Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome‐wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans

Although type 2 diabetes (T2D) results from metabolic defects in insulin secretion and insulin sensitivity, most of the genetic risk loci identified to date relates to insulin secretion. We reported that T2D loci influencing insulin sensitivity may be identified through interactions with insulin secretion loci, thereby leading to T2D. Here, we hypothesize that joint testing of variant main effects and interaction effects with an insulin secretion locus increases power to identify genetic interactions leading to T2D. We tested this hypothesis with an intronic MTNR1B SNP, rs10830963, which is associated with acute insulin response to glucose, a dynamic measure of insulin secretion. rs10830963 was tested for interaction and joint (main + interaction) effects with genome‐wide data in African Americans (2,452 cases and 3,772 controls) from five cohorts. Genome‐wide genotype data (Affymetrix Human Genome 6.0 array) was imputed to a 1000 Genomes Project reference panel. T2D risk was modeled using logistic regression with rs10830963 dosage, age, sex, and principal component as predictors. Joint effects were captured using the Kraft two degrees of freedom test. Genome‐wide significant (P < 5 × 10−8) interaction with MTNR1B and joint effects were detected for CMIP intronic SNP rs17197883 (Pinteraction = 1.43 × 10−8; Pjoint = 4.70 × 10−8). CMIP variants have been nominally associated with T2D, fasting glucose, and adiponectin in individuals of East Asian ancestry, with high‐density lipoprotein, and with waist‐to‐hip ratio adjusted for body mass index in Europeans. These data support the hypothesis that additional genetic factors contributing to T2D risk, including insulin sensitivity loci, can be identified through interactions with insulin secretion loci.
A new frequency‐uniform coercive boundary integral equation for acoustic scattering

A new boundary integral operator is introduced for the solution of the soundsoft acoustic scattering problem, i.e., for the exterior problem for the Helmholtz equation with Dirichlet boundary conditions. We prove that this integral operator is coercive in L2(Γ) (where Γ is the surface of the scatterer) for all Lipschitz star‐shaped domains. Moreover, the coercivity is uniform in the wavenumber k = ω/c, where ω is the frequency and c is the speed of sound. The new boundary integral operator, which we call the “star‐combined” potential operator, is a slight modification of the standard combined potential operator, and is shown to be as easy to implement as the standard one. Additionally, to the authors' knowledge, it is the only second‐kind integral operator for which convergence of the Galerkin method in L2(Γ) is proved without smoothness assumptions on Γ except that it is Lipschitz. The coercivity of the star‐combined operator implies frequency‐explicit error bounds for the Galerkin method for any approximation space. In particular, these error estimates apply to several hybrid asymptoticnumerical methods developed recently that provide robust approximations in the high‐frequency case. The proof of coercivity of the star‐combined operator critically relies on an identity first introduced by Morawetz and Ludwig in 1968, supplemented further by more recent harmonic analysis techniques for Lipschitz domains. © 2011 Wiley Periodicals, Inc.
Enhanced interplanetary panspermia in the TRAPPIST-1 system

Significance The search for extraterrestrial life is one of the most exciting frontiers in present-day astronomy. Recently, the TRAPPIST-1 star was discovered to host seven rocky planets with masses and radii similar to those of the Earth, of which at least three of them may be capable of supporting life. Our paper addresses the possibility that life on one of these planets can spread to others through the transfer of rocky material. We conclude that this process has a high probability of being operational, implying that this planetary system may possess multiple life-bearing planets. Thus, our work has profound theoretical and observational consequences for future studies of the TRAPPIST-1 system and the likelihood of life in our galaxy. We present a simple model for estimating the probability of interplanetary panspermia in the recently discovered system of seven planets orbiting the ultracool dwarf star TRAPPIST-1 and find that panspermia is potentially orders of magnitude more likely to occur in the TRAPPIST-1 system compared with the Earth-to-Mars case. As a consequence, we argue that the probability of abiogenesis is enhanced on the TRAPPIST-1 planets compared with the solar system. By adopting models from theoretical ecology, we show that the number of species transferred and the number of life-bearing planets are also likely to be higher because of the increased rates of immigration. We propose observational metrics for evaluating whether life was initiated by panspermia on multiple planets in the TRAPPIST-1 system. These results are also applicable to habitable exoplanets and exomoons in other planetary systems.
Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE ɛ4 carriers: a case–control study

Objectives Examine the role of single nucleotide polymorphisms (SNPs) in the oestrogen receptor (ER) genes: rs9340799, rs2234693, rs2228480 (in the ESR1 gene) and rs4986938 (in the ESR2 gene) as a risk factor for amnesic mild cognitive impairment (MCIa) and Alzheimer's disease (AD) and its possible association with the apolipoprotein E (APOE) gene. Design We have investigated the independent and combined association of different alleles of the oestrogen receptor genes and APOE*ɛ4 allele with cognitive impairment using a case–control design. Setting Participants were prospectively recruited from the neurology departments of several Basque Country hospitals. Participants This study comprised 816 Caucasian participants who were aged 50 years and older: 204 MCIa, 350 sporadic patients with AD and 262 healthy controls. Primary and secondary outcome measures Clinical criteria and neuropsychological tests were used to establish the diagnostic groups (MCIa, AD and healthy controls). A dichotomous variable was used for each allele and genotype and the association with MCIa and AD was established using Logistic Regression Models. Results Neither alleles nor genotypes of SNPs rs9340799, rs2234693, rs2228480 and rs4986938 of oestrogen receptor genes (ESR1 and ESR2) are independently associated with the risk of MCIa or AD. However, the genetic profile created with the combination of the less represented alleles of these SNPs (expressed as XPAA) was associated with an increased risk for MCIa (OR=3.30, 95% CI 1.28 to 8.54, p=0.014) and AD (OR=5.16, 95% CI 2.19 to 12.14, p<0.001) in women APOE*ɛ4 allele carriers. Conclusions The less represented alleles of SNPs studied are associated with MCIa and AD in APOE*E4 carriers. In particular, the genetic profile created with the less represented alleles of ESR1 and ESR2 SNPs are associated with an increased risk for MCIa and AD in women APOEɛ4 allele carriers.
A Brief Introduction to the Neuro-Genetics of Spirituality towards a Systemic Peace Propagation Model

When describing the scenario concerning the evolution of humanity towards Global Peace, each element of the system (each person) is first required to find and establish peace internally through their own connection with the Source of all Spiritual Values in order to become a living embodiment of them. As each part of a system affects the whole and every human being is responsible for his or her inner state of peace and harmony, then this choice (individual inner peace) is his or her contribution to Global Peace. This essay presents three main areas that are intimately related, however described separately in order to facilitate a clear picture of the complexities we are dealing with in a simplified manner: the biophysical, the spiritual and the social together with some ethical implications, all connected with a set of systems diagrams that aim to explain a process that will be described in this body of work as a dynamical system of Peace Propagation and Spiritual Values Propagation that we have called Melchidynamics.
Do Surrogate Markers for Adiposity Relate to Cytokines in Adolescents?

Purpose To determine the associations between field-collected surrogates of adiposity and concentrations of resistin, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and adiponectin in youth. Methods Cross-sectional data from 60 normal weight and 60 overweight adolescents, ages 10-14 years, were retrospectively examined. Body mass index (BMI) percentile, sum of subscapular and triceps skinfolds (SSF), and waist circumference (WC) were used to classify weight status (BMI) or adiposity (SSF and WC). Percentiles for each surrogate were used for comparison groups. Fasting TNF-α, IL-6, resistin, and adiponectin concentrations were measured in plasma. Results Multiple regression models, controlling for sex and ethnicity, indicated that TNF-α was associated with BMI percentile (R 2 = 0.107, P < 0.05) and SSF (R 2 = 0.085, P < 0.05), whereas resistin was associated with SSF (R 2 = 0.118, P < 0.05). Adiponectin was associated with all 3 adiposity markers: BMI percentile (R 2 = 0.298, P < 0.05), SSF (R 2 = 0.297, P < 0.05), and waist (R 2 = 0.278, P < 0.05). Analyses of variance indicated higher TNF-α and lower adiponectin concentrations in youth with a BMI higher than the 95th percentile (P = 0.014; P < 0.001) or SSF higher than the 95th percentile (P = 0.025; P < 0.001). Youth with WC higher than the 90th percentile had higher resistin (P = 0.029), higher IL-6 (P = 0.028), and lower adiponectin (P < 0.001) concentrations. Conclusions Of the 3 surrogates examined, differences in cytokine concentrations were mostly observed in youth who had WC percentiles higher than the 90th percentiles versus WC lower than the 75th percentiles. Alternatively, from the multiple-regression models SSF, an estimate of subcutaneous adiposity was the surrogate most consistently related to all cytokines, although the degrees of associations were low. The results suggest that although some surrogates were more strongly associated to certain cytokines, WC and SSF seemed more closely associated with cytokines than a BMI percentile indicating obesity.
Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America.

CONTEXT Early detection and prospective evaluation of individuals who will develop schizophrenia or other psychotic disorders are critical to efforts to isolate mechanisms underlying psychosis onset and to the testing of preventive interventions, but existing risk prediction approaches have achieved only modest predictive accuracy. OBJECTIVES To determine the risk of conversion to psychosis and to evaluate a set of prediction algorithms maximizing positive predictive power in a clinical high-risk sample. DESIGN, SETTING, AND PARTICIPANTS Longitudinal study with a 2 1/2-year follow-up of 291 prospectively identified treatment-seeking patients meeting Structured Interview for Prodromal Syndromes criteria. The patients were recruited and underwent evaluation across 8 clinical research centers as part of the North American Prodrome Longitudinal Study. MAIN OUTCOME MEASURE Time to conversion to a fully psychotic form of mental illness. RESULTS The risk of conversion to psychosis was 35%, with a decelerating rate of transition during the 2 1/2-year follow-up. Five features assessed at baseline contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse. Prediction algorithms combining 2 or 3 of these variables resulted in dramatic increases in positive predictive power (ie, 68%-80%) compared with the prodromal criteria alone. CONCLUSIONS These findings demonstrate that prospective ascertainment of individuals at risk for psychosis is feasible, with a level of predictive accuracy comparable to that in other areas of preventive medicine. They provide a benchmark for the rate and shape of the psychosis risk function against which standardized preventive intervention programs can be compared.
The Central and Eastern European Countries and the European Union: TFP, costs and public infrastructure: an equivocal relationship

This paper studies the impact of public infrastructure on economic performance. We employ three di¤erent methodologies to estimate the returns to public investment. First, we relate growth in total factor productivity to accumulation of public capital. Second, we assess the role of public capital as an input to production. Third, we evaluate the reduction in costs that can be attributed to the presence of public infrastructure. Using regional data for Italy, we . nd that the aggregate impact of public capital is positive and signi.cant under the . rst approach, slightly negative under the second, and virtually zero under the third. More coherent results obtain when disaggregating by geographical area and time period: under all three approaches, the e¤ectiveness of public investment seems to be increasing over time and to be higher in Central and Southern regions than in Northern ones. J.E. L. Classi.cation: H54, O47, C50
A multiarchitecture parallel-processing development environment

A description is given of the hardware and software of a multiprocessor test bed - the second generation Hypercluster system. The Hypercluster architecture consists of a standard hypercube distributed-memory topology, with multiprocessor shared-memory nodes. By using standard, off-the-shelf hardware, the system can be upgraded to use rapidly improving computer technology. The Hypercluster's multiarchitecture nature makes it suitable for researching parallel algorithms in computational field simulation applications (e.g., computational fluid dynamics). The dedicated test-bed environment of the Hypercluster and its custom-built software allows experiments with various parallel-processing concepts such as message passing algorithms, debugging tools, and computational 'steering'. Such research would be difficult, if not impossible, to achieve on shared, commercial systems.
The Disruption of Stellar Clusters Containing Massive Black Holes near the Galactic Center

We present results from dynamical Monte Carlo simulations of dense star clusters near the Galactic center. These clusters sink toward the center of the Galaxy by dynamical friction. During their in-spiral, they may undergo core collapse and form an intermediate-mass black hole through runaway collisions. Such a cluster can then reach within a parsec of the Galactic center before it completely disrupts, releasing many young stars in this region. This scenario provides a natural explanation for the presence of the young stars observed near the Galactic center. Here we determine the initial conditions for this scenario to work, and we derive the mass distribution of cluster stars as a function of distance from the Galactic center. For reasonable initial conditions, we find that clusters massive enough for rapid in-spiral would include a larger number of massive stars (m* ≳ 30 M☉) than currently observed in the in-spiral region. We point out several possible explanations for this apparent discrepancy.
Effects of Exercise-induced Fatigue on the Expression of BDNF and GFAP of Rats' Hippocampus and Striatum

To investigate BDNF and GFAP expression changes in rats' hippocampus and striatum after swimming and discuss the neurobiology mechanism of exercise-induced fatigue,24 rats were divided randomly into CG and EG(0EG,12EG,24EG) and BDNF and GFAP expression changes in hippocampus and striatum were observed using SABC method.After exercise-induced fatigue,cells arrange shows foul-up and loosen in cone district of hippocampus.Some cells crinkle,strut and chip.GFAP expression in cell's body becomes augment and shows wider axon.Expression of BDNF in 12EG,24EG significantly increased compared with CG(P 0.05,P 0.01),and 24EG also significantly increased compared with 0EG(P 0.05). Expression of GFAP significantly increased compared with CG(P 0.05,P 0.01). Exercise-induced fatigues have increased BDNF and GFAP expression.It has been proved that both of BDNF and GFAP may play an important role in the neurobiological modulation for exercise-induced fatigue.
Stability analysis of medial axis transform under relative Hausdorff distance

Medial axis transform (MAT) is a basic tool for shape analysis. However, in spite of its usefulness, it has some drawbacks, one of which is its instability under the boundary perturbation. We show that, although medial axis transform is unstable with respect to standard measures such as the Hausdorff distance, it is stable in a measure called relative Hausdorff distance for some "smoothed out" injective domains. In fact, we obtain an upper bound of the relative Hausdorff distance of the MAT of an injective domain with respect to the MAT of an arbitrary domain which is in small Hausdorff distance from the original injective domain. One consequence of the above result is that, by approximating a given domain with injective domains, we can extract the most "essential part" of the MAT within the prescribed error bound in Hausdorff distance. This introduces a new pruning strategy with precise error estimation. We illustrate our results with an example.
Greater Positive Affect Change after Mental Imagery than Verbal Thinking in a Student Sample

This study sought to replicate previous work concerning the impact of positive mental imagery on emotion. Previous experimental studies found that imagining positive events was superior to verbally processing the same events in producing positive affect, and further that field rather than observer perspective imagery had a more powerful impact (Holmes, Coughtrey, & Connor, 2008; Holmes, Mathews, Dalgleish, & Mackintosh, 2006). In the current study, 78 students listened to 100 positive events randomly allocated to one of three conditions (between-subjects): imagining them via a field or an observer perspective or listening to the same events while thinking about their verbal meaning. Positive affect was measured before and after the task. Positive affect change was greater after imagery (field and observer) than the verbal condition, replicating previous research. Contrary to predictions, there was no significant difference in affect change between the field and observer conditions. To explain the latter result, we reflect on methodological explanations. In conclusion, there was greater positive affect change after positive mental imagery than positive verbal thinking. If results can be translated from the lab to the clinic then imaging positive situations may help people feel more positive than only discussing them verbally in therapy.
Depression in Schizophrenia: Associations With Cognition, Functional Capacity, Everyday Functioning, and Self-Assessment

Depressed mood has a complex relationship with self-evaluation of personal competence in multiple populations. The absence of depression may be associated with overestimation of abilities, while mild depression seems to lead to accurate self-assessment. Significant depression may lead to underestimation of functioning. In this study, we expand on our previous work by directly comparing the association between different levels of depression, everyday functioning, cognitive and functional capacity performance, and self-assessment of everyday functioning in a large (n = 406) sample of outpatients with schizophrenia. Participants with very low self-reported depression overestimated their everyday functioning compared with informant reports. Higher levels of depression were associated with more accurate self-assessment, but no subgroup of patients underestimated their functioning. Depressive symptom severity was associated with poorer informant-rated social functioning, but there were no differences in vocational functioning, everyday activities, cognitive performance, and functional capacity associated with the severity of self-reported depression. There was minimal evidence of impact of depression on most aspects of everyday functioning and objective test performance and a substantial relationship between depression and accuracy of self-assessment.
Treatment history in the psychosis prodrome: characteristics of the North American Prodrome Longitudinal Study Cohort

Aim: Early identification and better characterization of the prodromal phase of psychotic illness can lead to targeted treatment and, perhaps, prevention of many of the devastating effects of a first psychotic episode. The primary aim of this manuscript is to describe the treatment histories of a large cohort of individuals who entered into one of seven prodromal research programs in a North American Prodrome Longitudinal Study consortium.
The Three Faces of IT Value: Theory and Evidence

The business value of information technology (IT) has been debated for a number of years. Some authors have found large productivity improvements attributable to computers, and casual observation suggests that IT has generated some benefits for consumers. However, others continue to question whether computers have had any bottom line impact on business performance. In this paper, we argue that productivity, consumer value and business performance are actually separate questions and that the empirical results on IT value depend heavily on which question is being addressed and what data are being used. Applying methods based on economic theory, we are able to test the relevant hypotheses for each of the three questions, using recent firm-level data on IT spending by 367 large firms. Our findings indicate that computers have led to higher productivity and created substantial value for consumers, but that these benefits have not resulted in measurable improvements in business performance. We conclude that while modeling techniques need to be improved, these results are consistent with economic theory, and thus there is no inherent contradiction between high productivity, high consumer value and low business performance.
Tangled nature: a model of evolutionary ecology.

We discuss a simple model of co-evolution. In order to emphasize the effect of interaction between individuals, the entire population is subjected to the same physical environment. Species are emergent structures and extinction, origination and diversity are entirely a consequence of co-evolutionary interaction between individuals. For comparison, we consider both asexual and sexually reproducing populations. In either case, the system evolves through periods of hectic reorganization separated by periods of coherent stable coexistence.
An Active TRIM5 Protein in Rabbits Indicates a Common Antiviral Ancestor for Mammalian TRIM5 Proteins

ABSTRACT The recent identification of antiretroviral tripartite motif-bearing restriction factors that protect against retroviral infection has revealed a novel branch of innate immunity. The factors target the retroviral capsid and inhibit infectivity soon after the capsid has entered the cytoplasm by an incompletely characterized mechanism. Restriction is species specific. For example, TRIM5α from Old World monkeys, but not humans, restricts human immunodeficiency virus type 1 infection. Here, we identify an antiviral TRIM5 molecule in rabbits that is closely related to antiviral TRIM5 of both primates and cattle. We demonstrate that the rabbit TRIM5 protein is active against divergent retroviruses and leads to a strong block to viral DNA synthesis and infectivity. Furthermore, we show that antiviral activity is directed against the viral capsid and that human TRIM5 proteins are dominant negative to restriction in rabbit cells. We propose that the sequence and restriction characteristics conserved between restriction factors from primates, cattle, and rabbits indicate that these factors have evolved from a common ancestor with antiretroviral properties.