Deep drawn shapes with orthogonal wall components are usually evaluated by shape accuracy and visual quality. There have been only a few investigations on the stability of such structures; however, the effect of the wrinkles on the stability of the wall is important for packaging applications and can support the shape accuracy. This paper focuses on the influences of process parameters on the stability of orthogonal walls of shapes produced by deep drawing with rigid tools and immediate compression. The wall stability was evaluated by tensile testing orthogonal to the direction of the wrinkles. The stability distribution was characterized with regard to the drawing height, and a comparison was made between the two different materials. The wall stability decreased with increases in the forming height. Furthermore, a blank holder force design and z-directional compression level improved the wall stability. Together with an elevated moisture content of the material and thermal energy supply that delivered two to three times higher resistance against wrinkle extension, these effects drastically improved the wall stability.

Background Identifying orthologous molecular markers that potentially resolve relationships at and below species level has been a major challenge in molecular phylogenetics over the past decade. Non-coding regions of nuclear low- or single-copy markers are a vast and promising source of data providing information for shallow-scale phylogenetics. Taking advantage of public transcriptome data from the One Thousand Plant Project (1KP), we developed a genome-scale mining strategy for recovering potentially orthologous single-copy markers to address low-scale phylogenetics. Our marker design targeted the amplification of intron-rich nuclear single-copy regions from genomic DNA. As a case study we used Hydrangea section Cornidia, one of the most recently diverged lineages within Hydrangeaceae (Cornales), for comparing the performance of three of these nuclear markers to other "fast" evolving plastid markers. Results Our data mining and filtering process retrieved 73 putative nuclear single-copy genes which are potentially useful for resolving phylogenetic relationships at a range of divergence depths within Cornales. The three assessed nuclear markers showed considerably more phylogenetic signal for shallow evolutionary depths than conventional plastid markers. Phylogenetic signal in plastid markers increased less markedly towards deeper evolutionary divergences. Potential phylogenetic noise introduced by nuclear markers was lower than their respective phylogenetic signal across all evolutionary depths. In contrast, plastid markers showed higher probabilities for introducing phylogenetic noise than signal at the deepest evolutionary divergences within the tribe Hydrangeeae (Hydrangeaceae). Conclusions While nuclear single-copy markers are highly informative for shallow evolutionary depths without introducing phylogenetic noise, plastid markers might be more appropriate for resolving deeper-level divergences such as the backbone relationships of the Hydrangeaceae family and deeper, at which non-coding parts of nuclear markers could potentially introduce noise due to elevated rates of evolution. The herein developed and demonstrated transcriptome based mining strategy has a great potential for the design of novel and highly informative nuclear markers for a range of plant groups and evolutionary scales.

Molecular docking has been extensively applied in virtual screening of small molecule libraries for lead identification and optimization. A necessary prerequisite for successful differentiation between active and non-active ligands is the accurate prediction of their binding affinities in the complex by use of docking scoring functions. However, many studies have shown rather poor correlations between docking scores and experimental binding affinities. Our work aimed to improve this correlation by implementing a multipose binding concept in the docking scoring scheme. Multipose binding, i.e., the property of certain protein-ligand complexes to exhibit different ligand binding modes, has been shown to occur in nature for a variety of molecules. We conducted a high-throughput docking study and implemented multipose binding in the scoring procedure by considering multiple docking solutions in binding affinity prediction. In general, improvement of the agreement between docking scores and experimental data was observed, and this was most pronounced in complexes with large and flexible ligands and high binding affinities. Further developments of the selection criteria for docking solutions for each individual complex are still necessary for a general utilization of the multipose binding concept for accurate binding affinity prediction by molecular docking.

Background: Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA). Methods: In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation. Results: The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a. Conclusions: The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction.

The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepatocyte ‘know’ when the organ has grown to its final size? This work considers the initial growth phase of liver regeneration after partial hepatectomy in which the mass is restored. There are strong and valid arguments that the trigger of proliferation after partial hepatectomy is mediated through the portal blood flow. It remains unclear, if either or both the concentration of metabolites in the blood or the shear stress are crucial to hepatocyte proliferation and liver size control. A cell-based mathematical model is developed that helps discriminate the effects of these two potential triggers. Analysis of the mathematical model shows that a metabolic load and a hemodynamical hypothesis imply different feedback mechanisms at the cellular scale. The predictions of the developed mathematical model are compared to experimental data in rats. The assumption that hepatocytes are able to buffer the metabolic load leads to a robustness against short-term fluctuations of the trigger which can not be achieved with a purely hemodynamical trigger.

Nearly all functional magnetic resonance imaging (fMRI) studies are conducted in the supine body posture, which has been discussed as a potential confounder of such examinations. The literature suggests that cognitive functions, such as problem solving or perception, differ between supine and upright postures. However, the effect of posture on many cognitive functions is still unknown. Therefore, the aim of the present study was to investigate the effects of body posture (supine vs. sitting) on one of the most frequently used paradigms in the cognitive sciences: the N-back working memory paradigm. Twenty-two subjects were investigated in a randomized within-subject design. Subjects performed the N-back task on two consecutive days in either the supine or the upright posture. Subjective sleep quality and chronic stress were recorded as covariates. Furthermore, changes in mood dimensions and heart rate variability (HRV) were assessed during the experiment. Results indicate that the quality of sleep strongly affects reaction times when subjects performed a working memory task in a supine posture. These effects, however, could not be observed in the sitting position. The findings can be explained by HRV parameters that indicated differences in autonomic regulation in the upright vs. the supine posture. The finding is of particular relevance for fMRI group comparisons when group differences in sleep quality cannot be ruled out.

Background: Nursing staff are often involved in counseling patients with regard to health behavior. Although care promoting healthy lifestyle choices is included in the curriculum of nursing students in Germany, several studies of nursing students have reported a high prevalence of unhealthy behavior. This paper focuses on the behavior of female nursing students with regard to body mass index (BMI), physical activity, and cigarette and alcohol consumption. It describes trends through the comparison of results from 2008 and 2013. Methods: Data was collected in two waves at a regional medical training college. First, 301 nursing students were asked to fill out a 12 page questionnaire on health behavior in 2008. The questioning was repeated in 2013 with 316 participating nursing students using the previous questionnaire. Results: 259 female nursing students completed the questionnaire in 2013. 31.6% of them were either overweight or obese, 28.5% exercised less than once a week, 42.9% smoked between 10 and 20 cigarettes a day and 72.6% drank alcohol, wherefrom 19.7% consumed alcohol in risky quantities. In comparison to the data of 266 female nursing students from 2008, there were significant differences in the BMI and alcohol consumption: The percentage of overweight and obese students and the percentage of alcohol consumers at risk increased significantly. Conclusions: Health behavior of female nursing students is often inadequate especially in regard to weight and cigarette and alcohol consumption. Strategies are required to promote healthy lifestyle choices.

Background: Only few studies deal with the workload of physical therapists and the health consequences, although this occupational group is quite important for the health care system in many industrialized countries (e.g. ca. 136 000 people are currently employed as physical therapists in Germany). Therefore, the current state of knowledge of work-related diseases and disorders of physical therapists is insufficient. The aim of the "Physical Therapist Cohort" (PTC) study is to analyze the association between work-related exposures and diseases among physical therapists in Germany. This article describes the protocol of the baseline assessment of the PTC study. Methods/Design: A cross-sectional study will be conducted as baseline assessment and will include a representative random sample of approximately 300 physical therapists employed in Germany (exposure group), and a population-based comparison group (n = 300). The comparison group will comprise a sample of working aged (18–65 years) inhabitants of a German city. Variables of interest will be assessed using a questionnaire manual including questions regarding musculoskeletal, dermal, and infectious diseases and disorders as well as psychosocial exposures, diseases and disorders. In addition to subjective measures, a clinical examination will be used to objectify the questionnaire-based results (n = 50). Discussion: The study, which includes extensive data collection, provides a unique opportunity to study the prospective association of work-related exposures and associated complaints of physical therapists. Baseline results will give first clues with regard to whether and how prevalent main exposures of physiotherapeutic work and typical work areas of physical therapists are associated with the development of work-related diseases. Thereby, this baseline assessment provides the basis for further investigations to examine causal relationships in accordance with a longitudinal design.

While previous studies successfully identified the core neural substrates of the animal subtype of specific phobia, only few and inconsistent research is available for dental phobia. These findings might partly relate to the fact that, typically, visual stimuli were employed. The current study aimed to investigate the influence of stimulus modality on neural fear processing in dental phobia. Thirteen dental phobics (DP) and thirteen healthy controls (HC) attended a block-design functional magnetic resonance imaging (fMRI) symptom provocation paradigm encompassing both visual and auditory stimuli. Drill sounds and matched neutral sinus tones served as auditory stimuli and dentist scenes and matched neutral videos as visual stimuli. Group comparisons showed increased activation in the insula, anterior cingulate cortex, orbitofrontal cortex, and thalamus in DP compared to HC during auditory but not visual stimulation. On the contrary, no differential autonomic reactions were observed in DP. Present results are largely comparable to brain areas identified in animal phobia, but also point towards a potential downregulation of autonomic outflow by neural fear circuits in this disorder. Findings enlarge our knowledge about neural correlates of dental phobia and may help to understand the neural underpinnings of the clinical and physiological characteristics of the disorder.

Behavioral adaptation and cognitive control are crucial for goal-reaching behaviors. Every creature is ubiquitously faced with choices between behavioral alternatives. Common sense suggests that errors are an important source of information in the regulation of such processes. Several theories exist regarding cognitive control and the processing of undesired outcomes. However, most of these models focus on the consequences of an error, and less attention has been paid to the mechanisms that underlie the commissioning of an error. In this article, we present an integrative review of neuro-cognitive models that detail the determinants of the occurrence of response errors. The factors that may determine the likelihood of committing errors are likely related to the stability of task-representations in prefrontal networks, attentional selection mechanisms and mechanisms of action selection in basal ganglia circuits. An important conclusion is that the likelihood of committing an error is not stable over time but rather changes depending on the interplay of different functional neuro-anatomical and neuro-biological systems. We describe factors that might determine the time-course of cognitive control and the need to adapt behavior following response errors. Finally, we outline the mechanisms that may proof useful for predicting the outcomes of cognitive control and the emergence of response errors in future research.