julilili42/papers huggingface dataset:
Identification of HCMV-derived T cell epitopes in seropositive individuals through viral deletion models
2019-12-20

In healthy individuals, immune control of persistent human cytomegalovirus (HCMV) infection is effectively mediated by virus-specific CD4+ and CD8+ T cells. However, identifying the repertoire of T cell specificities for HCMV is hampered by the immense protein coding capacity of this betaherpesvirus. Here, we present a novel approach that employs HCMV deletion mutant viruses lacking HLA class I immunoevasins and allows direct identification of naturally presented HCMV-derived HLA ligands by mass spectrometry. We identified 368 unique HCMV-derived HLA class I ligands representing an unexpectedly broad panel of 123 HCMV antigens. Functional characterization revealed memory T cell responses in seropositive individuals for a substantial proportion (28%) of these novel peptides. Multiple HCMV-directed specificities in the memory T cell pool of single individuals indicate that physiologic anti-HCMV T cell responses are directed against a broad range of antigens. Thus, the unbiased identification of naturally presented viral epitopes enabled a comprehensive and systematic assessment of the physiological repertoire of anti-HCMV T cell specificities in seropositive individuals.
Chromatic Full-Field Stimulus Threshold and Pupillography as Functional Markers for Late-Stage, Early-Onset Retinitis Pigmentosa Caused by CRB1 Mutations
2019-12-20

The functional measurements presented in this study present a valid clinical progression marker in late-stage early onset retinitis pigmentosa caused by biallelic <i>CRB1</i> mutations. Additionally, they can be used as outcome measures for safety and efficacy in clinical therapy trials.
Aicardi-Goutières syndrome due to a paternal mosaic IFIH1 mutation
2019-12-20

Progressive immune-mediated neurodegeneration is a central feature of Aicardi-Goutières syndrome (AGS), a monogenic disorder characterized by chronic activation of antiviral type I interferon (IFN).1 Typically, AGS presents as subacute infancy-onset encephalopathy with microcephaly, leukodystrophy, and basal ganglia calcification, resulting in global developmental delay. AGS is either caused by loss-of-function mutations in TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, or ADAR, encoding genes involved in the metabolism of nucleic acids, or by gain-of-function mutations in IFIH1 encoding the cytosolic RNA sensor melanoma differentiation-associated protein 5 (MDA5).1 The phenotypic spectrum of IFIH1-associated mutations includes intracerebral vasculopathy, bilateral striatal necrosis, and isolated spastic paraparesis.
Ge4Cl4[MCp(CO)3]4 (M = Cr, Mo, W): A Series of Transition Metal Substituted Four‐membered Cyclogermanes
2019-12-20

The reaction of GeCl 2 · dioxane with the sodium salts NaMCp(CO) 3 (M = Cr, Mo, W) leads to new four‐membered ring compounds Ge 4 Cl 4 [MCp(CO) 3 ] 4 , where the remaining chlorine atom cannot be substituted by another MCp(CO) 3 substituent. A large excess of the sodium salts only leads to some minor side‐reactions. All Ge 4 ‐compounds exhibit a non‐planar four‐membered Ge 4 ring, which can be traced back to electrostatic effects as shown by quantum chemical calculations. Furthermore, cluster build‐up reactions might be possible due to the halide substituents in the new ring compounds of germanium, showing that GeCl 2 · dioxane is an excellent starting material for the synthesis of cluster compounds of germanium.
BOSC 2019, the 20th annual Bioinformatics Open Source Conference
2019-12-20

<ns4:p>The Bioinformatics Open Source Conference is a volunteer-organized meeting that covers open source software development and open science in bioinformatics. Launched in 2000, BOSC has been held every year since. BOSC 2019, the 20th annual BOSC, took place as one of the Communities of Special Interest (COSIs) at the Intelligent Systems for Molecular Biology meeting (ISMB/ECCB 2019). The two-day meeting included a total of 46 talks and 55 posters, as well as eight Birds of a Feather interest groups. The keynote speaker was University of Cape Town professor Dr. Nicola Mulder, who spoke on “Building infrastructure for responsible open science in Africa”.</ns4:p><ns4:p> Immediately after BOSC 2019, about 50 people participated in the two-day CollaborationFest (CoFest for short), an open and free community-driven event at which participants work together to contribute to bioinformatics software, documentation, training materials, and use cases.</ns4:p>
Many-body correlations from integral geometry
2019-12-20

In a recent letter we presented a framework for predicting the concentrations of many-particle local structures inside the bulk liquid as a route to assessing changes in the liquid approaching dynamical arrest. Central to this framework was the morphometric approach, a synthesis of integral geometry and liquid-state theory, which has traditionally been derived from fundamental measure theory. We present the morphometric approach in a new context as a generalization of scaled-particle theory, and we derive several morphometric theories for hard spheres of fundamental and practical interest. Our central result is a new theory that is particularly suited to the treatment of many-body correlation functions in the hard-sphere liquid, which we demonstrate by numerical tests against simulation.
Decomposition diversity with symmetric data and codata
2019-12-20

The expression problem describes a fundamental trade-off in program design: Should a program's primary decomposition be determined by the way its domain objects are constructed ("functional" decomposition), or by the way they are destructed ("object-oriented" decomposition)? We argue that programming languages should not force one of these decompositions on the programmer; rather, a programming language should support both ways of decomposing a program in a symmetric way, with an easy translation between these decompositions. However, current programming languages are usually not symmetric and hence make it unnecessarily hard to switch the decomposition. We propose a language that is symmetric in this regard and allows a fully automatic translation between "functional" and "object-oriented" decomposition. We present a language with algebraic data types and pattern matching for "functional" decomposition and codata types and copattern matching for "object-oriented" decomposition, together with a bijective translation that turns a data type into a codata type ("destructorization") or vice versa ("constructorization"). We present the first symmetric programming language with support for local (co)pattern matching, which includes local anonymous function or object definitions, that allows an automatic translation as described above. We also present the first mechanical formalization of such a language and prove i) that the type system is sound, that the translations between data and codata types are ii) type-preserving, iii) behavior-preserving and iv) inverses of each other. We also extract a mechanically verified implementation from our formalization and have implemented an IDE with direct support for these translations.
Rethinking causality and data complexity in brain lesion-behaviour inference and its implications for lesion-behaviour modelling
2019-12-20

Abstract Modelling behavioural deficits based on structural lesion imaging is a popular approach to map functions in the human brain, and efforts to translationally apply lesion-behaviour modelling to predict post-stroke outcomes are on the rise. The high-dimensional complexity of lesion data, however, evokes challenges in both lesion behaviour mapping and post stroke outcome prediction. This paper aims to deepen the understanding of this complexity by reframing it from the perspective of causal and non-causal dependencies in the data, and by discussing what this complexity implies for different data modelling approaches. By means of theoretical discussion and empirical examination, several common strategies and views are challenged, and future research perspectives are outlined. A main conclusion is that lesion-behaviour inference is subject to a lesion-anatomical bias that cannot be overcome by using multivariate models or any other algorithm that is blind to causality behind relations in the data. This affects the validity of lesion behaviour mapping and might even wrongfully identify paradoxical effects of lesion-induced functional facilitation – but, as this paper argues, only to a minor degree. Thus, multivariate lesion-brain inference appears to be a valuable tool to deepen our understanding of the human brain, but only because it takes into account the functional relation between brain areas. The perspective of causality and inter-variable dependence is further used to point out challenges in improving lesion behaviour models. Firstly, the dependencies in the data open up different possible strategies of data reduction, and considering those might improve post-stroke outcome prediction. Secondly, the role of non-topographical causal predictors of post stroke behaviour is discussed. The present article argues that, given these predictors, different strategies are required in the evaluation of model quality in lesion behaviour mapping and post stroke outcome prediction.
Data-driven algorithm for the diagnosis of behavioral variant frontotemporal dementia
2019-12-20

Abstract INTRODUCTION Brain structural imaging is paramount for the diagnosis of behavioral variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. METHODS A total of 515 subjects from two different bvFTD databases (training and validation cohorts) were included to perform voxel-wise deformation-based morphometry analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from morphometric differences in isolation and together with bedside cognitive scores. RESULTS Average ten-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In a separate validation cohort of genetically confirmed bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added cognitive scores. DISCUSSION The random forest classifier developed can accurately predict bvFTD at the individual subject level.
Heavy meson hadroproduction:open issues
2019-12-20

We discuss open issues in the description of single-inclusive open heavy-meson production in and collisions, considering different flavour-number schemes. Solving these issues is important for improving the accuracy of PDF fits and of predictions in high-energy astroparticle physics.
Similar Expectation Effects for Immediate and Delayed Stimulus Repetitions
2019-12-20

A prior cue or stimulus allows prediction of the future occurrence of an event and therefore reduces the associated neural activity in several cortical areas. This phenomenon is labeled expectation suppression (ES) and has recently been shown to be independent of the generally observed effects of stimulus repetitions (repetition suppression, RS: reduced neuronal response after the repetition of a given stimulus). While it has been shown that attentional cueing is strongly affected by the length of the cue-target delay, we have no information on the temporal dynamics of expectation effects, as in most prior studies of ES the delay between the predictive cue and the target (i.e., the inter-stimulus interval, ISI) was in the range of a few hundred milliseconds. Hence, we presented participants with pairs of faces where the first face could be used to build expectations regarding the second one, in the sense that one gender indicated repetition of the same face while the other gender predicted the occurrence of novel faces. In addition, we presented the stimulus pairs with two different ISIs (0.5 s for Immediate and 1.75 or 3.75 s for Delayed ISIs). We found significant RS as well as a reduced response for correctly predicted when compared to surprising trials in the fusiform face area. Importantly, the effects of repetition and expectation were both independent of the length of the ISI period. This implies that Immediate and Delayed cue-target stimulus arrangements lead to similar expectation effects in the face sensitive-visual cortex.
A Brief Report on the Link between Perceived Coach Behaviour, Coach-Athlete Relationship Quality and Performance among South African Male Senior National Level Team Sport Para-Athletes
2019-12-22

A fundamental feature in successful coaching outcomes and athlete performance is rooted in the quality of the coach-athlete relationship which is impacted by coaches’ way of being. This investigation examined whether perceived coach behaviour associates with the coach-athlete relationship quality and self-rated season performance among members from two South African male senior national para-sport teams (n = 23, M age = 32.65). The predictive utility of coaches’ perceived behaviour on the dyadic relationship quality and athletes’ views on their own performance was also determined. Cross-sectional quantitative data were collected by means of the Coaching Behaviour Scale for Sport, Coach-Athlete Relationship Questionnaire and a Likert-scale item recording athletes’ subjective rating of perceived standard of performance for the respective competition season. The team members’ reported fairly good standard of season performances and sound relationship standings with their involved head coaches who were seen to exhibit behaviours most illustrative of mental preparation, personal rapport, and competition tactics. Inferences drawn from the correlation analyses advised that particular adoptive coach behaviour in para-sport coaching appears to be a meaningful construct associated with the establishment and maintenance of relationships with athletes. Regression analyses also exposed coaches’ competition strategy behaviour to be a significant predictor of complementarity in the coach-athlete relationship, which along with the noted positive correlations provide a good basis for further exploration in similar sport contexts.
Epistatic effect of TLR3 and cGAS‐STING‐IKKε‐TBK1‐IFN signaling variants on colorectal cancer risk
2019-12-23

Abstract Objective The TLR3/cGAS‐STING‐IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11‐2.53, P ‐value = .01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07‐3.84, P ‐value = .03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03‐2.27, P ‐value = .03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5‐6 risk alleles compared to those with 0‐2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair‐wise interactions within and between the CGAS, TMEM173, IKBKE , and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management.
KM3NeT front-end and readout electronics system: hardware, firmware, and software
2019-12-23

[EN] The KM3NeT research infrastructure being built at the bottom of the Mediterranean Sea will host&#13;\\nwater-Cherenkov telescopes for the detection of cosmic neutrinos. The neutrino telescopes will consist of large&#13;\\nvolume three-dimensional grids of optical modules to detect the Cherenkov light from charged particles produced&#13;\\nby neutrino-induced interactions. Each optical module houses 31 3-in. photomultiplier tubes, instrumentation for&#13;\\ncalibration of the photomultiplier signal and positioning of the optical module, and all associated electronics&#13;\\nboards. By design, the total electrical power consumption of an optical module has been capped at seven&#13;\\nWatts. We present an overview of the front-end and readout electronics system inside the optical module, which&#13;\\nhas been designed for a 1-ns synchronization between the clocks of all optical modules in the grid during a life&#13;\\ntime of at least 20 years.
The 5′ NAD Cap of RNAIII Modulates Toxin Production in Staphylococcus aureus Isolates
2019-12-23

Numerous organisms, including bacteria, are endowed with a 5′ NAD cap in specific RNAs. While the presence of the 5′ NAD cap modulates the stability of the modified RNA species, a significant biological function and phenotype have not been assigned so far. Here, we show the presence of a 5′ NAD cap in RNAIII from S. aureus , a dual-function regulatory RNA involved in quorum-sensing processes and regulation of virulence factor expression. We also demonstrate that altering the natural NAD modification ratio of RNAIII leads to a decrease in exotoxin production, thereby modulating the bacterium’s virulence. Our work unveils a new layer of regulation of RNAIII and the agr system that might be linked to the redox state of the NAD molecule in the cell.
A New Liver Expression Quantitative Trait Locus Map From 1,183 Individuals Provides Evidence for Novel Expression Quantitative Trait Loci of Drug Response, Metabolic, and Sex‐Biased Phenotypes
2019-12-23

Expression quantitative trait locus (eQTL) studies in human liver are crucial for elucidating how genetic variation influences variability in disease risk and therapeutic outcomes and may help guide strategies to obtain maximal efficacy and safety of clinical interventions. Associations between expression microarray and genome‐wide genotype data from four human liver eQTL studies ( n = 1,183) were analyzed. More than 2.3 million cis ‐eQTLs for 15,668 genes were identified. When eQTLs were filtered against a list of 1,496 drug response genes, 187,829 cis ‐eQTLs for 1,191 genes were identified. Additionally, 1,683 sex‐biased cis ‐eQTLs were identified, as well as 49 and 73 cis ‐eQTLs that colocalized with genome‐wide association study signals for blood metabolite or lipid levels, respectively. Translational relevance of these results is evidenced by linking DPYD eQTLs to differences in safety of chemotherapy, linking the sex‐biased regulation of PCSK9 expression to anti‐lipid therapy, and identifying the G‐protein coupled receptor GPR180 as a novel drug target for hypertriglyceridemia.
Identification of Ppar γ -modulated miRNA hubs that target the fibrotic tumor microenvironment
2019-12-23

Liver fibrosis interferes with normal liver function and facilitates hepatocellular carcinoma (HCC) development, representing a major threat to human health. Here, we present a comprehensive perspective of microRNA (miRNA) function on targeting the fibrotic microenvironment. Starting from a murine HCC model, we identify a miRNA network composed of 8 miRNA hubs and 54 target genes. We show that let-7, miR-30, miR-29c, miR-335, and miR-338 (collectively termed antifibrotic microRNAs [AF-miRNAs]) down-regulate key structural, signaling, and remodeling components of the extracellular matrix. During fibrogenic transition, these miRNAs are transcriptionally regulated by the transcription factor Ppar <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi>γ</mml:mi> </mml:math> and thus we identify a role of Ppar <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi>γ</mml:mi> </mml:math> as regulator of a functionally related class of AF-miRNAs. The miRNA network is active in human HCC, breast, and lung carcinomas, as well as in 2 independent mouse liver fibrosis models. Therefore, we identify a miRNA:mRNA network that contributes to formation of fibrosis in tumorous and nontumorous organs of mice and humans.
Time-evolution of nonlinear optomechanical systems: interplay of mechanical squeezing and non-Gaussianity
2019-12-23

Abstract We solve the time evolution of a nonlinear optomechanical Hamiltonian with arbitrary time-dependent mechanical displacement, mechanical single-mode squeezing and a time-dependent optomechanical coupling up to the solution of two second-order differential equations. The solution is based on identifying a minimal and finite Lie algebra that generates the time-evolution of the system. This reduces the problem to considering a finite set of coupled ordinary differential equations of real functions. To demonstrate the applicability of our method, we compute the degree of non-Gaussianity of the time-evolved state of the system by means of a measure based on the relative entropy of the non-Gaussian state and its closest Gaussian reference state. We find that the addition of a constant mechanical squeezing term to the standard optomechanical Hamiltonian generally decreases the overall non-Gaussian character of the state. For sinusoidally modulated squeezing, the two second-order differential equations mentioned above take the form of the Mathieu equation. We derive perturbative solutions for a small squeezing amplitude at parametric resonance and show that they correspond to the rotating-wave approximation at times larger than the scale set by the mechanical frequency. We find that the non-Gaussianity of the state increases with both time and the squeezing parameter in this specific regime.