Miracle-dz/UniFAR-FTUs huggingface dataset:
PUMA: A Unified Framework for Penalized Multiple Regression Analysis of GWAS Data

Penalized Multiple Regression (PMR) can be used to discover novel disease associations in GWAS datasets. In practice, proposed PMR methods have not been able to identify well-supported associations in GWAS that are undetectable by standard association tests and thus these methods are not widely applied. Here, we present a combined algorithmic and heuristic framework for PUMA (Penalized Unified Multiple-locus Association) analysis that solves the problems of previously proposed methods including computational speed, poor performance on genome-scale simulated data, and identification of too many associations for real data to be biologically plausible. The framework includes a new minorize-maximization (MM) algorithm for generalized linear models (GLM) combined with heuristic model selection and testing methods for identification of robust associations. The PUMA framework implements the penalized maximum likelihood penalties previously proposed for GWAS analysis (i.e. Lasso, Adaptive Lasso, NEG, MCP), as well as a penalty that has not been previously applied to GWAS (i.e. LOG). Using simulations that closely mirror real GWAS data, we show that our framework has high performance and reliably increases power to detect weak associations, while existing PMR methods can perform worse than single marker testing in overall performance. To demonstrate the empirical value of PUMA, we analyzed GWAS data for type 1 diabetes, Crohns's disease, and rheumatoid arthritis, three autoimmune diseases from the original Wellcome Trust Case Control Consortium. Our analysis replicates known associations for these diseases and we discover novel etiologically relevant susceptibility loci that are invisible to standard single marker tests, including six novel associations implicating genes involved in pancreatic function, insulin pathways and immune-cell function in type 1 diabetes; three novel associations implicating genes in pro- and anti-inflammatory pathways in Crohn's disease; and one novel association implicating a gene involved in apoptosis pathways in rheumatoid arthritis. We provide software for applying our PUMA analysis framework.
Effectivenessof Analysisof Free ThyroxinConcentrationin Serum for Diagnosisof Covert ThyroidDisease

The indirect indices of free-thyroxin concentration (fl4) are of limited effectiveness in diagnosing covert (mild) thyroid disease. We compared measurements of if4 and of normalized T4 (NT4, the effective thyroxin ratio) In a group of patients being treated for thyroid disease, most of whom were clinically euthyroid. Aithough if4 values correlated well with NT4, many of the patients (34% in one of the comparisons) had if4 and NT4 values that gave different indications of thyroid status. A review of the patients’ treatment and other biochemical indications revealed that measurements of fT4 were more effective in detecting mild disturbances of thyrometabolic status than were assays for NT4, total 14, total triiodothyronine, or thyrotropin. This study suggests that direct if4 assays are particularly useful in diagnosing covert thyroid disease.
Towards case-mix-adjusted international renal registry comparisons: how can we improve data collection practice?

1The Richard Bright Renal Unit, Southmead Hospital, Westbury on Trym, Bristol BS10 5BW, 2The Renal Association UK Renal Registry, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK, 3United States Renal Data System, 914 South 8th Street, Suite S-406, Minneapolis, MN, USA, 4Australia and New Zealand Dialysis and Transplant Registry, Queen Elizabeth Hospital, 28 Woodville Road, Woodville South 5011, South Australia and 5Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada
Structure and Physiological Actions of Ghrelin

Ghrelin is a gastric peptide hormone, discovered as being the endogenous ligand of growth hormone secretagogue receptor. Ghrelin is a 28 amino acid peptide presenting a unique n-octanoylation modification on its serine in position 3, catalyzed by ghrelin O-acyl transferase. Ghrelin is mainly produced by a subset of stomach cells and also by the hypothalamus, the pituitary, and other tissues. Transcriptional, translational, and posttranslational processes generate ghrelin and ghrelin-related peptides. Homo- and heterodimers of growth hormone secretagogue receptor, and as yet unidentified receptors, are assumed to mediate the biological effects of acyl ghrelin and desacyl ghrelin, respectively. Ghrelin exerts wide physiological actions throughout the body, including growth hormone secretion, appetite and food intake, gastric secretion and gastrointestinal motility, glucose homeostasis, cardiovascular functions, anti-inflammatory functions, reproductive functions, and bone formation. This review focuses on presenting the current understanding of ghrelin and growth hormone secretagogue receptor biology, as well as the main physiological effects of ghrelin.
The cognitive development and school achievement of adopted adolescents: The Greek “Metera” study

The cognitive development and school performance of 52 adopted adolescents, who spent their first two years of life in “Metera” Babies Center in Athens, Greece, were compared with those of 36 who were brought up in their biological families. Adopted adolescents had significantly lower cognitive development and school performance scores than their comparisons, although within the average range according to general population norms. The higher maternal education in the adoptive mothers was associated with higher cognitive scores in adolescence.
Transfer Shock in an Academic Discipline: The Relationship between Students' Majors and their Academic Performance

The study described in this report involved associate's degree recipients who were traditional age and enrolled full-time at a two-year college before pursuing their same majors at a four-year liberal arts college. Based on their majors, students were placed into four discipline categories: fine arts and humanities, mathematics and sciences, social sciences, and professions. The authors analyzed students' preand post-transfer GPAs using a 2 x 4 mixed model ANOVA to determine that no significant differences existed among mean community college GPAs relative to students' majors, and no significant difference existed between twoand four-year college GPAS for the entire sample. The ANOVA did indicate, however, an interaction between location and major on students' GPAs: Tukey's HSD tests revealed a significant decline in the mathematics and sciences mean GPA from the community college to the four-year institution. The authors conclude by defining avenues for further research.
Sexual Antimonies and Parent/Child Sex Education: Learning from Foreclosure

In the journal Sexualities, Jackson and Scott (2004, ‘Sexual Antimonies in Late Modernity’, Sexualities 7[2]: 233-48) express scepticism that current mores in relation to sexuality are increasingly liberal and ‘open’; instead, they suggest there are a number of antimonies or contradictions evident. One of the themes they raise relates to parental intentions (and ‘failures’) to be ‘open’ about sex with their children. I explore this antimony via data collected from parents about the sex education of their young children. I first describe responses to young children’s verbal questions about sex; the second section considers parental responses to questions raised by ‘protosexual play’. As the negotiations that take place between parents and children reveal, many interventions in this area are actually interesting inversions of a straightforward educational endeavour. Instead of ‘openness’, the forms of parental disclosure and foreclosure of sexual information enact a series of closures or enclosures in relation to the exchange of sexual information in the family. The article goes on to consider possible explanations and effects of these antimonies.
Mass segregation in rich LMC clusters from modelling of deep HST colour–magnitude diagrams

Aims. We used the deep colour–magnitude diagrams (CMDs) of five rich LMC clusters (NGC 1805, NGC 1818, NGC 1831, NGC 1868, and Hodge 14) observed with HST/WFPC2 to derive their present day mass function (PDMF) and its variation with position within the cluster. Methods. The PDMF was parameterized as a power law in the available main-sequence mass range of each cluster, typically 0.9 < m/M� < 2.5; its slope was determined at different positions spanning from the very centre out to several core radii. The CMDs in the central regions of the clusters were carefully studied earlier, resulting in accurate age, metallicity, distance modulus, and reddening values. The slope α (where Salpeter is 2.35) was determined in annuli by following two distinct methods: 1) a power law fit to the PDMF obtained from the systemic luminosity function (LF); 2) a statistical comparison between observed and model CMDs. In the second case, α is a free input parameter in the CMD modelling process where we incorporate photometric errors and the effect of binarity as a fraction of unresolved binaries (fbin = 100%) with random pairing of masses from the same PDMF. Results. In all clusters, significant mass segregation is found from the positional dependence of the PDMF slope: α < 1. 8f or R ≤ 1.0 Rcore and α ∼ Salpeter inside R = 2 ∼ 3 Rcore (except for Hodge 14, where α ∼ Salpeter for R ∼ 4 Rcore). The results are robust in the sense that they hold true for both methods used. The CMD method reveals that unresolved binaries flatten the PDMF obtained form the systemic LF, but this effect is smaller than the uncertainties in the α determination. For each cluster we estimated dynamical ages inside the core and for the entire system. In both cases we found a trend in the sense that older clusters have flatter PDMF, consistent with a dynamical mass segregation and stellar evaporation.
Reimagining mission in the public square: Engaging hills and valleys in the African City of Tshwane

This article seeks to map out the future of Christian mission in the city context. African cities like Tshwane are not only expanding, but also present the church with a new frontier that needs to be crossed without crossing geographical boundaries. This article indicates that life in the City of Tshwane is paradoxically placed. Whilst life in the valleys of Tshwane is like walking in the valley of the shadow of death, those on the high hills (the places of power) continue with their dominance and pretence as solution providers, whilst hiding the presence of those who are marginalised. This article proposes that the future of the Christian mission lies not only in identifying those powers, but also in engaging them in a transformative way so as to usher the justice and shalom of God into this highly contested space.
A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer.

PURPOSE Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. A Phase II trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC. EXPERIMENTAL DESIGN A total of 20 patients were treated with a 72-h continuous infusion of flavopiridol every 14 days at a dose of 50 mg/m(2)/day and a concentration of 0.1-0.2 mg/ml. Dose escalation to 60 mg/m(2)/day was permitted if no significant toxicity occurred. Response was initially assessed after every two infusions; patients treated longer than 8 weeks were then assessed after every four infusions. Plasma levels of flavopiridol were measured daily during the first two infusions to determine steady-state concentrations. RESULTS This study was designed to evaluate a total of 45 patients in two stages. However, because no objective responses were seen in the first 20 patients, the early-stopping rule was invoked, and patient accrual was halted. In four patients who received eight infusions, progression was documented at 15, 20, 40, and 65 weeks, respectively. The most common toxicities included grade 1 or 2 diarrhea in 11 patients, asthenia in 10 patients, and venous thromboses in 7 patients. The mean +/- SD steady-state concentration of drug during the first infusion was 200 +/- 89.9 nM, sufficient for cytostatic effects in in vitro models. CONCLUSIONS At the current doses and schedule, flavopiridol does not have cytotoxic activity in NSCLC, although protracted periods of disease stability were observed with an acceptable degree of toxicity.
How Media Frames Move Public Opinion: An Analysis of the Women's Movement

We examine the weekly print media's coverage of the women's move ment and ascertain the presence of five unique frames from the 1950s through the 1990s: a sex roles frame, a feminism frame, political rights frame, economic rights frame, and an anti-feminism frame. After describ ing the frames we discuss an experimental test of four of the media pack ages on voters' political attitudes using a non-random sample of adults. Experimental results indicate that the economic rights and anti-feminism frames had a strong, negative impact on subject attitudes toward gender equality, support for women's rights, support for non-traditional gender roles and the frequency with which subjects mentioned "women's issues" as among the most important issues facing the U.S. In addition, the femi nism frame also exerted negative effects; while, conversely, the political rights frame had a positive influence on similar gender attitudes. Results were moderated by respondent gender with men demonstrating greater susceptibility to issue framing than women.
Primary Cultures of Female Swine Genital Epithelial Cells In Vitro: a New Approach for the Study of Hormonal Modulation of Chlamydia Infection

ABSTRACT Previous studies have demonstrated that female reproductive hormones influence chlamydial infection both in vivo and in vitro. Due to the reduced availability of human genital tissues for research purposes, an alternative hormone-responsive model system was sought to study chlamydial pathogenesis. Mature female swine eliminated from breeding programs were selected as the animals of choice because of the similarity of a sexually transmitted disease syndrome and sequelae in swine to a disease syndrome and sequelae found in humans, because of the near identity of a natural infectious chlamydial isolate from swine to Chlamydia trachomatis serovar D from humans, and because a pig's epithelial cell physiology and the mean length of its estrous cycle are similar to those in humans. Epithelial cells from the cervix, uterus, and horns of the uterus were isolated, cultivated in vitro in Dulbecco's minimum essential medium-Hanks' F-12 (DMEM-F-12) medium with and without exogenous hormone supplementation, and analyzed for Chlamydia suis S-45 infectivity. The distribution of chlamydial inclusions in swine epithelial cells was uneven and was influenced by the genital tract site and hormone status. This study confirmed that, like primary human endometrial epithelial cells, estrogen-dominant swine epithelial cells are more susceptible to chlamydial infection than are progesterone-dominant cells. Further, the more differentiated luminal epithelial cells were more susceptible to infection than were glandular epithelial cells. Interestingly, chlamydial growth in mature luminal epithelia was morphologically more active than in glandular epithelia, where persistent chlamydial forms predominated. Attempts to reprogram epithelial cell physiology and thereby susceptibility to chlamydial infection by reverse-stage, exogenous hormonal supplementation were unsuccessful. Freshly isolated primary pig epithelial cells frozen at −80°C in DMEM-F-12 medium with 10% dimethyl sulfoxide for several weeks can, after thawing, reform characteristic polarized monolayers in 3 to 5 days. Thus, primary swine genital epithelia cultured ex vivo appear to be an excellent cell model for dissecting the hormonal modulation of several aspects of chlamydial pathogenesis and infection.
Diagnosis of asthma and permitted use of inhaled β2‐agonists in athletes

The prevalence of asthma and bronchial hyperreactivity has been reported to be higher in athletes than in the general population. This has also been related to reported asthma in order to obtain permitted use of β2‐agonists, whose assumption in athletes is ruled by anti‐doping regulations. The paper addresses the issue whether the recently established and evaluated rules of the International Olympic Committee on tests and procedures for diagnosis of asthma in athletes and permitted use of β2‐agonists are consistent with an adequate diagnosis and management of asthma according to international guidelines.
Peer-to-peer discovery of computational resources for Grid applications

Grid applications need to discover computational resources quickly, efficiently and scalably, but most importantly in an expressive manner. An expressive query may specify a variety of required metrics for the job, e.g., the number of hosts required, the amount of free CPU required on these hosts, and the minimum amount of RAM required on these hosts, etc. We present a peer-to-peer (P2P) solution to this problem, using structured naming to enable both (1) publishing of information about available computational resources, as well as (2) expressive and efficient querying of such resources. Extensive traces collected from hosts within the Computer Science department at UIUC are used to evaluate our proposed solution. Finally, our solutions are based upon a well known P2P system called Pastry, albeit for Grid applications; this is another step towards the much-needed convergence of Grid and P2P computing.
Coordinated Interactions of Multiple POT1-TPP1 Proteins with Telomere DNA*

Background: POT1 and TPP1 protect the ends of human telomeres. Results: The secondary structure of single-stranded DNA alters the coordinated binding of multiple POT1-TPP1 proteins. Conclusion: Single-stranded telomere DNA is more susceptible to DNase I digestion when coated with POT1-TPP1 proteins. Significance: By altering DNA properties, coating of telomere DNA by POT1-TPP1 proteins may have a functional role in telomere maintenance. Telomeres are macromolecular nucleoprotein complexes that protect the ends of eukaryotic chromosomes from degradation, end-to-end fusion events, and from engaging the DNA damage response. However, the assembly of this essential DNA-protein complex is poorly understood. Telomere DNA consists of the repeated double-stranded sequence 5′-TTAGGG-3′ in vertebrates, followed by a single-stranded DNA overhang with the same sequence. Both double- and single-stranded regions are coated with high specificity by telomere end-binding proteins, including POT1 and TPP1, that bind as a heterodimer to single-stranded telomeric DNA. Multiple POT1-TPP1 proteins must fully coat the single-stranded telomere DNA to form a functional telomere. To better understand the mechanism of multiple binding, we mutated or deleted the two guanosine nucleotides residing between adjacent POT1-TPP1 recognition sites in single-stranded telomere DNA that are not required for multiple POT1-TPP1 binding events. Circular dichroism demonstrated that spectra from the native telomere sequence are characteristic of a G-quadruplex secondary structure, whereas the altered telomere sequences were devoid of these signatures. The altered telomere strands, however, facilitated more cooperative loading of multiple POT1-TPP1 proteins compared with the wild-type telomere sequence. Finally, we show that a 48-nucleotide DNA with a telomere sequence is more susceptible to nuclease digestion when coated with POT1-TPP1 proteins than when it is left uncoated. Together, these data suggest that POT1-TPP1 binds telomeric DNA in a coordinated manner to facilitate assembly of the nucleoprotein complexes into a state that is more accessible to enzymatic activity.
Education for sale: at what cost? Lifelong learning and the marketplace

This paper examines the influence of the marketplace on discourses in lifelong learning and raises questions about the future direction of these discussions, drawing upon critical and feminist analyses. A brief overview of how the notion of lifelong learning has shifted from an emphasis on cooperation and shared development to a discourse of competition and individualism is given. Drawing upon the works of various educators, an overview is given of some of the ways in which the marketplace has influenced lifelong learning discourses and has become a pervasive presence in academia. Both critical and feminist analyses are used to examine how justice, equity issues, and critical thinking are suppressed when the marketplace becomes a predominant influence in education. An assessment of questions raised by educators working to challenge this marketplace orientation in lifelong learning and suggestions for further areas of research conclude the paper.
Comparative analysis of children’s narratives at different ages: A multimodal approach

This study addresses two questions. The first question is about how children integrate linguistic, prosodic and kinesic resources into organised discourse behaviour such as oral narratives. Three event reports produced spontaneously by 9- to 11-year-old French children during interviews with an adult were extracted from a video corpus. A detailed analysis of these on four dimensions (discourse construction, voice and prosody, co-speech gestures and facial expressions, gaze direction) reveals a remarkable ability in children of this age to use prosodic and kinesic resources to frame and structure their narrative, to dramatise and enliven the recounted events, and to comment on them or on the narration. The second question stresses the developmental aspect of multimodal narrative behaviour. 32 event reports extracted from the same corpus and produced by French children aged from 6 to 11 years were analysed in a similar way and rated by two independent coders. This second study leads us to distinguish between three levels of narrative performance which appear to coincide by age. The multimodal study of oral narratives thus shows how and when children gradually become genuine narrators.