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In this paper we present a mathematical model for a nonlinear damped pendulum. We compare the theoretical model with experimentally generated data recorded by a pendulum apparatus. We use a genetic algorithm to find the best fit model parameters. A detailed description of the algorithm is given and adapted for our pendulum model. We also illustrate that air friction and drag forces cannot always be ignored when modeling pendular motion. [ABSTRACT FROM AUTHOR]

A theoretical perspective on grandiose narcissism suggests four forms of it (sanctity, admiration, heroism, rivalry) and states that these forms conduce to different ways of thinking and acting. Guided by this perspective, we examined in a multinational and multicultural study (61 countries; N = 15,039) how narcissism forms are linked to cognitions and behaviors prompted by the COVID-19 pandemic. As expected, differences in cognitions and behaviors across narcissism forms emerged. For example, higher narcissistic rivalry predicted lower likelihood of enactment of COVID-19 prevention behaviors, but higher narcissistic sanctity predicted higher likelihood of enactment of COVID-19 prevention behaviors. Further, whereas the heroism, admiration, and rivalry narcissism forms acted in a typically antisocial manner, with high narcissism predicting greater endorsement of unfounded health beliefs, the sanctity form acted in a prosocial manner, with higher narcissism being linked to lower endorsement of unfounded COVID-19 health beliefs. Thus, the findings (a) support the idea of four narcissism forms acting differently, and (b) show that these differences reflect a double-edged sword, sometimes linking to an anti-social orientation, and sometimes linking to a pro-social orientation., (© 2024. The Author(s).)

Selecting the best model of sequence evolution for a multiple-sequence-alignment (MSA) constitutes the first step of phylogenetic tree reconstruction. Common approaches for inferring nucleotide models typically apply maximum likelihood (ML) methods, with discrimination between models determined by one of several information criteria. This requires tree reconstruction and optimisation which can be computationally expensive. We demonstrate that neural networks can be used to perform model selection, without the need to reconstruct trees, optimise parameters, or calculate likelihoods. We introduce ModelRevelator, a model selection tool underpinned by two deep neural networks. The first neural network, NNmodelfind, recommends one of six commonly used models of sequence evolution, ranging in complexity from Jukes and Cantor to General Time Reversible. The second, NNalphafind, recommends whether or not a Γ-distributed rate heterogeneous model should be incorporated, and if so, provides an estimate of the shape parameter, ɑ. Users can simply input an MSA into ModelRevelator, and swiftly receive output recommending the evolutionary model, inclusive of the presence or absence of rate heterogeneity, and an estimate of ɑ. We show that ModelRevelator performs comparably with likelihood-based methods and the recently published machine learning method ModelTeller over a wide range of parameter settings, with significant potential savings in computational effort. Further, we show that this performance is not restricted to the alignments on which the networks were trained, but is maintained even on unseen empirical data. We expect that ModelRevelator will provide a valuable alternative for phylogeneticists, especially where traditional methods of model selection are computationally prohibitive., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Coronavirus disease (COVID-19) has been a source of fear around the world. We asked whether the measurement of this fear is trustworthy and comparable across countries. In particular, we explored the measurement invariance and cross-cultural replicability of the widely used Fear of COVID-19 scale (FCV-19S), testing community samples from 48 countries (N = 14,558). The findings indicate that the FCV-19S has a somewhat problematic structure, yet the one-factor solution is replicable across cultural contexts and could be used in studies that compare people who vary on gender and educational level. The validity of the scale is supported by a consistent pattern of positive correlations with perceived stress and general anxiety. However, given the unclear structure of the FCV-19S, we recommend using latent factor scores, instead of raw scores, especially in cross-cultural comparisons. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Maximum likelihood and maximum parsimony are two key methods for phylogenetic tree reconstruction. Under certain conditions, each of these two methods can perform more or less efficiently, resulting in unresolved or disputed phylogenies. We show that a neural network can distinguish between four-taxon alignments that were evolved under conditions susceptible to either long-branch attraction or long-branch repulsion. When likelihood and parsimony methods are discordant, the neural network can provide insight as to which tree reconstruction method is best suited to the alignment. When applied to the contentious case of Strepsiptera evolution, our method shows robust support for the current scientific view, that is, it places Strepsiptera with beetles, distant from flies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19) 1 . The development of a vaccine is likely to take at least 12-18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose-response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod 2-4 and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from induced pluripotent stem cells, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.

Wikidata is a community-maintained knowledge base that has been assembled from repositories in the fields of genomics, proteomics, genetic variants, pathways, chemical compounds, and diseases, and that adheres to the FAIR principles of findability, accessibility, interoperability and reusability. Here we describe the breadth and depth of the biomedical knowledge contained within Wikidata, and discuss the open-source tools we have built to add information to Wikidata and to synchronize it with source databases. We also demonstrate several use cases for Wikidata, including the crowdsourced curation of biomedical ontologies, phenotype-based diagnosis of disease, and drug repurposing., Competing Interests: AW, GS, SB, BG, MG, OG, KH, HH, TH, KH, SK, MM, MM, DM, EM, AP, TP, AR, NQ, LS, TS, DS, RS, KT, GT, RT, SU, EW, CW, AS No competing interests declared, (© 2020, Waagmeester et al.)

Individual differences in mental accounting have rarely been studied, and empirical evidence regarding the relation between mental accounting and personality characteristics is scarce. The present paper reports three studies applying a Likert-type scale to assess the extent individuals engage in mental accounting practices. In each study, the five items of the measure loaded on a single dimension and had acceptable reliability, with a Cronbach's α between 0.72 and 0.77. Study 1 ( N = 165) regards the mental processing of prior losses in the theater-ticket problem (Tversky and Kahneman, 1981). Study 2 ( N = 114) is based on prior work on income source effects (Fogel, 1997) and analyzes mental accounting of prior gains. In both studies, individual differences in mental accounting moderated the effects of the experimental treatments. In an explorative survey conducted for Study 3 ( N = 373), the extent of engaging in mental accounting was found to be positively correlated with being female, with conscientiousness, and financial literacy, and negatively related with education and non-planning impulsivity. Identification of individual differences and their correlates adds to existing evidence for some of the core assumptions of mental accounting theory. A practical implication of the findings is that providers of financial services must take individual differences into account when designing trainings and supportive tools for money management., (Copyright © 2019 Muehlbacher and Kirchler.)

To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The chemical diversity and known safety profiles of drugs previously tested in humans make them a valuable set of compounds to explore potential therapeutic utility in indications outside those originally targeted, especially neglected tropical diseases. This practice of "drug repurposing" has become commonplace in academic and other nonprofit drug-discovery efforts, with the appeal that significantly less time and resources are required to advance a candidate into the clinic. Here, we report a comprehensive open-access, drug repositioning screening set of 12,000 compounds (termed ReFRAME; Repurposing, Focused Rescue, and Accelerated Medchem) that was assembled by combining three widely used commercial drug competitive intelligence databases (Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects), together with extensive patent mining of small molecules that have been dosed in humans. To date, 12,000 compounds (∼80% of compounds identified from data mining) have been purchased or synthesized and subsequently plated for screening. To exemplify its utility, this collection was screened against Cryptosporidium spp., a major cause of childhood diarrhea in the developing world, and two active compounds previously tested in humans for other therapeutic indications were identified. Both compounds, VB-201 and a structurally related analog of ASP-7962, were subsequently shown to be efficacious in animal models of Cryptosporidium infection at clinically relevant doses, based on available human doses. In addition, an open-access data portal (https://reframedb.org) has been developed to share ReFRAME screen hits to encourage additional follow-up and maximize the impact of the ReFRAME screening collection., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

With the advancement of genome-sequencing technologies, new genomes are being sequenced daily. Although these sequences are deposited in publicly available data warehouses, their functional and genomic annotations (beyond genes which are predicted automatically) mostly reside in the text of primary publications. Professional curators are hard at work extracting those annotations from the literature for the most studied organisms and depositing them in structured databases. However, the resources don't exist to fund the comprehensive curation of the thousands of newly sequenced organisms in this manner. Here, we describe WikiGenomes (wikigenomes.org), a web application that facilitates the consumption and curation of genomic data by the entire scientific community. WikiGenomes is based on Wikidata, an openly editable knowledge graph with the goal of aggregating published knowledge into a free and open database. WikiGenomes empowers the individual genomic researcher to contribute their expertise to the curation effort and integrates the knowledge into Wikidata, enabling it to be accessed by anyone without restriction., Database Url: www.wikigenomes.org., (© The Author(s) 2017. Published by Oxford University Press.)

Importance: Despite the unquestioned relationship of UV radiation (UVR) exposure and melanoma development, UVR-independent development of melanoma has only recently been described in mice. These findings in mice highlight the importance of the genetic background of the host and could be relevant for preventive measures in humans., Objective: To study the role of the melanocortin-1 receptor (MC1R) and melanoma risk independently from UVR in a clinical setting., Design, Setting, and Participants: Hospital-based case-control study, including genetic testing, questionnaires, and physical data (Molecular Markers of Melanoma Study data set) including 991 melanoma patients (cases) and 800 controls., Main Outcomes and Measures: Association of MC1R variants and melanoma risk independent from sun exposure variables., Results: The 1791 participants included 991 with a diagnosis of melanoma and 800 control patients (mean [SD] age, 59.2 [15.6] years; 50.5% male). Compared with wild-type carriers, carriers of MC1R variants were at higher melanoma risk after statistically adjusting for previous UVR exposure (represented by prior sunburns and signs of actinic skin damage identified by dermatologists), age, and sex compared with wild-type carriers (≥2 variants, OR, 2.13 [95% CI, 1.66-2.75], P < .001; P for trend <.001). After adjustment for sex, age, sunburns in the past, and signs of actinic skin damage, the associations remained significant (OR, 1.65 [95% CI, 1.02-2.67] for R/R, OR, 2.63 [95% CI, 1.82-3.81] for R/r; OR, 1.83 [95% CI, 1.36-2.48] for R/0; and OR, 1.50 [95% CI, 1.01-2.21] for r/r, with P values ranging from <.001 to .04 when adjusted for facial actinic skin damage; OR, 2.36 [95% CI, 1.62-3.43] for R/r; and OR, 1.47 [95% CI, 1.08-1.99] for R/0 with P values ranging from <.001 to .01 when adjusted for dorsal actinic skin damage; and OR, 2.54 [95% CI, 1.76-3.67] for R/r, OR, 1.75 [95% CI, 1.30-2.36] for R/0; and OR, 1.50 [95% CI, 1.02-2.20] for r/r with P values ranging from <.001 to .04 when adjusted for actinic skin damage on the hands)., Conclusions and Relevance: Carriers of MC1R variants were at increased melanoma risk independent of their sun exposure. Further studies are required to elucidate the causes of melanoma development in these individuals.

The last 20 years of advancement in sequencing technologies have led to sequencing thousands of microbial genomes, creating mountains of genetic data. While efficiency in generating the data improves almost daily, applying meaningful relationships between taxonomic and genetic entities on this scale requires a structured and integrative approach. Currently, knowledge is distributed across a fragmented landscape of resources from government-funded institutions such as National Center for Biotechnology Information (NCBI) and UniProt to topic-focused databases like the ODB3 database of prokaryotic operons, to the supplemental table of a primary publication. A major drawback to large scale, expert-curated databases is the expense of maintaining and extending them over time. No entity apart from a major institution with stable long-term funding can consider this, and their scope is limited considering the magnitude of microbial data being generated daily. Wikidata is an openly editable, semantic web compatible framework for knowledge representation. It is a project of the Wikimedia Foundation and offers knowledge integration capabilities ideally suited to the challenge of representing the exploding body of information about microbial genomics. We are developing a microbial specific data model, based on Wikidata's semantic web compatibility, which represents bacterial species, strains and the gene and gene products that define them. Currently, we have loaded 43,694 gene and 37,966 protein items for 21 species of bacteria, including the human pathogenic bacteriaChlamydia trachomatis.Using this pathogen as an example, we explore complex interactions between the pathogen, its host, associated genes, other microbes, disease and drugs using the Wikidata SPARQL endpoint. In our next phase of development, we will add another 99 bacterial genomes and their gene and gene products, totaling ∼900,000 additional entities. This aggregation of knowledge will be a platform for community-driven collaboration, allowing the networking of microbial genetic data through the sharing of knowledge by both the data and domain expert., (© The Author(s) 2016. Published by Oxford University Press.)

Open biological data are distributed over many resources making them challenging to integrate, to update and to disseminate quickly. Wikidata is a growing, open community database which can serve this purpose and also provides tight integration with Wikipedia. In order to improve the state of biological data, facilitate data management and dissemination, we imported all human and mouse genes, and all human and mouse proteins into Wikidata. In total, 59,721 human genes and 73,355 mouse genes have been imported from NCBI and 27,306 human proteins and 16,728 mouse proteins have been imported from the Swissprot subset of UniProt. As Wikidata is open and can be edited by anybody, our corpus of imported data serves as the starting point for integration of further data by scientists, the Wikidata community and citizen scientists alike. The first use case for these data is to populate Wikipedia Gene Wiki infoboxes directly from Wikidata with the data integrated above. This enables immediate updates of the Gene Wiki infoboxes as soon as the data in Wikidata are modified. Although Gene Wiki pages are currently only on the English language version of Wikipedia, the multilingual nature of Wikidata allows for usage of the data we imported in all 280 different language Wikipedias. Apart from the Gene Wiki infobox use case, a SPARQL endpoint and exporting functionality to several standard formats (e.g. JSON, XML) enable use of the data by scientists. In summary, we created a fully open and extensible data resource for human and mouse molecular biology and biochemistry data. This resource enriches all the Wikipedias with structured information and serves as a new linking hub for the biological semantic web. Database URL: https://www.wikidata.org/., (© The Author(s) 2016. Published by Oxford University Press.)

CDKN2A is the most prominent familial melanoma gene, with mutations occurring in up to 40% of the families. Numerous mutations in the gene are known, several of them representing regional founder mutations. We sought to determine, for the first time, germline mutations in CDKN2A in Austria to identify novel mutations. In total, 700 individuals (136 patients with a positive family history and 164 with at least two primary melanomas as the high-risk groups; 200 with single primary melanomas; and 200 healthy individuals as the control groups) were Sanger sequenced for CDKN2A exon 1α, 1β, and 2. The 136 patients with affected relatives were also sequenced for CDK4 exon 2. We found the disease-associated mutations p.R24P (8×), p.N71T (1×), p.G101W (1×), and p.V126D (1×) in the group with affected relatives and p.R24P (2×) in the group with several primary melanomas. Furthermore, we discovered four mutations of unknown significance, two of which were novel: p.A34V and c.151-4 G>C, respectively. Computational effect prediction suggested p.A34V as conferring a high risk for melanoma, whereas c.151-4 G>C, although being predicted as a splice site mutation by MutationTaster, could not functionally be confirmed to alter splicing. Moreover, computational effect prediction confirmed accumulation of high-penetrance mutations in high-risk groups, whereas mutations of unknown significance were distributed across all groups. p.R24P is the most common high-risk mutation in Austria. In addition, we discovered two new mutations in Austrian melanoma patients, p.A34V and c.151-4 G>C, respectively.

According to the prevailing multistep model of melanoma development, oncogenic BRAF or NRAS mutations are crucial initial events in melanoma development. It is not known whether melanocytic nevi that are found in association with a melanoma are more likely to carry BRAF or NRAS mutations than uninvolved nevi. By laser microdissection we were able to selectively dissect and genotype cells either from the nevus or from the melanoma part of 46 melanomas that developed in association with a nevus. In 25 cases we also genotyped a control nevus of the same patients. Available tissue was also immunostained using the BRAF(V600E)-mutation specific antibody VE1. The BRAF(V600E) mutation was found in 63.0% of melanomas, 65.2% of associated nevi and 50.0% of control nevi. No significant differences in the distribution of BRAF or NRAS mutations could be found between melanoma and associated nevi or between melanoma associated nevi and control nevi. In concordant cases immunohistochemistry showed a higher expression (intensity of immunohistochemistry) of the mutated BRAF(V600E)-protein in melanomas compared to their associated nevi. In this series the presence of a BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant transformation. Our findings do not support the current traditional model of stepwise tumor progression.

Forkhead box protein 3 (Foxp3) is indispensable for the development of CD4(+)CD25(+) regulatory T cells (Tregs). Here we analyzed three prominent evolutionary conserved regions (ECRs) upstream of the transcription start site of the human FOXP3 gene. We show that ECR2 and ECR3 fragments derived from positions -1.3 to -2.0 kb and -5.0 to -6.0 kb, respectively, display basal transcriptional activity. Reporter constructs derived from ECR1, located between -0.6 and +0.23 kb and thus the most proximal ECR in respect of transcription initiation, remained almost inactive. However, ECR1 was transactivated by the NF-kappaB subunit p65 in HEK 293 cells. In Jurkat and primary T cells, in addition to p65, a second stimulus delivered by either T-cell receptor stimulation or addition of PMA was needed. Co-expression of I kappaB alpha inhibited p65-mediated FOXP3 proximal promoter transactivation, and the NF-kappaB inhibitor curcumin reduced Foxp3 neoexpression in IL-2/CD3/CD28/TGF-beta stimulated PBMCs. Moreover, proximal FOXP3 promoter transactivation was inhibited by Foxp3 and the SP transcription factor family member SP3. Thus, the human proximal FOXP3 promoter is controlled by activation through the TCR involving PKC and the NF-kappaB subunit p65 and by inhibition through a negative feedback loop and SP3., ((c) 2010 Elsevier Ltd. All rights reserved.)

This study examines whether participating in governmental decisions influences taxpayers' cooperation. The results of experiment 1 show that participants tend to contribute more when they can vote on different rules for a public good game. Experiment 2 reveals that tax payments are lowest in a tax simulation when participants benefit from tax payments and can not vote. However, when the participants did not benefit from tax payments, voting had no impact and cooperation was about the same as when participants benefited and could vote. Furthermore, voting increases procedural fairness and trust mediates the effect of procedural fairness on tax payments.