julilili42/papers huggingface dataset:
Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications
2021-06-09

Objective: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation. Methods: A cohort of 3,649 individuals of European descent with epilepsy was deeply phenotyped and underwent single nucleotide polymorphism (SNP)-genotyping. We conducted genome-wide association analyses (GWASs) on responders to specific ASMs or groups of functionally related ASMs, using non-responders as controls. We performed a polygenic risk score (PRS) analyses based on risk variants for epilepsy and neuropsychiatric disorders and ASM resistance itself to delineate the polygenic burden of ASM-specific drug resistance. Results: We identified several potential regions of interest but did not detect genome-wide significant loci for ASM-specific response. We did not find polygenic risk for epilepsy, neuropsychiatric disorders, and drug-resistance associated with drug response to specific ASMs or mechanistically related groups of ASMs. Significance: This study could not ascertain the predictive value of common genetic variants for ASM responder status. The identified suggestive loci will need replication in future studies of a larger scale.
New ideas for handling of loop and angular integrals in D-dimensions in QCD
2021-06-09

A bstract We discuss new ideas for consideration of loop diagrams and angular integrals in D -dimensions in QCD. In case of loop diagrams, we propose the covariant formalism of expansion of tensorial loop integrals into the orthogonal basis of linear combinations of external momenta. It gives a very simple representation for the final results and is more convenient for calculations on computer algebra systems. In case of angular integrals we demonstrate how to simplify the integration of differential cross sections over polar angles. Also we derive the recursion relations, which allow to reduce all occurring angular integrals to a short set of basic scalar integrals. All order ε -expansion is given for all angular integrals with up to two denominators based on the expansion of the basic integrals and using recursion relations. A geometric picture for partial fractioning is developed which provides a new rotational invariant algorithm to reduce the number of denominators.
One WITH RECURSIVE is Worth Many GOTOs
2021-06-09

PL/SQL integrates an imperative statement-by-statement style of programming with the plan-based evaluation of SQL queries. The disparity of both leads to friction at runtime, slowing PL/SQL execution down significantly. This work describes a compiler from PL/SQL UDFs to plain SQL queries. Post-compilation, evaluation entirely happens on the SQL side of the fence. With the friction gone, we observe execution times to improve by about a factor of 2, even for complex UDFs. The compiler builds on techniques long established by the programming language community. In particular, it uses trampolined style to compile arbitrarily nested iterative control flow in PL/SQL into SQL's recursive common table expressions.
Cross-Species Comparisons of Nanoparticle Interactions with Innate Immune Systems: A Methodological Review
2021-06-09

Many components of the innate immune system are evolutionarily conserved and shared across many living organisms, from plants and invertebrates to humans. Therefore, these shared features can allow the comparative study of potentially dangerous substances, such as engineered nanoparticles (NPs). However, differences of methodology and procedure between diverse species and models make comparison of innate immune responses to NPs between organisms difficult in many cases. To this aim, this review provides an overview of suitable methods and assays that can be used to measure NP immune interactions across species in a multidisciplinary approach. The first part of this review describes the main innate immune defense characteristics of the selected models that can be associated to NPs exposure. In the second part, the different modes of exposure to NPs across models (considering isolated cells or whole organisms) and the main endpoints measured are discussed. In this synergistic perspective, we provide an overview of the current state of important cross-disciplinary immunological models to study NP-immune interactions and identify future research needs. As such, this paper could be used as a methodological reference point for future nano-immunosafety studies.
Impact of Packet Filtering on Time-Sensitive Networking Traffic
2021-06-09

The Industrial Internet of Things, Industry 4.0 and cloud computing are fundamentally transforming today's industrial networks towards high connectivity. At the same time, the number of cyber-attacks against industrial infrastructure increased drastically over the last years, requiring to tightly limit the connectivity between the networked devices of a plant. For both of these trends, there are mechanisms evolving and partially already in place. Network segmentation with packet filters is a key mechanism for achieving improved network security while Time-Sensitive Networking (TSN) is a promising option to realize advanced real-time applications in future industrial networks. However, although being built based on widely accepted standards and despite their practical relevance, these two concepts don't play together well. In this paper, we analyze the problems that arise when TSN networks are segmented using today's firewalls and packet filters. In particular, we discuss and quantify the impact of delay and jitter caused by packet filters on TSN traffic. We also show that the delays and jitter introduced by CPU-based filtering can be prohibitively high in real-time scenarios. Based on our analysis, we present and compare three approaches to overcome the challenges created by the combination of these two major trends in industrial networks.
Correlation between thoracolumbar disc degeneration and anatomical spinopelvic parameters in supine position on MRI
2021-06-09

Objective This study aims to investigate the correlation between spinopelvic parameters in supine position (pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL)), disc degeneration and herniation of the thoracolumbar spine, as well as cardiovascular risk factors and back pain in a southern German cohort from the general population. Methods This study is a cross-sectional, case–control study drawn from a prospective cohort of the “Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung in der Region Augsburg” study (KORA). In total, 374 participants (mean age 56.4 ± 9.2 years; 57.8% male) from the whole-body MRI cohort (FF4) were included. All participants underwent a standardized whole-body MRI on which disc degeneration of the thoracic and lumbar spine was evaluated using a sequence adapted Pfirrmann score. PI, PT, SS and LL were measured according to the description in the literature, using sagittal imaging. Furthermore, disc bulging and protrusion were assessed. Correlations were estimated by logistic regression models providing odds ratios. Results Mean PI was 54.0° ± 11.1°, PT 13.0° ± 5.8°, SS 40.2° ± 8.8° and LL 36.2° ± 9.6°. SS was greater in men (p&lt;0.05) and lumbar lordosis in women (p&lt;0.001). PT increased by 0.09° per age-year with rising age. Age was not associated with PI, SS and LL. Neither BMI, hypertension, cholesterol, lipid levels, nor physical activity were associated with PI, PT, SS or LL. Diabetes mellitus negatively correlated with SS (β = -4.19; 95%CI -7.31–1.06, p&lt;0.01). Smaller spinopelvic parameters (PI, SS and LL) where significantly (p&lt;0.05) correlated with an increased frequency of disc bulging, as well as a local clustering in the lumbar, but not the thoracic spine. Conclusion In conclusion, spinopelvic parameters, measured in supine position, are significantly correlated with disc bulging alone; there is no significant correlation between supine spinopelvic parameters and disc degeneration, back pain or cardiovascular risk factors.
Generation of ENSEMBL-based proteogenomics databases boosts the identification of non-canonical peptides
2021-06-09

Abstract Summary We have implemented the pypgatk package and the pgdb workflow to create proteogenomics databases based on ENSEMBL resources. The tools allow the generation of protein sequences from novel protein-coding transcripts by performing a three-frame translation of pseudogenes, lncRNAs, and other non-canonical transcripts, such as those produced by alternative splicing events. It also includes exonic out-of-frame translation from otherwise canonical protein-coding mRNAs. Moreover, the tool enables the generation of variant protein sequences from multiple sources of genomic variants including COSMIC, cBioportal, gnomAD, and mutations detected from sequencing of patient samples. pypgatk and pgdb provide multiple functionalities for database handling, notably optimized target/decoy generation by the algorithm DecoyPyrat . Finally, we perform a reanalysis of four public datasets in PRIDE by generating cell-type specific databases for 65 cell lines using the pypgatk and pgdb workflow, revealing a wealth of non-canonical or cryptic peptides amounting to more than 10% of the total number of peptides identified (43,501 out of 402,512). Availability The software is freely available. pypgatk : ( https://github.com/bigbio/py-pgatk/ ), and pgdb : ( https://github.com/nf-core/pgdb ) Contact Yasset Perez-Riverol ( yperez@ebi.ac.uk ), Rui Branca ( rui.mamede-branca@ki.se ) Supplementary information Supplementary data are available online.
Banded Charnockite: The Result of Crustal Magma Generation, Piecemeal Emplacement, and Fluid-Driven Mineral Replacement in High-Grade Crust (Central Dronning Maud Land, Antarctica)
2021-06-09

Our study of a banded charnockite complex of the Mühlig-Hofmannfjella in Dronning Maud Land, Antarctica, illustrates how the combination of high-temperature (re-)crystallization processes, melts, and volatile fluids leads to complex intrusive, metasomatic, and structural relationships. The igneous complex consists of gently dipping sets of charnockite interlayered with dolerite and leucogranite. The banded complex formed primarily by magmatic processes, but with superimposed modifications by metasomatism. The charnockite has a ferroan composition and contains both orthopyroxene (Fs80–84) and olivine (Fa94–96). Zircon U-Pb dates the emplacement of charnockite at 515 Ma, and inherited zircon cores and negative εNd values of −3 to −5 indicate that the age of the source of the magma was about 1100 Ma. Neodymium isotopes were not homogenized during the Cambrian magmatic event, which suggests that the generation and emplacement of the magma took place in separate batches during construction of the banded complex. By contrast, the Rb-Sr system in the charnockite was extensively homogenized, likely because of the superimposed late-magmatic fluid activity, which also produced the bands and networks of leucogranites. These events occurred during the late stages of the assembly of Gondwana, with postcollisional extension and mantle upwelling maintaining a high heat flow.
The Calculus of Natural Calculation
2021-06-09

Abstract The calculus of Natural Calculation is introduced as an extension of Natural Deduction by proper term rules. Such term rules provide the capacity of dealing directly with terms in the calculus instead of the usual reasoning based on equations, and therefore the capacity of a natural representation of informal mathematical calculations. Basic proof theoretic results are communicated, in particular completeness and soundness of the calculus; normalisation is briefly investigated. The philosophical impact on a proof theoretic account of the notion of meaning is considered.
Advanced Placement Course Credit and Undergraduate Student Success in Gateway Science Courses
2021-06-09

Approximately two million students take Advanced Placement (AP) examinations annually. However, departmental policies that allow students to replace introductory courses with AP credit greatly vary within and across universities, even across relatively similar universities. This study examines the impact of AP credit policies on subsequent course success in Biology, Chemistry, and Physics at six large public research universities (N = 48,230 students). Examining average treatment effects for students skipping college courses using inverse-probability weights with regression adjustment, we found that students who skipped actually performed similarly well or better in subsequent courses than students who did not skip, even in contexts where lower AP scores were accepted. We also discovered wide variation in percentage of students who chose to skip when meeting their local policies. Therefore, to reduce unnecessary coursework that is burdensome for both students and universities, we suggest that departments consider modifying AP credit policies and that advisors consider encouraging students to skip when they have eligible AP scores.
Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
2021-06-10

Abstract The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio &amp;gt;1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. Significance: Rare cancers are difficult to treat; in particular, molecular pathogenesis–oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials. See related commentary by Eggermont et al., p. 2677. This article is highlighted in the In This Issue feature, p. 2659
Automated scoring of pre-REM sleep in mice with deep learning
2021-06-10

Abstract Reliable automation of the labor-intensive manual task of scoring animal sleep can facilitate the analysis of long-term sleep studies. In recent years, deep-learning-based systems, which learn optimal features from the data, increased scoring accuracies for the classical sleep stages of Wake, REM, and Non-REM. Meanwhile, it has been recognized that the statistics of transitional stages such as pre-REM, found between Non-REM and REM, may hold additional insight into the physiology of sleep and are now under vivid investigation. We propose a classification system based on a simple neural network architecture that scores the classical stages as well as pre-REM sleep in mice. When restricted to the classical stages, the optimized network showed state-of-the-art classification performance with an out-of-sample F1 score of 0.95 in male C57BL/6J mice. When unrestricted, the network showed lower F1 scores on pre-REM (0.5) compared to the classical stages. The result is comparable to previous attempts to score transitional stages in other species such as transition sleep in rats or N1 sleep in humans. Nevertheless, we observed that the sequence of predictions including pre-REM typically transitioned from Non-REM to REM reflecting sleep dynamics observed by human scorers. Our findings provide further evidence for the difficulty of scoring transitional sleep stages, likely because such stages of sleep are under-represented in typical data sets or show large inter-scorer variability. We further provide our source code and an online platform to run predictions with our trained network.
Separation of Photochemical and Non-Photochemical Diurnal In-Stream Attenuation of Micropollutants
2021-06-10

For a better process understanding of in-stream attenuation of trace organic contaminants (TrOCs), quantitative comparisons between field studies under different environmental conditions and controlled laboratory experiments are important to separate different processes. However, this is hampered by the challenge to transfer kinetics from the laboratory to different field conditions due to the lack of good quantitative measures to account for different boundary conditions. For phototransformation, in situ light conditions in a river are difficult to determine because light is reduced, for instance, by absorption, scattering on suspended particles, and shading effects. In this study, we present an approach to separate photochemical from non-photochemical diurnal in-stream attenuation based on rate constants relative to diclofenac, as a reference compound, to account for the difference in the in situ light conditions combined with laboratory experiments. 12 out of 45 detected target TrOCs showed a diurnal attenuation at a selected river stretch. A non-photochemical process, potentially biotransformation, was responsible for the diurnal attenuation of bisoprolol, metoprolol, O-desmethylvenlafaxine, tramadol, and venlafaxine. Attenuation of amisulpride, flufenamic acid, hydrochlorothiazide, naproxen, and xipamide can be quantitatively explained by phototransformation, partially for sotalol. Attenuation rate constants of hydrochlorothiazide at different field sites from this study and from published data range over 2 orders of magnitude. Differences can be quantitatively explained by different light exposures but not by water chemical parameters.
An identical‐by‐descent novel splice‐donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families
2021-06-10

Abstract PRUNE1 is linked to a wide range of neurodevelopmental and neurodegenerative phenotypes. Multiple pathogenic missense and stop‐gain PRUNE1 variants were identified in its DHH and DHHA2 phosphodiesterase domains. Conversely, a single splice alteration was previously reported. We investigated five patients from two unrelated consanguineous Sudanese families with an inherited severe neurodevelopmental disorder using whole‐exome sequencing coupled with homozygosity mapping, segregation, and haplotype analysis. We identified a founder haplotype transmitting a homozygous canonical splice‐donor variant (NM_021222.3:c.132+2T &gt; C) in intron 2 of PRUNE1 segregated with the phenotype in all the patients. This splice variant possibly results in an in‐frame deletion in the DHH domain or premature truncation of the protein. The phenotypes of the affected individuals showed phenotypic similarities characterized by remarkable pyramidal dysfunction and prominent extrapyramidal features (severe dystonia and bradykinesia). In conclusion, we identified a novel founder variant in PRUNE1 and corroborated abnormal splicing events as a disease mechanism in PRUNE1‐ related disorders. Given the phenotypes’ consistency coupled with the founder effect, canonical and cryptic PRUNE1 splice‐site variants should be carefully evaluated in patients presenting with prominent dystonia and pyramidal dysfunction.
Decision-making in professional football: an empirical analysis of club members’ voting behaviour
2021-06-10

Research question Despite significantly increasing membership in professional football clubs over time, few members exercise their right to vote. We explore whether factors found to influence turnout to shareholder voting and political elections are also relevant in this peculiar setting. Given the geographically widespread distribution of members, a particular focus is put on the relevance of travel distance to the meeting place.Research methods Data come from an online survey of n = 9090 voting-eligible members of one of the biggest football clubs in Germany. A member’s ‘habit for voting’ serves as dependent variable in our regression models. Given the ordinal nature of this variable, ordered probit models were estimated which allow addressing the size and relevance of non-instrumental benefits from voting.Results and findings Next to some setting-specific variables, we find that several socio-demographic characteristics have statistically significant effects on the members’ habit for voting. Also in line with the general voting literature, the distance between one’s home and the meeting place is significantly and negatively related to the probability of voting. Remarkably, however, this effect is hardly big enough to materially change the habit for voting.Implications Our study provides some evidence of ‘temporal consistency’ and ‘setting independency’ for the factors associated with voter turnout. At the same time, it illustrates a practically highly relevant case where statistical and economic significance of a variable differ. Since the effect of distance between one’s home and the meeting place is comparably small, online voting or voting by mail might have little impact on turnout in practice.
The Moral Status of Cognitively Enhanced Monkeys and Other Novel Beings
2021-06-10

Abstract The discussion about the moral status of novel beings tends to focus on artificial intelligence, robots, and other man-made systems. We should, however, also consider a likelier kind of novel beings: animals that are genetically modified to develop human-like cognitive capabilities. This paper focuses on the possibility of conferring human characteristics on nonhuman primates (NHPs) in the context of neuroscientific research. It first discusses the use of NHPs for neuroscientific research and then, second, describes recent developments that promise to revolutionize the field and how that may lead to NHPs attaining human-like cognitive capabilities. Third, an account of moral status is developed to ground the central claim, that making the NHP brain more human-like is unproblematic as long as the NHPs do not become persons. In conclusion, this paper discusses the implications for the moral status of cognitively enhanced NHPs, as well as the implications for other novel beings.