitas, Ana Teresa
A1  - Bork, Peer
T1  - NG-meta-profiler: fast processing of metagenomes using NGLess, a domain-specific language
JF  - Microbiome
N2  - Background
Shotgun metagenomes contain a sample of all the genomic material in an environment, allowing for the characterization of a microbial community. In order to understand these communities, bioinformatics methods are crucial. A common first step in processing metagenomes is to compute abundance estimates of different taxonomic or functional groups from the raw sequencing data.

Given the breadth of the field, computational solutions need to be flexible and extensible, enabling the combination of different tools into a larger pipeline.

Results
We present NGLess and NG-meta-profiler. NGLess is a domain specific language for describing next-generation sequence processing pipelines. It was developed with the goal of enabling user-friendly computational reproducibility. It provides built-in support for many common operations on sequencing data and is extensible with external tools with configuration files.

Using this framework, we developed NG-meta-profiler, a fast profiler for metagenomes which performs sequence preprocessing, mapping to bundled databases, filtering of the mapping results, and profiling (taxonomic and functional). It is significantly faster than either MOCAT2 or htseq-count and (as it builds on NGLess) its results are perfectly reproducible.

Conclusions
NG-meta-profiler is a high-performance solution for metagenomics processing built on NGLess. It can be used as-is to execute standard analyses or serve as the starting point for customization in a perfectly reproducible fashion.

NGLess and NG-meta-profiler are open source software (under the liberal MIT license) and can be downloaded from https://ngless.embl.de or installed through bioconda.
KW  - metagenomics
KW  - next-generation sequencing
KW  - domain-specific language
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223161
VL  - 7
IS  - 84
ER  - 
TY  - JOUR
A1  - de Nijs, Laurence
A1  - Choe, Kyonghwan
A1  - Steinbusch, Hellen
A1  - Schijns, Olaf E. M. G.
A1  - Dings, Jim
A1  - van den Hove, Daniel L. A.
A1  - Rutten, Bart P. F.
A1  - Hoogland, Govert
T1  - DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures
JF  - Clinical Epigenetics
N2  - Background
Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS.

Results
We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls.

Conclusion
Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.
KW  - febrile seizures
KW  - temporal lobe epilepsy
KW  - epigenetics
KW  - DNA methylation
KW  - DNA methyltransferases
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223636
VL  - 11
ER  - 
TY  - JOUR
A1  - Kleinert, Evelyn
A1  - Müller, Frank
A1  - Furaijat, Ghefar
A1  - Hillermann, Nele
A1  - Jablonka, Alexandra
A1  - Happle, Christine
A1  - Simmenroth, Anne
T1  - Does refugee status matter? Medical needs of newly arrived asylum seekers and resettlement refugees - a retrospective observational study of diagnoses in a primary care setting
JF  - Conflict and Health
N2  - Background
Providing adequate healthcare to newly arrived refugees is considered one of the significant challenges for the German healthcare system. These refugees can be classified mainly into two groups: asylum seekers (who have applied for asylum after arrival in Germany and are waiting for the refugee-status decision) and resettlement refugees (who have already been granted asylum status before arriving in Germany). Whereas earlier studies have explored the health status of asylum seekers especially in terms of mental and behavioural disorders and infectious diseases without distinguishing between these two groups, our study aims to evaluate possible relationships of asylum status and medical needs of these two groups with a special focus on mental and behavioural disorders and infectious diseases.

Methods
In this retrospective observational study, collected data on all asylum-seeker and resettlement-refugee patients (N = 2252) of a German reception centre (August 2017 to August 2018) is analysed by absolute and relative frequencies and medians. Patient data, collected by chart review, include age, gender, country of origin, asylum status, and diagnoses (ICD-10). To describe the relationship between sociodemographic factors (including asylum status) and diagnoses, we used tests of significance and bivariate correlations with Spearman correlation coefficients. All collected data are pseudonymised.

Results
Of all 2252 patients, 43% were resettlement refugees. In almost all ICD-10 categories, asylum seekers received significantly more diagnoses than resettlement refugees. According to our data, asylum seekers presented with mental and behavioural disorders nine times more often (9%) than resettlement refugees (1%). In the case of infectious diseases, the results are mixed: asylum seekers were twice as frequently (11%) diagnosed with certain infectious and parasitic diseases than resettlement refugees (5%), but resettlement refugees were treated twice as often (22% of the asylum seekers and 41% of the resettlement refugees) for diseases of the respiratory system, of which 84% were acute respiratory infections (in both groups).

Conclusion
This study indicates that patients with unregulated migration more frequently present symptoms of psychiatric diseases and somatoform symptoms than resettlement refugees. A health policy approach within migration policy should aim to enable persecuted persons to migrate under regulated and safe conditions.

Trial registration
German Clinical Trials Register: DRKS00013076, retrospectively registered on 29.09.2017.
KW  - primary healthcare
KW  - resettlement refugees
KW  - asylum seekers
KW  - asylum status
KW  - common diseases
KW  - migrant
KW  - infections
KW  - mental health
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325869
VL  - 13
ER  - 
TY  - JOUR
A1  - Hrudka, Jan
A1  - Eis, Václav
A1  - Heřman, Josef
A1  - Prouzová, Zuzana
A1  - Rosenwald, Andreas
A1  - František, Duška
T1  - Panniculitis-like T-cell-lymphoma in the mesentery associated with hemophagocytic syndrome: autopsy case report
JF  - Diagnostic Pathology
N2  - Background
Panniculitis-like T-cell lymphoma is an uncommon type of non-Hodgkin lymphoma, occurring usually in the form of nodules within the subcutaneous fat tissue of the extremities or trunk. In the literature, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is described as a distinct type of T-cell lymphoma with a variable clinical behavior, depending on molecular phenotype of T-cell receptor (TCR) and on the presence or absence of hemophagocytic syndrome.

Case presentation
We present a bioptic and autoptic case of a 65-years old Caucasian man with panniculitic T-cell lymphoma with morphological and immunohistochemical features of SPTCL, limited to the retroperitoneal and mesenteric mass, i.e. without any cutaneous involvement, and associated with severe hemophagocytic lymphohistiocytosis.

Conclusion
A panniculitic T-cell lymphoma with morphological and molecular features of SPTCL, which is limited to mesentery, i.e. does not involve subcutaneous fat, seems to be exceedingly rare.
KW  - panniculitis
KW  - T-cell lymphoma
KW  - mesentery
KW  - hemophagocytosis
KW  - lymphohistiocytosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-322665
VL  - 14
ER  - 
TY  - JOUR
A1  - Nentwich, Julia
A1  - Ruf, Katharina
A1  - Girschick, Hermann
A1  - Holl-Wieden, Annette
A1  - Morbach, Henner
A1  - Hebestreit, Helge
A1  - Hofmann, Christine
T1  - Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis
JF  - Pediatric Rheumatology
N2  - Background
Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system of yet unknown etiology. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physical activity, fitness and health-related quality of life (HRQOL) in adolescents with established diagnosis of CNO versus healthy controls (HC).

Methods
15 patients with CNO and 15 age and gender matched HC aged 13–18 years, completed questionnaires, performed an incremental exercise test with gas exchange measures up to voluntary fatigue and wore an accelerometer over 7 days at home to assess physical activity behavior.

Results
At the time of assessment, 5 CNO patients were in clinical, one in radiological and 5 in clinical and radiological remission. 7 did not receive any therapy at the time of assessment. The results of the exercise test and of the accelerometry did not show any significant difference between CNO and HC. However, reported sports participation was lower in patients with CNO and PedsQL3.0 and 4.0 showed significant lower values in most of the scores indicating reduced HRQOL.

Conclusion
Although most CNO patients showed a favorable course of disease without any relevant differences in objective measurements of physical activity and fitness versus HC at the time of assessment, questionnaires revealed perceived limitations. Further studies are needed to measure HRQOL and to validate questionnaires in patients with CNO against objective measures including more participants with a higher level of disease activity.
KW  - chronic non-bacterial osteomyelitis
KW  - CRMO
KW  - HRQOL
KW  - physical activity
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323710
VL  - 17
ER  - 
TY  - JOUR
A1  - Hörterer, Hubert
A1  - Baumbach, Sebastian Felix
A1  - Lemperle, Stefan
A1  - Altenberger, Sebastian
A1  - Gottschalk, Oliver
A1  - Mehlhorn, Alexander Tobias
A1  - Röser, Anke
A1  - Walther, Markus
T1  - Clinical outcome and concomitant injuries in operatively treated fractures of the lateral process of the talus
JF  - BMC Musculoskeletal Disorders
N2  - Background
The aim of this study was to review the patient rated outcome (PROM) of surgically treated fractures to the lateral process of the talus (LPTF) and identify factors influencing the outcome.

Methods
Retrospective study with a current follow-up. Eligible were all patients treated surgically for a LPTF (n = 23) with a minimum follow-up of one year. Demographics, medical history, trauma mechanism, fracture characteristics, concomitant injuries, treatment details, complications, return to work and sports were assessed retrospectively. The current follow-up included the VAS FA, Karlsson Score, and SF-12. The primary outcome was the VAS FA. Secondary aim was the identification of parameters influencing the PROMs.

Results
22 patients (96% follow-up) with a mean age of 32 ± 9 (18 to 49) years were included. 73% suffered a Hawkins Type 1, 23% a Type 2, and one patient a Type 3 fracture. 82% suffered concomitant injuries. 9% suffered minor surgical side infections, 50% developed symptomatic subtalar osteoarthritis. At final follow-up (44 ± 2 (12 to 97) months), the mean VAS FA Overall was 77 ± 21 (20 to 100), the Karlsson Score 72 ± 21 (34 to 97), and for the SF 12 the PCS 53 ± 8 (36 to 64) and the MCS 53 ± 7 (32 to 63). 50% of patients returned to their previous level of sports. Hawkins Type 1 fractures resulted in better VAS FA Overall score than Type 2 fractures. Posttraumatic subtalar osteoarthritis was the independent factor associated to a poor patient rated outcome (VAS FA, Karlsson Score).

Conclusion
After a follow-up of over 3.5 years, surgically treated LPTF resulted in only moderate results. 50% suffered posttraumatic symptomatic subtalar osteoarthritis, which was the primary independent parameter for a poor outcome following LPTF.

Level of evidence
Level III.
KW  - fracture
KW  - snowboarder's ankle
KW  - snowboarder's fracture
KW  - lateral process of the talus
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321207
VL  - 20
ER  - 
TY  - JOUR
A1  - Kiener, Mirjam
A1  - Chen, Lanpeng
A1  - Krebs, Markus
A1  - Grosjean, Joȅl
A1  - Klima, Irena
A1  - Kalogirou, Charis
A1  - Riedmiller, Hubertus
A1  - Kneitz, Burkhard
A1  - Thalmann, George N.
A1  - Snaar-Jagalska, Ewa
A1  - Spahn, Martin
A1  - Kruithof-de Julio, Marianna
A1  - Zoni, Eugenio
T1  - miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo
JF  - BMC Cancer
N2  - Background
Despite latest advances in prostate cancer (PCa) therapy, PCa remains the third-leading cause of cancer-related death in European men. Dysregulation of microRNAs (miRNAs), small non-coding RNA molecules with gene expression regulatory function, has been reported in all types of epithelial and haematological cancers. In particular, miR-221-5p alterations have been reported in PCa.

Methods
miRNA expression data was retrieved from a comprehensive publicly available dataset of 218 PCa patients (GSE21036) and miR-221-5p expression levels were analysed. The functional role of miR-221-5p was characterised in androgen- dependent and androgen- independent PCa cell line models (C4–2 and PC-3M-Pro4 cells) by miR-221-5p overexpression and knock-down experiments. The metastatic potential of highly aggressive PC-3M-Pro4 cells overexpressing miR-221-5p was determined by studying extravasation in a zebrafish model. Finally, the effect of miR-221-5p overexpression on the growth of PC-3M-Pro4luc2 cells in vivo was studied by orthotopic implantation in male Balb/cByJ nude mice and assessment of tumor growth.

Results
Analysis of microRNA expression dataset for human primary and metastatic PCa samples and control normal adjacent benign prostate revealed miR-221-5p to be significantly downregulated in PCa compared to normal prostate tissue and in metastasis compared to primary PCa. Our in vitro data suggest that miR-221-5p overexpression reduced PCa cell proliferation and colony formation. Furthermore, miR-221-5p overexpression dramatically reduced migration of PCa cells, which was associated with differential expression of selected EMT markers. The functional changes of miR-221-5p overexpression were reversible by the loss of miR-221-5p levels, indicating that the tumor suppressive effects were specific to miR-221-5p. Additionally, miR-221-5p overexpression significantly reduced PC-3M-Pro4 cell extravasation and metastasis formation in a zebrafish model and decreased tumor burden in an orthotopic mouse model of PCa.

Conclusions
Together these data strongly support a tumor suppressive role of miR-221-5p in the context of PCa and its potential as therapeutic target.
KW  - prostate cancer
KW  - miR-221-5p
KW  - proliferation
KW  - migration
KW  - tumor suppressor miRNA
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325762
VL  - 19
ER  - 
TY  - JOUR
A1  - Klement, Rainer J.
A1  - Abbasi-Senger, N.
A1  - Adebahr, S.
A1  - Alheid, H.
A1  - Allgaeuer, M.
A1  - Becker, G.
A1  - Blanck, O.
A1  - Boda-Heggemann, J.
A1  - Brunner, T.
A1  - Duma, M.
A1  - Eble, M. J.
A1  - Ernst, I.
A1  - Gerum, S.
A1  - Habermehl, D.
A1  - Hass, P.
A1  - Henkenberens, C.
A1  - Hildebrandt, G.
A1  - Imhoff, D.
A1  - Kahl, H.
A1  - Klass, N. D.
A1  - Krempien, R.
A1  - Lewitzki, V.
A1  - Lohaus, F.
A1  - Ostheimer, C.
A1  - Papachristofilou, A.
A1  - Petersen, C.
A1  - Rieber, J.
A1  - Schneider, T.
A1  - Schrade, E.
A1  - Semrau, R.
A1  - Wachter, S.
A1  - Wittig, A.
A1  - Guckenberger, M.
A1  - Andratschke, N.
T1  - The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases
JF  - BMC Cancer
N2  - Background
The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer.

Methods
The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS.

Results
Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC.

Conclusion
In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.
KW  - colorectal cancer
KW  - illness-death model
KW  - liver metastases
KW  - lung metastases
KW  - tumor control probability
KW  - stereotactic body radiation therapy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325877
VL  - 19
ER  - 
TY  - JOUR
A1  - Hinkelbein, Jochen
A1  - Iovino, Ivan
A1  - De Robertis, Edoardo
A1  - Kranke, Peter
T1  - Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research
JF  - BMC Anesthesiology
N2  - Background
Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS).

Methods
Retrospective analysis. Data were identified by using MEDLINE® database and the terms “video laryngoscopy” and “video laryngoscope” limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding.

Results
In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items “time to intubation” (65.86%), “laryngeal view grade” (44.89%), “successful intubation rate” (36.56%), “number of intubation attempts” (23.39%), “complications” (21.24%), and “successful first-pass intubation rate” (19.09%) were reported most frequently. A total of 19 specific parameters is recommended.

Conclusions
In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., “time to intubation” (inserting the laryngoscope to first ventilation), “laryngeal view grade” (C&L and POGO), “successful intubation rate”, etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.
KW  - airway management
KW  - video laryngoscopy
KW  - primary outcome
KW  - primary endpoint
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320747
VL  - 19
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Blazhenets, Ganna
A1  - Schröter, Nils
A1  - Frings, Lars
A1  - Jost, Wolfgang H.
A1  - Lapa, Constantin
A1  - Meyer, Philipp T.
T1  - Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators
JF  - EJNMMI Physics
N2  - Background
The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible.

Methods
We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure.

Results
H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6%).

Conclusions
The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.
KW  - MIBG
KW  - collimator
KW  - heart-to-mediastinum ratio
KW  - linear conversion
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221675
VL  - 6
ER  - 
TY  - JOUR
A1  - Hetzer, Benjamin
A1  - Orth-Höller, Dorothea
A1  - Würzner, Reinhard
A1  - Kreidl, Peter
A1  - Lackner, Michaela
A1  - Müller, Thomas
A1  - Knabl, Ludwig
A1  - Geisler-Moroder, Daniel Rudolf
A1  - Mellmann, Alexander
A1  - Sesli, Özcan
A1  - Holzknecht, Jeanett
A1  - Noce, Damia
A1  - Akarathum, Noppadon
A1  - Chotinaruemol, Somporn
A1  - Prelog, Martina
A1  - Oberdorfer, Peninnah
T1  - “Enhanced acquisition of antibiotic-resistant intestinal E. coli during the first year of life assessed in a prospective cohort study”
JF  - Antimicrobial Resistance & Infection Control
N2  - Background
Increasing bacterial resistance to antibiotics is a serious problem worldwide. We sought to record the acquisition of antibiotic-resistant Escherichia coli (E. coli) in healthy infants in Northern Thailand and investigated potential determinants.

Methods
Stool samples from 142 infants after birth, at ages 2wk, 2mo, 4 to 6mo, and 1y, and parent stool samples were screened for E. coli resistance to tetracycline, ampicillin, co-trimoxazole, and cefazoline by culture, and isolates were further investigated for multiresistance by disc diffusion method. Pulsed-field gel electrophoresis was performed to identify persistent and transmitted strains. Genetic comparison of resistant and transmitted strains was done by multilocus sequence typing (MLST) and strains were further investigated for extra- and intra-intestinal virulence factors by multiplex PCR.

Results
Forty-seven (33%) neonatal meconium samples contained resistant E. coli. Prevalence increased continuously: After 1y, resistance proportion (tetracycline 80%, ampicillin 72%, co-trimoxazole 66%, cefazoline 35%) almost matched those in parents. In 8 infants (6%), identical E. coli strains were found in at least 3 sampling time points (suggesting persistence). Transmission of resistant E. coli from parents to child was observed in only 8 families. MLST showed high diversity. We could not identify any virulence genes or factors associated with persistence, or transmission of resistant E. coli. Full-term, vaginal birth and birth in rural hospital were identified as risk factors for early childhood colonization with resistant E. coli.

Conclusion
One third of healthy Thai neonates harboured antibiotic-resistant E. coli in meconium. The proportion of resistant E. coli increased during the first year of life almost reaching the value in adults. We hypothesize that enhancement of infection control measures and cautious use of antibiotics may help to control further increase of resistance.
KW  - Escherichia coli
KW  - antibiotic resistance
KW  - multiresistance
KW  - transmission
KW  - persistence
KW  - children
KW  - neonates
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320284
VL  - 8
ER  - 
TY  - JOUR
A1  - Moremi, Nyambura
A1  - Claus, Heike
A1  - Vogel, Ulrich
A1  - Mshana, Stephen E.
T1  - The role of patients and healthcare workers Staphylococcus aureus nasal colonization in occurrence of surgical site infection among patients admitted in two centers in Tanzania
JF  - Antimicrobial Resistance & Infection Control
N2  - Background
Colonization with Staphylococcus aureus has been identified as a risk for subsequent occurrence of infection. This study investigated the relationship between S. aureus colonization of patients and healthcare workers (HCWs), and subsequent surgical site infections (SSI).

Methods
Between December 2014 and September 2015, a total of 930 patients and 143 HCWs were enrolled from the Bugando Medical Centre and Sekou Toure hospital in Mwanza, Tanzania. On admission and discharge nasal swabs, with an additional of wound swab for those who developed SSI were collected from patients whereas HCWs were swabbed once. Identification and antimicrobial susceptibility testing were done by VITEK-MS and VITEK-2, respectively. Detection of Panton Valentine leukocidin (PVL) and mecA genes was done by PCR. S. aureus isolates were further characterized by spa typing and Multi-Locus Sequence Typing (MLST).

Results
Among 930 patients screened for S. aureus on admission, 129 (13.9%) were positive of which 5.4% (7/129) were methicillin-resistant S. aureus (MRSA). Amongst 363 patients rescreened on discharge, 301 patients had been tested negative on admission of whom 29 (9.6%) turned positive after their hospital stay. Three (10.3%) of the 29 acquired S. aureus were MRSA. Inducible Clindamycin resistance occurred more often among acquired S. aureus isolates than among isolates from admission [34.5% (10/29) vs. 17.1% (22/129), P = 0.018]. S. aureus contributed to 21.1% (n = 12) of the 57 cases of investigated SSIs among 536 patients followed. Seven out of eight S. aureus carriage/infection pairs had the same spa and sequence types. The previously reported dominant PVL-positive ST88 MRSA strain with spa type t690 was detected in patients and HCW.

Conclusion
A significant proportion of patients acquired S. aureus during hospitalization. The finding of more than 90% of S. aureus SSI to be of endogenous source underscores the need of improving infection prevention and control measures including screening and decolonization of high risk patients.
KW  - S. aureus
KW  - colonization
KW  - surgical site infection
KW  - Tanzania
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224185
VL  - 8
ER  - 
TY  - JOUR
T1  - FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2
JF  - European Physical Journal - Special Topics
N2  - In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today's technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.
KW  - Large Hadron Collider
KW  - Double-Beta Decay
KW  - e(+)e(-) Collisions
KW  - Flavor Violation
KW  - Electroweak Measurements
KW  - Bhabha Scattering
KW  - Missing Energy
KW  - Single-Photon
KW  - Neutrino Mass
KW  - Higgy-Boson
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226947
VL  - 228
IS  - 2
ER  - 
TY  - JOUR
T1  - FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1
JF  - European Physical Journal C
N2  - We review the physics opportunities of the Future Circular Collider, covering its e(+)e(-), pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics.
KW  - Electroweak Phase-Transition
KW  - By-Light Scattering
KW  - Deep Inelastic-scattering
KW  - Strange Baryon Production
KW  - Dark-Matter
KW  - Radiative-corrections
KW  - E(+)E(-) collicions
KW  - Transverse-Momentum
KW  - Top-Quark
KW  - Branching fractions
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226938
VL  - 79
IS  - 474
ER  - 
TY  - JOUR
T1  - HE-LHC: The High-Energy Large Hadron Collider : Future Circular Collider Conceptual Design Report Volume 4
JF  - European Physical Journal - Special Topics
N2  - In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries.
KW  - Event builder
KW  - Impact
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226928
VL  - 228
IS  - 5
ER  - 
TY  - JOUR
T1  - FCC-hh: The Hadron Collider: Future Circular Collider Conceptual Design Report Volume 3
JF  - European Physical Journal - Special Topics
N2  - In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100TeV. Its unprecedented centre of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries.
KW  - Multiple-Scattering
KW  - Top-Quark
KW  - CERN
KW  - Energy
KW  - Reduction
KW  - Impact
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226917
VL  - 228
ER  - 
TY  - JOUR
T1  - Search for diboson resonances in hadronic final states in 139 fb\(^{-1}\) of \(pp\) collisions at √\(s\)=13 TeV with the ATLAS detector
JF  - Journal of High Energy Physics
N2  - Narrow resonances decaying into WW, WZ or ZZ boson pairs are searched for in 139 fb(-1) of proton-proton collision data at a centre-of-mass energy of root s = 13TeV recorded with the ATLAS detector at the Large Hadron Collider from 2015 to 2018. The diboson system is reconstructed using pairs of high transverse momentum, large-radius jets. These jets are built from a combination of calorimeter- and tracker-inputs compatible with the hadronic decay of a boosted W or Z boson, using jet mass and substructure properties. The search is performed for diboson resonances with masses greater than 1.3TeV. No significant deviations from the background expectations are observed. Exclusion limits at the 95% confidence level are set on the production cross-section times branching ratio into dibosons for resonances in a range of theories beyond the Standard Model, with the highest excluded mass of a new gauge boson at 3.8TeV in the context of mass-degenerate resonances that couple predominantly to gauge bosons.
KW  - Hadron-Hadron scattering (experiments)
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226905
VL  - 09
IS  - 91
ER  - 
TY  - JOUR
T1  - Identification of boosted Higgs bosons decaying into \(b\)-quark pairs with the ATLAS detector at 13 TeV
JF  - European Physical Journal C
N2  - This paper describes a study of techniques for identifying Higgs bosons at high transverse momenta decaying into bottom-quark pairs, H -> b (b) over bar, for proton-proton collision data collected by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy root s = 13 TeV. These decays are reconstructed from calorimeter jets found with the anti-k(t) R = 1.0 jet algorithm. To tag Higgs bosons, a combination of requirements is used: b-tagging of R = 0.2 track-jets matched to the large-R calorimeter jet, and requirements on the jet mass and other jet substructure variables. The Higgs boson tagging efficiency and corresponding multijet and hadronic top-quark background rejections are evaluated using Monte Carlo simulation. Several benchmark tagging selections are defined for different signal efficiency targets. The modelling of the relevant input distributions used to tag Higgs bosons is studied in 36 fb(-1) of data collected in 2015 and 2016 using g -> b (b) over bar and Z(-> b (b) over bar)gamma event selections in data. Both processes are found to be well modelled within the statistical and systematic uncertainties.
KW  - Parton distributions
KW  - PP collisions
KW  - search
KW  - MASS
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226812
VL  - 79
IS  - 836
ER  - 
TY  - JOUR
T1  - Measurement of the inclusive cross-section for the production of jets in association with a \(Z\) boson in proton-proton collisions at 8 TeV using the ATLAS detector
JF  - European Physical Journal C
N2  - The inclusive cross-section for jet production in association with a Z boson decaying into an electronpositron pair is measured as a function of the transverse momentum and the absolute rapidity of jets using 19.9 fb(-1) of root s = 8 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. The measured Z + jets cross-section is unfolded to the particle level. The cross-section is compared with state-of-the-art Standard Model calculations, including the next-to-leading-order and next-to-next-to-leading-order perturbative QCD calculations, corrected for non-perturbative and QED radiation effects. The results of the measurements cover final-state jets with transverse momenta up to 1 TeV, and show good agreement with fixed-order calculations.
KW  - P(P) over-bar collisions
KW  - +
KW  - distributions
KW  - decay
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226821
VL  - 79
IS  - 847
ER  - 
TY  - JOUR
T1  - Measurement of the cross-section and charge asymmetry of W bosons produced in proton-proton collisions at √\(s\)=8 TeV with the ATLAS detector
JF  - European Physical Journal C
N2  - This paper presents measurements of the W+->mu+nu and W-->mu-nu cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton-proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2fb(-1). The precision of the cross-section measurements varies between 0.8 and 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.
KW  - Pair Production
KW  - Monte-Carlo
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226850
VL  - 79
IS  - 760
ER  - 
TY  - JOUR
T1  - Measurement of distributions sensitive to the underlying event in inclusive Z boson production in \(pp\) collisions at √\(s\)=13 TeV with the ATLAS detector
JF  - European Physical Journal C
N2  - This paper presents measurements of charged-particle distributions sensitive to the properties of the underlying event in events containing a Z boson decaying into a muon pair. The data were obtained using the ATLAS detector at the LHC in proton-proton collisions at a centre-of-mass energy of 13 TeV with an integrated luminosity of 3.2 fb(-1). Distributions of the charged-particle multiplicity and of the charged-particle transverse momentum are measured in regions of the azimuth defined relative to the Z boson direction. The measured distributions are compared with the predictions of various Monte Carlo generators which implement different underyling event models. The Monte Carlo model predictions qualitatively describe the data well, but with some significant discrepancies.
KW  - Cross-Section
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226883
VL  - 79
IS  - 666
ER  - 
TY  - JOUR
T1  - Observation of Light-by-Light Scattering in Ultraperipheral Pb + Pb Collisions with the ATLAS Detector
JF  - Physical Review Letters
N2  - This Letter describes the observation of the light-by-light scattering process, gamma gamma -> gamma gamma, in Pb + Pb collisions at root S-NN = 5.02 TeV. The analysis is conducted using a data sample corresponding to an integrated luminosity of 1.73 nb(-1), collected in November 2018 by the ATLAS experiment at the LHC. Light-by-light scattering candidates are selected in events with two photons produced exclusively, each with transverse energy E-T(gamma) > 3 GeV and pseudorapidity vertical bar eta(gamma)vertical bar < 2.4, diphoton invariant mass above 6 GeV, and small diphoton transverse momentum and acoplanarity. After applying all selection criteria, 59 candidate events are observed for a background expectation of 12 +/- 3 events. The observed excess of events over the expected background has a significance of 8.2 standard deviations. The measured fiducial cross section is 78 +/- 13(stat) +/- 7(syst) +/- 3(lumi) nb.
KW  - Ultrarelativistic Heavy-Ion
KW  - Delbruck Scattering
KW  - Physics
KW  - Relativistic heavy-ion collisions
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226892
VL  - 123
ER  - 
TY  - JOUR
T1  - Search for a heavy charged boson in events with a charged lepton and missing transverse momentum from \(pp\) collisions at √\(s\)=13 TeV with the ATLAS detector
JF  - Physical Review D
N2  - A search for a heavy charged-boson resonance decaying into a charged lepton (electron or muon) and a neutrino is reported. A data sample of 139 fb(-1) of proton-proton collisions at root s = 13 TeV collected with the ATLAS detector at the LHC during 2015-2018 is used in the search. The observed transverse mass distribution computed from the lepton and missing transverse momenta is consistent with the distribution expected from the Standard Model, and upper limits on the cross section for pp -> W'-> lv are extracted (l = e or mu). These vary between 1.3 pb and 0.05 tb depending on the resonance mass in the range between 0.15 and 7.0 TeV at 95% confidence level for the electron and muon channels combined. Gauge bosons with a mass below 6.0 and 5.1 TeV are excluded in the electron and muon channels, respectively, in a model with a resonance that has couplings to fermions identical to those of the Standard Model W boson. Cross-section limits are also provided for resonances with several fixed Gamma/m values in the range between 1% and 15%. Model-independent limits are derived in single-bin signal regions defined by a varying minimum transverse mass threshold. The resulting visible cross-section upper limits range between 4.6 (15) ph and 22 (22) ab as the threshold increases from 130 (110) GeV to 5.1 (5.1) TeV in the electron (muon) channel.
KW  - Pair Production
KW  - Symmetry
KW  - Decay
KW  - Monte-Carlo
KW  - semileptonic & radiative decays
KW  - Leptonic
KW  - Hadron-hadron interactions
KW  - Extensions of gauge sector
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226835
VL  - 100
ER  - 
TY  - JOUR
T1  - Search for electroweak diboson production in association with a high-mass dijet system in semileptonic final states in \(pp\) collisions at √\(s\) =13 TeV with the ATLAS detector
JF  - Physical Review D
N2  - This paper reports on a search for electroweak diboson (WW/WZ/ZZ) production in association with a high-mass dijet system, using data from proton-proton collisions at a center-of-mass energy of N root s = 13 TeV. The data, corresponding to an integrated luminosity of 35.5 fb(-1), were recorded with the ATLAS detector in 2015 and 2016 at the Large Hadron Collider. The search is performed in final states in which one boson decays leptonically, and the other boson decays hadronically. The hadronically decaying W/Z boson is reconstructed as either two small-radius jets or one large-radius jet using jet substructure techniques. The electroweak production of WW/WZ/ZZ in association with two jets is measured with an observed (expected) significance of 2.7 (2.5) standard deviations, and the fiducial cross section is measured to be 45.1 +/- 8.6(stat.)(-14.6)(+15.9)(syst.) fb.
KW  - Proton-Proton Collisions
KW  - 2 Jets
KW  - Parton Distributions
KW  - Weak-Interactions
KW  - Cross-Section
KW  - High-Energies
KW  - Boson
KW  - Constraints
KW  - Scattering
KW  - Couplings
KW  - Particle accelerators
KW  - Hadron colliders
KW  - W & Z bosons
KW  - Gauge bosons
KW  - Quantum electrodynamics
KW  - Electroweak interaction
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226877
VL  - 100
ER  - 
TY  - JOUR
T1  - Resolution of the ATLAS muon spectrometer monitored drift tubes in LHC Run 2
JF  - Journal of Instrumentation
N2  - The momentum measurement capability of the ATLAS muon spectrometer relies fundamentally on the intrinsic single-hit spatial resolution of the monitored drift tube precision tracking chambers. Optimal resolution is achieved with a dedicated calibration program that addresses the specific operating conditions of the 354 000 high-pressure drift tubes in the spectrometer. The calibrations consist of a set of timing offsets and drift time to drift distance transfer relations, and result in chamber resolution functions. This paper describes novel algorithms to obtain precision calibrations from data collected by ATLAS in LHC Run 2 and from a gas monitoring chamber, deployed in a dedicated gas facility. The algorithm output consists of a pair of correction constants per chamber which are applied to baseline calibrations, and determined to be valid for the entire ATLAS Run 2. The final single-hit spatial resolution, averaged over 1172 monitored drift tube chambers, is 81.7 +/- 2.2 mu m.
KW  - Gaseous detectors
KW  - Chambers
KW  - Muon spectrometers
KW  - Particle tracking detectors (Gaseous detectors)
KW  - Wire chambers (MWPC, Thin-gap chambers, drift chambers, drift tubes, proportional chambers etc)
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226869
VL  - 14
ER  - 
TY  - JOUR
T1  - Search for high-mass dilepton resonances using 139 fb\(^{-1}\) of \(pp\) collision data collected at root \(s\)=13 TeV with the ATLAS detector
JF  - Physics Letters B
N2  - A search for high-mass dielectron and dimuon resonances in the mass range of 250 GeV to 6TeV is presented. The data were recorded by the ATLAS experiment in proton-proton collisions at a centre-ofmass energy of root s = 13 TeV during Run 2 of the Large Hadron Collider and correspond to an integrated luminosity of 139 fb(-1). A functional form is fitted to the dilepton invariant-mass distribution to model the contribution from background processes, and a generic signal shape is used to determine the significance of observed deviations from this background estimate. No significant deviation is observed and upper limits are placed at the 95% confidence level on the fiducial cross-section times branching ratio for various resonance width hypotheses. The derived limits are shown to be applicable to spin-0, spin-1 and spin-2 signal hypotheses. For a set of benchmark models, the limits are converted into lower limits on the resonance mass and reach 4.5 TeV for the E-6-motivated Z(psi)' boson. Also presented are limits on Heavy Vector Triplet model couplings. (C) 2019 The Author. Published by Elsevier B.V.
KW  - Monte-Carlo
KW  - Bosons
KW  - Decay
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226844
VL  - 796
ER  - 
TY  - JOUR
T1  - Search for heavy particles decaying into a top-quark pair in the fully hadronic final state in \({pp}\) collisions at root s=13 TeV with the ATLAS detector
JF  - Physical Review D
N2  - A search for new particles decaying into a pair of top quarks is performed using proton-proton collision data recorded with the ATLAS detector at the Large Hadron Collider at a center-of-mass energy of root s = 13 TeV corresponding to an integrated luminosity of 36.1 fb(-1). Events consistent with top-quark pair production and the fully hadronic decay mode of the top quarks are selected by requiring multiple high transverse momentum jets including those containing b-hadrons. Two analysis techniques, exploiting dedicated top-quark pair reconstruction in different kinematic regimes, are used to optimize the search sensitivity to new hypothetical particles over a wide mass range. The invariant mass distribution of the two reconstructed top-quark candidates is examined for resonant production of new particles with various spins and decay widths. No significant deviation from the Standard Model prediction is observed and limits are set on the production cross-section times branching fraction for new hypothetical Z' bosons, dark-matter mediators, Kaluza-Klein gravitons and Kaluza-Klein gluons. By comparing with the predicted production cross sections, the Z' boson in the topcolor-assisted-technicolor model is excluded for masses up to 3.1-3.6 TeV, the dark-matter mediators in a simplified framework are excluded in the mass ranges from 0.8 to 0.9 TeV and from 2.0 to 2.2 TeV, and the Kaluza-Klein gluon is excluded for masses up to 3.4 TeV, depending on the decay widths of the particles.
KW  - Parton distributions
KW  - ++
KW  - Algorithm
KW  - Cross-section
KW  - Physics
KW  - LHC
KW  - Gravitons
KW  - Hypothetical gauge bosons
KW  - Top quark
KW  - Hadron colliders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-317362
VL  - 99
IS  - 9
ER  - 
TY  - JOUR
T1  - Search for light resonances decaying to boosted quark pairs and produced in association with a photon or a jet in proton-proton collisions at root s=13 TeV with the ATLAS detector
JF  - Physics Letters B
N2  - This Letter presents a search for new light resonances decaying to pairs of quarks and produced in association with a high-p(T) photon or jet. The dataset consists of proton-proton collisions with an integrated luminosity of 36.1 fb(-1) at a centre-of-mass energy of root s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Resonance candidates are identified as massive large-radius jets with substructure consistent with a particle decaying into a quark pair. The mass spectrum of the candidates is examined for local excesses above background. No evidence of a new resonance is observed in the data, which are used to exclude the production of a lepto-phobic axial-vector Z' boson. (C) 2018 The Author(s). Published by Elsevier B.V.
KW  - Parton Distributions
KW  - Dark-matter
KW  - Constraints
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319552
VL  - 788
ER  - 
TY  - JOUR
A1  - Rager, Sabrina
A1  - Jakowetz, Andreas C.
A1  - Gole, Bappaditya
A1  - Beuerle, Florian
A1  - Medina, Dana D.
A1  - Bein, Thomas
T1  - Scaffold-Induced Diketopyrrolopyrrole Molecular Stacks in a Covalent Organic Framework
JF  - Chemistry of Materials
N2  - In recent years, covalent organic frameworks (COFs) have attracted considerable attention due to their crystalline and porous nature, which positions them as intriguing candidates for diverse applications such as catalysis, sensing, or optoelectronics. The incorporation of dyes or semiconducting moieties into a rigid two-dimensional COF can offer emergent features such as enhanced light harvesting or charge transport. However, this approach can be challenging when dealing with dye molecules that exhibit a large aromatic backbone, since the steric demand of solubilizing side chains also needs to be integrated into the framework. Here, we report the successful synthesis of DPP2-HHTP-COF consisting of diketopyrrolopyrrole (DPP) diboronic acid and hexahydroxytriphenylene (HHTP) building blocks. The well-known boronate ester coupling motif guides the formation of a planar and rigid backbone and long-range molecular DPP stacks, resulting in a highly crystalline and porous material. DPP2-HHTP-COF exhibits excellent optical properties including strong absorption over the visible spectral range, broad emission into the NIR and a singlet lifetime of over 5 ns attributed to the formation of molecular stacks with J-type interactions between the DPP subcomponents in the COF. Electrical measurements of crystalline DPP2-HHTP-COF pellets revealed conductivity values of up to 10(-6) S cm(-1).
KW  - Polymers
KW  - Electron
KW  - Design
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224927
VL  - 31
IS  - 8
ER  - 
TY  - JOUR
A1  - Lux, Thomas J.
A1  - Hu, Xiawei
A1  - Ben-Kraiem, Adel
A1  - Blum, Robert
A1  - Chen, Jeremy Tsung-Chieh
A1  - Rittner, Heike L.
T1  - Regional differences in tight junction protein expression in the blood−DRG barrier and their alterations after nerve traumatic injury in rats
JF  - International Journal of Molecular Sciences
N2  - The nervous system is shielded by special barriers. Nerve injury results in blood–nerve barrier breakdown with downregulation of certain tight junction proteins accompanying the painful neuropathic phenotype. The dorsal root ganglion (DRG) consists of a neuron-rich region (NRR, somata of somatosensory and nociceptive neurons) and a fibre-rich region (FRR), and their putative epi-/perineurium (EPN). Here, we analysed blood–DRG barrier (BDB) properties in these physiologically distinct regions in Wistar rats after chronic constriction injury (CCI). Cldn5, Cldn12, and Tjp1 (rats) mRNA were downregulated 1 week after traumatic nerve injury. Claudin-1 immunoreactivity (IR) found in the EPN, claudin-19-IR in the FRR, and ZO-1-IR in FRR-EPN were unaltered after CCI. However, laser-assisted, vessel specific qPCR, and IR studies confirmed a significant loss of claudin-5 in the NRR. The NRR was three-times more permeable compared to the FRR for high and low molecular weight markers. NRR permeability was not further increased 1-week after CCI, but significantly more CD68\(^+\) macrophages had migrated into the NRR. In summary, NRR and FRR are different in naïve rats. Short-term traumatic nerve injury leaves the already highly permeable BDB in the NRR unaltered for small and large molecules. Claudin-5 is downregulated in the NRR. This could facilitate macrophage invasion, and thereby neuronal sensitisation and hyperalgesia. Targeting the stabilisation of claudin-5 in microvessels and the BDB barrier could be a future approach for neuropathic pain therapy.
KW  - tight junction
KW  - claudin-5
KW  - neuropathic pain
KW  - nerve injury
KW  - dorsal root ganglion
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285029
SN  - 1422-0067
VL  - 21
IS  - 1
ER  - 
TY  - JOUR
A1  - Gablonski, Thorsten-Christian
A1  - Pryss, Rüdiger
A1  - Probst, Thomas
A1  - Vogel, Carsten
A1  - Andreas, Sylke
T1  - Intersession-Online: A smartphone application for systematic recording and controlling of intersession experiences in psychotherapy
JF  - J — Multidisciplinary Scientific Journal
N2  - Mobile health technologies have become more and more important in psychotherapy research and practice. The market is being flooded by several psychotherapeutic online services for different purposes. However, mobile health technologies are particularly suitable for data collection and monitoring, as data can be recorded economically in real time. Currently, there is no appropriate method to assess intersession experiences systematically in psychotherapeutic practice. The aim of our project was the development of a smartphone application framework for systematic recording and controlling of intersession experiences. Intersession-Online, an iOS- and Android-App, offers the possibility to collect data on intersession experiences easily, to provide the results to therapists in an evaluated form and, if necessary, to induce or interrupt intersession experiences with the primary aim to improve outcome of psychotherapy. In general, the smartphone application could be a helpful, evidence-based tool for research and practice. Overall speaking, further research to investigate the efficacy of Intersession-Online is necessary.
KW  - intersession experiences
KW  - intersession processes
KW  - psychotherapy
KW  - mobile app
KW  - smartphone app
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285597
SN  - 2571-8800
VL  - 2
IS  - 4
SP  - 480
EP  - 495
ER  - 
TY  - JOUR
A1  - Mammadova-Bach, Elmina
A1  - Braun, Attila
T1  - Zinc homeostasis in platelet-related diseases
JF  - International Journal of Molecular Sciences
N2  - Zn\(^{2+}\) deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn\(^{2+}\)-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn\(^{2+}\) deficiency, clinical symptoms are associated with impaired wound healing, alopecia, diarrhea, poor growth, dysfunction of the immune and nervous system with congenital abnormalities and bleeding disorders. Poor nutritional Zn\(^{2+}\) status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn\(^{2+}\) uptake in the gut using different nutritional supplementation of Zn\(^{2+}\) could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn\(^{2+}\) diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn\(^{2+}\) in hemostasis. Storage protein metallothionein maintains or releases Zn\(^{2+}\) in the cytoplasm, and the dynamic change of this cytoplasmic Zn\(^{2+}\) pool is regulated by the redox status of the cell. An increase of labile Zn\(^{2+}\) pool can be toxic for the cells, and therefore cytoplasmic Zn\(^{2+}\) levels are tightly regulated by several Zn\(^{2+}\) transporters located on the cell surface and also on the intracellular membrane of Zn\(^{2+}\) storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn\(^{2+}\) is a critical cofactor for more than 2000 transcription factors and 300 enzymes, regulating cell differentiation, proliferation, and basic metabolic functions of the cells, the molecular mechanisms of Zn\(^{2+}\) transport and the physiological role of Zn\(^{2+}\) store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn\(^{2+}\) to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn\(^{2+}\) homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases.
KW  - Zinc
KW  - platelets
KW  - hemostasis
KW  - thrombosis
KW  - ischemic stroke
KW  - storage-pool diseases
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285554
SN  - 1422-0067
VL  - 20
IS  - 21
ER  - 
TY  - JOUR
A1  - Breitenbach, Tim
A1  - Lorenz, Kristina
A1  - Dandekar, Thomas
T1  - How to steer and control ERK and the ERK signaling cascade exemplified by looking at cardiac insufficiency
JF  - International Journal of Molecular Sciences
N2  - Mathematical optimization framework allows the identification of certain nodes within a signaling network. In this work, we analyzed the complex extracellular-signal-regulated kinase 1 and 2 (ERK1/2) cascade in cardiomyocytes using the framework to find efficient adjustment screws for this cascade that is important for cardiomyocyte survival and maladaptive heart muscle growth. We modeled optimal pharmacological intervention points that are beneficial for the heart, but avoid the occurrence of a maladaptive ERK1/2 modification, the autophosphorylation of ERK at threonine 188 (ERK\(^{Thr188}\) phosphorylation), which causes cardiac hypertrophy. For this purpose, a network of a cardiomyocyte that was fitted to experimental data was equipped with external stimuli that model the pharmacological intervention points. Specifically, two situations were considered. In the first one, the cardiomyocyte was driven to a desired expression level with different treatment strategies. These strategies were quantified with respect to beneficial effects and maleficent side effects and then which one is the best treatment strategy was evaluated. In the second situation, it was shown how to model constitutively activated pathways and how to identify drug targets to obtain a desired activity level that is associated with a healthy state and in contrast to the maleficent expression pattern caused by the constitutively activated pathway. An implementation of the algorithms used for the calculations is also presented in this paper, which simplifies the application of the presented framework for drug targeting, optimal drug combinations and the systematic and automatic search for pharmacological intervention points. The codes were designed such that they can be combined with any mathematical model given by ordinary differential equations.
KW  - optimal pharmacological modulation
KW  - efficient intervention points
KW  - ERK signaling
KW  - optimal treatment strategies
KW  - optimal drug targeting
KW  - optimal drug combination
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285164
SN  - 1422-0067
VL  - 20
IS  - 9
ER  - 
TY  - JOUR
A1  - Herrmann, Marietta
A1  - Hildebrand, Maria
A1  - Menzel, Ursula
A1  - Fahy, Niamh
A1  - Alini, Mauro
A1  - Lang, Siegmund
A1  - Benneker, Lorin
A1  - Verrier, Sophie
A1  - Stoddart, Martin J.
A1  - Bara, Jennifer J.
T1  - Phenotypic characterization of bone marrow mononuclear cells and derived stromal cell populations from human iliac crest, vertebral body and femoral head
JF  - International Journal of Molecular Sciences
N2  - (1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14–91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45−CD34−CD73+, CD45−CD34−CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.
KW  - bone marrow stromal cells
KW  - MSC
KW  - pericytes
KW  - femoral head
KW  - vertebral body
KW  - iliac crest
KW  - chondrogenesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285054
SN  - 1422-0067
VL  - 20
IS  - 14
ER  - 
TY  - JOUR
A1  - Rapa, Shara Francesca
A1  - Di Iorio, Biagio Raffaele
A1  - Campiglia, Pietro
A1  - Heidland, August
A1  - Marzocco, Stefania
T1  - Inflammation and oxidative stress in chronic kidney disease — Potential therapeutic role of minerals, vitamins and plant-derived metabolites
JF  - International Journal of Molecular Sciences
N2  - Chronic kidney disease (CKD) is a debilitating pathology with various causal factors, culminating in end stage renal disease (ESRD) requiring dialysis or kidney transplantation. The progression of CKD is closely associated with systemic inflammation and oxidative stress, which are responsible for the manifestation of numerous complications such as malnutrition, atherosclerosis, coronary artery calcification, heart failure, anemia and mineral and bone disorders, as well as enhanced cardiovascular mortality. In addition to conventional therapy with anti-inflammatory and antioxidative agents, growing evidence has indicated that certain minerals, vitamins and plant-derived metabolites exhibit beneficial effects in these disturbances. In the current work, we review the anti-inflammatory and antioxidant properties of various agents which could be of potential benefit in CKD/ESRD. However, the related studies were limited due to small sample sizes and short-term follow-up in many trials. Therefore, studies of several anti-inflammatory and antioxidant agents with long-term follow-ups are necessary.
KW  - chronic kidney disease (CKD)
KW  - inflammation
KW  - oxidative stress
KW  - uremic toxins
KW  - minerals
KW  - vitamins
KW  - plant-derived metabolites
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284998
SN  - 1422-0067
VL  - 21
IS  - 1
ER  - 
TY  - JOUR
A1  - Rasche, Leo
A1  - Kumar, Manoj
A1  - Gershner, Grant
A1  - Samant, Rohan
A1  - Van Hemert, Rudy
A1  - Heidemeier, Anke
A1  - Lapa, Constantin
A1  - Bley, Thorsten
A1  - Buck, Andreas
A1  - McDonald, James
A1  - Hillengass, Jens
A1  - Epstein, Joshua
A1  - Thanendrarajan, Sharmilan
A1  - Schinke, Carolina
A1  - van Rhee, Frits
A1  - Zangari, Maurizio
A1  - Barlogie, Bart
A1  - Davies, Faith E.
A1  - Morgan, Gareth J.
A1  - Weinhold, Niels
T1  - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis?
JF  - Theranostics
N2  - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM.
KW  - multiple myeloma
KW  - diffusion weighted mri
KW  - spleen
KW  - tumor burden
KW  - high risk
KW  - extramedullary hematopoiesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982
VL  - 9
IS  - 16
ER  - 
TY  - JOUR
A1  - Schmalzl, J.
A1  - Plumhoff, P.
A1  - Gilbert, F.
A1  - Gohlke, F.
A1  - Konrads, C.
A1  - Brunner, U.
A1  - Jakob, F.
A1  - Ebert, R.
A1  - Steinert, AF
T1  - The inflamed biceps tendon as a pain generator in the shoulder: A histological and biomolecular analysis
JF  - Journal of Orthopaedic Surgery
N2  - Introduction: The long head of the biceps (LHB) is often resected in shoulder surgery. However, its contribution to inflammatory processes in the shoulder remains unclear. In the present study, inflamed and noninflamed human LHBs were comparatively characterized for features of inflammation. Materials and methods: Twenty-two resected LHB tendons were classified into inflamed (n = 11) and noninflamed (n = 11) samples. For histological examination, samples were stained with hematoxylin eosin, Azan, van Gieson, and Masson Goldner trichrome. Neuronal tissue was immunohistochemically visualized. In addition, specific inflammatory marker gene expression of primary LHB-derived cell cultures were analyzed. Results: Features of tendinopathy, such as collagen disorganization, infiltration by inflammatory cells, neovascularization, and extensive neuronal innervation were found in the tendinitis group. Compared to noninflamed samples, inflamed LHBs showed a significantly increased inflammatory marker gene expression Conclusion: Structural and biomolecular differences of both groups suggest that the LHB tendon acts as an important pain generator in the shoulder joint. These findings can, on the one hand, contribute to the understanding of the biomolecular genesis of LHB tendinitis and, on the other hand, provide possibilities for new therapeutic approaches.
KW  - biceps tendinitis
KW  - biomolecular processes
KW  - inflammatory gene
KW  - interleukin
KW  - long head of biceps tendon
KW  - pain generator
KW  - shoulder pain
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228611
VL  - 27
IS  - 1
ER  - 
TY  - JOUR
A1  - Bothe, Friederike
A1  - Deubel, Anne-Kathrin
A1  - Hesse, Eliane
A1  - Lotz, Benedict
A1  - Groll, Jürgen
A1  - Werner, Carsten
A1  - Richter, Wiltrud
A1  - Hagmann, Sebastien
T1  - Treatment of focal cartilage defects in minipigs with zonal chondrocyte/mesenchymal progenitor cell constructs
JF  - International Journal of Molecular Sciences
N2  - Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.
KW  - cartilage repair
KW  - osteochondral defect
KW  - tissue engineering
KW  - starPEG hydrogel
KW  - chondrocyte
KW  - MSC
KW  - zonal construct
KW  - minipig
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285118
SN  - 1422-0067
VL  - 20
IS  - 3
ER  - 
TY  - JOUR
A1  - Rice, Carmel
A1  - Eikema, Dirk-Jan
A1  - Marsh, Judith C. W.
A1  - Knol, Cora
A1  - Hebert, Kyle
A1  - Putter, Hein
A1  - Peterson, Eefke
A1  - Deeg, H. Joachim
A1  - Halkes, Stijn
A1  - Pidala, Joseph
A1  - Anderlini, Paolo
A1  - Tischer, Johanna
A1  - Kroger, Nicolaus
A1  - McDonald, Andrew
A1  - Antin, Joseph H.
A1  - Schaap, Nicolaas P.
A1  - Hallek, Michael
A1  - Einsele, Herman
A1  - Mathews, Vikram
A1  - Kapoor, Neena
A1  - Boelens, Jaap-Jan
A1  - Mufti, Ghulam J.
A1  - Potter, Victoria
A1  - de la Tour, Régis Pefault
A1  - Eapen, Mary
A1  - Dufour, Carlo
T1  - Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50 Years or Older with Severe Aplastic Anemia
JF  - Biology of Blood and Marrow Transplantation
N2  - We report on 499 patients with severe aplastic anemia aged >= 50 years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n = 275, 55%) or HLA-matched (8/8) unrelated donors (n =187, 37%) between 2005 and 2016. The median age at HCT was 57.8 years; 16% of patients were 65 to 77 years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90% (hazard ratio HR], 1.41; 95% confidence interval [CI], 1.03 to 1.92; P= .03) and after unrelated donor transplantation (HR, 1.47; 95% CI,1 to 2.16; P = .05). The 3-year probabilities of survival for patients with performance scores of 90 to 100 and less than 90 after HLA-matched sibling transplant were 66% (range, 57% to 75%) and 57% (range, 47% to 76%), respectively. The corresponding probabilities after HLA-matched unrelated donor transplantation were 57% (range, 48% to 67%) and 48% (range, 36% to 59%). Age at transplantation was not associated with survival, but grades II to IV acute graft-versus-host disease (GVHD) risks were higher for patients aged 65 years or older (subdistribution HR [sHR], 1.7; 95% confidence interval, 1.07 to 2.72; P= .026). Chronic GVHD was lower with the GVHD prophylaxis regimens calcineurin inhibitor (CNI) + methotrexate (sHR, .52; 95% CI, .33 to .81; P= .004) and CNI alone or with other agents (sHR, .27; 95% CI, .14 to .53; P < .001) compared with CNI + mycophenolate. Although donor availability is modifiable only to a limited extent, choice of GVHD prophylaxis and selection of patients with good performance scores are key for improved outcomes. (C) 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
KW  - Aplastic anemia
KW  - Hematopoietic cell transplant
KW  - Survival
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225229
VL  - 25
IS  - 3
ER  - 
TY  - JOUR
A1  - Wiechmann, Tobias
A1  - Röh, Simone
A1  - Sauer, Susann
A1  - Czamara, Darina
A1  - Arloth, Janine
A1  - Ködel, Maik
A1  - Beintner, Madita
A1  - Knop, Lisanne
A1  - Menke, Andreas
A1  - Binder, Elisabeth B.
A1  - Provençal, Nadine
T1  - Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus
JF  - Clinical Epigenetics
N2  - Background
Epigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported.

Results
We repeatedly measured DNAm in human peripheral blood samples from 2 independent cohorts exposed to the GC agonist dexamethasone (DEX) using a targeted bisulfite sequencing approach, complemented by data from Illumina 450K arrays. We detected differentially methylated CpGs in enhancers co-localizing with GC receptor binding sites after acute DEX treatment (1 h, 3 h, 6 h), which returned to baseline levels within 23 h. These changes withstood correction for immune cell count differences. While we observed main effects of sex, age, body mass index, smoking, and depression symptoms on FKBP5 methylation levels, only the functional FKBP5 SNP (rs1360780) moderated the dynamic changes following DEX. This genotype effect was observed in both cohorts and included sites previously shown to be associated with ELS.

Conclusion
Our study highlights that DNAm levels within regulatory regions of the FKBP5 locus show dynamic changes following a GC challenge and suggest that factors influencing the dynamics of this regulation may contribute to the previously reported alterations in DNAm associated with current and past ELS exposure.
KW  - DNA methylation
KW  - FKBP5
KW  - glucocorticoid receptor
KW  - early-life stress
KW  - targeted bisulfite sequencing
KW  - dexamethasone
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233673
VL  - 11
ER  - 
TY  - JOUR
A1  - Loeffler-Wirth, Henry
A1  - Kreuz, Markus
A1  - Hopp, Lydia
A1  - Arakelyan, Arsen
A1  - Haake, Andrea
A1  - Cogliatti, Sergio B.
A1  - Feller, Alfred C.
A1  - Hansmann, Martin-Leo
A1  - Lenze, Dido
A1  - Möller, Peter
A1  - Müller-Hermelink, Hans Konrad
A1  - Fortenbacher, Erik
A1  - Willscher, Edith
A1  - Ott, German
A1  - Rosenwald, Andreas
A1  - Pott, Christiane
A1  - Schwaenen, Carsten
A1  - Trautmann, Heiko
A1  - Wessendorf, Swen
A1  - Stein, Harald
A1  - Szczepanowski, Monika
A1  - Trümper, Lorenz
A1  - Hummel, Michael
A1  - Klapper, Wolfram
A1  - Siebert, Reiner
A1  - Loeffler, Markus
A1  - Binder, Hans
T1  - A modular transcriptome map of mature B cell lymphomas
JF  - Genome Medicine
N2  - Background
Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt’s lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma.

Methods
We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics.

Results
We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt’s lymphoma and particularly on ‘double-hit’ MYC and BCL2 transformed lymphomas.

Conclusions
The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.
KW  - tumor heterogeneity
KW  - B cell malignancies
KW  - gene regulation
KW  - molecular subtypes
KW  - machine learning
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237262
VL  - 11
ER  - 
TY  - JOUR
A1  - Neugebauer, Hermann
A1  - Schneider, Hauke
A1  - Kollmar, Rainer
T1  - Letter by Neugebauer et al. regarding article “Hypothermia after decompressive hemicraniectomy in treatment of malignant middle cerebral artery stroke: comment on the randomized clinical trial”
JF  - Critical Care
N2  - No abstract available.
KW  - stroke
KW  - hypothermia
KW  - hemicraniectomy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232268
VL  - 23
ER  - 
TY  - JOUR
A1  - König, Kirsten
A1  - Pechmann, Astrid
A1  - Thiele, Simone
A1  - Walter, Maggie C.
A1  - Schorling, David
A1  - Tassoni, Adrian
A1  - Lochmüller, Hanns
A1  - Müller-Reible, Clemens
A1  - Kirschner, Janbernd
T1  - De-duplicating patient records from three independent data sources reveals the incidence of rare neuromuscular disorders in Germany
JF  - Orphanet Journal of Rare Diseases
N2  - Background
Estimation of incidence in rare diseases is often challenging due to unspecific and incomplete coding and recording systems. Patient- and health care provider-driven data collections are held with different organizations behind firewalls to protect the privacy of patients. They tend to be fragmented, incomplete and their aggregation leads to further inaccuracies, as the duplicated records cannot easily be identified. We here report about a novel approach to evaluate the incidences of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) in Germany.

Methods
We performed a retrospective epidemiological study collecting data from patients with dystrophinopathies (DMD and Becker muscular dystrophy) and SMA born between 1995 and 2018. We invited all neuromuscular centers, genetic institutes and the patient registries for DMD and SMA in Germany to participate in the data collection. A novel web-based application for data entry was developed converting patient identifying information into a hash code. Duplicate entries were reliably allocated to the distinct patient.

Results
We collected 5409 data entries in our web-based database representing 1955 distinct patients with dystrophinopathies and 1287 patients with SMA. 55.0% of distinct patients were found in one of the 3 data sources only, while 32.0% were found in 2, and 13.0% in all 3 data sources. The highest number of SMA patients was reported by genetic testing laboratories, while for DMD the highest number was reported by the clinical specialist centers. After the removal of duplicate records, the highest yearly incidence for DMD was calculated as 2.57:10,000 in 2001 and the highest incidence for SMA as 1.36:10,000 in 2014.

Conclusion
With our novel approach (compliant with data protection regulations), we were able to identify unique patient records and estimate the incidence of DMD and SMA in Germany combining and de-duplicating data from patient registries, genetic institutes, and clinical care centers. Although we combined three different data sources, an unknown number of patients might not have been reported by any of these sources. Therefore, our results reflect the minimal incidence of these diseases.
KW  - incidence
KW  - neuromuscular disease
KW  - spinal muscular atrophy
KW  - duchenne muscular dystrophy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222807
VL  - 14
ER  - 
TY  - JOUR
A1  - Leistner, Marcus
A1  - Sommer, Stefanie
A1  - Kanofsky, Peer
A1  - Leyh, Rainer
A1  - Sommer, Sebastian-Patrick
T1  - Ischemia time impacts on respiratory chain functions and Ca\(^{2+}\)-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury
JF  - Journal of Cardiothoracic Surgery
N2  - Background
Mitochondrial impairment can result from myocardial ischemia reperfusion injury (IR). Despite cardioplegic arrest, IR-associated cardiodepression is a major problem in heart surgery. We determined the effect of increasing ischemia time on the respiratory chain (RC) function, the inner membrane polarization and Ca\(^{2+}\) homeostasis of rat cardiac subsarcolemmal mitochondria (SSM).

Methods
Wistar rat hearts were divided into 4 groups of stop-flow induced warm global IR using a pressure-controlled Langendorff system: 0, 15, 30 and 40 min of ischemia with 30 min of reperfusion, respectively. Myocardial contractility was determined from left ventricular pressure records (dP/dt, dPmax) with an intraventricular balloon. Following reperfusion, SSM were isolated and analyzed regarding electron transport chain (ETC) coupling by polarography (Clark-Type electrode), membrane polarization (JC1 fluorescence) and Ca2+-handling in terms of Ca\(^{2+}\)-induced swelling and Ca\(^{2+}\)-uptake/release (Calcium Green-5 N® fluorescence).

Results
LV contractility and systolic pressure during reperfusion were impaired by increasing ischemic times. Ischemia reduced ETC oxygen consumption in IR40/30 compared to IR0/30 at complex I-V (8.1 ± 1.2 vs. 18.2 ± 2.0 nmol/min) and II-IV/V (16.4 ± 2.6/14.8 ± 2.3 vs. 2.3 ± 0.6 nmol/min) in state 3 respiration (p < 0.01). Relative membrane potential revealed a distinct hyperpolarization in IR30/30 and IR40/30 (171.5 ± 17.4% and 170.9 ± 13.5%) compared to IR0/30 (p < 0.01), wearing off swiftly after CCCP-induced uncoupling. Excess mitochondrial permeability transition pore (mPTP)-gated Ca\(^{2+}\)-induced swelling was recorded in all groups and was most pronounced in IR40/30. Pyruvate addition for mPTP blocking strongly reduced SSM swelling in IR40/30 (relative AUC, ± pyruvate; IR0/30: 1.00 vs. 0.61, IR15/30: 1.68 vs. 1.00, IR30/30: 1.42 vs. 0.75, IR40/30: 1.97 vs. 0.85; p < 0.01). Ca2+-uptake remained unaffected by previous IR. Though Ca\(^{2+}\)-release was delayed for ≥30 min of ischemia (p < 0.01), Ca\(^{2+}\) retention was highest in IR15/30 (RFU; IR0/30: 6.3 ± 3.6, IR 15/30 42.9 ± 5.0, IR30/30 15.9 ± 3.8, IR40/30 11.5 ± 6.6; p ≤ 0.01 for IR15/30 against all other groups).

Conclusions
Ischemia prolongation in IR injury gradually impaired SSM in terms of respiratory chain function and Ca\(^{2+}\)-homeostasis. Membrane hyperpolarization appears to be responsible for impaired Ca2+-cycling and ETC function. Ischemia time should be considered an important factor influencing IR experimental data on subsarcolemmal mitochondria. Periods of warm global ischemia should be minimized during cardiac surgery to avoid excessive damage to SSMs.
KW  - subsarcolemmal mitochondria
KW  - ischemia reperfusion injury
KW  - ischemia time
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236455
VL  - 14
ER  - 
TY  - JOUR
A1  - Rubo, Marius
A1  - Gamer, Matthias
T1  - Visuo-tactile congruency influences the body schema during full body ownership illusion
JF  - Consciousness and Cognition
N2  - Previous research showed that full body ownership illusions in virtual reality (VR) can be robustly induced by providing congruent visual stimulation, and that congruent tactile experiences provide a dispensable extension to an already established phenomenon. Here we show that visuo-tactile congruency indeed does not add to already high measures for body ownership on explicit measures, but does modulate movement behavior when walking in the laboratory. Specifically, participants who took ownership over a more corpulent virtual body with intact visuo-tactile congruency increased safety distances towards the laboratory's walls compared to participants who experienced the same illusion with deteriorated visuo-tactile congruency. This effect is in line with the body schema more readily adapting to a more corpulent body after receiving congruent tactile information. We conclude that the action-oriented, unconscious body schema relies more heavily on tactile information compared to more explicit aspects of body ownership.
KW  - Full body ownership illusion
KW  - Visuo-tactile congruency
KW  - Body schema
KW  - Movement behavior
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227095
VL  - 73
ER  - 
TY  - JOUR
A1  - Minev, Boris R.
A1  - Lander, Elliot
A1  - Feller, John F.
A1  - Berman, Mark
A1  - Greenwood, Bernadette M.
A1  - Minev, Ivelina
A1  - Santidrian, Antonio F.
A1  - Nguyen, Duong
A1  - Draganov, Dobrin
A1  - Killinc, Mehmet O.
A1  - Vyalkova, Anna
A1  - Kesari, Santosh
A1  - McClay, Edward
A1  - Carabulea, Gabriel
A1  - Marincola, Francesco M.
A1  - Butterfield, Lisa H.
A1  - Szalay, Aladar A.
T1  - First-in-human study of TK-positive oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells
JF  - Journal of Translational Medicine
N2  - Background
ACAM2000, a thymidine kinase (TK)-positive strain of vaccinia virus, is the current smallpox vaccine in the US. Preclinical testing demonstrated potent oncolytic activity of ACAM2000 against several tumor types. This Phase I clinical trial of ACAM2000 delivered by autologous adipose stromal vascular fraction (SVF) cells was conducted to determine the safety and feasibility of such a treatment in patients with advanced solid tumors or acute myeloid leukemia (AML).

Methods
Twenty-four patients with solid tumors and two patients with AML participated in this open-label, non-randomized dose-escalation trial. All patients were treated with SVF derived from autologous fat and incubated for 15 min to 1 h with ACAM2000 before application. Six patients received systemic intravenous application only, one patient received intra-tumoral application only, 15 patients received combination intravenous with intra-tumoral deployment, 3 patients received intravenous and intra-peritoneal injection and 1 patient received intravenous, intra-tumoral and intra-peritoneal injections. Safety at each dose level of ACAM2000 (1.4 × 106 plaque-forming units (PFU) to 1.8 × 107 PFU) was evaluated. Blood samples for PK assessments, flow cytometry and cytokine analysis were collected at baseline and 1 min, 1 h, 1 day, 1 week, 1 month, 3 months and 6 months following treatment.

Results
No serious toxicities (> grade 2) were reported. Seven patients reported an adverse event (AE) in this study: self-limiting skin rashes, lasting 7 to 18 days—an expected adverse reaction to ACAM2000. No AEs leading to study discontinuation were reported. Viral DNA was detected in all patients’ blood samples immediately following treatment. Interestingly, in 8 patients viral DNA disappeared 1 day and re-appeared 1 week post treatment, suggesting active viral replication at tumor sites, and correlating with longer survival of these patients. No major increase in cytokine levels or correlation between cytokine levels and skin rashes was noted. We were able to assess some initial efficacy signals, especially when the ACAM2000/SVF treatment was combined with checkpoint inhibition.

Conclusions
Treatment with ACAM2000/SVF in patients with advanced solid tumors or AML is safe and well tolerated, and several patients had signals of an anticancer effect. These promising initial clinical results merit further investigation of therapeutic utility.

Trial registration Retrospectively registered (ISRCTN#10201650) on October 22, 2018.
KW  - clinical trial
KW  - oncolytic vaccinia virus
KW  - stromal vascular fraction
KW  - immunotherapy of cancer
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224105
VL  - 17
ER  - 
TY  - JOUR
A1  - Draganov, Dobrin D.
A1  - Santidrian, Antonio F.
A1  - Minev, Ivelina
A1  - Duong, Nguyen
A1  - Kilinc, Mehmet Okyay
A1  - Petrov, Ivan
A1  - Vyalkova, Anna
A1  - Lander, Elliot
A1  - Berman, Mark
A1  - Minev, Boris
A1  - Szalay, Aladar A.
T1  - Delivery of oncolytic vaccinia virus by matched allogeneic stem cells overcomes critical innate and adaptive immune barriers
JF  - Journal of Translational Medicine
N2  - Background
Previous studies have identified IFNγ as an important early barrier to oncolytic viruses including vaccinia. The existing innate and adaptive immune barriers restricting oncolytic virotherapy, however, can be overcome using autologous or allogeneic mesenchymal stem cells as carrier cells with unique immunosuppressive properties.

Methods
To test the ability of mesenchymal stem cells to overcome innate and adaptive immune barriers and to successfully deliver oncolytic vaccinia virus to tumor cells, we performed flow cytometry and virus plaque assay analysis of ex vivo co-cultures of stem cells infected with vaccinia virus in the presence of peripheral blood mononuclear cells from healthy donors. Comparative analysis was performed to establish statistically significant correlations and to evaluate the effect of stem cells on the activity of key immune cell populations.

Results
Here, we demonstrate that adipose-derived stem cells (ADSCs) have the potential to eradicate resistant tumor cells through a combination of potent virus amplification and sensitization of the tumor cells to virus infection. Moreover, the ADSCs demonstrate ability to function as a virus-amplifying Trojan horse in the presence of both autologous and allogeneic human PBMCs, which can be linked to the intrinsic immunosuppressive properties of stem cells and their unique potential to overcome innate and adaptive immune barriers. The clinical application of ready-to-use ex vivo expanded allogeneic stem cell lines, however, appears significantly restricted by patient-specific allogeneic differences associated with the induction of potent anti-stem cell cytotoxic and IFNγ responses. These allogeneic responses originate from both innate (NK)- and adaptive (T)- immune cells and might compromise therapeutic efficacy through direct elimination of the stem cells or the induction of an anti-viral state, which can block the potential of the Trojan horse to amplify and deliver vaccinia virus to the tumor.

Conclusions
Overall, our findings and data indicate the feasibility to establish simple and informative assays that capture critically important patient-specific differences in the immune responses to the virus and stem cells, which allows for proper patient-stem cell matching and enables the effective use of off-the-shelf allogeneic cell-based delivery platforms, thus providing a more practical and commercially viable alternative to the autologous stem cell approach.
KW  - vaccinia
KW  - cancer
KW  - stem Cells
KW  - oncolysis
KW  - oncolytic virus
KW  - virotherapy
KW  - immunity
KW  - immunotherapy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226312
SN  - 100
VL  - 17
ER  - 
TY  - JOUR
A1  - Bartel, Karin
A1  - Pein, Helmut
A1  - Popper, Bastian
A1  - Schmitt, Sabine
A1  - Janaki-Raman, Sudha
A1  - Schulze, Almut
A1  - Lengauer, Florian
A1  - Koeberle, Andreas
A1  - Werz, Oliver
A1  - Zischka, Hans
A1  - Müller, Rolf
A1  - Vollmar, Angelika M.
A1  - Schwarzenberg, Karin von
T1  - Connecting lysosomes and mitochondria – a novel role for lipid metabolism in cancer cell death
JF  - Cell Communication and Signaling
N2  - Background
The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood.

Methods
LC-MS/MS analysis was performed to investigate lipid distribution in cells. Cell survival and signaling pathways were analyzed by means of cell biological methods (qPCR, Western Blot, flow cytometry, CellTiter-Blue). Mitochondrial structure was analyzed by confocal imaging and electron microscopy, their function was determined by flow cytometry and seahorse measurements.

Results
Our data reveal that interfering with lysosomal function changes composition and subcellular localization of triacylglycerids accompanied by an upregulation of PGC1α and PPARα expression, master regulators of energy and lipid metabolism. Furthermore, cardiolipin content is reduced driving mitochondria into fission, accompanied by a loss of membrane potential and reduction in oxidative capacity, which leads to a deregulation in cellular ROS and induction of mitochondria-driven apoptosis. Additionally, cells undergo a metabolic shift to glutamine dependency, correlated with the fission phenotype and sensitivity to lysosomal inhibition, most prominent in Ras mutated cells.

Conclusion
This study sheds mechanistic light on a largely uninvestigated triangle between lysosomes, lipid metabolism and mitochondrial function. Insight into this organelle crosstalk increases our understanding of mitochondria-driven cell death. Our findings furthermore provide a first hint on a connection of Ras pathway mutations and sensitivity towards lysosomal inhibitors.
KW  - lysosome
KW  - V-ATPase
KW  - mitochondria
KW  - fission
KW  - apoptosis
KW  - lipid metabolism
KW  - cardiolipin
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221524
VL  - 17
ER  - 
TY  - JOUR
A1  - Rödel, Michaela
A1  - Teßmar, Jörg
A1  - Groll, Jürgen
A1  - Gbureck, Uwe
T1  - Tough and Elastic alpha-Tricalcium Phosphate Cement Composites with Degradable PEG-Based Cross-Linker
JF  - Materials
N2  - Dual setting cements composed of an in situ forming hydrogel and a reactive mineral phase combine high compressive strength of the cement with sufficient ductility and bending strength of the polymeric network. Previous studies were focused on the modification with non-degradable hydrogels based on 2-hydroxyethyl methacrylate (HEMA). Here, we describe the synthesis of suitable triblock degradable poly(ethylene glycol)-poly(lactide) (PEG-PLLA) cross-linker to improve the resorption capacity of such composites. A study with four different formulations was established. As reference, pure hydroxyapatite (HA) cements and composites with 40 wt% HEMA in the liquid cement phase were produced. Furthermore, HEMA was modified with 10 wt% of PEG-PLLA cross-linker or a test series containing only 25% cross-linker was chosen for composites with a fully degradable polymeric phase. Hence, we developed suitable systems with increased elasticity and 5-6 times higher toughn ess values in comparison to pure inorganic cement matrix. Furthermore, conversion rate from alpha-tricalcium phosphate (alpha-TCP) to HA was still about 90% for all composite formulations, whereas crystal size decreased. Based on this material development and advancement for a dual setting system, we managed to overcome the drawback of brittleness for pure calcium phosphate cements.
KW  - dual setting system
KW  - bending strength
KW  - calcium phosphate cement
KW  - composite material
KW  - HEMA
KW  - hydroxyapatite
KW  - free radical polymerization
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226437
VL  - 12
IS  - 53
ER  - 
TY  - JOUR
A1  - Sepahi, Ilnaz
A1  - Faust, Ulrike
A1  - Sturm, Marc
A1  - Bosse, Kristin
A1  - Kehrer, Martin
A1  - Heinrich, Tilman
A1  - Grundman-Hauser, Kathrin
A1  - Bauer, Peter
A1  - Ossowski, Stephan
A1  - Susak, Hana
A1  - Varon, Raymonda
A1  - Schröck, Evelin
A1  - Niederacher, Dieter
A1  - Auber, Bernd
A1  - Sutter, Christian
A1  - Arnold, Norbert
A1  - Hahnen, Eric
A1  - Dworniczak, Bernd
A1  - Wang-Gorke, Shan
A1  - Gehrig, Andrea
A1  - Weber, Bernhard H. F.
A1  - Engel, Christoph
A1  - Lemke, Johannes R.
A1  - Hartkopf, Andreas
A1  - Huu Phuc, Nguyen
A1  - Riess, Olaf
A1  - Schroeder, Christopher
T1  - Investigating the effects of additional truncating variants in DNA-repair genes on breast cancer risk in BRCA1-positive women
JF  - BMC Cancer
N2  - Background
Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic variant is 72%. The lifetime risk varies between families and even within affected individuals of the same family. The cause of this variability is largely unknown, but it is hypothesized that additional genetic factors contribute to differences in age at onset (AAO). Here we investigated whether truncating and rare missense variants in genes of different DNA-repair pathways contribute to this phenomenon.

Methods
We used extreme phenotype sampling to recruit 133 BRCA1-positive patients with either early breast cancer onset, below 35 (early AAO cohort) or cancer-free by age 60 (controls). Next Generation Sequencing (NGS) was used to screen for variants in 311 genes involved in different DNA-repair pathways.

Results
Patients with an early AAO (73 women) had developed breast cancer at a median age of 27 years (interquartile range (IQR); 25.00–27.00 years). A total of 3703 variants were detected in all patients and 43 of those (1.2%) were truncating variants. The truncating variants were found in 26 women of the early AAO group (35.6%; 95%-CI 24.7 - 47.7%) compared to 16 women of controls (26.7%; 95%-CI 16.1 to 39.7%). When adjusted for environmental factors and family history, the odds ratio indicated an increased breast cancer risk for those carrying an additional truncating DNA-repair variant to BRCA1 mutation (OR: 3.1; 95%-CI 0.92 to 11.5; p-value = 0.07), although it did not reach the conventionally acceptable significance level of 0.05.

Conclusions
To our knowledge this is the first time that the combined effect of truncating variants in DNA-repair genes on AAO in patients with hereditary breast cancer is investigated. Our results indicate that co-occurring truncating variants might be associated with an earlier onset of breast cancer in BRCA1-positive patients. Larger cohorts are needed to confirm these results.
KW  - breast cancer
KW  - age at onset
KW  - DNA-repair genes
KW  - next-generation-sequencing
KW  - panel sequencing
KW  - extreme phenotypes
KW  - hereditary breast and ovarian cancer
KW  - BRCA1
KW  - DNA-repair
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237676
VL  - 19
ER  - 
TY  - JOUR
A1  - Ebner, Florian
A1  - Wöckel, Achim
A1  - Schwentner, Lukas
A1  - Blettner, Maria
A1  - Janni, Wolfgang
A1  - Kreienberg, Rolf
A1  - Wischnewsky, Manfred
T1  - Does the number of removed axillary lymphnodes in high risk breast cancer patients influence the survival?
JF  - BMC Cancer
N2  - Background
The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions:

(1)
Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN?

(2)
Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN?

(3)
In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed?

Methods
A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines.

Results
2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy.

Conclusion
The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients.
KW  - advanced breast cancer
KW  - axillary dissection
KW  - lymph nodes
KW  - number of
KW  - sentinel
KW  - survival
KW  - guideline adherent treatment
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226445
VL  - 19
ER  - 
TY  - JOUR
A1  - Kolb-Mäurer, Annette
A1  - Sunderkötter, Cord
A1  - Kukowski, Borries
A1  - Meuth, Sven G.
T1  - An update on Peginterferon beta-1a Management in Multiple Sclerosis: results from an interdisciplinary Board of German and Austrian Neurologists and dermatologists
JF  - BMC Neurology
N2  - Background: 
Interferon (IFN) beta drugs have been approved for the treatment of relapsing forms of multiple sclerosis (RMS) for more than 20years and are considered to offer a favourable benefit-risk profile. In July 2014, subcutaneous (SC) peginterferon beta-1a 125g dosed every 2weeks, a pegylated form of interferon beta-1a, was approved by the EMA for the treatment of adult patients with RRMS and in August 2014 by the FDA for RMS. Peginterferon beta-1a shows a prolonged half-life and increased systemic drug exposure resulting in a reduced dosing frequency compared to other available interferon-based products in MS. In the Phase 3 ADVANCE trial peginterferon beta-1a demonstrated significant positive effects on clinical and MRI outcome measures versus placebo after one year. Furthermore, in the ATTAIN extension study, sustained efficacy with long-term treatment for nearly 6years was shown.

Main text
In July 2016, an interdisciplinary panel of German and Austrian experts convened to discuss the management of side effects associated with peginterferon beta-1a and other interferon beta-based treatments in MS in daily practice. The panel was composed of experts from university hospitals and private clinics comprised of neurologists, dermatologists, and an MS nurse. In this paper we report recommendations regarding best practices for adverse event management, focussing on peginterferon beta-1a. Injection site reactions (ISRs) and influenza-like illness are the most common adverse effects of interferon beta therapies and can present a burden for MS patients leading to non-adherence and discontinuation of therapy. Peginterferon beta-1a shows improved pharmacological properties. In clinical trials, the adverse event (AE) profile of peginterferon beta-1a was similar to other interferon beta formulations. The most common AEs were mild to moderate ISRs, influenza-like illness, pyrexia, and headache. Current information on the underlying cause of skin reactions associated with SC interferon treatment, and the management strategies for these AEs are limited. In pivotal trials, ISRs were mainly characterized and classified by neurologists, while dermatologists were only rarely consulted.

Conclusions
This report addresses expert recommendations on the management of most relevant adverse effects related to peginterferon beta-1a and other interferon betas, based on literature and interdisciplinary experience.
KW  - multiple sclerosis
KW  - peginterferon bet-1a
KW  - interferon beta
KW  - flu-like symptoms
KW  - injection site reactions
KW  - management
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224646
VL  - 19
ER  - 
TY  - JOUR
A1  - Rasche, Leo
A1  - Kortüm, K. Martin
A1  - Raab, Marc S.
A1  - Weinhold, Niels
T1  - The impact of tumor heterogeneity on diagnostics and novel therapeutic strategies in multiple myeloma
JF  - International Journal of Molecular Sciences
N2  - Myeloma is characterized by extensive inter-patient genomic heterogeneity due to multiple different initiating events. A recent multi-region sequencing study demonstrated spatial differences, with progression events, such as TP53 mutations, frequently being restricted to focal lesions. In this review article, we describe the clinical impact of these two types of tumor heterogeneity. Target mutations are often dominant at one site but absent at other sites, which poses a significant challenge to personalized therapy in myeloma. The same holds true for high-risk subclones, which can be locally restricted, and as such not detectable at the iliac crest, which is the usual sampling site. Imaging can improve current risk classifiers and monitoring of residual disease, but does not allow for deciphering the molecular characteristics of tumor clones. In the era of novel immunotherapies, the clinical impact of heterogeneity certainly needs to be re-defined. Yet, preliminary observations indicate an ongoing impact of spatial heterogeneity on the efficacy of monoclonal antibodies. In conclusion, we recommend combining molecular tests with imaging to improve risk prediction and monitoring of residual disease. Overcoming intra-tumor heterogeneity is the prerequisite for curing myeloma. Novel immunotherapies are promising but research addressing their impact on the spatial clonal architecture is highly warranted.
KW  - multiple myeloma
KW  - spatial heterogeneity
KW  - risk stratification
KW  - minimal residual disease
KW  - targeted therapy
KW  - clinical imaging
KW  - immunotherapy
KW  - daratumumab
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285402
SN  - 1422-0067
VL  - 20
IS  - 5
ER  - 
TY  - JOUR
A1  - Radchuk, Volodymyr
A1  - Rajiv, Sharma
A1  - Potokina, Elena
A1  - Radchuk, Ruslana
A1  - Weier, Diana
A1  - Munz, Eberhard
A1  - Schreiber, Miriam
A1  - Mascher, Martin
A1  - Stein, Nils
A1  - Wicker, Thomas
A1  - Kilian, Benjamin
A1  - Borisjuk, Ljudmilla
T1  - The highly divergent \(Jekyll\) genes, required for sexual reproduction, are lineage specific for the related grass tribes Triticeae and Bromeae
JF  - Plant Journal
N2  - Phylogenetically related groups of species contain lineage-specific genes that exhibit no sequence similarity to any genes outside the lineage. We describe here that the Jekyll gene, required for sexual reproduction, exists in two much diverged allelic variants, Jek1 and Jek3. Despite low similarity, the Jek1 and Jek3 proteins share identical signal peptides, conserved cysteine positions and direct repeats. The Jek1/Jek3 sequences are located at the same chromosomal locus and inherited in a monogenic Mendelian fashion. Jek3 has a similar expression as Jek1 and complements the Jek1 function in Jek1-deficient plants. Jek1 and Jek3 allelic variants were almost equally distributed in a collection of 485 wild and domesticated barley accessions. All domesticated barleys harboring the Jek1 allele belong to single haplotype J1-H1 indicating a genetic bottleneck during domestication. Domesticated barleys harboring the Jek3 allele consisted of three haplotypes. Jekyll-like sequences were found only in species of the closely related tribes Bromeae and Triticeae but not in other Poaceae. Non-invasive magnetic resonance imaging revealed intrinsic grain structure in Triticeae and Bromeae, associated with the Jekyll function. The emergence of Jekyll suggests its role in the separation of the Bromeae and Triticeae lineages within the Poaceae and identifies the Jekyll genes as lineage-specific.
KW  - gene alleles
KW  - lineage-specific genes
KW  - Triticeae
KW  - Hordeum vulgare
KW  - Triticum aestivum
KW  - gene family evolution
KW  - plant reproduction
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224769
VL  - 98
IS  - 6
ER  - 
TY  - JOUR
A1  - Reinermann, Sophie
A1  - Gessner, Ursula
A1  - Asam, Sarah
A1  - Kuenzer, Claudia
A1  - Dech, Stefan
T1  - The Effect of Droughts on Vegetation Condition in Germany: An Analysis Based on Two Decades of Satellite Earth Observation Time Series and Crop Yield Statistics
JF  - Remote Sensing
N2  - Central Europe experienced several droughts in the recent past, such as in the year 2018, which was characterized by extremely low rainfall rates and high temperatures, resulting in substantial agricultural yield losses. Time series of satellite earth observation data enable the characterization of past drought events over large temporal and spatial scales. Within this study, Moderate Resolution Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI) (MOD13Q1) 250 m time series were investigated for the vegetation periods of 2000 to 2018. The spatial and temporal development of vegetation in 2018 was compared to other dry and hot years in Europe, like the drought year 2003. Temporal and spatial inter- and intra-annual patterns of EVI anomalies were analyzed for all of Germany and for its cropland, forest, and grassland areas individually. While vegetation development in spring 2018 was above average, the summer months of 2018 showed negative anomalies in a similar magnitude as in 2003, which was particularly apparent within grassland and cropland areas in Germany. In contrast, the year 2003 showed negative anomalies during the entire growing season. The spatial pattern of vegetation status in 2018 showed high regional variation, with north-eastern Germany mainly affected in June, north-western parts in July, and western Germany in August. The temporal pattern of satellite-derived EVI deviances within the study period 2000-2018 were in good agreement with crop yield statistics for Germany. The study shows that the EVI deviation of the summer months of 2018 were among the most extreme in the study period compared to other years. The spatial pattern and temporal development of vegetation condition between the drought years differ.
KW  - drought
KW  - time series
KW  - heat wave
KW  - agriculture
KW  - climate extremes
KW  - climate change
KW  - crop statistics
KW  - MODIS
KW  - Germany
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225165
VL  - 11
IS  - 15
ER  - 
TY  - JOUR
A1  - Schlottmann, Elisabeth
A1  - Schicke, David
A1  - Krüger, Felix
A1  - Lingnau, Benjamin
A1  - Schneider, Christian
A1  - Höfling, Sven
A1  - Lüdge, Kathy
A1  - Porte, Xavier
A1  - Reitzenstein, Stephan
T1  - Stochastic polarization switching induced by optical injection in bimodal quantum-dot micropillar lasers
JF  - Optics Express
N2  - Mutual coupling and injection locking of semiconductor lasers is of great interest in non-linear dynamics and its applications for instance in secure data communication and photonic reservoir computing. Despite its importance, it has hardly been studied in microlasers operating at mu W light levels. In this context, vertically emitting quantum dot micropillar lasers are of high interest. Usually, their light emission is bimodal, and the gain competition of the associated linearly polarized fundamental emission modes results in complex switching dynamics. We report on selective optical injection into either one of the two fundamental mode components of a bimodal micropillar laser. Both modes can lock to the master laser and influence the non-injected mode by reducing the available gain. We demonstrate that the switching dynamics can be tailored externally via optical injection in very good agreement with our theory based on semi-classical rate equations. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
KW  - Nonlinear Dynamics
KW  - Bistability
KW  - Generation
KW  - Subject
KW  - Regimes
KW  - Physics
KW  - Vcsels
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228603
VL  - 27
IS  - 20
ER  - 
TY  - JOUR
A1  - Radeva, Mariya Y.
A1  - Walter, Elias
A1  - Stach, Ramona Alexandra
A1  - Yazdi, Amir S.
A1  - Schlegel, Nicolas
A1  - Sarig, Ofer
A1  - Sprecher, Eli
A1  - Waschke, Jens
T1  - ST18 Enhances PV-IgG-Induced Loss of Keratinocyte Cohesion in Parallel to Increased ERK Activation
JF  - Frontiers in Immunology
N2  - Pemphigus is an autoimmune blistering disease targeting the desmosomal proteins desmoglein (Dsg) 1 and Dsg3. Recently, a genetic variant of the Suppression of tumorigenicity 18 (ST18) promoter was reported to cause ST18 up-regulation, associated with pemphigus vulgaris (PV)-IgG-mediated increase in cytokine secretion and more prominent loss of keratinocyte cohesion. Here we tested the effects of PV-IgG and the pathogenic pemphigus mouse anti-Dsg3 antibody AK23 on cytokine secretion and ERK activity in human keratinocytes dependent on ST18 expression. Without ST18 overexpression, both PV-IgG and AK23 induced loss of keratinocyte cohesion which was accompanied by prominent fragmentation of Dsg3 immunostaining along cell borders. In contrast, release of pro-inflammatory cytokines such as IL-1 alpha, IL-6, TNF alpha, and IFN-gamma was not altered significantly in both HaCaT and primary NHEK cells. These experiments indicate that cytokine expression is not strictly required for loss of keratinocyte cohesion. Upon ST18 overexpression, fragmentation of cell monolayers increased significantly in response to autoantibody incubation. Furthermore, production of IL-1 alpha and IL-6 was enhanced in some experiments but not in others whereas release of TNF-alpha dropped significantly upon PV-IgG application in both EV- and ST18-transfected HaCaT cells. Additionally, in NHEK, application of PV-IgG but not of AK23 significantly increased ERK activity. In contrast, ST18 overexpression in HaCaT cells augmented ERK activation in response to both c-IgG and AK23 but not PV-IgG. Because inhibition of ERK by U0126 abolished PV-IgG- and AK23-induced loss of cell cohesion in ST18-expressing cells, we conclude that autoantibody-induced ERK activation was relevant in this scenario. In summary, similar to the situation in PV patients carrying ST18 polymorphism, overexpression of ST18 enhanced keratinocyte susceptibility to autoantibody-induced loss of cell adhesion, which may be caused in part by enhanced ERK signaling.
KW  - pemphigus
KW  - desmosome
KW  - desmoglein
KW  - ST18
KW  - ERK
KW  - cytokines
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224910
VL  - 10
ER  - 
TY  - JOUR
A1  - Thölken, Clemens
A1  - Thamm, Markus
A1  - Erbacher, Christoph
A1  - Lechner, Marcus
T1  - Sequence and structural properties of circular RNAs in the brain of nurse and forager honeybees (Apis mellifera)
JF  - BMC Genomics
N2  - Background 
The honeybee (Apis mellifera) represents a model organism for social insects displaying behavioral plasticity. This is reflected by an age-dependent task allocation. The most protruding tasks are performed by young nurse bees and older forager bees that take care of the brood inside the hive and collect food from outside the hive, respectively. The molecular mechanism leading to the transition from nurse bees to foragers is currently under intense research. Circular RNAs, however, were not considered in this context so far. As of today, this group of non-coding RNAs was only known to exist in two other insects, Drosophila melanogaster and Bombyx mori. Here we complement the state of circular RNA research with the first characterization in a social insect.

Results
We identified numerous circular RNAs in the brain of A. mellifera nurse bees and forager bees using RNA-Seq with exonuclease enrichment. Presence and circularity were verified for the most abundant representatives. Back-splicing in honeybee occurs further towards the end of transcripts and in transcripts with a high number of exons. The occurrence of circularized exons is correlated with length and CpG-content of their flanking introns. The latter coincides with increased DNA-methylation in the respective loci. For two prominent circular RNAs the abundance in worker bee brains was quantified in TaqMan assays. In line with previous findings of circular RNAs in Drosophila, circAmrsmep2 accumulates with increasing age of the insect. In contrast, the levels of circAmrad appear age-independent and correlate with the bee's task. Its parental gene is related to amnesia-resistant memory.

Conclusions
We provide the first characterization of circRNAs in a social insect. Many of the RNAs identified here show homologies to circular RNAs found in Drosophila and Bombyx, indicating that circular RNAs are a common feature among insects. We find that exon circularization is correlated to DNA-methylation at the flanking introns. The levels of circAmrad suggest a task-dependent abundance that is decoupled from age. Moreover, a GO term analysis shows an enrichment of task-related functions. We conclude that circular RNAs could be relevant for task allocation in honeybee and should be investigated further in this context.
KW  - circRNA
KW  - circular transcriptome sequencing
KW  - honeybee
KW  - brain
KW  - neuronal
KW  - Methylation
KW  - CpG
KW  - alternative splicing
KW  - behavioral plasticity
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241302
VL  - 20
ER  - 
TY  - JOUR
A1  - Grebinyk, Anna
A1  - Prylutska, Svitlana
A1  - Grebinyk, Sergii
A1  - Prylutskyy, Yuriy
A1  - Ritter, Uwe
A1  - Matyshevska, Olga
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - Complexation with C\(_{60}\) fullerene increases doxorubicin efficiency against leukemic cells in vitro
JF  - Nanoscale Research Letters
N2  - Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C\(_{60}\) fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells.Here, we studied the physicochemical properties and anticancer activity of C\(_{60}\) fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C\(_{60}\)-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C\(_{60}\) fullerene considerable nanocarrier function.The results of this study indicated that C\(_{60}\) fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.
KW  - C-60 fullerene
KW  - doxorubicin
KW  - noncovalent complex
KW  - leukemic cells
KW  - cytotoxicity
KW  - accumulation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228257
VL  - 14
IS  - 61
ER  - 
TY  - JOUR
A1  - Richter, Julia
A1  - Hüttmann, Andreas
A1  - Rekowski, Jan
A1  - Schmitz, Christine
A1  - Gärtner, Selina
A1  - Rosenwald, Andreas
A1  - Hansmann, Martin-Leo
A1  - Hartmann, Sylvia
A1  - Möller, Peter
A1  - Wacker, Hans-Heinrich
A1  - Feller, Alfred
A1  - Thorns, Christoph
A1  - Müller, Stefan
A1  - Dührsen, Ulrich
A1  - Klapper, Wolfram
T1  - Molecular characteristics of diffuse large B-cell lymphoma in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin lymphomas (PETAL) trial: correlation with interim PET and outcome
JF  - Blood Cancer Journal
N2  - No abstract available
KW  - Cancer genetics
KW  - Medical research
KW  - Translational research
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226185
VL  - 9
ER  - 
TY  - JOUR
A1  - Akshat, Puri
A1  - Aaboud, M.
A1  - Aad, G.
A1  - Abbott, B.
A1  - Abdinov, O.
A1  - Abeloos, B.
A1  - Abhayasinghe, D. K.
A1  - Abidi, S. H.
A1  - Abou Zeid, O. S.
A1  - Abraham, N. L.
A1  - Abramowicz, H.
A1  - Abreu, H.
A1  - Abulaiti, Y.
A1  - Acharya, B. S.
A1  - Adachi, S.
A1  - Adam, L.
A1  - Adamczyk, L.
A1  - Adelman, J.
A1  - Adersberger, M.
A1  - Adiguzel, A.
A1  - Adye, T.
A1  - Affolder, A. A.
A1  - Afik, Y.
A1  - Agheorghiesei, C.
A1  - Aguilar-Saavedra, J. A.
A1  - Ahmadov, F.
A1  - Aiellil, G.
A1  - Akatsuka, S.
A1  - Akesson, T. P. A.
A1  - Akilli, E.
A1  - Akimov, A. V.
A1  - Alberghi, G. L.
A1  - Albert, J.
A1  - Albicocco, P.
A1  - Alconada Verzini, M. J.
A1  - Alderweireld, S.
A1  - Aleksa, M.
A1  - Aleksandrov, I. N.
A1  - Alexa, C.
A1  - Alexopoulos, T.
A1  - Alhroob, M.
A1  - Ali, B.
A1  - Alimonti, G.
A1  - Alison, J.
A1  - Andre, S. P.
A1  - Allaire, C.
A1  - Allbrooke, B. M. M.
A1  - Allen, B. W.
A1  - Allport, P. P.
A1  - Aloisio, A.
A1  - Alonso, A.
A1  - Alonso, F.
A1  - Alpigiani, C.
A1  - Alshehri, A. A.
A1  - Alstaty, M. I.
A1  - Alvarez, Gonzalez B.
A1  - Alvarez Piqueras, D.
A1  - Alviggi, M. G.
A1  - Amadio, B. T.
A1  - Amaral, Coutinho, Y.
A1  - Ambler, A.
A1  - Ambroz, L.
A1  - Amelung, C.
A1  - Amidei, D.
A1  - Amor Dos Santos, S. P.
A1  - Amoroso, S.
A1  - Amrouche, C. S.
A1  - Anastopoulos, C.
A1  - Ancu, L. S.
A1  - Andari, N.
A1  - Andeen, T.
A1  - Anders, C. F.
A1  - Anders, J. K.
A1  - Anderson, K. J.
A1  - Andreazza, A.
A1  - Andrei, V.
A1  - et al, 
T1  - Measurement of angular and momentum distributions of charged particles within and around jets in Pb plus Pb and pp collisions at root s(NN)=5.02 TeV with ATLAS at the LHC : XXVIIth International Conference on Ultrarelativistic Nucleus-Nucleus Collisions
(Quark Matter 2018)
JF  - Nuclear Physics A
N2  - Studies of the fragmentation of jets into charged particles in heavy-ion collisions can help in understanding the mechanism of jet quenching by the hot and dense QCD matter created in such collisions, the quark-gluon plasma. These proceedings present a measurement of the angular distribution of charged particles around the jet axis in root s(NN) = 5.02 TeV Pb+Pb and pp collisions, done using the ATLAS detector at the LHC. The measurement is performed inside jets reconstructed with the anti-k(t) algorithm with radius parameter R = 0.4, and is extended to regions outside the jet cone. Results are presented as a function of Pb+Pb collision centrality, and both jet and charged-particle transverse momenta.
KW  - jets
KW  - fragmentation functions
KW  - jet shapes
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224703
VL  - 982
IS  - 2
ER  - 
TY  - JOUR
A1  - Rademaker, Manuel E.
A1  - Schuberth, Florian
A1  - Dijkstra, Theo K.
T1  - Measurement error correlation within blocks of indicators in consistent partial least squares : Issues and remedies
JF  - Internet Research
N2  - Purpose The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors. Design/methodology/approach Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted. Findings In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators. Originality/value Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling.
KW  - Monte Carlo simulation
KW  - Structural equation modelling
KW  - Consistent partial least squares
KW  - Measurement error correlation
KW  - Model specification
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224901
VL  - 29
IS  - 3
ER  - 
TY  - JOUR
A1  - Ruiz, E. Josue
A1  - Diefenbacher, Markus E.
A1  - Nelson, Jessica K.
A1  - Sancho, Rocio
A1  - Pucci, Fabio
A1  - Chakraborty, Atanu
A1  - Moreno, Paula
A1  - Annibaldi, Alessandro
A1  - Liccardi, Gianmaria
A1  - Encheva, Vesela
A1  - Mitter, Richard
A1  - Rosenfeldt, Mathias
A1  - Snijders, Ambrosius P.
A1  - Meier, Pascal
A1  - Calzado, Marco A.
A1  - Behrens, Axel
T1  - LUBAC determines chemotherapy resistance in squamous cell lung cancer
JF  - Journal of Experimental Medicine
N2  - Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
KW  - Solid tumors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227146
VL  - 216
IS  - 2
ER  - 
TY  - JOUR
A1  - Robin, Marie
A1  - de Wreede, Liesbeth C.
A1  - Wolschke, Christine
A1  - Schetelig, Johannes
A1  - Eikema, Diderik-Jan
A1  - Van Lint, Maria Teresa
A1  - Knelange, Nina Simone
A1  - Beelen, Dietrich
A1  - Brecht, Arne
A1  - Niederwieser, Dietger
A1  - Vitek, Antonin
A1  - Bethge, Wolfgang
A1  - Arnold, Renate
A1  - Finke, Jürgen
A1  - Volin, Liisa
A1  - Yakoub-Agha, Ibrahim
A1  - Nagler, Arnon
A1  - Poiré, Xavier
A1  - Einsele, Hermann
A1  - Chevallier, Patrice
A1  - Holler, Ernst
A1  - Ljungman, Per
A1  - Robinson, Stephen
A1  - Radujkovic, Alekxandar
A1  - McLornan, Donal
A1  - Chalandon, Yves
A1  - Kröger, Nicolaus
T1  - Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis
JF  - Haematologica
N2  - Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged <45 years and 33% (13-53%) in patients aged >= 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.
KW  - Prognostic scoring system
KW  - Societe Francaise
KW  - Gruppo-italiano
KW  - European group
KW  - Late mortality
KW  - Midollo-Osseo
KW  - LATE DEATHS
KW  - Survival
KW  - Blood
KW  - Ruxolitinib
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226386
VL  - 104
IS  - 9
ER  - 
TY  - JOUR
A1  - Radeloff, Katrin
A1  - Radeloff, Andreas
A1  - Tirado, Mario Ramos
A1  - Scherzad, Agmal
A1  - Hagen, Rudolf
A1  - Kleinsasser, Norbert H.
A1  - Hackenberg, Stephan
T1  - Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells
JF  - Materials
N2  - Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 mu g/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.
KW  - zinc oxide
KW  - nanoparticles
KW  - toxicity
KW  - differentiation potential
KW  - human adipose-derived stromal cells
KW  - stem cells
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224779
VL  - 12
IS  - 1823
ER  - 
TY  - JOUR
A1  - Rudelius, Martina
A1  - Rosenfeldt, Mathias Tillmann
A1  - Leich, Ellen
A1  - Rauert-Wunderlich, Hilka
A1  - Solimando, Antonio Giovanni
A1  - Ott, German
A1  - Rosenwald, Andreas
A1  - Beilhack, Andreas
T1  - Inhibition of focal adhesion kinase overcomes resistance of mantle cell lymphoma to ibrutinib in the bone marrow microenvironment
JF  - Haematologica
N2  - Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells co-cultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi-based focal adhesion kinase silencing was performed. We showed that focal adhesion kinase is highly expressed in bone marrow infiltrates of mantle cell lymphoma and in mantle cell lymphoma cell lines. Stroma-mediated activation of focal adhesion kinase led to activation of multiple kinases (AKT, p42/44 and NF-kappa B), that are important for prosurvival and proliferation signaling. Interestingly, RNAi-based focal adhesion kinase silencing or inhibition with small molecule inhibitors (FAKi) resulted in blockage of targeted cell invasion and induced apoptosis by inactivation of multiple signaling cascades, including the classic and alternative NF-kappa B pathway. In addition, the combined treatment of ibrutinib and FAKi was highly synergistic, and ibrutinib resistance of mantle cell lymphoma could be overcome. These data demonstrate that focal adhesion kinase is important for stroma-mediated survival and drug resistance in mantle cell lymphoma, providing indications for a targeted therapeutic strategy.
KW  - NF-Kappa-B
KW  - Stromal cells
KW  - Induced apoptosis
KW  - Fak regulation
KW  - Phase-
KW  - Multiple
KW  - Activation
KW  - Mechanisms
KW  - Migration
KW  - Pathogenesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227117
VL  - 103
IS  - 1
ER  - 
TY  - JOUR
A1  - Stuckensen, Kai
A1  - Lamo-Espinosa, José M.
A1  - Muiños-López, Emma
A1  - Ripalda-Cemboráin, Purificación
A1  - López-Martínez, Tania
A1  - Iglesias, Elena
A1  - Abizanda, Gloria
A1  - Andreu, Ion
A1  - Flandes-Iparraguirre, María
A1  - Pons-Villanueva, Juan
A1  - Elizalde, Reyes
A1  - Nickel, Joachim
A1  - Ewald, Andrea
A1  - Gbureck, Uwe
A1  - Prósper, Felipe
A1  - Groll, Jürgen
A1  - Granero-Moltó, Froilán
T1  - Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP−2 and enhanced bone regeneration
JF  - Materials
N2  - In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
KW  - rhBMP–2
KW  - collagen sponge
KW  - cryostructured scaffolds
KW  - bone critical size defect
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195966
SN  - 1996-1944
VL  - 12
IS  - 19
ER  - 
TY  - JOUR
A1  - Näschen, Kristian
A1  - Diekkrüger, Bernd
A1  - Evers, Mariele
A1  - Höllermann, Britta
A1  - Steinbach, Stefanie
A1  - Thonfeld, Frank
T1  - The impact of land use/land cover change (LULCC) on water resources in a tropical catchment in Tanzania under different climate change scenarios
JF  - Sustainability
N2  - Many parts of sub-Saharan Africa (SSA) are prone to land use and land cover change (LULCC). In many cases, natural systems are converted into agricultural land to feed the growing population. However, despite climate change being a major focus nowadays, the impacts of these conversions on water resources, which are essential for agricultural production, is still often neglected, jeopardizing the sustainability of the socio-ecological system. This study investigates historic land use/land cover (LULC) patterns as well as potential future LULCC and its effect on water quantities in a complex tropical catchment in Tanzania. It then compares the results using two climate change scenarios. The Land Change Modeler (LCM) is used to analyze and to project LULC patterns until 2030 and the Soil and Water Assessment Tool (SWAT) is utilized to simulate the water balance under various LULC conditions. Results show decreasing low flows by 6–8% for the LULC scenarios, whereas high flows increase by up to 84% for the combined LULC and climate change scenarios. The effect of climate change is stronger compared to the effect of LULCC, but also contains higher uncertainties. The effects of LULCC are more distinct, although crop specific effects show diverging effects on water balance components. This study develops a methodology for quantifying the impact of land use and climate change and therefore contributes to the sustainable management of the investigated catchment, as it shows the impact of environmental change on hydrological extremes (low flow and floods) and determines hot spots, which are critical for environmental development.
KW  - SWAT model
KW  - Land Change Modeler
KW  - Scenario analysis
KW  - Extreme flows
KW  - Tanzania
KW  - Kilombero
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193825
SN  - 2071-1050
VL  - 11
IS  - 24
ER  - 
TY  - JOUR
A1  - Villalobos, Alvaro S.
A1  - Wiese, Jutta
A1  - Imhoff, Johannes F.
A1  - Dorador, Cristina
A1  - Keller, Alexander
A1  - Hentschel, Ute
T1  - Systematic affiliation and genome analysis of Subtercola vilae DB165T with particular emphasis on cold adaptation of an isolate from a high-altitude cold volcano lake
JF  - Microorganisms
N2  - Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake.
KW  - cold adaptation
KW  - Subtercola vilae
KW  - genome analysis
KW  - systematic affiliation
KW  - Llullaillaco Volcano
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197394
SN  - 2076-2607
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - González, María Magdalena
A1  - Dorner, Daniela
A1  - Bretz, Thomas
A1  - García-González, José Andrés
T1  - Unbiased long-term monitoring at TeV energies
JF  - Galaxies
N2  - For the understanding of the variable, transient and non-thermal universe, unbiased long-term monitoring is crucial. To constrain the emission mechanisms at the highest energies, it is important to characterize the very high energy emission and its correlation with observations at other wavelengths. At very high energies, only a limited number of instruments is available. This article reviews the current status of monitoring of the extra-galactic sky at TeV energies.
KW  - monitoring
KW  - very high energies (VHE)
KW  - TeV energies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197389
SN  - 2075-4434
VL  - 7
IS  - 2
ER  - 
TY  - JOUR
A1  - Wick, Christoph
A1  - Hartelt, Alexander
A1  - Puppe, Frank
T1  - Staff, symbol and melody detection of Medieval manuscripts written in square notation using deep Fully Convolutional Networks
JF  - Applied Sciences
N2  - Even today, the automatic digitisation of scanned documents in general, but especially the automatic optical music recognition (OMR) of historical manuscripts, still remains an enormous challenge, since both handwritten musical symbols and text have to be identified. This paper focuses on the Medieval so-called square notation developed in the 11th–12th century, which is already composed of staff lines, staves, clefs, accidentals, and neumes that are roughly spoken connected single notes. The aim is to develop an algorithm that captures both the neumes, and in particular its melody, which can be used to reconstruct the original writing. Our pipeline is similar to the standard OMR approach and comprises a novel staff line and symbol detection algorithm based on deep Fully Convolutional Networks (FCN), which perform pixel-based predictions for either staff lines or symbols and their respective types. Then, the staff line detection combines the extracted lines to staves and yields an F\(_1\) -score of over 99% for both detecting lines and complete staves. For the music symbol detection, we choose a novel approach that skips the step to identify neumes and instead directly predicts note components (NCs) and their respective affiliation to a neume. Furthermore, the algorithm detects clefs and accidentals. Our algorithm predicts the symbol sequence of a staff with a diplomatic symbol accuracy rate (dSAR) of about 87%, which includes symbol type and location. If only the NCs without their respective connection to a neume, all clefs and accidentals are of interest, the algorithm reaches an harmonic symbol accuracy rate (hSAR) of approximately 90%. In general, the algorithm recognises a symbol in the manuscript with an F\(_1\) -score of over 96%.
KW  - optical music recognition
KW  - historical document analysis
KW  - medieval manuscripts
KW  - neume notation
KW  - fully convolutional neural networks
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197248
SN  - 2076-3417
VL  - 9
IS  - 13
ER  - 
TY  - JOUR
A1  - Mayr, Stefan
A1  - Kuenzer, Claudia
A1  - Gessner, Ursula
A1  - Klein, Igor
A1  - Rutzinger, Martin
T1  - Validation of earth observation time-series: a review for large-area and temporally dense land surface products
JF  - Remote Sensing
N2  - Large-area remote sensing time-series offer unique features for the extensive investigation of our environment. Since various error sources in the acquisition chain of datasets exist, only properly validated results can be of value for research and downstream decision processes. This review presents an overview of validation approaches concerning temporally dense time-series of land surface geo-information products that cover the continental to global scale. Categorization according to utilized validation data revealed that product intercomparisons and comparison to reference data are the conventional validation methods. The reviewed studies are mainly based on optical sensors and orientated towards global coverage, with vegetation-related variables as the focus. Trends indicate an increase in remote sensing-based studies that feature long-term datasets of land surface variables. The hereby corresponding validation efforts show only minor methodological diversification in the past two decades. To sustain comprehensive and standardized validation efforts, the provision of spatiotemporally dense validation data in order to estimate actual differences between measurement and the true state has to be maintained. The promotion of novel approaches can, on the other hand, prove beneficial for various downstream applications, although typically only theoretical uncertainties are provided.
KW  - accuracy
KW  - error estimation
KW  - global
KW  - intercomparison
KW  - remote sensing
KW  - uncertainty
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193202
SN  - 2072-4292
VL  - 11
IS  - 22
ER  - 
TY  - JOUR
A1  - Walther, Grit
A1  - Wagner, Lysett
A1  - Kurzai, Oliver
T1  - Updates on the taxonomy of Mucorales with an emphasis on clinically important taxa
JF  - Journal of Fungi
N2  - Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. Several taxa cause life-threatening infections, predominantly in patients with impaired immunity. The order Mucorales has now been assigned to the phylum Mucoromycota and is comprised of 261 species in 55 genera. Of these accepted species, 38 have been reported to cause infections in humans, as a clinical entity known as mucormycosis. Due to molecular phylogenetic studies, the taxonomy of the order has changed widely during the last years. Characteristics such as homothallism, the shape of the suspensors, or the formation of sporangiola are shown to be not taxonomically relevant. Several genera including Absidia, Backusella, Circinella, Mucor, and Rhizomucor have been amended and their revisions are summarized in this review. Medically important species that have been affected by recent changes include Lichtheimia corymbifera, Mucor circinelloides, and Rhizopus microsporus. The species concept of Rhizopus arrhizus (syn. R. oryzae) is still a matter of debate. Currently, species identification of the Mucorales is best performed by sequencing of the internal transcribed spacer (ITS) region. Ecologically, the Mucorales represent a diverse group but for the majority of taxa, the ecological role and the geographic distribution remain unknown. Understanding the biology of these opportunistic fungal pathogens is a prerequisite for the prevention of infections, and, consequently, studies on the ecology of the Mucorales are urgently needed.
KW  - Mucorales
KW  - taxonomy
KW  - pathogens
KW  - identification
KW  - ecology
KW  - Circinella
KW  - Lichtheimia
KW  - Mucor
KW  - Rhizomucor
KW  - Rhizopus
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193081
SN  - 2309-608X
VL  - 5
IS  - 4
ER  - 
TY  - JOUR
A1  - Grebinyk, Anna
A1  - Prylutska, Svitlana
A1  - Chepurna, Oksana
A1  - Grebinyk, Sergii
A1  - Prylutskyy, Yuriy
A1  - Ritter, Uwe
A1  - Ohulchanskyy, Tymish Y.
A1  - Matyshevska, Olga
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - Synergy of chemo- and photodynamic therapies with C\(_{60}\) Fullerene-Doxorubicin nanocomplex
JF  - Nanomaterials
N2  - A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C\(_{60}\) fullerene (C\(_{60}\)) were applied in 1:1 and 2:1 molar ratio, exploiting C\(_{60}\) both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C\(_{60}\)'s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox's antiproliferative activity and C\(_{60}\)'s photoinduced pro-oxidant activity. When cells were treated with 2:1 C\(_{60}\)-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C\(_{60}\)-Dox enabled a nanomolar concentration of Dox and C\(_{60}\) to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC\(_{50}\) 16, 9 and 7 × 10\(^3\)-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C\(_{60}\)'s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C\(_{60}\)-mediated Dox delivery and C\(_{60}\) photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C\(_{60}\)-Dox nanoformulation provides a promising synergetic approach for cancer treatment.
KW  - photodynamic chemotherapy
KW  - synergistic effect
KW  - C\(_{60}\) fullerene
KW  - Doxorubicin
KW  - nanocomplex
KW  - leukemic cells
KW  - apoptosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193140
SN  - 2079-4991
VL  - 9
IS  - 11
ER  - 
TY  - JOUR
A1  - Latifi, Hooman
A1  - Heurich, Marco
T1  - Multi-scale remote sensing-assisted forest inventory: a glimpse of the state-of-the-art and future prospects
JF  - Remote Sensing
N2  - Advances in remote inventory and analysis of forest resources during the last decade have reached a level to be now considered as a crucial complement, if not a surrogate, to the long-existing field-based methods. This is mostly reflected in not only the use of multiple-band new active and passive remote sensing data for forest inventory, but also in the methodic and algorithmic developments and/or adoptions that aim at maximizing the predictive or calibration performances, thereby minimizing both random and systematic errors, in particular for multi-scale spatial domains. With this in mind, this editorial note wraps up the recently-published Remote Sensing special issue “Remote Sensing-Based Forest Inventories from Landscape to Global Scale”, which hosted a set of state-of-the-art experiments on remotely sensed inventory of forest resources conducted by a number of prominent researchers worldwide.
KW  - remote sensing
KW  - forest resources inventory
KW  - spatial scale
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197358
SN  - 2072-4292
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Molinas-González, Carlos R.
A1  - Castro, Jorge
A1  - González-Megías, Adela
A1  - Leverkus, Alexandro B.
T1  - Effects of post-fire deadwood management on soil macroarthropod communities
JF  - Forests
N2  - Dead wood comprises a vast amount of biological legacies that set the scene for ecological regeneration after wildfires, yet its removal is the most frequent management strategy worldwide. Soil-dwelling organisms are conspicuous, and they provide essential ecosystem functions, but their possible affection by different post-fire management strategies has so far been neglected. We analyzed the abundance, richness, and composition of belowground macroarthropod communities under two contrasting dead-wood management regimes after a large wildfire in the Sierra Nevada Natural and National Park (Southeast Spain). Two plots at different elevation were established, each containing three replicates of two experimental treatments: partial cut, where trees were cut and their branches lopped off and left over the ground, and salvage logging, where all the trees were cut, logs were piled, branches were mechanically masticated, and slash was spread on the ground. Ten years after the application of the treatments, soil cores were extracted from two types of microhabitat created by these treatments: bare-soil (in both treatments) and under-logs (in the partial cut treatment only). Soil macroarthropod assemblages were dominated by Hemiptera and Hymenoptera (mostly ants) and were more abundant and richer in the lowest plot. The differences between dead-wood treatments were most evident at the scale of management interventions: abundance and richness were lowest after salvage logging, even under similar microhabitats (bare-soil). However, there were no significant differences between microhabitat types on abundance and richness within the partial cut treatment. Higher abundance and richness in the partial cut treatment likely resulted from higher resource availability and higher plant diversity after natural regeneration. Our results suggest that belowground macroarthropod communities are sensitive to the manipulation of dead-wood legacies and that management through salvage logging could reduce soil macroarthropod recuperation compared to other treatments with less intense management even a decade after application.
KW  - forest fire
KW  - burnt-wood
KW  - species richness
KW  - soil fauna
KW  - post-fire management
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193079
SN  - 1999-4907
VL  - 10
IS  - 11
ER  - 
TY  - JOUR
A1  - Brodehl, Andreas
A1  - Pour Hakimi, Seyed Ahmad
A1  - Stanasiuk, Caroline
A1  - Ratnavadivel, Sandra
A1  - Hendig, Doris
A1  - Gaertner, Anna
A1  - Gerull, Brenda
A1  - Gummert, Jan
A1  - Paluszkiewicz, Lech
A1  - Milting, Hendrik
T1  - Restrictive cardiomyopathy is caused by a novel homozygous desmin (DES) mutation p.Y122H leading to a severe filament assembly defect
JF  - Genes
N2  - Here, we present a small Iranian family, where the index patient received a diagnosis of restrictive cardiomyopathy (RCM) in combination with atrioventricular (AV) block. Genetic analysis revealed a novel homozygous missense mutation in the DES gene (c.364T > C; p.Y122H), which is absent in human population databases. The mutation is localized in the highly conserved coil-1 desmin subdomain. In silico, prediction tools indicate a deleterious effect of the desmin (DES) mutation p.Y122H. Consequently, we generated an expression plasmid encoding the mutant and wildtype desmin formed, and analyzed the filament formation in vitro in cardiomyocytes derived from induced pluripotent stem cells and HT-1080 cells. Confocal microscopy revealed a severe filament assembly defect of mutant desmin supporting the pathogenicity of the DES mutation, p.Y122H, whereas the wildtype desmin formed regular intermediate filaments. According to the guidelines of the American College of Medical Genetics and Genomics, we classified this mutation, therefore, as a novel pathogenic mutation. Our report could point to a recessive inheritance of the DES mutation, p.Y122H, which is important for the genetic counseling of similar families with restrictive cardiomyopathy caused by DES mutations.
KW  - cardiovascular genetics
KW  - restrictive cardiomyopathy
KW  - desmin
KW  - intermediate filaments
KW  - desmin-related myopathy
KW  - cardiomyopathy
KW  - desminopathy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193121
SN  - 2073-4425
VL  - 10
IS  - 11
ER  - 
TY  - JOUR
A1  - Latifi, Hooman
A1  - Valbuena, Ruben
T1  - Current trends in forest ecological applications of three-dimensional remote sensing: Transition from experimental to operational solutions?
JF  - Forests
N2  - The alarming increase in the magnitude and spatiotemporal patterns of changes in composition, structure and function of forest ecosystems during recent years calls for enhanced cross-border mitigation and adaption measures, which strongly entail intensified research to understand the underlying processes in the ecosystems as well as their dynamics. Remote sensing data and methods are nowadays the main complementary sources of synoptic, up-to-date and objective information to support field observations in forest ecology. In particular, analysis of three-dimensional (3D) remote sensing data is regarded as an appropriate complement, since they are hypothesized to resemble the 3D character of most forest attributes. Following their use in various small-scale forest structural analyses over the past two decades, these sources of data are now on their way to be integrated in novel applications in fields like citizen science, environmental impact assessment, forest fire analysis, and biodiversity assessment in remote areas. These and a number of other novel applications provide valuable material for the Forests special issue “3D Remote Sensing Applications in Forest Ecology: Composition, Structure and Function”, which shows the promising future of these technologies and improves our understanding of the potentials and challenges of 3D remote sensing in practical forest ecology worldwide.
KW  - 3D remote sensing
KW  - composition
KW  - forest ecology
KW  - function
KW  - structure
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193282
SN  - 1999-4907
VL  - 10
IS  - 10
ER  - 
TY  - JOUR
A1  - Weigand, Matthias
A1  - Wurm, Michael
A1  - Dech, Stefan
A1  - Taubenböck, Hannes
T1  - Remote sensing in environmental justice research—a review
JF  - ISPRS International Journal of Geo-Information
N2  - Human health is known to be affected by the physical environment. Various environmental influences have been identified to benefit or challenge people's physical condition. Their heterogeneous distribution in space results in unequal burdens depending on the place of living. In addition, since societal groups tend to also show patterns of segregation, this leads to unequal exposures depending on social status. In this context, environmental justice research examines how certain social groups are more affected by such exposures. Yet, analyses of this per se spatial phenomenon are oftentimes criticized for using “essentially aspatial” data or methods which neglect local spatial patterns by aggregating environmental conditions over large areas. Recent technological and methodological developments in satellite remote sensing have proven to provide highly detailed information on environmental conditions. This narrative review therefore discusses known influences of the urban environment on human health and presents spatial data and applications for analyzing these influences. Furthermore, it is discussed how geographic data are used in general and in the interdisciplinary research field of environmental justice in particular. These considerations include the modifiable areal unit problem and ecological fallacy. In this review we argue that modern earth observation data can represent an important data source for research on environmental justice and health. Especially due to their high level of spatial detail and the provided large-area coverage, they allow for spatially continuous description of environmental characteristics. As a future perspective, ongoing earth observation missions, as well as processing architectures, ensure data availability and applicability of ’big earth data’ for future environmental justice analyses.
KW  - satellite remote sensing
KW  - review
KW  - environmental justice
KW  - big earth data
KW  - urban environments
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196950
SN  - 2220-9964
VL  - 8
IS  - 1
ER  - 
TY  - JOUR
A1  - Abdullahi, Sahra
A1  - Wessel, Birgit
A1  - Huber, Martin
A1  - Wendleder, Anna
A1  - Roth, Achim
A1  - Kuenzer, Claudia
T1  - Estimating penetration-related X-band InSAR elevation bias: a study over the Greenland ice sheet
JF  - Remote Sensing
N2  - Accelerating melt on the Greenland ice sheet leads to dramatic changes at a global scale. Especially in the last decades, not only the monitoring, but also the quantification of these changes has gained considerably in importance. In this context, Interferometric Synthetic Aperture Radar (InSAR) systems complement existing data sources by their capability to acquire 3D information at high spatial resolution over large areas independent of weather conditions and illumination. However, penetration of the SAR signals into the snow and ice surface leads to a bias in measured height, which has to be corrected to obtain accurate elevation data. Therefore, this study purposes an easy transferable pixel-based approach for X-band penetration-related elevation bias estimation based on single-pass interferometric coherence and backscatter intensity which was performed at two test sites on the Northern Greenland ice sheet. In particular, the penetration bias was estimated using a multiple linear regression model based on TanDEM-X InSAR data and IceBridge laser-altimeter measurements to correct TanDEM-X Digital Elevation Model (DEM) scenes. Validation efforts yielded good agreement between observations and estimations with a coefficient of determination of R\(^2\) = 68% and an RMSE of 0.68 m. Furthermore, the study demonstrates the benefits of X-band penetration bias estimation within the application context of ice sheet elevation change detection.
KW  - InSAR height
KW  - penetration bias
KW  - cryosphere
KW  - TanDEM-X
KW  - Greenland ice sheet
KW  - DEM
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193902
SN  - 2072-4292
VL  - 11
IS  - 24
ER  -