n-Doping of organic semiconductors for enhanced electron extraction from solution processed solar cells using alkali metals

To improve charge carrier injection into or extraction from organic optoelectronic devices, electrically doped layers are often employed. Whereas n-doping of organic semiconductors has been widely used in vacuum processed optoelectronic devices, adequate solution processes to enable future device printing are underdeveloped. In this work, we study n-doping of 1,3,5-tris(1-phenyl-1H-benzimidazol-2-yl)benzene (TPBi) in a solution process, using sodium as the electron donor. Upon addition of elementary sodium to a clear TPBi/toluene solution, we observed a change in color, indicating charge carrier transfer between sodium and TPBi. The optical and electrical properties of doped and undoped TPBi were characterized in solution and in the corresponding thin-films. Electron Paramagnetic Resonance (EPR) measurements revealed an increase of the number of unpaired spins upon doping, indicating the presence of doping-induced charge carriers. Implementing TPBi:Na as electron extraction layers in organic solar cells, we found almost the same device performance as compared to state-of-the-art solar cells comprising zinc oxide electron extraction layers

Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies

Context: Polymorphisms in the gene encoding the glucocorticoid receptor (GR) regulating co-chaperone FKBP5 have been shown to alter GR sensitivity and are associated with an increased risk to develop posttraumatic stress disorder (PTSD). Objective: To investigate interactions of the FKBP5 single-nucleotide polymorphism rs9296158 and PTSD symptoms on baseline cortisol level, low-dose dexamethasone suppression, and whole-blood gene expression. Design: Association of FKBP5 genotypes and PTSD symptoms with endocrine measures and genome-wide expression profiles. Setting: Waiting rooms of general medical and gynecological clinics of an urban hospital at Emory University. Participants: The 211 participants were primarily African American (90.05%) and of low socioeconomic status and had high rates of trauma and PTSD. Main Outcome Measures: Baseline and post-dexamethasone suppression cortisol measures and gene expression levels. Results: In our endocrine study, we found that only risk allele A carriers of rs9296158 showed GR supersensitivity with PTSD; in contrast, baseline cortisol levels were decreased in PTSD only in patients with the GG genotype. Expression of 183 transcripts was significantly correlated with PTSD symptoms after multiple testing corrections. When adding FKBP5 genotype and its interaction with PTSD symptoms, expression levels of an additional 32 genes were significantly regulated by the interaction term. Within these 32 genes, previously reported PTSD candidates were identified, including FKBP5 and the IL18 and STAT pathways. Significant overrepresentation of steroid hormone transcription factor binding sites within these 32 transcripts was observed, highlighting the fact that the earlier-described genotype and PTSDdependent differences in GR sensitivity could drive the observed gene expression pattern. Results were validated by reverse transcriptase-polymerase chain reaction and replicated in an independent sample (N=98). Conclusions: These data suggest that the inheritance of GR sensitivity-moderating FKBP5 polymorphisms can determine specific types of hypothalamic-pituitaryadrenal axis dysfunction within PTSD, which are also reflected in gene-expression changes of a subset of GRresponsive genes. Thus, these findings indicate that functional variants in FKBP5 are associated with biologically distinct subtypes of PTSD

HICFD – Highly Efficient Implementation of CFD Codes for HPC Many-Core Architectures

The objective of the German BMBF research project Highly Efficient Implementation of CFD Codes for HPC Many-Core Architectures (HICFD) is to develop new methods and tools for the analysis and optimization of the performance of parallel computational fluid dynamics (CFD) codes on high performance computer systems with many-core processors. In the work packages of the project it is investigated how the performance of parallel CFD codes written in C can be increased by the optimal use of all parallelism levels. On the highest level MPI is utilized. Furthermore, on the level of the many-core architecture, highly scaling, hybrid OpenMP/MPI methods are implemented. On the level of the processor cores the parallel SIMD units provided by modern CPUs are exploited

Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus

Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3'-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Completeness of the operating room to intensive care unit handover: a matter of time?

Background Handovers of post-anesthesia patients to the intensive care unit (ICU) are often unstructured and performed under time pressure. Hence, they bear a high risk of poor communication, loss of information and potential patient harm. The aim of this study was to investigate the completeness of information transfer and the quantity of information loss during post anesthesia handovers of critical care patients. Methods Using a self-developed checklist, including 55 peri-operative items, patient handovers from the operation room or post anesthesia care unit to the ICU staff were observed and documented in real time. Observations were analyzed for the amount of correct and completely transferred patient data in relation to the written documentation within the anesthesia record and the patient's chart. Results During a ten-week study period, 97 handovers were included. The mean duration of a handover was 146 seconds, interruptions occurred in 34% of all cases. While some items were transferred frequently (basic patient characteristics [72%], surgical procedure [83%], intraoperative complications [93.8%]) others were commonly missed (underlying diseases [23%], long-term medication [6%]). The completeness of information transfer is associated with the handover's duration [B coefficient (95% CI): 0.118 (0.084-0.152), p<0.001] and increases significantly in handovers exceeding a duration of 2 minutes (24% +/- 11.7 vs. 40% +/- 18.04, p<0.001). Conclusions Handover completeness is affected by time pressure, interruptions, and inappropriate surroundings, which increase the risk of information loss. To improve completeness and ensure patient safety, an adequate time span for handover, and the implementation of communication tools are required

jTraqX: a free, platform independent tool for isobaric tag quantitation at the protein level

Many proteomic studies focus on quantitative aspects, using different stable isotope labeling techniques that require specialized software to analyze the generated data. Here we present jTraqX, an easy-to-use tool for processing and visualizing protein quantification data. jTraqX is platform independent and is compatible with all available 4-plex isobaric tags. jTraqX can be freely downloaded at http://sourceforge.net/projects/protms

Antibiotic-induced gut microbiota depletion exacerbates host hypercholesterolemia

Hypercholesterolemia is a major driver of atherosclerosis, thus contributing to high morbidity and mortality worldwide. Gut microbiota have been identified as modulator of blood lipids including cholesterol levels. Few studies have already linked certain bacteria and microbial mechanisms to host cholesterol. However, in particular mouse models revealed conflicting results depending on genetics and experimental protocol. To gain further insights into the relationship between intestinal bacteria and host cholesterol metabolism, we first per-formed fecal 16S rRNA targeted metagenomic sequencing in a human cohort (n = 24) naive for cholesterol lowering drugs. Here, we show alterations in the gut microbiota composition of hypercholesterolemic patients with depletion of Bifidobacteria, expansion of Clostridia and increased Firmicutes/Bacteroidetes ratio. To test whether pharmacological intervention in gut microbiota impacts host serum levels of cholesterol, we treated hypercholesterolemic Apolipoprotein E knockout with oral largely non-absorbable antibiotics. Antibiotics increased serum cholesterol, but only when mice were fed normal chow diet and cholesterol was measured in the random fed state. These elevations in cholesterol already occurred few days after treatment initiation and were reversible after stopping antibiotics with re-acquisition of intestinal bacteria. Gene expression analyses pointed to increased intestinal cholesterol uptake mediated by antibiotics in the fed state. Non-targeted serum metab-olomics suggested that diminished plant sterol levels and reduced bile acid cycling were involved microbial mechanisms. In conclusion, our work further enlightens the link between gut microbiota and host cholesterol metabolism. Pharmacological disruption of the gut flora by antibiotics was able to exacerbate serum cholesterol and may impact cardiovascular disease