julilili42/papers huggingface dataset:
Der unvergleichliche Gott—Psalm 113 im Spiegel von 1 Sam 2:1-10
2016-03-21

The study represents the theory of a literary and thematic dependency of Psalm 113 upon 1 Samuel 2:1-10. The ‘Song of Hannah’ (c. 7th Century bc ?) is older than Psalm 113 (c. 6th Century bc ?). Both psalms place emphasis upon the uniqueness of Jahwe. The theological skopos of Psalm 113 aims primarily at the affirmation of Jahwe as the incomparable God (v.5). This topic allows itself to present Psalm 113 from 1 Sam 2:1-10. The author of Psalm 113, with the help of ‘The Song of Hannah’ in 1 Sam 2:1-10 has made Ps 113 a hymn of the community of Jahwe about the incomparable God.
Excreted Cytoplasmic Proteins Contribute to Pathogenicity in Staphylococcus aureus
2016-03-22

ABSTRACT Excretion of cytoplasmic proteins in pro- and eukaryotes, also referred to as “nonclassical protein export,” is a well-known phenomenon. However, comparatively little is known about the role of the excreted proteins in relation to pathogenicity. Here, the impact of two excreted glycolytic enzymes, aldolase (FbaA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on pathogenicity was investigated in Staphylococcus aureus . Both enzymes bound to certain host matrix proteins and enhanced adherence of the bacterial cells to host cells but caused a decrease in host cell invasion. FbaA and GAPDH also bound to the cell surfaces of staphylococcal cells by interaction with the major autolysin, Atl, that is involved in host cell internalization. Surprisingly, FbaA showed high cytotoxicity to both MonoMac 6 (MM6) and HaCaT cells, while GAPDH was cytotoxic only for MM6 cells. Finally, the contribution of external FbaA and GAPDH to S. aureus pathogenicity was confirmed in an insect infection model.
Primary Metastatic Synovial Sarcoma: Experience of the CWS Study Group
2016-03-22

Background Prognostic factors for localized synovial sarcoma are well defined. However, few data exist regarding patients with metastases at diagnosis. Poor outcome is described but the optimal therapeutic regimen remains unclear. Our aim was to assess the outcome, identify prognostic factors, and analyze treatment strategies. Methods Patients &lt;21 years with synovial sarcoma and primary distant metastases treated in the consecutive prospective European Cooperative Weichteilsarkom Studiengruppe trials 1980–2010 were analyzed. Results Twenty‐nine of 296 patients had primary metastases. Twenty‐seven could be included. Median age was 16.7 years. Primaries were mainly located in the limbs (78%) and 74% were ≥10 cm. Metastases involved the lungs in all patients. Two patients presented with synchronous bone metastases. Sixty‐three percent of patients achieved a first remission, whereas only 26% maintained it. Relapses were metastatic with pulmonary metastases in nearly all patients. Five‐year event‐free survival and overall survival (OS) rates were 26% and 30%, respectively. Prognosis was best for patients with oligometastatic lung metastases (5‐year OS probability 85%). Prognosis was worse for patients with multiple bilateral lung metastases (5‐year OS 13%) and even poorer for those with concurrent bone metastases. Treatment elements associated with superior survival were adequate local therapy of the primary tumor and, if feasible, for metastases, chemotherapy with an ifosfamide/doxorubicin‐based regimen. The use of whole lung irradiation was not correlated with better outcomes. Conclusions The overall prognosis of primary metastatic synovial sarcoma is poor. However, individuals with oligometastatic lung metastases had very good chance for long‐term survival when treated with adequate multimodal therapy.
Reliability Analysis of Operating Systems and Software Stack for Embedded Systems
2016-03-22

In this paper, we investigate how the presence of a general purpose operating system influences the reliability of modern embedded Systems-on-Chips (SoCs). We experimentally study the difference in the neutron-induced error rate of SoCs when executing the application bare to the metal (i.e., without an underlying operating system) and on top of the Linux kernel. Our analysis demonstrates that Linux presence barely affects the Silent Data Corruption (SDC) rate whereas it greatly increases the system Functional Interruption (SEFI) rate (up to 7.48 times) if no preventive measures are taken. Nevertheless, we experimentally demonstrate that cache conflicts between the operating system and application can be leveraged to significantly reduce the Linux-induced SEFI rate increase. Moreover, we evaluate the OS software stack masking effect and show that the higher the abstraction layer in which an application is implemented, the lower its SDC rate. Furthermore, we analyze system reliability taking into account not only the resulting failure rates, but also the execution (and, thus, exposure) times.
Influence of Birch Bark Triterpenes on Keratinocytes and Fibroblasts from Diabetic and Nondiabetic Donors
2016-03-22

Impaired wound healing is one of the main risk factors associated with diabetes mellitus. Few options are available to treat diabetic wounds, and therefore efficient remedies are urgently needed. An interesting option might be an extract of birch bark (TE) that has been clinically proven to accelerate acute wound healing. We investigated the effects of TE and its main components betulin and lupeol in cultured normal keratinocytes and dermal fibroblasts from diabetic and nondiabetic donors. These in vitro models can provide insights into possible beneficial effects in wound healing. TE and betulin treatment led to increased mRNA levels of chemokines, pro-inflammatory cytokines, and mediators important in wound healing, e.g., IL-6, TNFα, IL-8, and RANTES. We observed a pronounced upregulation of MIF, IL-8, and RANTES on the protein level. Furthermore, a shape change of the actin cytoskeleton was seen in keratinocytes and fibroblasts, and the Rho-GTPases and p38-MAPK were found to be activated in keratinocytes. On the basis of our results, TE is worthy of further study as a potential option to influence wound-healing processes under diabetic conditions. These first insights need to be confirmed by clinical studies with diabetic patients.
Balanced excitation and inhibition decorrelates visual feature representation in the mammalian inner retina
2016-03-22

SUMMARY The retina extracts visual features for transmission to the brain. Different types of bipolar cell split the photoreceptor input into parallel channels and provide the excitatory drive for downstream visual circuits. Anatomically, mouse bipolar cell types have been described down to the ultrastructural level, but a similarly deep understanding of their functional diversity is lacking. By imaging light-driven glutamate release from more than 11,000 bipolar cell axon terminals in the intact retina, we here show that bipolar cell functional diversity is generated by the balanced interplay of dendritic excitatory inputs and axonal inhibitory inputs. The resultant centre and surround components of bipolar cell receptive fields interact to decorrelate bipolar cell output in the spatial and temporal domain. Our findings highlight the importance of inhibitory circuits in generating functionally diverse excitatory pathways and suggest that decorrelation of parallel visual pathways begins already at the second synapse of the mouse visual system.
Can electron capture tell us the mass of the neutrino?
2016-03-22

The neutrino masses are one of the most important open problems in particle physics. Presently major efforts are underway to measure the electron antineutrino-mass by the triton beta decay [1] and the effective Majorana neutrino mass by the double beta decay [2]. The best way to determine the neutrino mass by electron capture was assumed to be in . The total decay energy of the excited daughter atom has for all excitations the same upper energy limit of the Q-value minus the mass of the electron neutrino. Recently Robertson [3] claimed, that the excitation of the two-hole states makes the determination of the neutrino mass by this method practically impossible. But Faessler and Simkovic [4] showed, that the influence of the two-hole states is less than 1% near the Q-value, the area relevant for the determination of the neutrino mass. Even weaker are the contributions of the three-hole states [5]. The upper end of the calorimetric deexcitation spectrum of Dy is dominated by the highest energy one-hole resonance. With a Lorentzian profile of this resonance one has to fit after including the experimental sensitivity four parameters: (1) the neutrino mass, (2) the Q-value, (3) the width of the resonance and (4) its strength. This contribution discusses the problems of the determination of the neutrino mass by electron capture in . The conclusion of this work is, that the determination of the electron neutrino mass by electron capture in is difficult, but (probably) not impossible.
Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms
2016-03-23

A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.594-2A > C. The combined odds for causality considering case-control, segregation and breast tumor pathology information was 3.23 × 10<sup>-8</sup> Our data indicate that c.594-2A > C is always in cis with c.641A > G. The spliceogenic effect of c.[594-2A > C;641A > G] was characterized using RNA analysis of human samples and splicing minigenes. As expected, c.[594-2A > C; 641A > G] caused exon 10 skipping, albeit not due to c.594-2A > C impairing the acceptor site but rather by c.641A > G modifying exon 10 splicing regulatory element(s). Multiple blood-based RNA assays indicated that the variant allele did not produce detectable levels of full-length transcripts, with a per allele BRCA1 expression profile composed of ≈70-80% truncating transcripts, and ≈20-30% of in-frame Δ9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm that BRCA1c.[594-2A > C;641A > G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.
Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data
2016-03-24

UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud Trust, National Institutes of Health, "Investissements d'Avenir" ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, National Institute for Health Research, National Institute on Aging, National Institutes of Health.
The snow and the willows: earlier spring snowmelt reduces performance in the low‐lying alpine shrub Salix herbacea
2016-03-24

Summary Current changes in shrub abundance in alpine and arctic tundra ecosystems are primarily driven by climate change. However, while taller shrub communities are expanding, dwarf shrub communities show reductions under climate warming, and the mechanisms driving the latter (such as warming temperatures or accelerated spring snowmelt) may be complex. To determine and disentangle the response of a widespread arctic–alpine prostrate dwarf shrub to both climate warming and changes in snowmelt time, we investigated phenology, clonal and sexual reproduction, leaf size, wood tissue carbon balance and leaf damage in 480 patches of Salix herbacea , along its elevational and snowmelt microhabitat range over 3 years in a space‐for‐time substitution. Earlier snowmelt was associated with longer phenological development periods, an increased likelihood of herbivory and fungal damage, lower stem density, smaller leaves and lower end‐of‐season wood reserve carbohydrates. Furthermore, while early snowmelt was associated with an increased proportion of flowering stems, the proportion of fruiting stems was not, as fruit set decreased significantly with earlier snowmelt. Warmer temperatures at lower elevations were associated with lower stem numbers and larger leaves. Synthesis . Our study indicates that phenology, fitness proxies and fungal/insect damage of the dwarf shrub S. herbacea are strongly influenced by snowmelt timing, and that earlier spring snowmelt reduced performance in S. herbacea . The likely mechanisms for many of the observed patterns are related to adverse temperature conditions in the early growing season. Reductions in clonal (stem number) and sexual reproduction (reduced fruit set) under earlier snowmelt, in addition to increasing damage probability, will likely lead to lower fitness and poorer performance, particularly in shrubs growing in early‐exposure microhabitats. Further, we saw few concurrent benefits of higher temperatures for S. herbacea , particularly as warming was associated with lower clonal growth. As growing seasons become warmer and longer in arctic and alpine tundra ecosystems, early snowmelt is a critical mechanism reducing fitness and performance in a widespread dwarf shrub and may ultimately reduce dwarf shrub communities in tundra biomes.
Functional characterization and anti-cancer action of the clinical phase II cardiac Na+/K+ ATPase inhibitor istaroxime: in vitro and in vivo properties and cross talk with the membrane androgen receptor
2016-03-24

Sodium potassium pump (Na+/K+ ATPase) is a validated pharmacological target for the treatment of various cardiac conditions. Recent published data with Na+/K+ ATPase inhibitors suggest a potent anti-cancer action of these agents in multiple indications. In the present study, we focus on istaroxime, a Na+/K+ ATPase inhibitor that has shown favorable safety and efficacy properties in cardiac phase II clinical trials. Our experiments in 22 cancer cell lines and in prostate tumors in vivo proved the strong anti-cancer action of this compound. Istaroxime induced apoptosis, affected the key proliferative and apoptotic mediators c-Myc and caspase-3 and modified actin cystoskeleton dynamics and RhoA activity in prostate cancer cells. Interestingly, istaroxime was capable of binding to mAR, a membrane receptor mediating rapid, non-genomic actions of steroids in prostate and other cells. These results support a multi-level action of Na+/K+ ATPase inhibitors in cancer cells and collectively validate istaroxime as a strong re-purposing candidate for further cancer drug development.
Roll rate perceptual thresholds in active and passive curve driving simulation
2016-03-24

In driving simulation, simulator tilt is used to reproduce sustained linear acceleration. In order to feel realistic, this tilt is performed at a rate below the human tilt rate detection threshold, which is usually assumed constant. However, it is known that many factors affect the threshold, such as visual information, simulator motion in additional directions, or the driver’s active effort required for controlling the vehicle. Here we investigated the effect of these factors on the roll rate detection threshold during simulated curve driving. Ten participants reported whether they detected roll motion in multiple trials during simulated curve driving, while roll rate was varied over trials. Roll rate detection thresholds were measured under four conditions. In the first three conditions, participants were moved passively through a curve with the following: (i) roll only in darkness; (ii) combined roll/sway in darkness; (iii) combined roll/sway and visual information. In the fourth (iv) condition participants actively drove through the curve. The results showed that roll rate thresholds in simulated curve driving increase, that is, sensitivity decreases, when the roll tilt is combined with sway motion. Moreover, an active control task seemed to further increase the detection threshold, that is, impair motion sensitivity, but with large individual differences. We hypothesize that this is related to the level of immersion during the task.
MicroProtein-Mediated Recruitment of CONSTANS into a TOPLESS Trimeric Complex Represses Flowering in Arabidopsis
2016-03-25

MicroProteins are short, single domain proteins that act by sequestering larger, multi-domain proteins into non-functional complexes. MicroProteins have been identified in plants and animals, where they are mostly involved in the regulation of developmental processes. Here we show that two Arabidopsis thaliana microProteins, miP1a and miP1b, physically interact with CONSTANS (CO) a potent regulator of flowering time. The miP1a/b-type microProteins evolved in dicotyledonous plants and have an additional carboxy-terminal PF(V/L)FL motif. This motif enables miP1a/b microProteins to interact with TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins. Interaction of CO with miP1a/b/TPL causes late flowering due to a failure in the induction of FLOWERING LOCUS T (FT) expression under inductive long day conditions. Both miP1a and miP1b are expressed in vascular tissue, where CO and FT are active. Genetically, miP1a/b act upstream of CO thus our findings unravel a novel layer of flowering time regulation via microProtein-inhibition.
Hyperthermia Synergizes with Chemotherapy by Inhibiting PARP1-Dependent DNA Replication Arrest
2016-03-25

Abstract Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here, we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and whether this mechanism is involved in its sensitizing effect in BRCA-competent models of ovarian and colon cancer. Notably, we found that hyperthermia delayed the repair of DNA damage caused by cisplatin or doxorubicin, acting upstream of different repair pathways to block histone polyADP-ribosylation (PARylation), a known effect of chemotherapy. Furthermore, hyperthermia blocked this histone modification as efficiently as pharmacologic inhibitors of PARP (PARPi), producing comparable delay in DNA repair, induction of double-strand breaks (DSB), and cell cytotoxicity after chemotherapy. Mechanistic investigations indicated that inhibiting PARylation by either hyperthermia or PARPi induced lethal DSB upon chemotherapy treatment not only by reducing DNA repair but also by preventing replication fork slowing. Overall, our work reveals how PARP blockade, either by hyperthermia or small-molecule inhibition, can increase chemotherapy-induced damage in BRCA-competent cells. Cancer Res; 76(10); 2868–75. ©2016 AACR.
White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network
2016-03-26

Objective White matter hyperintensities (WMHs) are areas of increased signal on T2‐weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1 , PSEN2 , and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. Methods The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first‐degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed‐effects piece‐wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. Results Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. Interpretation Autosomal‐dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929–939
Classification based hypothesis testing in neuroscience: Below‐chance level classification rates and overlooked statistical properties of linear parametric classifiers
2016-03-26

Abstract Multivariate pattern analysis (MVPA) has recently become a popular tool for data analysis. Often, classification accuracy as quantified by correct classification rate (CCR) is used to illustrate the size of the effect under investigation. However, we show that in low sample size (LSS), low effect size (LES) data, which is typical in neuroscience, the distribution of CCRs from cross‐validation of linear MVPA is asymmetric and can show classification rates considerably below what would be expected from chance classification. Conversely, the mode of the distribution in these cases is above expected chance levels, leading to a spuriously high number of above chance CCRs. This unexpected distribution has strong implications when using MVPA for hypothesis testing. Our analyses warrant the conclusion that CCRs do not well reflect the size of the effect under investigation. Moreover, the skewness of the null‐distribution precludes the use of many standard parametric tests to assess significance of CCRs. We propose that MVPA results should be reported in terms of P values, which are estimated using randomization tests. Also, our results show that cross‐validation procedures using a low number of folds, e.g. twofold, are generally more sensitive, even though the average CCRs are often considerably lower than those obtained using a higher number of folds. Hum Brain Mapp 37:1842–1855, 2016 . © 2016 Wiley Periodicals, Inc .
A smooth particle hydrodynamics code to model collisions between solid, self-gravitating objects
2016-03-28

Modern graphics processing units (GPUs) lead to a major increase in the\\nperformance of the computation of astrophysical simulations. Owing to the\\ndifferent nature of GPU architecture compared to traditional central processing\\nunits (CPUs) such as x86 architecture, existing numerical codes cannot be\\neasily migrated to run on GPU. Here, we present a new implementation of the\\nnumerical method smooth particle hydrodynamics (SPH) using CUDA and the first\\nastrophysical application of the new code: the collision between Ceres-sized\\nobjects. The new code allows for a tremendous increase in speed of\\nastrophysical simulations with SPH and self-gravity at low costs for new\\nhardware. We have implemented the SPH equations to model gas, liquids and\\nelastic, and plastic solid bodies and added a fragmentation model for brittle\\nmaterials. Self-gravity may be optionally included in the simulations and is\\ntreated by the use of a Barnes-Hut tree. We find an impressive performance gain\\nusing NVIDIA consumer devices compared to our existing OpenMP code. The new\\ncode is freely available to the community upon request.\\n