@article{MartratMaxwellTominagaetal.2011, author = {Martrat, Griselda and Maxwell, Christopher A. and Tominaga, Emiko and Porta-de-la-Riva, Montserrat and Bonifaci, N{\´u}ria and G{\´o}mez-Bald{\´o}, Laia and Bogliolo, Massimo and L{\´a}zaro, Conxi and Blanco, Ignacio and Brunet, Joan and Neveling, Kornelia and et al,}, title = {Exploring the link between MORF4L1 and risk of breast cancer}, series = {Breast Cancer Research}, volume = {13}, journal = {Breast Cancer Research}, number = {R40}, doi = {10.1186/bcr2862}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169119}, pages = {1-14}, year = {2011}, abstract = {Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.}, language = {en} } @article{EgetemeirStennekenKoehleretal.2011, author = {Egetemeir, Johanna and Stenneken, Prisca and Koehler, Saskia and Fallgatter, Andreas J. and Herrmann, Martin J.}, title = {Exploring the neural basis of real-life joint action: measuring brain activation during joint table setting with functional near-infrared spectroscopy}, series = {FRONTIERS IN HUMAN NEUROSCIENCE}, volume = {5}, journal = {FRONTIERS IN HUMAN NEUROSCIENCE}, number = {9, Artikel 95}, doi = {10.3389/fnhum.2011.00095}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137054}, pages = {1-9}, year = {2011}, abstract = {Many every-day life situations require two or more individuals to execute actions together. Assessing brain activation during naturalistic tasks to uncover relevant processes underlying such real-life joint action situations has remained a methodological challenge. In the present study, we introduce a novel joint action paradigm that enables the assessment of brain activation during real-life joint action tasks using functional near-infrared spectroscopy (fNIRS). We monitored brain activation of participants who coordinated complex actions with a partner sitting opposite them. Participants performed table setting tasks, either alone (solo action) or in cooperation with a partner (joint action), or they observed the partner performing the task (action observation). Comparing joint action and solo action revealed stronger activation (higher [oxy-Hb]-concentration) during joint action in a number of areas. Among these were areas in the inferior parietal lobule (IPL) that additionally showed an overlap of activation during action observation and solo action. Areas with such a close link between action observation and action execution have been associated with action simulation processes. The magnitude of activation in these IPL areas also varied according to joint action type and its respective demand on action simulation. The results validate fNIRS as an imaging technique for exploring the functional correlates of interindividual action coordination in real-life settings and suggest that coordinating actions in real-life situations requires simulating the actions of the partner.}, language = {en} } @article{BaptistellaFlorenceMassudaBroeckeretal.2011, author = {Baptistella Florence, Michelle Etienne and Massuda, Juliana Yumi and Br{\"o}cker, Eva-Bettina and Metze, Konradin and Cintra, Maria Leticia and de Souza, Elemir Macedo}, title = {Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers}, series = {CLINICS}, volume = {66}, journal = {CLINICS}, number = {3}, doi = {10.1590/S1807-59322011000300018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133650}, pages = {465-468}, year = {2011}, abstract = {OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.}, language = {en} } @article{NiewaldaVoellerEschbachetal.2011, author = {Niewalda, Thomas and V{\"o}ller, Thomas and Eschbach, Claire and Ehmer, Julia and Wen-Chuang, Chou and Timme, Marc and Fiala, Andr{\´e} and Gerber, Bertram}, title = {A Combined Perceptual, Physico-Chemical, and Imaging Approach to 'Odour-Distances' Suggests a Categorizing Function of the Drosophila Antennal Lobe}, series = {PLoS One}, volume = {6}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0024300}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133510}, pages = {e24300}, year = {2011}, abstract = {How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours.}, language = {en} } @article{MontenegroDannemann2011, author = {Montenegro, Sergio and Dannemann, Frank}, title = {Experiences and Best Practice Requirements Engineering for Small Satellites}, series = {Computing Science and Technology International Journal}, volume = {1}, journal = {Computing Science and Technology International Journal}, number = {2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153307}, year = {2011}, abstract = {The design and implementation of a satellite mission is divided into several different phases. Parallel to these phases an evolution of requirements will take place. Because so many people in different locations and from different background have to work in different subsystems concurrently the ideas and concepts of different subsystems and different locations will diverge. We have to bring them together again. To do this we introduce synchronization points. We bring representatives from all subsystems and all location in a Concurrent Engineering Facility (CEF) room together. Between CEF sessions the different subsystems will diverge again, but each time the diversion will be smaller. Our subjective experience from test projects says this CEF sessions are most effective in the first phases of the development, from Requirements engineering until first coarse design. After Design and the concepts are fix, the developers are going to implementation and the concept divergences will be much smaller, therefore the CEF sessions are not a very big help any more.}, language = {en} } @article{ArltBiehlTayloretal.2011, author = {Arlt, Wiebke and Biehl, Michael and Taylor, Angela E. and Hahner, Stefanie and Lib{\´e}, Rossella and Hughes, Beverly A. and Schneider, Petra and Smith, David J. and Stiekema, Han and Krone, Nils and Porfiri, Emilio and Opocher, Giuseppe and Bertherat, Jer{\^o}me and Mantero, Franco and Allolio, Bruno and Terzolo, Massimo and Nightingale, Peter and Shackleton, Cedric H. L. and Bertagna, Xavier and Fassnacht, Martin and Stewart, Paul M.}, title = {Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors}, series = {The Journal of Clinical Endocrinology \& Metabolism}, volume = {96}, journal = {The Journal of Clinical Endocrinology \& Metabolism}, number = {12}, doi = {10.1210/jc.2011-1565}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154682}, pages = {3775 -- 3784}, year = {2011}, abstract = {Context: Adrenal tumors have a prevalence of around 2\% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2-11\% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values. Objective: Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy. Design: Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19-84 yr) and 45 ACC patients (20-80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26-201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids. Results: Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90\% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88\% (area under the curve = 0.96) when using only the nine most differentiating markers. Conclusions: Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.}, language = {en} } @article{SchmidtkeFindeissSharmaetal.2011, author = {Schmidtke, Cornelius and Findeiß, Sven and Sharma, Cynthia M. and Kuhfuss, Juliane and Hoffmann, Steve and Vogel, J{\"o}rg and Stadler, Peter F. and Bonas, Ulla}, title = {Genome-wide transcriptome analysis of the plant pathogen Xanthomonas identifies sRNAs with putative virulence functions}, series = {Nucleic Acids Research}, volume = {40}, journal = {Nucleic Acids Research}, number = {5}, doi = {10.1093/nar/gkr904}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131781}, pages = {2020 -- 2031}, year = {2011}, abstract = {The Gram-negative plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) is an important model to elucidate the mechanisms involved in the interaction with the host. To gain insight into the transcriptome of the Xcv strain 85-10, we took a differential RNA sequencing (dRNA-seq) approach. Using a novel method to automatically generate comprehensive transcription start site (TSS) maps we report 1421 putative TSSs in the Xcv genome. Genes in Xcv exhibit a poorly conserved -10 promoter element and no consensus Shine-Dalgarno sequence. Moreover, 14\% of all mRNAs are leaderless and 13\% of them have unusually long 5'-UTRs. Northern blot analyses confirmed 16 intergenic small RNAs and seven cis-encoded antisense RNAs in Xcv. Expression of eight intergenic transcripts was controlled by HrpG and HrpX, key regulators of the Xcv type III secretion system. More detailed characterization identified sX12 as a small RNA that controls virulence of Xcv by affecting the interaction of the pathogen and its host plants. The transcriptional landscape of Xcv is unexpectedly complex, featuring abundant antisense transcripts, alternative TSSs and clade-specific small RNAs.}, language = {en} } @article{DuhrKennKickuthetal.2011, author = {Duhr, Carolin D. and Kenn, Werner and Kickuth, Ralph and Kerscher, Alexander G. and Germer, Christoph-Thomas and Hahn, Dietbert and Pelz, Joerg O. W.}, title = {Optimizing of preoperative computed tomography for diagnosis in patients with peritoneal carcinomatosis}, series = {World Journal of Surgical Oncology}, volume = {9}, journal = {World Journal of Surgical Oncology}, number = {171}, doi = {10.1186/1477-7819-9-171}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138024}, year = {2011}, abstract = {Background and Objective This study evaluates whether Computer Tomography is an effective procedure for preoperative staging of patients with Peritoneal Carcinomatosis. Method A sample of 37 patients was analyzed with contrast enhanced abdominal Computer Tomography, followed by surgical staging. All Computer Tomography scans were evaluated 3 times by 2 radiologists with one radiologist reviewing 2 times. The efficacy of Computer Tomography was evaluated using the Spearman correlation coefficient. Correlations were analyzed by abdominopelvic region to assess results of the Peritoneal Carcinomatosis Index (PCI) aggregating the 13 regions. Surgical findings were compared to radiological findings. Results Results indicate high correlations between the surgical and radiological Peritoneal Carcinomatosis Indices. Analyses of the intra-class correlation between the first and second reading of one radiologist suggest high intra-observer reliability. Correlations by abdominopelvic region show higher values in the upper and middle regions and relatively lower values in the lower regions and the small bowel (correlation coefficients range between 0.418 and 0.726, p < 0.010; sensitivities range between 50\% and 96\%; and specificities range between 62\% and 100\%). Conclusion Computer Tomography represents an effective procedure in the preoperative staging of patients with PC. However, results by abdominopelvic region show lower correlation, therefore suggest lower efficacy. These results are supported by analyses of sensitivity and accuracy by lesion size. This suggests that Computer Tomography is an effective procedure for pre-operative staging but less for determining a tumor's accurate extent.}, language = {en} } @article{SchwindtKneisel2011, author = {Schwindt, Daniel and Kneisel, Christof}, title = {Optimisation of quasi-3D electrical resistivity imaging - application and inversion for investigating heterogeneous mountain permafrost}, series = {The Cryosphere Discuss}, volume = {5}, journal = {The Cryosphere Discuss}, doi = {10.5194/tcd-5-3383-2011}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138017}, pages = {3383-3421}, year = {2011}, abstract = {This study aimed to optimise the application, efficiency and interpretability of quasi-3D resistivity imaging for investigating the heterogeneous permafrost distribution at mountain sites by a systematic forward modelling approach. A three dimensional geocryologic model, representative for most mountain permafrost settings, was developed. Based on this geocryologic model quasi-3D models were generated by collating synthetic orthogonal 2D arrays, demonstrating the effects of array types and electrode spacing on resolution and interpretability of the inversion results. The effects of minimising the number of 2D arrays per quasi-3D grid were tested by enlarging the spacing between adjacent lines and by reducing the number of perpendicular tie lines with regard to model resolution and loss of information value. Synthetic and measured quasi-3D models were investigated with regard to the lateral and vertical resolution, reliability of inverted resistivity values, the possibility of a quantitative interpretation of resistivities and the response of the inversion process on the validity of quasi-3D models. Results show that setups using orthogonal 2D arrays with electrode spacings of 2 m and 3 m are capable of delineating lateral heterogeneity with high accuracy and also deliver reliable data on active layer thickness. Detection of permafrost thickness, especially if the permafrost base is close to the penetration depth of the setups, and the reliability of absolute resistivity values emerged to be a weakness of the method. Quasi-3D imaging has proven to be a promising tool for investigating permafrost in mountain environments especially for delineating the often small-scale permafrost heterogeneity, and therefore provides an enhanced possibility for aligning permafrost distribution with site specific surface properties and morphological settings.}, language = {en} } @article{GuckenbergerSweeneyFlickingeretal.2011, author = {Guckenberger, Matthias and Sweeney, Reinhart A. and Flickinger, John C. and Gerszten, Peter C. and Kersh, Ronald and Sheehan, Jason and Sahgal, Arjun}, title = {Clinical practice of image-guided spine radiosurgery - results from an international research consortium}, series = {Radiation Oncology}, volume = {6}, journal = {Radiation Oncology}, number = {172}, doi = {10.1186/1748-717X-6-172}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138006}, year = {2011}, abstract = {Background Spinal radiosurgery is a quickly evolving technique in the radiotherapy and neurosurgical communities. However, the methods of spine radiosurgery have not been standardized. This article describes the results of a survey about the methods of spine radiosurgery at five international institutions. Methods All institutions are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided radiosurgery. The questionnaire consisted of 75 items covering all major steps of spine radiosurgery. Results Strong agreement in the methods of spine radiosurgery was observed. In particular, similarities were observed with safety and quality assurance playing an important role in the methods of all institutions, cooperation between neurosurgeons and radiation oncologists in case selection, dedicated imaging for target- and organ-at-risk delineation, application of proper safety margins for the target volume and organs-at-risk, conformal planning and precise image-guided treatment delivery, and close clinical and radiological follow-up. In contrast, three major areas of uncertainty and disagreement were identified: 1) Indications and contra-indications for spine radiosurgery; 2) treatment dose and fractionation and 3) tolerance dose of the spinal cord. Conclusions Results of this study reflect the current practice of spine radiosurgery in large academic centers. Despite close agreement was observed in many steps of spine radiosurgery, further research in form of retrospective and especially prospective studies is required to refine the details of spinal radiosurgery in terms of safety and efficacy.}, language = {en} }