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We examined more than 97,000 families from four neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents contributing to neurodevelopmental disease risk in children. We identified within- and cross-disorder correlations between six phenotypes in parents and children, such as obsessive-compulsive disorder (R = 0.32–0.38, p < 10−126). We also found that measures of sub-clinical autism features in parents are associated with several autism severity measures in children, including biparental mean Social Responsiveness Scale scores and proband Repetitive Behaviors Scale scores (regression coefficient = 0.14, p = 3.38 × 10−4). We further describe patterns of phenotypic similarity between spouses, where spouses show correlations for six neurological and psychiatric phenotypes, including a within-disorder correlation for depression (R = 0.24–0.68, p < 0.001) and a cross-disorder correlation between anxiety and bipolar disorder (R = 0.09–0.22, p < 10−92). Using a simulated population, we also found that assortative mating can lead to increases in disease liability over generations and the appearance of "genetic anticipation" in families carrying rare variants. We identified several families in a neurodevelopmental disease cohort where the proband inherited multiple rare variants in disease-associated genes from each of their affected parents. We further identified parental relatedness as a risk factor for neurodevelopmental disorders through its inverse relationship with variant pathogenicity and propose that parental relatedness modulates disease risk by increasing genome-wide homozygosity in children (R = 0.05–0.26, p < 0.05). Our results highlight the utility of assessing parent phenotypes and genotypes toward predicting features in children who carry rare variably expressive variants and implicate assortative mating as a risk factor for increased disease severity in these families. [Display omitted] Many rare genetic variants are variably expressive, conferring risk for a range of clinical features with incomplete penetrance. We implicate assortative mating as a risk factor for disease in families carrying these variants by increasing genetic disease liability over generations, leading to the "genetic anticipation" observed in these families. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that individual variants do not sufficiently explain the variable expressivity of phenotypes observed in complex disorders. For example, the 16p12.1 deletion is associated with developmental delay and neuropsychiatric features in affected individuals, but is inherited in > 90% of cases from a mildly-affected parent. While children with the deletion are more likely to carry additional "second-hit" variants than their parents, the mechanisms for how these variants contribute to phenotypic variability are unknown. Methods: We performed detailed clinical assessments, whole-genome sequencing, and RNA sequencing of lymphoblastoid cell lines for 32 individuals in five large families with multiple members carrying the 16p12.1 deletion. We identified contributions of the 16p12.1 deletion and "second-hit" variants towards a range of expression changes in deletion carriers and their family members, including differential expression, outlier expression, alternative splicing, allele-specific expression, and expression quantitative trait loci analyses. Results: We found that the deletion dysregulates multiple autism and brain development genes such as FOXP1, ANK3, and MEF2. Carrier children also showed an average of 5323 gene expression changes compared with one or both parents, which matched with 33/39 observed developmental phenotypes. We identified significant enrichments for 13/25 classes of "second-hit" variants in genes with expression changes, where 4/25 variant classes were only enriched when inherited from the noncarrier parent, including loss-of-function SNVs and large duplications. In 11 instances, including for ZEB2 and SYNJ1, gene expression was synergistically altered by both the deletion and inherited "second-hits" in carrier children. Finally, brain-specific interaction network analysis showed strong connectivity between genes carrying "second-hits" and genes with transcriptome alterations in deletion carriers. Conclusions: Our results suggest a potential mechanism for how "second-hit" variants modulate expressivity of complex disorders such as the 16p12.1 deletion through transcriptomic perturbation of gene networks important for early development. Our work further shows that family-based assessments of transcriptome data are highly relevant towards understanding the genetic mechanisms associated with complex disorders. [ABSTRACT FROM AUTHOR]

Cybersecurity groups navigate complex, challenging environments in their mission to protect their organizations. They experience uncertainty from adaptive threats from external attackers and unpredictable stakeholders. Under such volatility, business groups operate best when they are psychologically empowered. Recognizing the potential for empowerment to reduce organizational risk, we sought to learn how cybersecurity groups come to be (dis)empowered and how this (dis)empowerment is sustained. Instead of the conventional view of the empowerment process as designed, we advance an emergent view of the empowerment process. We abductively surface this process from our case analyses of 15 U.S.organizations. We offer three insights: First, organizations with empowered cybersecurity groups enjoy an enhanced level of protection from breaches. Second, we highlight generative rules through which groups become empowered—via their bridging initiatives that co-opt stakeholders into security behaviors and stakeholder responsiveness to bridging, rather than unilaterally applied buffering initiatives. Third, we highlight reinforcing rules through which empowered states persist—via the group’s ability to safeguard organizational information assets, thereby ensuring cybersecurity group viability, continued bridging, and motivated stakeholder responsiveness. For practitioners, our study underscores the interdependence between cybersecurity groups and their stakeholders in securing an organization and posits processes for empowering cybersecurity groups. [ABSTRACT FROM AUTHOR]

While rare pathogenic copy-number variants (CNVs) are associated with both neuronal and non-neuronal phenotypes, functional studies evaluating these regions have focused on the molecular basis of neuronal defects. We report a systematic functional analysis of non-neuronal defects for homologs of 59 genes within ten pathogenic CNVs and 20 neurodevelopmental genes in Drosophila melanogaster. Using wing-specific knockdown of 136 RNA interference lines, we identified qualitative and quantitative phenotypes in 72/79 homologs, including 21 lines with severe wing defects and six lines with lethality. In fact, we found that 10/31 homologs of CNV genes also showed complete or partial lethality at larval or pupal stages with ubiquitous knockdown. Comparisons between eye and wing-specific knockdown of 37/45 homologs showed both neuronal and non-neuronal defects, but with no correlation in the severity of defects. We further observed disruptions in cell proliferation and apoptosis in larval wing discs for 23/27 homologs, and altered Wnt, Hedgehog and Notch signaling for 9/14 homologs, including AATF/Aatf, PPP4C/Pp4-19C, and KIF11/Klp61F. These findings were further supported by tissue-specific differences in expression patterns of human CNV genes, as well as connectivity of CNV genes to signaling pathway genes in brain, heart and kidney-specific networks. Our findings suggest that multiple genes within each CNV differentially affect both global and tissue-specific developmental processes within conserved pathways, and that their roles are not restricted to neuronal functions. Author summary: Rare copy-number variants (CNVs), or large deletions and duplications in the genome, are associated with both neuronal and non-neuronal clinical features. Previous functional studies for these disorders have primarily focused on understanding the cellular mechanisms for neurological and behavioral phenotypes. To understand how genes within these CNVs contribute to developmental defects in non-neuronal tissues, we assessed 79 homologs of CNV and known neurodevelopmental genes in Drosophila models. We found that most homologs showed developmental defects when knocked down in the adult fly wing, ranging from mild size changes to severe wrinkled wings or lethality. Although a majority of tested homologs showed defects when knocked down specifically in wings or eyes, we found no correlation in the severity of the observed defects in these two tissues. A subset of the homologs showed disruptions in cellular processes in the developing fly wing, including alterations in cell proliferation, apoptosis, and cellular signaling pathways. Furthermore, human CNV genes also showed differences in gene expression patterns and interactions with signaling pathway genes across multiple human tissues. Our findings suggest that genes within CNV disorders affect global developmental processes in both neuronal and non-neuronal tissues. [ABSTRACT FROM AUTHOR]

The 1.6 Mbp deletion on chromosome 3q29 is associated with a range of neurodevelopmental disorders, including schizophrenia, autism, microcephaly, and intellectual disability. Despite its importance towards neurodevelopment, the role of individual genes, genetic interactions, and disrupted biological mechanisms underlying the deletion have not been thoroughly characterized. Here, we used quantitative methods to assay Drosophila melanogaster and Xenopus laevis models with tissue-specific individual and pairwise knockdown of 14 homologs of genes within the 3q29 region. We identified developmental, cellular, and neuronal phenotypes for multiple homologs of 3q29 genes, potentially due to altered apoptosis and cell cycle mechanisms during development. Using the fly eye, we screened for 314 pairwise knockdowns of homologs of 3q29 genes and identified 44 interactions between pairs of homologs and 34 interactions with other neurodevelopmental genes. Interestingly, NCBP2 homologs in Drosophila (Cbp20) and X. laevis (ncbp2) enhanced the phenotypes of homologs of the other 3q29 genes, leading to significant increases in apoptosis that disrupted cellular organization and brain morphology. These cellular and neuronal defects were rescued with overexpression of the apoptosis inhibitors Diap1 and xiap in both models, suggesting that apoptosis is one of several potential biological mechanisms disrupted by the deletion. NCBP2 was also highly connected to other 3q29 genes in a human brain-specific interaction network, providing support for the relevance of our results towards the human deletion. Overall, our study suggests that NCBP2-mediated genetic interactions within the 3q29 region disrupt apoptosis and cell cycle mechanisms during development. Author summary: Rare copy-number variants, or large deletions and duplications in the genome, are associated with a wide range of neurodevelopmental disorders. The 3q29 deletion confers an increased risk for schizophrenia, autism, and microcephaly. To understand the conserved biological mechanisms that are disrupted by this deletion, we systematically tested 14 individual homologs and 314 pairwise interactions of 3q29 genes for neuronal, cellular, and developmental phenotypes in Drosophila melanogaster and Xenopus laevis models. We found that multiple homologs of genes within the deletion region contribute towards developmental defects, such as larval lethality and disrupted cellular organization. Interestingly, we found that NCBP2 acts as a key modifier gene within the region, enhancing the developmental phenotypes of each of the homologs for other 3q29 genes and leading to disruptions in apoptosis and cell cycle pathways. Our results suggest that multiple genes within the 3q29 region interact with each other through shared mechanisms and jointly contribute to neurodevelopmental defects. [ABSTRACT FROM AUTHOR]

Protein phase transitions (PPTs) from the soluble state to a dense liquid phase (forming droplets via liquid-liquid phase separation) or to solid aggregates (such as amyloids) play key roles in pathological processes associated with age-related diseases such as Alzheimer's disease. Several computational frameworks are capable of separately predicting the formation of droplets or amyloid aggregates based on protein sequences, yet none have tackled the prediction of both within a unified framework. Recently, large language models (LLMs) have exhibited great success in protein structure prediction; however, they have not yet been used for PPTs. Here, we fine-tune a LLM for predicting PPTs and demonstrate its usage in evaluating how sequence variants affect PPTs, an operation useful for protein design. In addition, we show its superior performance compared to suitable classical benchmarks. Due to the "black-box" nature of the LLM, we also employ a classical random forest model along with biophysical features to facilitate interpretation. Finally, focusing on Alzheimer's disease-related proteins, we demonstrate that greater aggregation is associated with reduced gene expression in Alzheimer's disease, suggesting a natural defense mechanism. [ABSTRACT FROM AUTHOR]

This article critically reviews the arguments for and against the view that 1 Thess. 2.13-16 is a post-Pauline interpolation. It starts with the four arguments that are forwarded to promote the view that it is an interpolation: form-critical/literary, grammatical/syntactical, historical, and theological. After this, a briefer second section outlines the four arguments defending the authenticity of the verses: textual, contextual, traditional, and rhetorical. [ABSTRACT FROM AUTHOR]

This article argues that the unique element of the semantic domain of ἀπείθεια, ἀπειθέω, and ἀπειθής is the cognitive category "unpersuaded." Consequently, the accepted gloss "disobedience" should not be the default. After reviewing the definitions in the standard lexicons, I argue, on the basis of word combinations and lexical choice, that in the New Testament the ἀπείθ- word group should have as its primary definition "being unpersuaded." This proposal is then tested by examining every New Testament occurrence of members of the word group. [ABSTRACT FROM AUTHOR]

Variably expressive copy-number variants (CNVs) are characterized by extensive phenotypic heterogeneity of neuropsychiatric phenotypes. Approaches to identify single causative genes for these phenotypes within each CNV have not been successful. Here, we posit using multiple lines of evidence, including pathogenicity metrics, functional assays of model organisms, and gene expression data, that multiple genes within each CNV region are likely responsible for the observed phenotypes. We propose that candidate genes within each region likely interact with each other through shared pathways to modulate the individual gene phenotypes, emphasizing the genetic complexity of CNV-associated neuropsychiatric features. [ABSTRACT FROM AUTHOR]

The 22q11.2 deletion syndrome (22q11DS), the most common survivable human genetic deletion disorder, is caused by a hemizygous deletion of 30–40 contiguous genes on chromosome 22, many of which have not been well characterized. Clinical features seen in patients with this deletion, including intellectual disability, are not completely penetrant and vary in severity between patients, suggesting the involvement of variants elsewhere in the genome in the manifestation of the phenotype. Given that it is a relatively rare disorder (1/2000-6000 in humans), limited research has shed light into the contribution of these second-site variants to the developmental pathogenesis that underlies 22q11DS. As CNVs throughout the genome might constitute such a genetic risk factor for variability in the 22q11DS phenotypes such as intellectual disability, we sought to determine if the overall burden of rare CNVs in the genetic background influenced the phenotypic variability. We analyzed CNV and clinical data from 66 individuals with 22q11DS, and found that 77% (51/66) of individuals with the 22q11DS also carry additional rare CNVs (<0.1% frequency). We observed several trends between CNV burden and phenotype, including that the burden of large rare CNVs (>200 Kb in size) was significantly higher in 22q11DS individuals with intellectual disability than with normal IQ. Our analysis shows that rare CNVs may contribute to intellectual disability 22q11DS, and further analysis on larger 22q11DS cohorts should be performed to confirm this correlation. [ABSTRACT FROM AUTHOR]

Renewable production of hydrocarbons is being pursued as a petroleum‐independent source of commodity chemicals and replacement for biofuels. The bacterial biosynthesis of long‐chain olefins represents one such platform. The process is initiated by OleA catalyzing the condensation of two fatty acyl‐coenzyme A substrates to form a β‐keto acid. Here, the mechanistic role of the conserved His285 is investigated through mutagenesis, activity assays, and X‐ray crystallography. Our data demonstrate that His285 is required for product formation, influences the thiolase nucleophile Cys143 and the acyl‐enzyme intermediate before and after transesterification, and orchestrates substrate coordination as a defining component of an oxyanion hole. As a consequence, His285 plays a key role in enabling a mechanistic strategy in OleA that is distinct from other thiolases. [ABSTRACT FROM AUTHOR]

This paper describes a novel method for extended expansion in a rotary combustion engine running ordinary gasoline. The engine consists of a toroidal-shaped piston that rotates around a drum to expand and evacuate the hot gas. There are several problems with today’s internal combustion (IC) engines. Current IC engines do not always have the necessary internal volume to extract the maximum work possible, and since the whole process of compression, combustion, and expansion happen within the same space, excess heat builds up and increases emissions of nitric oxides and nitrogen dioxide. The proposed solution is to redesign the IC engine in order to supply greater expansion ratio by separating the compression and expansion processes. With the concept rotary engine, extending the expansion process showed improvements in the thermal and fuel efficiencies. Using a stroke length between 20 and 25 cm with a compression ratio of 10:1 produced the most efficient results with an efficiency range between 32 and 35%. [ABSTRACT FROM AUTHOR]

In the interest of decreasing dependence on fossil fuels, microbial hydrocarbon biosynthesis pathways are being studied for renewable, tailored production of specialty chemicals and biofuels. One candidate is long-chain olefin biosynthesis, a widespread bacterial pathway that produces waxy hydrocarbons. Found in three- and four-gene clusters, oleABCD encodes the enzymes necessary to produce cis-olefins that differ by alkyl chain length, degree of unsaturation, and alkyl chain branching. The first enzyme in the pathway, OleA, catalyzes the Claisen condensation of two fatty acyl-coenzyme A (CoA) molecules to form a β-keto acid. In this report, the mechanistic role of Xanthomonas campestris OleA Glu117 is investigated through mutant enzymes. Crystal structures were determined for each mutant as well as their complex with the inhibitor cerulenin. Complemented by substrate modeling, these structures suggest that Glu117 aids in substrate positioning for productive carbon-carbon bond formation. Analysis of acyl-CoA substrate hydrolysis shows diminished activity in all mutants. When the active site lacks an acidic residue in the 117 position, OleA cannot form condensed product, demonstrating that Glu117 has a critical role upstream of the essential condensation reaction. Profiling of pH dependence shows that the apparent pKa for Glu117 is affected by mutagenesis. Taken together, we propose that Glu117 is the general base needed to prime condensation via deprotonation of the second, non-covalently bound substrate during turnover. This is the first example of a member of the thiolase superfamily of condensing enzymes to contain an active site base originating from the second monomer of the dimer. [ABSTRACT FROM AUTHOR]

A mild, inexpensive, and operationally simple pyrazole halogenation method utilizing Oxone and sodium halide salts is reported. This work documents 17 examples of alkyl, aryl, allyl, and benzyl substituted 4-chloro and 4-bromopyrazoles, obtained in up to 93% yield. Reactions are performed in water under ambient conditions and generation of organic byproducts is avoided. [ABSTRACT FROM AUTHOR]

Online product reviews are influential sources of information that some companies attempt to manipulate by compensating reviewers for favorable comments. The U.S. Federal Trade Commission has mandated disclosure of reviewer compensation to address this potential conflict of interest, but the effect of such disclosures on consumer attitudes is unknown. By extending prominence–interpretation theory, this work reconciles conflicting empirical results by introducing two novel elements of prominence (i.e., proximity and embedding) and demonstrating the effect disclosures have on reviewer credibility through two experiments (N = 750). The effects of social consensus and prior warnings on how consumers interpret disclosures are also studied. Using a general population sample (N = 346), Experiment 1 demonstrated that proximity to review increased disclosure prominence while embedding the disclosure in the review decreased disclosure prominence. More prominent disclosures reduced reviewer credibility, but less prominent disclosures had no effect. Using a student sample (N = 404), Experiment 2 demonstrated that disclosure interpretation is affected by prior warnings about conflicts of interest and the consensus of other reviews. When there was disagreement between reviews and prior warnings were provided, disclosures reduced reviewer credibility, but when there was a consensus of positive reviews or no consensus information was provided, disclosures had no effect. Our studies show that both prominence and interpretation are important to consider in understanding the effects of disclosure statements. However, variables associated with prominence produced the most robust results. The theoretical implications of these results and the practical implications for consumers, companies, and policymakers are discussed. [ABSTRACT FROM AUTHOR]

Phylogenetically diverse microbes that produce long chain, olefinic hydrocarbons have received much attention as possible sources of renewable energy biocatalysts. One enzyme that is critical for this process is OleA, a thiolase superfamily enzyme that condenses two fatty acyl-CoA substrates to produce a-ketoacid product and initiates the biosynthesis of long chain olefins in bacteria. Thiolases typically utilize a ping-pong mechanism centered on an active site cysteine residue. Reaction with the first substrate produces a covalent cysteine-thioester tethered acyl group that is transferred to the second substrate through formation of a carbon-carbon bond. Although the basics of thiolase chemistry are precedented, the mechanism by which OleA accommodates two substrates with extended carbon chains and a coenzyme moiety--unusual for a thiolase-- are unknown. Gaining insights into this process could enable manipulation of the system for large scale olefin production with hydrocarbon chains lengths equivalent to those of fossil fuels. In this study, mutagenesis of the active site cysteine in Xanthomonas campestris OleA (Cys143) enabled trapping of two catalytically relevant species in crystals. In the resulting structures, long chain alkyl groups (C12 and C14) and phosphopantetheinate define three substrate channels in a T-shaped configuration, explaining how OleA coordinates its two substrates and product. The C143A OleA co-crystal structure possesses a single bound acyl-CoA representing the Michaelis complex with the first substrate, whereas the C143S co-crystal structure contains both acyl-CoA and fatty acid, defining how a second substrate binds to the acyl-enzyme intermediate. An active site glutamate (Gluβ117) is positioned to deprotonate bound acyl-CoA and initiate carbon-carbon bond formation. [ABSTRACT FROM AUTHOR]

This article critically surveys the rules that have been followed for ascertaining the subject of ... and explores the implications of the findings for interpreting John's Gospel and First Letter. Following a review of the positions of Lane C. McGaughy, D. A. Carson, and Daniel B. Wallace, I argue that the subject of ... in John 20:31, 1 John 2:22, 4:15, 5:1, and 5:5 is the articular noun. I discuss the implication of the syntax for the historical setting, purpose, and audience of the texts. I argue that the five clauses answer the Jewish question about the identity of "the Christ, the Son of God." [ABSTRACT FROM AUTHOR]

An experiment examined how veracity, modality, and experimenter sanctioning of deception influenced credibility assessments made by professionals who conducted interviews face-to-face (FtF) or by video conference (VC). Participants (N = 243) completed a trivia game with a confederate who encouraged cheating. Some lies were sanctioned by the experimenter and others were unsanctioned. The professional interviewers educed a high number of confessions in the sanctioned (58%) and unsanctioned (79%) lie conditions. Overall accuracy of the interviewers ranged from 45% to 67%. Interviewers were more accurate when judging veracity FtF than in VC. Those in the deceptive VC conditions (especially sanctioned liars) were rated by interviewers as more dominant, involved, relaxed, and active than those in the FtF condition, revealing that modality affected deceivers’ demeanor. [ABSTRACT FROM PUBLISHER]

This article argues that the description of Noah as the eighth proclaimer of righteousness can be understood as an explicit reference to the number of generations from Enosh, which is the time when men first began to proclaim the Lord’s name (Gen. 4.26). After critically reviewing three interpretations of ‘eighth’ (ὄγδοος) in 2 Pet. 2.5, and the suggested justifications for the description of Noah as a proclaimer of righteousness, the article examines Gen. 4.26 and the description of people proclaiming the Lord’s name for the first time. It suggests that Noah is the eighth generation from Enosh to proclaim the Lord’s name. [ABSTRACT FROM PUBLISHER]

Growth characteristics surrounding halophilic archaeal organisms are extremely limited in the scientific literature, with studies tending toward observing changes in cellular generation times under growth conditions limited to changes in temperature and sodium chloride concentrations. Currently, knowledge of the ionic stress experienced by haloarchaeal species through an excess or depletion of other required ions is lacking at best. The halophilic archaeon, Haloarcula marismortui, was analyzed under extreme ionic stress conditions with a specific focus on induced potassium ion stress using growth curves and analysis of the intracellular ion concentrations. Generation times were determined under potassium chloride concentrations ranging from 8 to 720 mM, and also in the presence of the alternative monovalent cations of lithium, rubidium, and cesium under limiting potassium conditions. Intracellular ion concentrations, as determined by inductively coupled mass spectrometry (ICP-MS), indicate a minimum intracellular total ion requirement of 1.13 M while tolerating up to 2.43 M intracellular concentrations. The presence of intracellular rubidium and cesium indicates that monovalent ion transport is important for energy production. Comparison of eight archaeal genomes indicates an increased diversity of potassium transport complex subunits in the halophilic organisms. Analysis of the generation times, intracellular concentrations and genome survey shows Har. marismortui exhibits an ability to cope with monovalent cation concentration changes in its native environment and provides insight into the organisms ion transport capability and specificity. [ABSTRACT FROM AUTHOR]

A large percentage of single-vehicle automobile crashes involve a situation called run-off-road (ROR) where the vehicle leaves the roadway and travels on the surfaces adjacent to the road. Present solutions such as roadway infrastructure modifications and vehicle safety systems have helped to mitigate some ROR events but remain limited in their approach. A complete solution must also directly address the primary factor contributing to ROR crashes, which is driver performance errors. In this paper, four vehicle safety control systems, based on sliding (SL) control, linear quadratic (LQ), state flow, and classical theories, were developed to autonomously recover a vehicle from ROR without driver intervention. The vehicle response was simulated for each controller under a variety of common road departure and return scenarios. The results showed that the LQ and SL control methodologies outperformed the other controllers in terms of overall stability. However, the LQ controller was the only design to safely recover the vehicle in all of the simulation conditions examined. On average, it performed the recovery almost 50% faster and with 40% less lateral error than the SL controller at the expense of higher yaw rates. [ABSTRACT FROM PUBLISHER]

With the proliferating use of information and communication technologies (ICTs), deception is increasingly being perpetrated through technology-mediated channels. Deception can result in substantial costs to individuals and organizations. However, the mechanisms by which ICT capabilities influence the detection of deception remain largely unexplored. This paper discusses how specific ICT capabilities can be leveraged to detect deception before, during and after the exchange of deceptive messages. We develop an integrated theoretical model and detail propositions grouped under two broad media capabilities-transmissibility and extensibility-derived from Saussurean structuralist theory that views ideas and artifacts in terms of binary opposition. Further, our theoretical model includes two key contingencies that affect deception detection-the overtness of deception and the skill disparity between the deceiver and the receiver. Finally, we conclude by discussing the implications of our theory for practice and offer suggestions for future research. [ABSTRACT FROM AUTHOR]

Distinct neurodevelopmental disorders have a common genetic etiology that explains the high degree of comorbidity among these disorders. A recent study sought to identify copy number variants across five neurodevelopmental disorders, and detected an enrichment for chromosome 9p24.3 duplication encompassing DOCK8 and KANK1 in affected individuals. Such large-scale studies will help uncover additional causative and modifier loci within common pathways, which will enable the development of therapeutic targets for the treatment of multiple disorders. [ABSTRACT FROM AUTHOR]

Researchers have overwhelmingly concluded that substantial benefits can be achieved by organizations increasing the level of interactivity on their websites. However, interactivity, with its emphasis on facilitating visitors' unconstrained exchanges and control over website content, may undermine the communicative purpose of an organization's website. Taking a perspective based on the duality of goals, we argue that interactivity may not be desirable for some supporting organizations. We tested these ideas by examining the features of interactivity on 105 websites that are supported by national and international groups. Some of the websites are supported by ideological groups that have a strong interest in controlling their messages and clearly articulating their ideology to the public. A subset of the ideological groups also sanctions acts of violence in support of their ideology. As predicted, we found substantial differences in the level of interactivity between the violent groups and other ideological and non-ideological groups, with the greatest disparity occurring in social media. We conclude that for violent groups the need for control over website content and representation outweighs the benefits of interactivity. Surprisingly, we found little difference between nonviolent ideological and non-ideological groups. Implications for theory and practice are discussed. [ABSTRACT FROM AUTHOR]

This paper examines how power differences and deception jointly influence interactional dominance, credibility, and the outcomes of decision-making. Two theories, interpersonal deception theory and dyadic power theory, were merged to produce hypotheses about the effects of power and deception. A 3 (power: unequal-high, unequal-low, equal) x 3 (deception: truth-truth, truthful with deceptive partner, deceptive with truthful partner) experiment (N = 120) was conducted in which participants were asked to make a series of mock hiring decisions. Actor-partner analyses revealed that participants in the deception condition reported a significant increase in perceptions of their own power whereas their truthful partners reported a significant decrease in perceptions of their own power. Further, interactional dominance fostered credibility and goal attainment (i.e., making the best hiring decision in the truthful condition and hiring a friend in the deceptive condition) for both truth-tellers and deceivers. [ABSTRACT FROM AUTHOR]

This article argues that the present tense-form (ἐρΧόμενον) used in the confession of 2 John 7 should be understood as parallel to the perfect tense-form (ἐληλυθότα) used in the confession of t John 4:2. After critically reviewing the five current ways the present tense-form is interpreted, the article outlines how recent research into verbal aspect indicates that the present and perfect tense-forms are closely related. Evidence of this relationship is then provided from 1 John allowing some conclusions to be drawn about the five current interpretive options. [ABSTRACT FROM AUTHOR]

Neural culture of human pluripotent stem cells is useful for neuroscience research, but the optimal feeding schedule for these in vitro systems is unclear. We evaluated the survival and neural differentiation profiles of human embryonic and induced pluripotent stem cells cultured with medium exchange schedules of five, six, or seven days weekly through two months of differentiation. No significant differences were seen in cell numbers or neural differentiation markers through this culture interval with either human pluripotent cell type. We conclude that there is unlikely to be an advantage of feeding more than five days weekly for this culture system. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of death and disability, and current treatments to limit tissue injury and improve recovery are limited. Cerebral infarction is accompanied by intense brain tissue inflammation involving many inflammatory cell types that may cause both negative and positive effects on outcomes. Many potential neuroprotective and neurorestorative treatments may affect, and be affected by, this inflammatory cell infiltration, so that accurate quantification of this tissue response is needed. We performed a systematic review of histological methods to quantify brain tissue inflammatory cell infiltration after cerebral infarction. We found reports of multiple techniques to quantify different inflammatory cell types. We found no direct comparison studies and conclude that more research is needed to optimize the assessment of this important stroke outcome. [ABSTRACT FROM AUTHOR]

This article outlines and reviews many of the proposals for the structure and argument of 1 John. The article has two elements: first, it groups together scholars who use similar techniques to divide 1 John into its parts and so discern a structure; second, it outlines the methods used to analyse the relationships between the constituent parts of the structure and in so doing evaluates many of the proposed understandings of the argument of 1 John. [ABSTRACT FROM PUBLISHER]

Accurate histological quantification of astrocytosis after cerebral infarction is needed as this process may affect, and be affected by, many potential restorative treatments under investigation. We performed a systematic review to determine the most reliable histological method reported for measurement of postinfarction astrocytosis. We found reports of multiple techniques to quantify various parameters of immunohistochemical staining for the astrocyte marker glial fibrillary acidic protein on photomicrographs with several software packages. We found no studies directly comparing techniques. We conclude that the reported methods seem reasonable, but the descriptions were often insufficiently detailed to allow for replication, and the lack of comparison data makes the best method unclear. Further research is needed to optimize the analysis of this important tissue outcome after cerebral infarction. [ABSTRACT FROM AUTHOR]

Background and purpose Periprosthetic fracture is a devastating complication of total knee replacement (TKR). Most published studies have not comprehensively assessed clinical and demographic predictors. We wanted to determine the incidence and predictors of postoperative periprosthetic fracture after primary and revision TKR. Patients and methods We used prospectively collected data in the Mayo Clinic Total Joint Registry on all patients who underwent primary or revision TKR at the Mayo Clinic, Rochester, from 1989 through 2008. We assessed incidence of postoperative periprosthetic fractures and modifiable (comorbidity, body mass index) and unmodifiable factors (age, sex, operative diagnosis, ASA class, previous cardiac disease, and previous thromboembolic disease) as predictors of postoperative periprosthetic fractures. We used multivariable-adjusted Cox regression analyses separately for primary and revision TKR. Results 12,914 patients underwent 17,633 primary TKRs and 3,286 patients underwent 4,090 revision TKRs during the period 1989-2008. 1.1% of patients (188/17,633) after primary TKR and 2.5% of patients (104/4,090) after revision TKR sustained a postoperative periprosthetic fracture on or after postoperative day 1. Older age was associated with lower risk of periprosthetic fractures after primary TKR (p < 0.001). Compared to ≤ 60 years, risk was lower for ages 61-70 years (hazard ratio (HR) = 0.5, 95% confidence interval (CI): 0.3-0.7)) and 71-80 years (HR = 0.6, CI: 0.4-0.8), but not for age > 80 years (HR = 0.9, CI: 0.5-1.6). In revision TKR cohort, a diagnosis of non-union (HR = 4.9, CI: 1.2-20), infection (HR = 2.9, CI: 1.3-6.4) or previous surgery with components removed (HR = 2.1, CI: 1.3-3.4) increased the risk of postoperative periprosthetic fracture, compared to a diagnosis of loosening/wear/osteolysis. Interpretation We identified significant risk factors for periprosthetic fracture after primary and revision TKR. Patients with these risk factors can be informed by their surgeons of increased risk of this uncommon, but serious complication of TKR. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of disability, and current treatments to improve recovery are limited. Part of the natural recovery process after brain injury is angiogenesis. The formation of new blood vessels around the infarct appears to be important for restoration of adequate perfusion to allow for healing of brain tissue. Many potential restorative treatments may affect, and be affected by, angiogenesis, so accurate quantification of this outcome is needed. We performed a systematic review of histological methods to quantify angiogenesis after cerebral infarction. We found reports of the use of a variety of histological and general and immunostaining techniques in conjunction with a variety of analysis methods. We found no direct comparison studies and concluded that more research is needed to optimize the assessment of this important stroke outcome. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of disability, and current treatments to improve recovery are limited. Part of the natural recovery process after brain injury is angiogenesis. The formation of new blood vessels around the infarct appears to be important for restoration of adequate perfusion to allow for healing of brain tissue. Many potential restorative treatments may affect, and be affected by, angiogenesis, so accurate quantification of this outcome is needed. We performed a systematic review of histological methods to quantify angiogenesis after cerebral infarction. We found reports of the use of a variety of histological and general and immunostaining techniques in conjunction with a variety of analysis methods. We found no direct comparison studies and concluded that more research is needed to optimize the assessment of this important stroke outcome. [ABSTRACT FROM AUTHOR]

In this paper we discuss the relationships among negotiations, integrative and distributive speech acts, and classification of negotiation outcome. Our findings present how using automated linguistic analysis can show the trajectory of negotiations towards convergence (resolution) or divergence (non-resolution) and how these trajectories accurately classify negotiation outcomes. Consequently, we present the results of our negotiation outcome classification study, in which we use a corpus of 20 transcripts of actual face-to-face negotiations to build and test two classification models. The first model uses language features and speech acts to place negotiation utterances onto an integrative and distributive scale. The second uses that scale to classify the negotiations themselves as successful or unsuccessful at the midpoint, three-quarters of the way through, and at the end of the negotiation. Classification accuracy rates were 80, 75, and 85 % respectively. [ABSTRACT FROM AUTHOR]

This article proposes a structure and argument for 1 John based on the locations of both the verb γράϕω and the vocative forms. It argues that 1 John has two parts: an extended introduction that orientates the reader to the themes of sin and love (1.1–2.11), and a body in which the historical situation is addressed (2.15–5.21). It divides 1 John into units based on vocabulary associated with each theme and then appeals to literary devices to verify each unit. The relationship between each unit is investigated in order to ascertain the structure. [ABSTRACT FROM AUTHOR]

This study proposed that criminal guilt interacts with dominance and interview question to affect linguistic properties during criminal interviews. A field experiment tested effects of criminal guilt, dominance, and question on linguistic properties of suspects’ responses using a 2 (criminal guilt: guilty/innocent) × 4 (question: Q1/Q2/Q3/Q4) mixed-model design with dominance as a covariate and question as a repeated factor. Analysis of linguistic properties from 37 criminal interviews indicated a hypothesized two-way interaction among dominance and guilt on immediacy and a three-way interaction among dominance, question, and guilt on complexity explored as part of the research question. Several other direct effects for dominance and question were noted. Implications, limitations, and future research directions are discussed. [ABSTRACT FROM PUBLISHER]

Increased global use of motorized vehicles has led to a higher number of automotive crashes involving human injuries and fatalities. Greater driver awareness through haptic feedback can provide vital information from the vehicle and surroundings to the driver while minimizing driver distraction. In this paper, steering wheel haptic feedback will be provided to increase the drivers' knowledge of the roadway and driving conditions. This increased knowledge should enable the driver to avoid obstacles presented in the roadway earlier than without any feedback. A high-fidelity customizable driving simulator was utilized to provide nine different levels of sinusoidal haptic feedback via the steering wheel. Mathematical models for the vehicle steering system, with adjustable controller gains, were developed to create torsional feedback. The testing included 25 human subjects ranging in age and driving experience. Driver preferences for feedback amplitude and frequency were gathered, whereas driver/vehicle performance was used as the measure of feedback effectiveness. The laboratory results demonstrate that haptic steering feedback improved driver performance as measured by a 62% reduction in obstacle hit rates, small reductions in peak steering wheel angle and peak vehicle yaw rate, as well as a nearly 10 m (32.8 ft) increase in reaction distance to the obstacles. The research contribution is the successful application of an advanced steering simulator with a steering control strategy to introduce supplemental haptic feedback to the driver through the steering system for roadway avoidance notification. [ABSTRACT FROM PUBLISHER]

Stroke is a leading cause of death and disability, leading to the development of various stroke models to test new treatments, most commonly in the rat. Human stroke trials focus on disability, related primarily to neurological deficits. To better model the clinical application of these treatments, many behavioral tests have been developed using the rat stroke model. We performed a systematic review of all the behavioral outcome measures used in published studies of human neural stem cell transplantation in rat stroke models. The reviewed tests include motor, sensory, cognitive, activity, and combination tests. For each test, we give a brief description, trace the origin of the test, and discuss test performance in the reviewed studies. We conclude that while many behavioral tests are available for this purpose, there does not appear to be consensus on an optimal testing strategy. [ABSTRACT FROM AUTHOR]

This article outlines an approach for automatically extracting behavioral indicators from video, audio, and text and explores the possibility of using those indicators to predict human-interpretable judgments of involvement, dominance, tension, and arousal. We utilized two-dimensional spatial inputs extracted from video, acoustic properties extracted from audio and verbal content transcribed from face-to-face interactions to construct a set of multimodal features. Multiple predictive models were created using the extracted features as predictors and human-coded perceptions of involvement, tenseness, and arousal as the criterion. These predicted perceptions were then used as independent variables in classifying truth and deception. Though the predicted values for perceptions performed comparably to human-coded perceptions in detecting deception, the results were not satisfying. Thus, the extracted multimodal features were used to predict deception directly. Classification accuracy was substantially higher than typical human deception detection performance. Through this research, we consider the feasibility and validity of the approach and identify how such an approach could contribute to the broader community. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder, intellectual disability, developmental disability, and epilepsy are characterized by abnormal brain development that may affect cognition, learning, behavior, and motor skills. High co-occurrence (comorbidity) of NDDs indicates a shared, underlying biological mechanism. The genetic heterogeneity and overlap observed in NDDs make it difficult to identify the genetic causes of specific clinical symptoms, such as seizures. Methods: We present a computational method, MAGI-S, to discover modules or groups of highly connected genes that together potentially perform a similar biological function. MAGI-S integrates protein-protein interaction and co-expression networks to form modules centered around the selection of a single "seed" gene, yielding modules consisting of genes that are highly co-expressed with the seed gene. We aim to dissect the epilepsy phenotype from a general NDD phenotype by providing MAGI-S with high confidence NDD seed genes with varying degrees of association with epilepsy, and we assess the enrichment of de novo mutation, NDD-associated genes, and relevant biological function of constructed modules. Results: The newly identified modules account for the increased rate of de novo non-synonymous mutations in autism, intellectual disability, developmental disability, and epilepsy, and enrichment of copy number variations (CNVs) in developmental disability. We also observed that modules seeded with genes strongly associated with epilepsy tend to have a higher association with epilepsy phenotypes than modules seeded at other neurodevelopmental disorder genes. Modules seeded with genes strongly associated with epilepsy (e.g., SCN1A, GABRA1, and KCNB1) are significantly associated with synaptic transmission, long-term potentiation, and calcium signaling pathways. On the other hand, modules found with seed genes that are not associated or weakly associated with epilepsy are mostly involved with RNA regulation and chromatin remodeling. Conclusions: In summary, our method identifies modules enriched with de novo non-synonymous mutations and can capture specific networks that underlie the epilepsy phenotype and display distinct enrichment in relevant biological processes. MAGI-S is available at https://github.com/jchow32/magi-s. [ABSTRACT FROM AUTHOR]

Many birds undertake long biannual voyages during the night. During these times of the year birds drastically reduce their amount of sleep, yet curiously perform as well on tests of physical and cognitive performance than during non-migrating times of the year. This inherent physiological protection disappears when birds are forced to stay awake at other times of the year; thus these protective changes are only associated with the nocturnal migratory state. The goal of the current study was to identify the physiological mechanisms that confer protection against the consequences of sleep loss while simultaneously allowing for the increased physical performance required for migration. We performed RNA-seq analyses of heart and liver collected from birds at different times of day under different migratory states and analyzed these data using differential expression, pathway analysis and WGCNA. We identified changes in gene expression networks implicating multiple systems and pathways. These pathways regulate many aspects of metabolism, immune function, wound repair, and protection of multiple organ systems. Consequently, the circannual program controlling the appearance of the migratory phenotype involves the complex regulation of diverse gene networks associated with the physical demands of migration. [ABSTRACT FROM AUTHOR]

While precision medicine applications of radiomics analysis are promising, differences in image acquisition can cause "batch effects" that reduce reproducibility and affect downstream predictive analyses. Harmonization methods such as ComBat have been developed to correct these effects, but evaluation methods for quantifying batch effects are inconsistent. In this study, we propose the use of the multivariate statistical test PERMANOVA and the Robust Effect Size Index (RESI) to better quantify and characterize batch effects in radiomics data. We evaluate these methods in both simulated and real radiomics features extracted from full-field digital mammography (FFDM) data. PERMANOVA demonstrated higher power than standard univariate statistical testing, and RESI was able to interpretably quantify the effect size of site at extremely large sample sizes. These methods show promise as more powerful and interpretable methods for the detection and quantification of batch effects in radiomics studies. [ABSTRACT FROM AUTHOR]

Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements' sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type-specific gene regulation in various types of glia and neurons. The elements' evolutionary history suggests that new regulatory information in the brain emerges primarily via smaller sequence mutations within conserved mammalian elements rather than entirely new human-or primate-specific sequences. However, primate-specific candidate elements, particularly those active during fetal brain development and in excitatory neurons and astrocytes, are implicated in the heritability of brain-related human traits. Additionally, we introduce PsychSCREEN, a web-based platform offering interactive visualization of PsychENCODE-generated genetic and epigenetic data from diverse brain cell types in individuals with psychiatric disorders and healthy controls. [ABSTRACT FROM AUTHOR]