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The paper brings another view on detecting the dead-point positions of an arbitrary planar pin-connected linkage by employing the duality principle of graph theory. It is first shown how the dead-point positions are derived through the interplay between the linkage and its dual determinate truss--the relation developed in the previous works by means of graph theory. At the next stage, the process is shown to be performed solely upon the linkage by employing a new variable, the dual of potential, termed face force. Since the mathematical .foundation of the presented method is discrete mathematics, the paper points to possible computerization of the method. Keywords: dead-point position, duality, graph theory, double-butterfly linkage, face force

Niue represents one of many important steppingstones facilitating the dispersal of marine organisms across the tropical Pacific Ocean. This study is part of a collaborative expedition involving National Geographic Pristine Seas, the government of Niue, Oceans 5, and the Pacific Community. We present the first survey documenting the species richness of foraminiferal communities in Niue and nearby Beveridge Reef and explore their significance for ecosystem integrity. A substantial portion (59%) of Niue's foraminiferal assemblages is Large Benthic Foraminifera (LBF), a symbiont-bearing group known as ecosystem engineers and indicators of coral reef regime shifts. LBF species reported here reflect the gradual decrease of tropical diversity from the Coral Triangle towards the central Pacific Ocean. Calcarinidae, an LBF family represented in this study by two species, is the easternmost ever recorded in published literature, and the biogeographical dispersal of this temperature-controlled group is of great importance to future global warming related studies. Foraminifera are an important component of beach development in Niue, with a close relationship between source and depositional zones. These essential ecological–sedimentary linkages highlight the importance of habitat conservation not only as a means to safeguard biodiversity, but also for its role in the island's physical framework.

Background During a period of intensified exercise (e.g. training/identification camps), often undertaken by competitive youth athletes, the maintenance of muscle function and peak performance can become challenging due to an accumulation of fatigue. The provision of post-exercise dairy protein in adults has been previously shown to accelerate recovery; however, its efficacy in youth athletes is currently unknown. Therefore, the purpose of this study was to examine the effects of increased dairy protein consumption with plain Greek yogurt (GY) on performance and recovery indices during an intensified soccer training camp in adolescent female soccer players. Methods Thirteen players (14.3 ± 1.3 years) participated in a randomized, double blinded, crossover design study where they received 3 servings/day of either GY (~115 kcal, 17 g protein, ~11.5 g carbohydrates) or an isoenergetic carbohydrate control (CHO, ~115 kcal, 0.04 g protein, ~28.6 g carbohydrates) during two 5-day soccer-specific training camps. Performance was assessed before and after each training camp. Fasted, morning, creatine kinase (CK), insulin-like growth factor-1 (IGF-1), C-reactive protein (CRP), interleukin 6 (IL6), interleukin 10 (IL10) and tumor necrosis factor-α (TNFα) were measured in plasma pre- and post-training. Results Training led to decrements in counter-movement jump (p = 0.01), broad jump (p = 0.04) and aerobic capacity (p = 0.006), with no effect of GY. A significant increase in anti-inflammatory cytokine IL10 was observed from pre- to post-training in GY (+26% [p = 0.008]) but not in CHO (p = 0.89). CRP and CK increased (+65% [p = 0.005] and +119% [p ≤ 0.001], respectively), while IGF-1 decreased (−34% [p ≤ 0.001]) from pre- to post-training with no difference between conditions. Conclusions These results demonstrate that consumption of GY did not offer any added recovery benefit with respect to measures of performance and in the attenuation of exercise-induced muscle damage above that achieved with energy-matched carbohydrate in this group of young female soccer players. However, regular consumption of GY may assist with the acute anti-inflammatory response during periods of intensified training in adolescent athletes.

Abstract In March 2020, an unusually intense storm system struck the Gulf of Aqaba‐Eilat, resulting in severe shoreline damage. This brief account examines post‐storm observations of inconsistent damage patterns and structural changes along a specific coastal stretch located at the south beach of Eilat. Certain sections of the coastline experienced direct impact from extreme waves on the south‐southeast‐facing shallow reef, resulting in areas where rocks were completely stripped of corals due to sediment backwash. Conversely, areas characterized by ridges and deep troughs saw the loss of branching corals and some massive colonies, while many small corals survived. A neighboring area with a well‐developed fringing reef suffered lesser damage. Between the severely affected shallow reef and the robust fringing reef lies an unconsolidated slope that migrated eastward by at least 2 m following the storm, incorporating numerous coral colonies dislodged by the event. We propose that this slope advances with each major storm occurrence, influencing the characteristics of nearby shores and coral reefs. This case demonstrates how storm events, in conjunction with geomorphology, have a cumulative and significant impact not only on the structure of coral communities but also on the fundamental shape of coral reefs themselves. As climate change amplifies the range, intensity, and frequency of storms, comprehending these processes becomes increasingly crucial.

Tissue-specific transcription factors (TFs) control the transcriptome through an association with noncoding regulatory regions (cistromes). Identifying the combination of TFs that dictate specific cell fate, their specific cistromes and examining their involvement in complex human traits remain a major challenge. Here, we focus on the retinal pigmented epithelium (RPE), an essential lineage for retinal development and function and the primary tissue affected in age-related macular degeneration (AMD), a leading cause of blindness. By combining mechanistic findings in stem-cell-derived human RPE, in vivo functional studies in mice and global transcriptomic and proteomic analyses, we revealed that the key developmental TFs LHX2 and OTX2 function together in transcriptional module containing LDB1 and SWI/SNF (BAF) to regulate the RPE transcriptome. Importantly, the intersection between the identified LHX2-OTX2 cistrome with published expression quantitative trait loci, ATAC-seq data from human RPE, and AMD genome-wide association study (GWAS) data, followed by functional validation using a reporter assay, revealed a causal genetic variant that affects AMD risk by altering TRPM1 expression in the RPE through modulation of LHX2 transcriptional activity on its promoter. Taken together, the reported cistrome of LHX2 and OTX2, the identified downstream genes and interacting co-factors reveal the RPE transcription module and uncover a causal regulatory risk single-nucleotide polymorphism (SNP) in the multifactorial common blinding disease AMD.

Abstract Background The dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development. It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. Subsequently, it becomes the definitive roof plate (RP) of the central nervous system. The RP, in turn, constitutes a patterning center for dorsal interneuron development. The factors underlying establishment of the definitive RP and its segregation from NC and dorsal interneurons are currently unknown. Results We performed a transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity, both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population. Conclusions Collectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC.

At the awakening of the 5G network, efforts of operators and vendors are being put in achieving understandable reliability of services in evolutionary network. The increasing users' requirements with regard to the received service jointly to the evolving networking environment have introduced many challenges to service reliability. If the network operators will be not able to offer required quality services even under changing conditions, the customers will lose quickly trustiness in those services. In this case, the current services will difficultly survive to the introduction of thousands of new services appearing with 5G network. How to maintain high quality services regardless of the variability of the underlying network is an interesting research issue for network operators. In this paper, we present a system for monitoring the quality of services offered by the network operators, as well as the quality of experience perceived by end customers. The system will be managed by the network operators, service providers and content providers at their premises. We tested the monitoring system in video on demand service.

Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

This study constitutes one of the first investigations aiming to examine the association between traumatic experiences within religious settings and symptoms of post-traumatic stress among religious lesbians, gays, and bisexuals. Furthermore, the study tested whether the anticipated positive link between those traumatic experiences and post-traumtic stress is influenced by a positive perception of God's image. The sample consisted of 146 Israeli Jewish lesbians, gays, and bisexuals who professed a belief in God or demonstrated religious inclinations either presently or in the past. They completed self-report measures via an online questionnaire, assessing traumatic experiences within religious settings, post-traumtic stress symptoms, and positive perceptions of God's image. The findings revealed a significant and robust positive connection between traumatic experiences within religious settings and post-traumtic stress. A positive perception of God's image exhibited a negative correlation with post-traumtic stress but did not moderate the relationship traumatic experiences within religious settings and symptoms of post-traumatic stress. These findings highlight the significance of traumatic experiences within religious settings as a distinct potential risk factor of post-traumtic stress among lesbians, gays, and bisexuals and underscore the necessity of enhancing awareness among mental health professionals, religious leaders, and legal entities regarding the detrimental effects of those expereinces.

This study examines the effect on time preferences and the purchase of insurance by persons closely acquainted with someone who was in danger of physical injury (trauma) during Israel's military operation in the Gaza Strip in 2014. To this end, I use panel data to track the same individuals before and after the trauma. My results reveal that experiencing trauma increases individuals' purchases of insurance, and in particular supplementary health and long-term care insurance. Investigating the mechanisms behind the results, I find that people become more future-oriented after someone close to them was in danger of physical injury during that military operation. However, I cannot completely rule out other causes such as an increase in risk aversion or changes in individuals' beliefs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

This study examines how armed conflict affects individuals' religious behaviors (e.g., praying) and beliefs. The direction of the effect is theoretically not clear: war exposure may strengthen individuals' religiosity. Alternatively, after war exposure, individuals may stop following religion, and decrease their faith in God. To assess the direction of this effect, this study examines individuals' religiosity before and after a war between Israel and a Lebanese terror organization in 2006. Using both longitudinal and cross-section datasets, I find that being exposed to war or residing in war-affected regions increases individuals' religious behaviors and beliefs. These results are more pronounced among lower-educated individuals and among those who were not religious prior to the violence. Exploring possible mechanisms, I show that individuals become more religious as a means for coping with the adverse psychological effects of the war. Placebo tests using the pre-war period and individuals' views unrelated to war exposure strengthen my main findings., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study examines the effect of employment on elderly men's health. A typical OLS analysis yields a positive relationship between employment and health for individuals in their sixties. Causality, however, is difficult to infer because healthier individuals are more capable of working than others. To overcome this endogeneity problem, this paper exploits the increase in the full retirement age for men in Israel from sixty-five to sixty-seven in 2004. After this change, the employment rate of men in this age bracket jumped significantly compared to the last cohort that was able to retire at sixty-five. Using the new retirement law as an exogenous source of variation in the employment status of elderly men, a significant causal relationship in the opposite direction of the correlation is found: employment at older ages impairs health. These findings are found across a broad array of datasets and health outcomes. The results are significantly stronger among less-educated workers, suggesting that employment in physically demanding occupations is more detrimental to health. Placebo analyses using the years preceding the new retirement regime and other health measures unrelated to employment (e.g., dentist visits) reinforce a causal interpretation of my main findings., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Autotaxin is an extracellular, two zinc-centered enzyme that hydrolyzes lysophosphatidyl choline to lysophosphatidic acid, involved in various cancerous processes, e.g. migration, proliferation and tumor progression. We examined the autotaxin inhibitory properties of extended structure carbamoylphosphonates (CPOs) PhOC(6)H(4)SO(2)NH(CH(2))nNHCOPO(3)H(2), with increasing lengths of methylene chains, (CH(2))(n), n = 4-8. Carbamoylphosphonates having n = 6, 7, 8 inhibited autotaxin in vitro with IC(50) ≈ 1.5 µM. Using an imaging probe we demonstrated that compound n = 6 inhibits recombinant autotaxin activity in vitro and in vivo, following oral CPO administration. Additionally, daily oral administration of compound n = 7 inhibited over 90% of lung metastases in a murine melanoma metastasis model. Both the carbamoylphosphonates and the enzymes reside and interact in the extracellular space expecting minimal toxic side effects, and presenting a novel approach for inhibiting tumor proliferation and metastasis dissemination.

Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a 'splicing code', which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.

We carried out the first analysis of alternative splicing complexity in human tissues using mRNA-Seq data. New splice junctions were detected in approximately 20% of multiexon genes, many of which are tissue specific. By combining mRNA-Seq and EST-cDNA sequence data, we estimate that transcripts from approximately 95% of multiexon genes undergo alternative splicing and that there are approximately 100,000 intermediate- to high-abundance alternative splicing events in major human tissues. From a comparison with quantitative alternative splicing microarray profiling data, we also show that mRNA-Seq data provide reliable measurements for exon inclusion levels.

To identify human intronic sequences associated with 5' splice site recognition, we performed a systematic search for motifs enriched in introns downstream of both constitutive and alternative cassette exons. Significant enrichment was observed for U-rich motifs within 100 nucleotides downstream of 5' splice sites of both classes of exons, with the highest enrichment between positions +6 and +30. Exons adjacent to U-rich intronic motifs contain lower frequencies of exonic splicing enhancers and higher frequencies of exonic splicing silencers, compared with exons not followed by U-rich intronic motifs. These findings motivated us to explore the possibility of a widespread role for U-rich motifs in promoting exon inclusion. Since cytotoxic granule-associated RNA binding protein (TIA1) and TIA1-like 1 (TIAL1; also known as TIAR) were previously shown in vitro to bind to U-rich motifs downstream of 5' splice sites, and to facilitate 5' splice site recognition in vitro and in vivo, we investigated whether these factors function more generally in the regulation of splicing of exons followed by U-rich intronic motifs. Simultaneous knockdown of TIA1 and TIAL1 resulted in increased skipping of 36/41 (88%) of alternatively spliced exons associated with U-rich motifs, but did not affect 32/33 (97%) alternatively spliced exons that are not associated with U-rich motifs. The increase in exon skipping correlated with the proximity of the first U-rich motif and the overall "U-richness" of the adjacent intronic region. The majority of the alternative splicing events regulated by TIA1/TIAL1 are conserved in mouse, and the corresponding genes are associated with diverse cellular functions. Based on our results, we estimate that approximately 15% of alternative cassette exons are regulated by TIA1/TIAL1 via U-rich intronic elements.

Outpatient commitment under court order is a controversial issue among mental health professionals in different countries. This kind of outpatient involuntary treatment is provided for mental patients suspected to have committed a crime endangering society while in a severe psychotic state. Despite their dangerousness, the Israeli Mental Health Law of 1991 provides outpatient commitment under court order as an alternative to inpatient commitment. This legal provision raises several concerns and important ethical questions. A major dilemma is the question of whether this legal tool is efficacious in stabilizing the mental condition of criminal mental patients in order to prevent the perpetuation of violent crimes in an open setting such as outpatient clinics. Other major concerns are: (a) who bears the responsibility for the implementation of the enforcement? (b) how the enforcement might be implemented? This paper discusses this complex issue and presents some possible solutions aimed at improving the practical use of this important component of the comprehensive modern system of care for mental patients.

Background: Alternative splicing (AS) functions to expand proteomic complexity and plays numerous important roles in gene regulation. However, the extent to which AS coordinates functions in a cell and tissue type specific manner is not known. Moreover, the sequence code that underlies cell and tissue type specific regulation of AS is poorly understood., Results: Using quantitative AS microarray profiling, we have identified a large number of widely expressed mouse genes that contain single or coordinated pairs of alternative exons that are spliced in a tissue regulated fashion. The majority of these AS events display differential regulation in central nervous system (CNS) tissues. Approximately half of the corresponding genes have neural specific functions and operate in common processes and interconnected pathways. Differential regulation of AS in the CNS tissues correlates strongly with a set of mostly new motifs that are predominantly located in the intron and constitutive exon sequences neighboring CNS-regulated alternative exons. Different subsets of these motifs are correlated with either increased inclusion or increased exclusion of alternative exons in CNS tissues, relative to the other profiled tissues., Conclusion: Our findings provide new evidence that specific cellular processes in the mammalian CNS are coordinated at the level of AS, and that a complex splicing code underlies CNS specific AS regulation. This code appears to comprise many new motifs, some of which are located in the constitutive exons neighboring regulated alternative exons. These data provide a basis for understanding the molecular mechanisms by which the tissue specific functions of widely expressed genes are coordinated at the level of AS.

Motivation: Alternative splicing (AS) is a frequent step in metozoan gene expression whereby the exons of genes are spliced in different combinations to generate multiple isoforms of mature mRNA. AS functions to enrich an organism's proteomic complexity and regulates gene expression. Despite its importance, the mechanisms underlying AS and its regulation are not well understood, especially in the context of global gene expression patterns. We present here an algorithm referred to as the Generative model for the Alternative Splicing Array Platform (GenASAP) that can predict the levels of AS for thousands of exon skipping events using data generated from custom microarrays. GenASAP uses Bayesian learning in an unsupervised probability model to accurately predict AS levels from the microarray data. GenASAP is capable of learning the hybridization profiles of microarray data, while modeling noise processes and missing or aberrant data. GenASAP has been successfully applied to the global discovery and analysis of AS in mammalian cells and tissues., Results: GenASAP was applied to data obtained from a custom microarray designed for the monitoring of 3126 AS events in mouse cells and tissues. The microarray design included probes specific for exon body and junction sequences formed by the splicing of exons. Our results show that GenASAP provides accurate predictions for over one-third of the total events, as verified by independent RT-PCR assays., Supplementary Information: http://www.psi.toronto.edu/GenASAP.

Sequence-based analyses have predicted that approximately 35% of mammalian alternative splicing (AS) events produce premature termination codon (PTC)-containing splice variants that are targeted by the process of nonsense-mediated mRNA decay (NMD). This led to speculation that AS may often regulate gene expression by activating NMD. Using AS microarrays, we show that PTC-containing splice variants are generally produced at uniformly low levels across diverse mammalian cells and tissues, independently of the action of NMD. Our results suggest that most PTC-introducing AS events are not under positive selection pressure and therefore may not contribute important functional roles.

We describe the application of a microarray platform, which combines information from exon body and splice-junction probes, to perform a quantitative analysis of tissue-specific alternative splicing (AS) for thousands of exons in mammalian cells. Through this system, we have analyzed global features of AS in major mouse tissues. The results provide numerous inferences for the functions of tissue-specific AS, insights into how the evolutionary history of exons can impact on their inclusion levels, and also information on how global regulatory properties of AS define tissue type. Like global transcription profiles, global AS profiles reflect tissue identity. Interestingly, we find that transcription and AS act independently on different sets of genes in order to define tissue-specific expression profiles. These results demonstrate the utility of our quantitative microarray platform and data for revealing important global regulatory features of AS.