Search

Purpose: This study aims to revisit the relationship between the stringency of employment protection legislation and entrepreneurship at the macro-level using time series data from 28 OECD countries. Design/methodology/approach: To address model uncertainty, a Bayesian model averaging methodology is employed, overcoming issues related to predictor selection. Additionally, the study delves into the interaction between employment protection legislation and the rule of law, considering potential unintended consequences and overlapping effects. Heterogeneity within self-employment is explored, making a distinction between solo self-employment and employer entrepreneurship. Findings: The findings reveal that the impact of employment protection legislation, both for regular and temporary employment, on aggregate solo self-employment rates is contingent upon the level of practical regulatory compliance. The legislation can either stimulate or hinder entrepreneurship, highlighting the nuanced nature of its influence on macro-level entrepreneurial activities. Practical implications: The results of this study provide valuable insights for policymakers and regulators by emphasizing the complexity of the relationships under consideration. Understanding the potential interactions between employment protection legislation, rule of law and practical regulatory compliance is crucial for designing an effective and conducive regulatory environment for entrepreneurship. Originality/value: This research offers a unique contribution to the literature in three distinct ways: by addressing model uncertainty through Bayesian model averaging, examining the interaction between employment protection legislation and the rule of law and differentiating between solo self-employment and employer entrepreneurship. These distinctive elements enhance the originality and value of the study, providing a more nuanced understanding of the intricate relationship between legal frameworks and macro-level entrepreneurship. [ABSTRACT FROM AUTHOR]

Public transport plays a fundamental role in providing access to urban opportunities. People with mobility restrictions face greater obstacles than other members of society. This article seeks to explore the obstacles faced by wheelchair users in Montevideo, Uruguay. To do so, we designed a set of trips to actual destinations for five types of activities to compare time costs between wheelchair users and people without mobility restrictions. We estimated time costs for sidewalk segments, waiting time, onboard bus travel time, and coupling time (i.e., idle time due to the lack of bus provision closer to the activity starting times) and found that, relative to people without mobility restrictions, each of these transit components poses high costs for wheelchair users. From a policymaking perspective, our findings point out the importance of expanding universal design in public transport. They also call attention to other factors that explain travel time such as sidewalks segments and the temporal organization of urban activities that may turn into schedule mismatches. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA's high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most prevalent and debilitating health conditions worldwide; unfortunately, many patients do not respond to traditional antidepressant medication or talk therapy approaches. Deep transcranial magnetic stimulation (Deep TMS) has emerged as an effective treatment option for such "treatment-resistant" cases; however, the mechanisms by which Deep TMS attenuates depressive symptoms are still ambiguous. In the current study, resting-state quantitative electroencephalography (QEEG) measures were assessed pre-and-post treatment to illustrate neurophysiological changes resulting from Deep TMS. The results showed reduced slow-frequency brain activity (delta and theta waves) in the prefrontal cortex following 36 treatments. Additionally, baseline QEEG measures predicted treatment response with 93 % accuracy. These findings provide preliminary evidence that TMS improves depressive symptoms by mitigating slow-wave brain activity in the prefrontal cortex. Deep TMS paired with QEEG should continue to be utilized for treatment of MDD in clinical practice and future studies should explore its potential for other neuropsychiatric conditions. • Thirty-six sessions of Deep TMS led to significant reductions in depression from pre-treatment to post-treatment. • TMS led to significant reductions in slow-wave brain activity in prefrontal regions as measured by resting-state QEEG. • Prefrontal QEEG values at baseline discriminated responders from non-responders with 93 % accuracy [ABSTRACT FROM AUTHOR]

Learning and decision-making are greatly influenced by context. When navigating a complex social world, individuals must quickly ascertain where to gain important resources and which group members are useful sources of such information. Such dynamic behavioural processes require neural mechanisms that are flexible across contexts. Here we examine how the social context influences the learning response during a cue discrimination task and the neural activity patterns that underlie acquisition of this novel information. Using the cichlid fish, Astatotilapia burtoni, we show that learning of the task is faster in social groups than in a non-social context. We quantify the neural activity patterns by examining the expression of Fos, an immediate-early gene, across brain regions known to play a role in social behaviour and learning (such as the putative teleost homologues of the mammalian hippocampus, basolateral amygdala and medial amygdala/BNST complex). We find that neural activity patterns differ between social and non-social contexts. Taken together, our results suggest that while the same brain regions may be involved in the learning of a cue association, the activity in each region reflects an individual's social context. [ABSTRACT FROM AUTHOR]

Background: Glenohumeral instability caused by bone loss requires adequate bony restoration for successful surgical stabilization. Coracoid transfer has been the gold standard bone graft; however, it has high complication rates. Alternative autologous free bone grafts, which include the distal clavicle and scapular spine, have been suggested. Study Design: Controlled laboratory study. Purpose: The purpose of this study was to determine the percentage of glenoid bone loss (GBL) restored via coracoid, distal clavicle, and scapular spine bone grafts using a patient cohort and a cadaveric evaluation. Methods: Autologous bone graft dimensions from a traditional Latarjet, congruent arc Latarjet, distal clavicle, and scapular spine were measured in a 2-part study using 52 computed tomography (CT) scans and 10 unmatched cadaveric specimens. The amount of GBL restored using each graft was calculated by comparing the graft thickness with the glenoid diameter. Results: Using CT measurements, we found the mean percentage of glenoid restoration for each graft was 49.5% ± 6.7% (traditional Latarjet), 45.1% ± 4.9% (congruent arc Latarjet), 42.2% ± 7.7% (distal clavicle), and 26.2% ± 8.1% (scapular spine). Using cadaveric measurements, we found the mean percentage of glenoid restoration for each graft was 40.2% ± 5.0% (traditional Latarjet), 53.4% ± 4.7% (congruent arc Latarjet), 45.6% ± 8.4% (distal clavicle), and 28.2% ± 7.7% (scapular spine). With 10% GBL, 100% of the coracoid and distal clavicle grafts, as well as 88% of scapular spine grafts, could restore the defect (P <.001). With 20% GBL, 100% of the coracoid and distal clavicle grafts but only 66% of scapular spine grafts could restore the defect (P <.001). With 30% GBL, 100% of coracoid grafts, 98% of distal clavicle grafts, and 28% of scapular spine grafts could restore the defect (P <.001). With 40% GBL, a significant difference was identified (P =.001), as most coracoid grafts still provided adequate restoration (congruent arc Latarjet, 82.7%; traditional Latarjet, 76.9%), but distal clavicle grafts were markedly reduced, with only 51.9% of grafts maintaining sufficient dimensions. Conclusions: The coracoid and distal clavicle grafts reliably restored up to 30% GBL in nearly all patients. The coracoid was the only graft that could reliably restore up to 40% GBL. Clinical Relevance: With "subcritical" GBL (>13.5%), all autologous bone grafts can be used to adequately restore the bony defect. However, with "critical" GBL (≥20%), only the coracoid and distal clavicle can reliably restore the bony defect. [ABSTRACT FROM AUTHOR]

Dominant individuals are often most influential in their social groups, affecting movement, opinion, and performance across species and contexts. Yet, behavioral traits like aggression, intimidation, and coercion, which are associated with and in many cases define dominance, can be socially aversive. The traits that make dominant individuals influential in one context may therefore reduce their influence in other contexts. Here, we examine this association between dominance and influence using the cichlid fish Astatotilapia burtoni, comparing the influence of dominant and subordinate males during normal social interactions and in a more complex group consensus association task. We find that phenotypically dominant males are aggressive, socially central, and that these males have a strong influence over normal group movement, whereas subordinate males are passive, socially peripheral, and have little influence over normal movement. However, subordinate males have the greatest influence in generating group consensus during the association task. Dominant males are spatially distant and have lower signal-to-noise ratios of informative behavior in the association task, potentially interfering with their ability to generate group consensus. In contrast, subordinate males are physically close to other group members, have a high signal-to-noise ratio of informative behavior, and equivalent visual connectedness to their group as dominant males. The behavioral traits that define effective social influence are thus highly context specific and can be dissociated with social dominance. Thus, processes of hierarchical ascension in which the most aggressive, competitive, or coercive individuals rise to positions of dominance may be counterproductive in contexts where group performance is prioritized. [ABSTRACT FROM AUTHOR]

Selecting an attractive mate can involve trade-offs related to investment in sampling effort. Glucocorticoids like corticosterone (CORT) are involved in resolving energetic trade-offs. However, CORT is rarely studied in the context of mate choice, despite its elevated levels during reproductive readiness and the energetic transitions that characterize reproduction. Few systems are as well suited as anuran amphibians to evaluate how females resolve energetic trade-offs during mate choice. Phonotaxis tests provide a robust bioassay of mate choice that permit the precise measurement of inter-individual variation in traits such as choosiness–the willingness to pursue the most attractive mate despite costs. In Cope's gray treefrogs (Hyla chrysoscelis), females exhibit remarkable variation in circulating CORT as well as choosiness during mate choice, and a moderate dose of exogenous CORT rapidly (<1 h) and reliably induce large increases in choosiness. Here we measured the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors in the brains of females previously treated with exogenous CORT and tested for mate choosiness. We report a large decrease in GR expression in the hindbrain and midbrain of females that were treated with the moderate dosage of CORT–the same treatment group that exhibited a dramatic increase in choosiness following CORT treatment. This association, however, does not appear to be causal, as only forebrain GR levels, which are not affected by CORT injection, are positively associated with variation in choosiness. No strong effects were found for MR. We discuss these findings and suggest future studies to test the influence of glucocorticoids on mate choice. • An inverted-U function exists between female frog mate choosiness and CORT dose. • A moderate dosage of CORT alone increases mate choosiness. • CORT treatment also rapidly (<1 h) changes CORT receptor levels in the brain. • High glucocorticoid receptor levels in forebrain are associated with choosiness. [ABSTRACT FROM AUTHOR]

Many psychiatric disorders are associated with cognitive dysfunction that is ineffectively treated by existing pharmacotherapies and which may contribute to poor real-world functioning. D-cycloserine (DCS) is a partial N -methyl- D -aspartate (NMDA) agonist that has attracted attention because of its cognitive enhancing properties, including in people with post-traumatic stress disorder (PTSD). Here, we examined the effect of DCS on reversal learning - a type of cognitive flexibility – following exposure to single prolonged stress (SPS), a rodent model of PTSD. Male Sprague Dawley rats ( n  = 64) were trained to press levers in an operant chamber, matched for performance and assigned to SPS or control (unstressed) groups. Following SPS, rats received three additional lever press sessions, followed by a side bias test on day three. One day later they learned a response discrimination rule (press left or right lever, opposite to side bias) and on a subsequent day were trained (and tested) for reversal to the opposite lever. DCS (15 mg/kg) or vehicle was administered 30 minutes prior to the reversal session. No between-group differences were found in acquisition or retrieval of the initial rule, but a significant drug x stress interaction on response discrimination reversal indicated that DCS had a greater beneficial effect on SPS rats’ cognitive flexibility than it did on performance in controls. These findings add to a growing literature on the beneficial effects of DCS for treating a wide variety of deficits that develop following exposure to extreme stress and may have implications for the development of novel pharmacotherapies for PTSD. [ABSTRACT FROM AUTHOR]

We assessed the relationship between the altitude of municipalities and the incidence, mortality, and fatality from COVID-19 and excess of mortality in Colombia between 2020 and 2022. We conducted an ecologic study including all 1122 municipalities in Colombia and used categories of altitude as main independent variable. We fit multivariable regression models for incidence, mortality, fatality rates, and excess of mortality controlling for several variables at municipality level. There was a higher incidence rate, similar mortality rate and lower case-fatality rate for COVID-19 during 2020–2022 in municipalities in the upper category of altitude (>=2500 masl) compared to the lower category (<1000 masl). The excess of mortality was lower but not statistically different in municipalities in the upper category of altitude, and significantly lower in the intermediate altitude category compared to the lowlands. Our findings provide evidence that municipalities with high altitude had similar mortality rate, and lower case-fatality rate and excess of mortality for COVID-19 compared to lowlands in Colombia. • The association between altitude and COVID-19 has been inconsistent. • We analyzed altitude and COVID-19 indicators adjusting for multiple confounders. • Highlands (>2500 m) compared to lowlands (<1000) had similar mortality rate. • Highlands showed lower excess of mortality for COVID-19 compared to lowlands. [ABSTRACT FROM AUTHOR]

Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population. Methods The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample ( n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population. Results Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis. Conclusions We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring. [ABSTRACT FROM AUTHOR]

Motivation: Fine mapping is a widely used approach for identifying the causal variant(s) at disease-associated loci. Standard methods (e.g. multiple regression) require individual level genotypes. Recent fine mapping methods using summary-level data require the pairwise correlation coefficients (r2) of the variants. However, haplotypes rather than pairwise r2, are the true biological representation of linkage disequilibrium (LD) among multiple loci. In this article, we present an empirical iterative method, HAPlotype Regional Association analysis Program (HAPRAP), that enables fine mapping using summary statistics and haplotype information from an individual-level reference panel. Results: Simulations with individual-level genotypes show that the results of HAPRAP and multiple regression are highly consistent. In simulation with summary-level data, we demonstrate that HAPRAP is less sensitive to poor LD estimates. In a parametric simulation using Genetic Investigation of ANthropometric Traits height data, HAPRAP performs well with a small training sample size (N<2000) while other methods become suboptimal. Moreover, HAPRAP's performance is not affected substantially by single nucleotide polymorphisms (SNPs) with low minor allele frequencies. We applied the method to existing quantitative trait and binary outcome metaanalyses (human height, QTc interval and gallbladder disease); all previous reported association signals were replicated and two additional variants were independently associated with human height. Due to the growing availability of summary level data, the value of HAPRAP is likely to increase markedly for future analyses (e.g. functional prediction and identification of instruments for Mendelian randomization). [ABSTRACT FROM AUTHOR]

Mutations in the U2 snRNP component SF3B1 are prominent in myelodysplastic syndromes (MDSs) and other cancers and have been shown recently to alter branch site (BS) or 3' splice site selection in splicing. However, the molecular mechanism of altered splicing is not known. We show here that hsh155 mutant alleles in Saccharomyces cerevisiae, counterparts of SF3B1 mutations frequently found in cancers, specifically change splicing of suboptimal BS pre-mRNA substrates. We found that Hsh155p interacts directly with Prp5p, the first ATPase that acts during spliceosome assembly, and localized the interacting regions to HEAT (Huntingtin, EF3, PP2A, and TOR1) motifs in SF3B1 associated with disease mutations. Furthermore, we show that mutations in these motifs from both human disease and yeast genetic screens alter the physical interaction with Prp5p, alter branch region specification, and phenocopy mutations in Prp5p. These and other data demonstrate that mutations in Hsh155p and Prp5p alter splicing because they change the direct physical interaction between Hsh155p and Prp5p. This altered physical interaction results in altered loading (i.e., "fidelity") of the BS-U2 duplex into the SF3B complex during prespliceosome formation. These results provide a mechanistic framework to explain the consequences of intron recognition and splicing of SF3B1 mutations found in disease. [ABSTRACT FROM AUTHOR]

There are several chemical and electrochemical reactions that occur on a solvated magnesium surface, many of which contribute to the localized corrosion of magnesium and its alloys. The hydrogen evolution reaction (HER) is of particular interest because corrosion rates for different Mg alloys can be estimated by in situ monitoring of HER from a corroding sample surface. Therefore, a detailed mechanism for the HER on magnesium is proposed that connects the initial water dissociation reaction with the Tafel reaction through a self-consistent pathway involving adsorbed species. First principles modeling using Density Functional Theory (DFT) is used to map this reaction pathway on Mg(0001) and to determine the thermodynamic variables and kinetic barriers for each reaction in the scheme. An alternative mechanism for HER is also modeled that involves subsurface hydrogen, but this mechanism is found to have a negligible Gibbs free energy. It is also found that water dissociation occurs over the Mg Mg bridging site and has a large thermodynamic driving force. Reactions involving multiple water molecules and adsorbed species are modeled, as well, and it is found that the presence of H ads and OH ads provides a thermodynamic driving force for water dissociation while also increasing the activation barrier for the Tafel reaction. Hence, DFT calculations show that the presence of adsorbed species can have a large impact on the kinetics of chemical and electrochemical reactions that occur on the Mg surface. [ABSTRACT FROM AUTHOR]

Exposure to stressful or traumatic events is associated with increased vulnerability to post-traumatic stress disorder (PTSD). This vulnerability may be partly mediated by effects of stress on the prefrontal cortex (PFC) and associated circuitry. The PFC mediates critical cognitive functions, including cognitive flexibility, which reflects an organism's ability to adaptively alter behavior in light of changing contingencies. Prior work suggests that chronic or acute stress exerts complex effects on different forms of cognitive flexibility, via actions on the PFC. Similarly, PFC dysfunction is reported in PTSD, as are executive function deficits. Animal models that permit study of the effects of stress/trauma on cognitive flexibility may be useful in illuminating ways in which stress-linked cognitive changes contribute to PTSD. Here, we examined the behavioral effects of a rodent model of PTSD – single prolonged stress (SPS) – on performance of two forms of cognitive flexibility: reversal learning and strategy set-shifting. SPS did not impair acquisition of either a response or visual-cue discrimination but did cause slight impairments in the retrieval of the visual-cue rule. During response discrimination reversal, SPS rats made more perseverative errors. In comparison, during set-shifting from the visual-cue to response discrimination, SPS rats did not show enhanced perseveration, but did display increased never-reinforced errors, indicative of impairment in selecting a novel strategy. These data demonstrate that SPS leads to a complex and intriguing pattern of deficits in flexible responding and suggest that impairments in executive functioning associated with PTSD could, in part, be a neuro-cognitive consequence of trauma exposure. [ABSTRACT FROM AUTHOR]

Recent technological advances have created challenges for geneticists and a need to adapt to a wide range of new bioinformatics tools and an expanding wealth of publicly available data (e.g., mutation databases, and software). This wide range of methods and a diversity of file formats used in sequence analysis is a significant issue, with a considerable amount of time spent before anyone can even attempt to analyse the genetic basis of human disorders. Another point to consider that is although many possess “just enough” knowledge to analyse their data, they do not make full use of the tools and databases that are available and also do not fully understand how their data was created. The primary aim of this review is to document some of the key approaches and provide an analysis schema to make the analysis process more efficient and reliable in the context of discovering highly penetrant causal mutations/genes. This review will also compare the methods used to identify highly penetrant variants when data is obtained from consanguineous individuals as opposed to nonconsanguineous; and when Mendelian disorders are analysed as opposed to common-complex disorders. [ABSTRACT FROM AUTHOR]

Rationale: Post-traumatic stress disorder (PTSD) is a chronic, debilitating disorder. Only two pharmacological agents are approved for PTSD treatment, and they often do not address the full range of symptoms nor are they equally effective in all cases. Animal models of PTSD are critical for understanding the neurobiology involved and for identification of novel therapeutic targets. Using the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant excitatory neural transmission and glucocorticoid receptor (GR) upregulation in the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory abnormalities associated with PTSD. Objective: The objective of this study is to examine the potential protective effect of antiepileptic phenytoin (PHE) administration on SPS-induced extinction retention deficits and GR expression. Methods: Forty-eight SPS-treated male Sprague Dawley rats or controls were administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors; then, fear conditioning, extinction, and extinction retention were tested. Results: Fear conditioning and extinction were unaffected by SPS or PHE, but SPS impaired extinction retention, and both doses of PHE rescued this impairment. Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE prevented SPS-induced GR upregulation in the mPFC. Conclusions: These data demonstrate that PHE administration can prevent the development of extinction retention deficits and upregulation of GR. PHE exerts inhibitory effects on voltage-gated sodium channels and decreases excitatory neural transmission via glutamate antagonism. If glutamate hyperactivity in the days following SPS contributes to SPS-induced deficits, then these data may suggest that the glutamatergic system constitutes a target for secondary prevention. [ABSTRACT FROM AUTHOR]

Abstract: In this work, an atmospheric pressure plasma jet (APPJ) was investigated for developing hydrophobic thin film coatings on ultra-high molecular weight polyethylene (UHMWPE) films. Fluoroalkyl silanes, (CH3CH2O)3SiCH2CH2(CF2)7CF3 and (CH3O)3SiCH2CH2CF3 and fluoroaryl silane, F5ArSi(OCH2CH3)3 monomers with different fluorocarbon chain lengths were polymerized via plasma enhanced chemical vapor deposition (PECVD). These precursors in addition to other deposition processing conditions such as electrode-substrate gap distance and deposition time were investigated to understand the influence these parameters have on the overall deposition characteristics and hydrophobic behavior of the as-deposited thin film coatings. Attenuated total reflectance–Fourier transform infrared (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) techniques revealed that the chemical composition of the coatings retained a bulk of the monomer chemistry, signifying a low degree of fragmentation of the precursor in the plasma. This was particularly demonstrated by the coatings obtained with the fluoroaryl silane precursor, where the aromatic structure was kept intact. The hydrophobicity of the coatings was assessed using water contact angle (WCA) measurements and the thickness and morphology were examined using profilometry, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Variations in the composition of fluorocarbon coatings were observed as a result of deposition conditions, however the dominant parameter was found to be the monomer precursor. Optimal hydrophobic behavior was observed from coatings derived from the monomer with the longest fluorocarbon chain, as demonstrated from trends seen in WCA and CFn group concentrations. [Copyright &y& Elsevier]

Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10−20) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some. [ABSTRACT FROM AUTHOR]

SUMMARY Haptoglobin binds free haemoglobin that prevents oxidative damage produced by haemolysis. There is a copy number variant (CNV) in the haptoglobin gene ( HP) consisting of two alleles, Hp1 (no duplication), and Hp2 (1.7kb duplication involving two exons). The spread of the Hp2 allele is believed to have taken place under selective pressures conferred by malaria resistance. However, molecular evidence is lacking and Hp did not emerge in genomewide SNPs surveys for evidence of selection. In Europe, there is geographical constancy of Hp2 frequency, indicative of absence of clinal pressures and that modern day European alleles represent a 'snapshot' of their out-of-Africa migrations. In this work we test for signatures of natural selection acting on the Hp CNV in a sample from the UK population (Avon Longitudinal Study of Parents and Children, ALSPAC). We present here heterozygosity decay, pairwise FST values observed between ALSPAC and 301 populations from all five populated continents, extended haplotype homozygosity analyses involving the CNV and 80 SNPs surrounding the CNV ∼500kb in each direction, and linkage disequilibrium and pairwise haplotypic analyses involving 160 SNPs on chromosome 16q22.1. Taken together, our results represent the first molecular analysis of natural selection in the Hp CNV genetic region. [ABSTRACT FROM AUTHOR]

WIRIS quizzes are an online mathematics tool for educational purposes that upgrade Moodle quizzes and allow the development of personalized quizzes using random data and conditional instructions. WIRIS quizzes can be used in any mathematics or science degree; their complex operators allow it to be used to solve electrical circuits. This tool promotes autonomous student learning and enables teachers to monitor that learning and make adjustments if necessary. Therefore, this tool improves teaching quality. It can also be used as an assessment tool by both the teacher and the student. This paper shows how WIRIS quizzes have been integrated into the virtual campus of the Polytechnic University of Catalonia (UPC), Spain, to teach electrical circuits. Lessons learned in performing and using WIRIS quizzes with second-year students at the UPC are shown. [ABSTRACT FROM PUBLISHER]

Abstract: HP and HPR are related and contiguous genes in strong linkage disequilibrium (LD), encoding haptoglobin and haptoglobin-related protein. These bind and chaperone free Hb for recycling, protecting against oxidation. A copy number variation (CNV) within HP (Hp1/Hp2) results in different possible haptoglobin complexes which have differing properties. HPR rs2000999 (G/A), identified in meta-GWAS, influences total cholesterol (TC) and LDL-cholesterol (LDL-C). We examined the relationship between HP CNV, HPR rs2000999, Hb, red cell count (RCC), LDL-C and TC in the British Women''s Heart and Health Study (n=2779 for samples having CNV, rs2000999, and phenotypes). Analysing single markers by linear regression, rs2000999 was associated with LDL-C (β=0.040mmol/L, p=0.023), TC (β=−0.040mmol/L, p=0.019), Hb (β=−0.044g/dL, p=0.028) and borderline with RCC (β=−0.032×1012/L, p=0.066). Analysis of CNV by linear regression revealed an association with Hb (Hp1 vs Hp2, β=0.057g/dL, p=0.004), RCC (β=0.045×1012/L, p=0.014), and showed a trend with LDL-C and TC. There were 3 principal haplotypes (Hp1-G 36%; Hp2-G 45%; Hp2-A 18%). Haplotype comparisons showed that LDL-C and TC associations were from rs2000999; Hb and RCC associations derived largely from the CNV. Distinct genotype–phenotype effects are evident at the genetic epidemiological level once LD has been analysed, perhaps reflecting HP–HPR functional biology and evolutionary history. The derived Hp2 allele of the HP gene has apparently been subject to malaria-driven positive selection. Haptoglobin-related protein binds Hb and apolipoprotein-L, i.e. linking HPR to the cholesterol system; and the HPR/apo-L complex is specifically trypanolytic. Our analysis illustrates the complex interplay between functions and haplotypes of adjacent genes, environmental context and natural selection, and offers insights into potential use of haptoglobin or haptoglobin-related protein as therapeutic agents. [Copyright &y& Elsevier]

Abstract: Surface protonation reactions play an important role in the behavior of mineral and colloidal systems, specifically in hydrothermal aqueous environments. However, studies addressing the reactions at the solid/liquid interface at temperatures above 100°C are scarce. In this study, newly and previously obtained high temperature electrophoresis data (up to 260°C) – zeta potentials and isoelectric points – for metal oxides, including SiO2, SnO2, ZrO2, TiO2, and Fe3O4, were used in thermodynamic analysis to derive the standard enthalpies of their surface protonation. Two different approaches were used for calculating the protonation enthalpy: one is based on thermodynamic description of the 1-pKa model for surface protonation, and another one – on a combination of crystal chemistry and solvation theories which link the relative permittivity of the solid phase and the ratio of the Pauling bond strength and bond length to standard protonation enthalpy. From this analysis, two expressions relating the protonation enthalpy to the relative permittivity of the solid phase were obtained. [Copyright &y& Elsevier]

A sparse linear system constitutes a valid model for a broad range of physical systems, such as electric power networks, industrial processes, control systems or traffic models. The physical magnitudes in those systems may be directly measured by means of sensor networks that, in conjunction with data obtained from contextual and boundary constraints, allow the estimation of the state of the systems. The term observability refers to the capability of estimating the state variables of a system based on the available information. In the case of linear systems, diffierent graphical approaches were developed to address this issue. In this paper a new unified graph based technique is proposed in order to determine the observability of a sparse linear physical system or, at least, a system that can be linearized after a first order derivative, using a given sensor set. A network associated to a linear equation system is introduced, which allows addressing and solving three related problems: the characterization of those cases for which algebraic and topological observability analysis return contradictory results; the characterization of a necessary and sufficient condition for topological observability; the determination of the maximum observable subsystem in case of unobservability. Two examples illustrate the developed techniques. [ABSTRACT FROM AUTHOR]

Iron is one of the most abundant metals found in senile plaques of post mortem patients with Alzheimer's disease. However, the interaction mode between iron ions and β-amyloid peptide as well as their precise affinity is unknown. In this study we apply ab initio computational methodology to calculate binding energies of Fe2+/3+ with the His 13-His 14 sequence of Aβ, as well as other important ligands such as His6 and Tyr10. Calculations were carried out at the "MP2/6-311+G(2df,2p)" // B3LYP/6-31+G(d) level of theory and solvent effects included by the IEFPCM procedure. Several reaction paths for the binding of imidazole, phenol, and the His13-His14 fragment (modeled by N-(2-(1H-imidazol-4-yl)ethyl)-3-(1H-imidazol-4-yl)propanamide) were sequentially explored. The results show that the most stable complexes containing His13-His14 and phenolate of Tyr10 are the pentacoordinated [Fe2+(O-HisHis)(PhO)(H2O)]+ and [Fe3+(N-HisHis)(PhO)(H2O)]+ compounds and that simultaneous coordination of tyrosine and His13-His14 to Fe2+/3+ is thermodynamically favorable in water at physiological pH. Computed Raman spectra confirm the conclusion obtained by Miura et al. (Biochemistry 2000, 39, 7024) that tyrosine is coordinated to Fe3+ but do not exclude coordination of imidazoles. Finally, calculations of standard reduction potentials indicate that phenol coordination reduces the redox activity of the iron/Aβ complexes. [ABSTRACT FROM AUTHOR]

Abstract: Magnetite (Fe3O4) is one of the most common oxides forming deposits and particulate phases in industrial high temperature water circuits. Its colloidal characteristics play a principal role in the mechanism of deposit formation and can be used as controlling factors to prevent or minimize deposit formation and damage of industrial pipelines due to under-deposit corrosion. In this study, a high temperature particle electrophoresis technique was employed to measure the zeta potential at the magnetite/water interface—the parameter that controls colloidal stability of particles, their aggregation, and deposition. The measurements were made at temperatures up to 200°C over a wide range of pH. The isoelectric points of magnetite, at which the deposition of particles is increased, were determined at pH 6.35, 6.00, 5.25, and 5.05 for temperatures 25, 100, 150, and 200°C, respectively. The observed temperature dependence of zeta potential and the isoelectric pH point of magnetite can help to explain the extent of interactions between the colloidal particles and the steel wall surfaces under hydrothermal conditions, and indicate methods for controlling and mitigating oxide deposition in high temperature water cycles. [Copyright &y& Elsevier]

CYP2A6 influences smoking uptake in adolescence. Genetic variation in the CHRNA5–CHRNA3 region influences smoking behaviour in adults. However, their combined effects on smoking in adolescence have not been tested to date. We present data on 1450 adolescents from the Ten Towns Heart Health Study (TTHHS) extensively phenotyped for smoking-related traits during adolescence. Single nucleotide polymorphisms from CHRNA5 and CHRNA3 (previously associated with smoking), were typed in our study population, previously genotyped for CYP2A6. Association analyses between each genotype and both smoking status and behavioural markers of smoking were performed. rs16969968 in CHRNA5 was associated both at 13–15 years and 18 years with current smoking amongst adolescents who had tried smoking (OR = 1.82, CI = 1.10–3.01, p = 0.02 at age 13–15; OR = 2.39, CI = 1.37–4.17, p = 0.002 at age 18). No association was found for rs578776 in CHRNA3. The effects of CHRNA5 and CYP2A6 genotypes in TTHHS appeared to be independent, with each approximately doubling the odds of being a regular smoker by age 18 years. CYP2A6 genotype insufficiency increases adolescent likelihood of being a regular smoker but increases later life quitting likelihood and reduces average consumption. In contrast, CHRNA5 genotype, acting recessively, affects smoking similarly in adolescents and older adults. These contrasting actions, in digenic combination, illustrate behavioural genetic complexity. [ABSTRACT FROM PUBLISHER]

Background: Filaggrin is a major protein in the epidermis. Several mutations in the filaggrin gene (FLG) have been associated with a number of conditions. Filaggrin is expressed in the tympanic membrane and could alter its mechanical properties, but the relationship between genetic variation in FLG and hearing has not yet been tested. Methodology/Principal Findings: We examined whether loss-of function mutations R501X and 2282del4 in the FLG gene affected hearing in children. Twenty eight hearing variables representing five different aspects of hearing at age nine years in 5,377 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort were tested for association with these mutations. No evidence of association was found between R501X or 2282del4 (or overall FLG mutation carrier status) and any of the hearing phenotypes analysed. Conclusions/Significance: In conclusion, carrier status for common filaggrin mutations does not affect hearing in children. [ABSTRACT FROM AUTHOR]

The electrophoretic mobility, which reflects the zeta potential of a solid material, is an important experimental quantity providing information about the electrical double layer at the solid/liquid interface. A new high temperature electrophoresis cell was developed suitable for electrophoretic mobility measurements of dispersed nanosize particles up to 150 °C and 40 bars. Amorphous silica (SiO2) particle size standards were used to test the particle size detection limit of the new instrument at 25, 100, and 150 °C and several pH values. The microscopic detection of the particles was enabled by dark-field illumination, which allowed extending the previously available capabilities and provided higher accuracy of the electrophoretic mobility data. The electrophoretic mobility measurements for SiO2 at temperatures above 100 °C were reported for the first time and indicated a gradual increase in particle electrophoretic response with increasing temperature. The obtained data indicated negatively charged SiO2 surface throughout the pH and temperature ranges studied. [ABSTRACT FROM AUTHOR]

The diastereoselectivity of the nucleophilic epoxidation of γ-hydroxy-α,β-unsaturated esters having a methyl substituent at the α- or β-position was investigated. Epoxidation of the α-methyl-substituted enoate was highly stereoselective, giving rise to the syn isomer. This finding was used to perform an enantioselective synthesis of a natural product having a β-hydroxy-α-methylene-γ-butyrolactone motif. The nucleophilic epoxidation of enoates was found to be irreversible. Models to explain the observed stereoselectivities are proposed. [ABSTRACT FROM AUTHOR]

The human growth hormone gene ( GH1) and the insulin-like growth factor 1 and 2 genes ( IGF1 and IGF2) encode the central elements of a key pathway influencing growth in humans. This “growth pathway” also includes transcription factors, agonists, antagonists, receptors, binding proteins, and endocrine factors that constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled with other genes in linkage disequilibrium in 17q24.2, and the same applies to IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage disequilibrium with neighbouring genes. Knowledge of the functional architecture of these regions is important for the understanding of the combined evolution and function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements. The constellation of genes in this key pathway contains potential candidates in a number of complex diseases, including growth disorders, metabolic syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous system diseases, and in longevity, aging and cancer. We review these genes and their associations with disease phenotypes, with special attention to metabolic risk traits. [ABSTRACT FROM AUTHOR]

The mechanisms by which organisms recognize the 'self' from the 'non-self' remain poorly understood. Moreover, the capability of transplanted tissue to functionally integrate is unclear in many organisms. Here, we report that two injured Mnemiopsis leidyi individuals, a species of planktonic animals known as comb jellies or ctenophores, are capable of rapidly fusing into a single entity in which some physiological functions are integrated. Our results highlight two interesting phenomena. First, ctenophores may lack an allorecognition mechanism that prevents fusion events between conspecifics. Second, fused individuals rapidly integrate and share physiological functions and neurobehavioral outputs. Ctenophores are among the earliest-branching animal groups of extant metazoans 1 and possess a unique nervous system with enigmatic homology to other phyla2. Our observations warrant further research into understanding the evolution of self–nonself recognition systems and the functional integration of neuronal structures in ctenophores. Jokura et al. report that two injured Mnemiopsis leidyi individuals are capable of rapidly fusing into a single entity in which some physiological functions are integrated. [ABSTRACT FROM AUTHOR]

The gas-phase reactivity of Ni+(urea) has been investigated by means of mass spectrometry techniques and density functional calculations. The major fragmentations observed in the MIKE spectrum of [Ni-urea]+ correspond to the loss of CO, NH3, and HNCO. The electrospray MS/MS spectrum shows also these fragmentations; however, an additional intense peak is detected matching to the elimination of water. To explain the differences observed in the reactivity under FAB or ESI conditions, several pathways leading to the experimental fragmentations have been considered theoretically. The exploration of the potential energy surfaces has shown that, although the elimination of NH3 mainly arises from the noninsertion mechanisms, the elimination of CO and HNCO arises exclusively from the insertion mechanisms. Elimination of water shows larger barriers, but under electrospray conditions, the presence of the solvent can reduce these energy barriers leading to isomerizations of the [Ni-urea]+ complex in the source region. The results obtained have been also compared to those previously reported for Cu+. Calculations show that the most stable Ni+-urea complex has the Ni+ cation interacting with the oxygen, with the computed binding energy being 66.3 kcal/mol. [ABSTRACT FROM AUTHOR]

Presents facts on the distribution of earnings, income, and wealth in the U.S. based on data from the 1998 Survey of Consumer Finances. Description of factors affecting inequality; Details of statistical facts to highlight earnings, income, and wealth inequality; Discussion on earnings and income mobility; Changes in inequality and mobility during the 1990s.

Examines the frequency and strength of overall and interallelic disequilibrium between pairs of 12 microsatellite loci spanning 19 cM on human chromosome 11p15 from a large sample of Galician population in northwest Spain. Relationship of disequilibrium with frequency of recombination and physical distance; Overall nonrandom associations between loci.

B Introduction: b Inflation of the endotracheal cuff looks like an innocuous part of the rapid sequence intubation process. B Discussion: b Historically, the balloon palpation method has been used but it has poor sensitivity recognizing cuff hyperinflation. [Extracted from the article]

Examines the proton transfer reaction in neutral and radical cations of salicylic acid, 0-hydroxybenzaldehyde, and salicylaldimine. Utilization of B3LYP density functional method; Probe on intramolecular proton transfer processes; Characterization of nonzwitterionic compound; Importance of ionized pi states in the proton transfer process.

Presents a study which used different structures of the Cu(NO2)2 complex to investigate the coordination of two NO2 (nitrogen oxides) ligands. Comparison of Mg(NO2)2 and Cu(NO3)2; Clarification on the structure of Cu(NO2)2; Details on single-point CCSD(T) calculations.

Presents COES, an ongoing project developed at the Universidad Politecnica de Madrid, whose goal is the creation of some specialized computer tools for the Spanish language. Main objectives established for COES; Brief description of the Spanish grammatical features; Method used to build the COES tools; Evaluation results of COES' performance.

Examines the interaction of NO2 with Cu+ ions in the gas phase and in zeolites. Observation of some activation of Cu+ and other transition metal ions by ligands; Reference to the important role that ligans play in activating transition metal cations; Identification of the unique feature of transition metal ions.

The molecular mechanism of the Thioflavin-T (Th-T) binding to amyloids remains unknown. By combining experimental analysis of Th-T excitation and emission spectra with theoretical calculations we suggest that Th-T fluorescence changes upon interaction with amyloids may arise from the formation of an excimer with an oblique angle of ∼120 degrees. [ABSTRACT FROM AUTHOR]

Insecure attachment has been described as mediating the relationship between childhood trauma and dysfunctional personality traits in different mental disorders. Despite the role insecure attachment and childhood trauma have independently demonstrated to play as determinants of borderline personality disorder, less is known about the mediating mechanisms explaining these associations. For the first time, we assessed adult attachment, childhood trauma and dimensional personality pathology in a sample of outpatients with borderline personality disorder and tested whether the association between childhood trauma and personality dysfunction was at least partially attributable to insecure attachment. The results showed that attachment anxiety fully mediated the relationship between specific types of trauma (emotional abuse and physical neglect) and emotional dysregulation. Further, emotional abuse was both directly associated with dissocial behaviour and indirectly via attachment anxiety (partial mediation). Emotional abuse has been described as an essential environmental factor for the development of borderline personality disorder and emotional dysregulation, on its part, as the core feature of the condition. Our results indicate that attachment anxiety explains the link between these central aspects of borderline personality disorder. Our findings are consistent with previous research and current etiological understanding of the condition and provide support for recommending a careful assessment of childhood traumatic experiences and adult attachment style to gain a more comprehensive insight into the symptoms and its heterogeneity. As a secondary aim, we assessed the effect parental mental illness may have in these mediation models, but no significant influence on childhood trauma, attachment or personality was found. [ABSTRACT FROM AUTHOR]

Transformer rectifier units (TRUs) are a reliable way for dc generation in several electric applications. These units are formed by multiple three-phase uncontrolled bridge rectifiers connected according to two main topologies (parallel and series), and fed by a phase-shifting transformer, which can have different configurations. Fault diagnosis of the uncontrolled bridge rectifier diodes is one of the most important concerns on the electronic devices, nonetheless, rectifier units are inherently not protected in front of open-circuit (O/C) faults, which cause malfunction and performance deterioration. In order to solve this drawback, the proposed fault diagnosis method is based on the O/C fault signature observed in the dc-link output voltage of TRUs rectifier. It allows detecting the O/C diodes of parallel and series TRUs with different phase-shifting transformer configurations and for the most usual fault scenarios. Moreover, it also helps the prediction of diodes that could be exposed to failure after the fault, which provides corrective maintenance for the TRU development. The proposed method is illustrated from MATLAB numerical simulations of a 12-pulse TRU, and is validated with experimental tests. [ABSTRACT FROM AUTHOR]