TY - JOUR A1 - Haunert, Jan-Henrik A1 - Wolff, Alexander T1 - Beyond maximum independent set: an extended integer programming formulation for point labeling JF - ISPRS International Journal of Geo-Information N2 - Map labeling is a classical problem of cartography that has frequently been approached by combinatorial optimization. Given a set of features in a map and for each feature a set of label candidates, a common problem is to select an independent set of labels (that is, a labeling without label–label intersections) that contains as many labels as possible and at most one label for each feature. To obtain solutions of high cartographic quality, the labels can be weighted and one can maximize the total weight (rather than the number) of the selected labels. We argue, however, that when maximizing the weight of the labeling, the influences of labels on other labels are insufficiently addressed. Furthermore, in a maximum-weight labeling, the labels tend to be densely packed and thus the map background can be occluded too much. We propose extensions of an existing model to overcome these limitations. Since even without our extensions the problem is NP-hard, we cannot hope for an efficient exact algorithm for the problem. Therefore, we present a formalization of our model as an integer linear program (ILP). This allows us to compute optimal solutions in reasonable time, which we demonstrate both for randomly generated point sets and an existing data set of cities. Moreover, a relaxation of our ILP allows for a simple and efficient heuristic, which yielded near-optimal solutions for our instances. KW - integer linear programming KW - cartographic requirements KW - map labeling KW - point-feature label placement KW - NP-hard Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158960 VL - 6 IS - 11 ER - TY - JOUR A1 - Collenburg, Lena A1 - Beyersdorf, Niklas A1 - Wiese, Teresa A1 - Arenz, Christoph A1 - Saied, Essa M. A1 - Becker-Flegler, Katrin Anne A1 - Schneider-Schaulies, Sibylle A1 - Avota, Elita T1 - The activity of the neutral sphingomyelinase is important in T cell recruitment and directional migration JF - Frontiers in Immunology N2 - Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton. KW - LFA-1 KW - neutral sphingomyelinase KW - T cell migration KW - ceramide KW - polarization KW - adhesion Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158944 VL - 8 IS - 1007 ER - TY - JOUR A1 - Hampe, Irene A. I. A1 - Friedman, Justin A1 - Edgerton, Mira A1 - Morschhäuser, Joachim T1 - An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses JF - PLoS Pathogens N2 - The opportunistic fungal pathogen Candida albicans frequently produces genetically altered variants to adapt to environmental changes and new host niches in the course of its life-long association with the human host. Gain-of-function mutations in zinc cluster transcription factors, which result in the constitutive upregulation of their target genes, are a common cause of acquired resistance to the widely used antifungal drug fluconazole, especially during long-term therapy of oropharyngeal candidiasis. In this study, we investigated if C. albicans also can develop resistance to the antimicrobial peptide histatin 5, which is secreted in the saliva of humans to protect the oral mucosa from pathogenic microbes. As histatin 5 has been shown to be transported out of C. albicans cells by the Flu1 efflux pump, we screened a library of C. albicans strains that contain artificially activated forms of all zinc cluster transcription factors of this fungus for increased FLU1 expression. We found that a hyperactive Mrr1, which confers fluconazole resistance by upregulating the multidrug efflux pump MDR1 and other genes, also causes FLU1 overexpression. Similarly to the artificially activated Mrr1, naturally occurring gain-of-function mutations in this transcription factor also caused FLU1 upregulation and increased histatin 5 resistance. Surprisingly, however, Mrr1-mediated histatin 5 resistance was mainly caused by the upregulation of MDR1 instead of FLU1, revealing a previously unrecognized function of the Mdr1 efflux pump. Fluconazole-resistant clinical C. albicans isolates with different Mrr1 gain-of-function mutations were less efficiently killed by histatin 5, and this phenotype was reverted when MRR1 was deleted. Therefore, antimycotic therapy can promote the evolution of strains that, as a consequence of drug resistance mutations, simultaneously have acquired increased resistance against an innate host defense mechanism and are thereby better adapted to certain host niches. KW - antimicrobial resistance KW - transcriptional control KW - Candida albicans KW - transcription factors KW - mutation KW - hyperexpression techniques KW - antifungals KW - point mutation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158883 VL - 13 IS - 9 ER - TY - JOUR A1 - Jakubietz, Rafael G. A1 - Nickel, Aljoscha A1 - Neshkova, Iva A1 - Schmidt, Karsten A1 - Gilbert, Fabian A1 - Meffert, Rainer H. A1 - Jakubietz, Michael G. T1 - Long-term patency of twisted vascular pedicles in perforator-based propeller flaps JF - Plastic and Reconstructive Surgery Global Open N2 - Background: Propeller flaps require torsion of the vascular pedicle of up to 180 degrees. Contrary to free flaps, where the relevance of an intact vascular pedicle has been documented, little is known regarding twisted pedicles of propeller flaps. As secondary surgeries requiring undermining of the flap are common in the extremities, knowledge regarding the necessity to protect the pedicle is relevant. The aim of this study was a long-term evaluation of the patency of vascular pedicle of propeller flaps. Methods: In a retrospective clinical study, 22 patients who underwent soft-tissue reconstruction with a propeller flap were evaluated after 43 months. A Doppler probe was used to locate and evaluate the patency of the vascular pedicle of the flap. Results: The flaps were used in the lower extremity in 19 cases, on the trunk in 3 cases. All flaps had healed. In all patients, an intact vascular pedicle could be found. Flap size, source vessel, or infection could therefore not be linked to an increased risk of pedicle loss. Conclusions: The vascular pedicle of propeller flaps remains patent in the long term. This allows reelevation and undermining of the flap. We therefore recommend protecting the pedicle in all secondary cases to prevent later flap loss. KW - long-term patency Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158870 VL - 5 IS - 10 ER - TY - JOUR A1 - Jakubietz, Michael G. A1 - Jakubietz, Rafael G. A1 - Meffert, Rainer H. A1 - Schmidt, Karsten A1 - Zahn, Robert K. T1 - Biomechanical properties of first dorsal extensor compartment regarding adequacy as a bone-ligament-bone graft JF - Plastic and Reconstructive Surgery Global Open N2 - Background: Bone-ligament-bone grafts for reconstruction of the scapholunate ligament are a valuable tool to prevent disease progression to carpal collapse. Locally available grafts do not require an additional donor site. The first extensor compartment was evaluated biomechanically regarding its possible use as an autograft. Methods: Twelve native fresh-frozen, human cadaver specimens were tested by applying axial tension in a Zwick Roell machine. Load to failure, transplant elongation, and bony avulsion were recorded. The load to failure was quantitated in newtons (N) and the displacement in length (millimeters). Parameters were set at distinct points as start of tension, 1 mm stretch and 1.5 mm dissociation, failure and complete tear, and were evaluated under magnified visual control. Although actual failure occurred at higher tension, functional failure was defined at a stretch of 1.5 mm. Results: Mean load at 1 mm elongation was 44.1 ± 28 N and at 1.5 mm elongation 57.5 ± 42 N. Failure occurred at 111 ± 83.1 N. No avulsion of the bony insertion was observed. Half the transplants failed in the central part of the ligament, while the rest failed near the insertion but not at the insertion itself. Analysis of tension strength displayed a wide range from 3.8 to 83.7 N/mm at a mean of 33.4 ± 28.4 N/mm. Conclusions: The biomechanical tensile properties of the first dorsal extensor compartment are similar to those of the dorsal part of the scapholunate ligament. A transplant with a larger bone stock and a longer ligament may display an advantage, as insertion is possible in the dorsal, easily accessible part of the carpal bones rather than in the arête-like region adjacent to the insertion of the scapholunate ligament. In this study, 1.5 mm lengthening of the bone–ligament–bone transplant was defined as clinical failure, as such elongation will cause severe gapping and is considered as failure of the transplant. KW - bone ligament graft Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158851 VL - 5 IS - 7 ER - TY - JOUR A1 - Müller, Bettina A1 - Richter, Tobias A1 - Karageorgos, Panagiotis A1 - Krawietz, Sabine A1 - Ennemoser, Marco T1 - Effects of a syllable-based reading intervention in poor-reading fourth graders JF - Frontiers in Psychology N2 - In transparent orthographies, persistent reading fluency difficulties are a major cause of poor reading skills in primary school. The purpose of the present study was to investigate effects of a syllable-based reading intervention on word reading fluency and reading comprehension among German-speaking poor readers in Grade 4. The 16-session intervention was based on analyzing the syllabic structure of words to strengthen the mental representations of syllables and words that consist of these syllables. The training materials were designed using the 500 most frequent syllables typically read by fourth graders. The 75 poor readers were randomly allocated to the treatment or the control group. Results indicate a significant and strong effect on the fluency of recognizing single words, whereas text-level reading comprehension was not significantly improved by the training. The specific treatment effect provides evidence that a short syllable-based approach works even in older poor readers at the end of primary school. KW - word reading fluency KW - syllable-based intervention KW - older poor readers KW - primary school KW - reading comprehension Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158841 VL - 8 IS - 1635 ER - TY - JOUR A1 - Dick, Julia A1 - Krauß, Patrizia A1 - Hillenkamp, Jost A1 - Kohlmorgen, Britta A1 - Schoen, Christoph T1 - Postoperative Tropheryma whipplei endophthalmitis – a case report highlighting the additive value of molecular testing JF - JMM Case Reports N2 - Introduction. Tropheryma whipplei is the causative agent of Whipple’s disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms. Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1–2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei. Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple’s disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative. KW - intravitreal vancomycin and amikacin KW - intravenous ceftriaxone KW - topic ofloxacin KW - Whipple's disease KW - endophthalmitis KW - Tropheryma whipplei KW - ocular infection KW - vitrectomy KW - oral cefpodoxime KW - oral doxycycline Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158823 VL - 4 ER - TY - JOUR A1 - Tawk, Caroline A1 - Sharan, Malvika A1 - Eulalio, Ana A1 - Vogel, Jörg T1 - A systematic analysis of the RNA-targeting potential of secreted bacterial effector proteins JF - Scientific Reports N2 - Many pathogenic bacteria utilize specialized secretion systems to deliver proteins called effectors into eukaryotic cells for manipulation of host pathways. The vast majority of known effector targets are host proteins, whereas a potential targeting of host nucleic acids remains little explored. There is only one family of effectors known to target DNA directly, and effectors binding host RNA are unknown. Here, we take a two-pronged approach to search for RNA-binding effectors, combining biocomputational prediction of RNA-binding domains (RBDs) in a newly assembled comprehensive dataset of bacterial secreted proteins, and experimental screening for RNA binding in mammalian cells. Only a small subset of effectors were predicted to carry an RBD, indicating that if RNA targeting was common, it would likely involve new types of RBDs. Our experimental evaluation of effectors with predicted RBDs further argues for a general paucity of RNA binding activities amongst bacterial effectors. We obtained evidence that PipB2 and Lpg2844, effector proteins of Salmonella and Legionella species, respectively, may harbor novel biochemical activities. Our study presenting the first systematic evaluation of the RNA-targeting potential of bacterial effectors offers a basis for discussion of whether or not host RNA is a prominent target of secreted bacterial proteins. KW - pathogens KW - bacterial secretion Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158815 VL - 7 ER - TY - JOUR A1 - Sperlich, Billy A1 - Becker, Martin A1 - Hotho, Andreas A1 - Wallmann-Sperlich, Birgit A1 - Sareban, Mahdi A1 - Winkert, Kay A1 - Steinacker, Jürgen M. A1 - Treff, Gunnar T1 - Sedentary behavior among national elite rowers during off-training — a pilot study JF - Frontiers in Physiology N2 - The aim of this pilot study was to analyze the off-training physical activity (PA) profile in national elite German U23 rowers during 31 days of their preparation period. The hours spent in each PA category (i.e., sedentary: <1.5 metabolic equivalents (MET); light physical activity: 1.5–3 MET; moderate physical activity: 3–6 MET and vigorous intense physical activity: >6 MET) were calculated for every valid day (i.e., >480 min of wear time). The off-training PA during 21 weekdays and 10 weekend days of the final 11-week preparation period was assessed by the wrist-worn multisensory device Microsoft Band II (MSBII). A total of 11 rowers provided valid data (i.e., >480 min/day) for 11.6 week days and 4.8 weekend days during the 31 days observation period. The average sedentary time was 11.63 ± 1.25 h per day during the week and 12.49 ± 1.10 h per day on the weekend, with a tendency to be higher on the weekend compared to weekdays (p = 0.06; d = 0.73). The average time in light, moderate and vigorous PA during the weekdays was 1.27 ± 1.15, 0.76 ± 0.37, 0.51 ± 0.44 h per day, and 0.67 ± 0.43, 0.59 ± 0.37, 0.53 ± 0.32 h per weekend day. Light physical activity was higher during weekdays compared to the weekend (p = 0.04; d = 0.69). Based on our pilot study of 11 national elite rowers we conclude that rowers display a considerable sedentary off-training behavior of more than 11.5 h/day. KW - recovery KW - sedentary behavior KW - accelerometer KW - microsoft band 2 KW - multi-sensor KW - wearable Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158753 VL - 8 IS - 655 ER - TY - JOUR A1 - Tiffe, Theresa A1 - Wagner, Martin A1 - Rücker, Viktoria A1 - Morbach, Caroline A1 - Gelbrich, Götz A1 - Störk, Stefan A1 - Heuschmann, Peter U. T1 - Control of cardiovascular risk factors and its determinants in the general population – findings from the STAAB cohort study JF - BMC Cardiovascular Disorders N2 - Background: While data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD). Methods: Data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of Würzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed. Results: Between December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9% were female; 30.8% were physically inactive, 55.2% overweight, 19.3% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8%, 57.6%, and 3.9%, respectively. Treatment goals were not reached despite medication in 52.7% of hypertensive, in 37.3% of hyperlipidemic and in 44.0% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95%CI 1.44–2.61), higher age (OR for 30–39 years vs. 70–79 years 4.01, 95%CI 1.94–8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95%CI 1.48–3.11). Conclusions: In the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population. KW - population-based study KW - prevalence KW - risk factor control KW - guideline adherence KW - primary prevention Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159391 VL - 17 IS - 276 ER -