Miracle-dz/UniFAR-FTUs huggingface dataset:
Shc adaptor proteins are key transducers of mitogenic signaling mediated by the G protein‐coupled thrombin receptor.

The serine protease thrombin activates G protein signaling systems that lead to Ras activation and, in certain cells, proliferation. Whereas the steps leading to Ras activation by G protein‐coupled receptors are not well defined, the mechanisms of Ras activation by receptor tyrosine kinases have recently been elucidated biochemically and genetically. The present study was undertaken to determine whether common signaling components are used by these two distinct classes of receptors. Here we report that the adaptor protein Shc, is phosphorylated on tyrosine residues following stimulation of the thrombin receptor in growth‐responsive CCL39 fibroblasts. Shc phosphorylation by thrombin or the thrombin receptor agonist peptide is maximal by 15 min and persists for > or = 2 h. Following thrombin stimulation, phosphorylated Shc is recruited to Grb2 complexes. One or more pertussis toxin‐insensitive proteins appear to mediate this effect, since (i) pertussis toxin pre‐treatment of cells does not blunt the action of thrombin and (ii) Shc phosphorylation on tyrosine can be stimulated by the muscarinic m1 receptor. Shc phosphorylation does not appear to involve protein kinase C, since the addition of 4‐beta‐phorbol‐12,13‐dibutyrate has no effect. Rather, thrombin‐induced Shc phosphorylation is enhanced in cells depleted of phorbol ester‐sensitive protein kinase C isoforms. Expression of mutant Shc proteins defective in Grb2 binding displays a dominant‐negative effect on thrombin‐stimulated p44 MAP kinase activation, gene induction and cell growth. From these data, we conclude that Shc represents a crucial point of convergence between signaling pathways activated by receptor tyrosine kinases and G protein‐coupled receptors.
Type, Content, and Source of Social Support Perceived by Women during Pregnancy: Evidence from Matlab, Bangladesh

Specific and contextualized data on social support during distinct health events are needed to improve social support interventions. This study identified the type, content, and source of social support perceived by women during pregnancy. In-depth interviews with 25 women, aged 18-49 years, living in Matlab, Bangladesh, were conducted. The findings demonstrated that women perceived, the receipt of eight distinct types of support. The four most frequently-mentioned types included: practical help with routine activities, information/advice, emotional support and assurance, as well as the provision of resources and material goods. Sources varied by type of support and most frequently included-—mothers, mothers-in-law, sisters-in-law, and husbands. Examples depicting the content of each type of support revealed culturally-specific issues that can inform community-based social support interventions.
Impact of ACA Insurance Coverage Expansion on Perforated Appendix Rates Among Young Adults

Background:The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act allowed young adults to remain on their parents’ health insurance plans until age 26 years. Although the provision improved coverage and survey-reported access to care, little is known regarding its impact on timely access for acute conditions. This study aims to assess changes in insurance coverage and perforation rates among young adults with acute appendicitis—an established metric for population-level health care access—after the DCP. Methods:The National Inpatient Sample and difference-in-differences linear regression were used to assess prepolicy/postpolicy changes for policy-eligible young adults (aged 19–25 y) compared with a slightly older, policy-ineligible comparator group (aged 26–34 y). Results:After adjustment for covariates, 19–25 year olds experienced a 3.6-percentage point decline in the uninsured rate after the DCP (baseline 22.5%), compared with 26–34 year olds (P<0.001). This coincided with a 1.4-percentage point relative decline in perforated appendix rate for 19–25 year olds (baseline 17.5%), compared with 26–34 year olds (P=0.023). All subgroups showed significant reductions in uninsured rates; however, statistically significant reductions in perforation rates were limited to racial/ethnic minorities, patients from lower-income communities, and patients presenting to urban teaching hospitals. Conclusions:Reductions in uninsured rates among young adults after the DCP were associated with significant reductions in perforated appendix rates relative to a comparator group, suggesting that insurance expansion could lead to fewer delays in seeking and accessing care for acute conditions. Greater relative declines in perforation rates among the most at-risk subpopulations hold important implications for the use of coverage expansion to mitigate existing disparities in access to care.
Thyroid hormones and cytogenetic outcomes in backpack sprayers using ethylenebis(dithiocarbamate) (EBDC) fungicides in Mexico.

Ethylenebis(dithiocarbamate) (EBDC) fungicides are used heavily in the United States. EBDCs (e.g., mancozeb, maneb) are metabolized to ethylene thiourea (ETU). The EPA classifies ETU as a carcinogen, based on thyroid and other cancers in rodents, and has restricted the use of EBDCs, while requiring workers to use protective equipment. There are no data on the potential carcinogenicity of EBDCs in humans, and there is only one study on human genotoxicity. ETU is known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. We have studied cytogenetic outcomes and serum thyroid hormone levels among 49 heavily exposed workers without protective equipment spraying EBDC on tomatoes in Mexico. We also studied 14 lightly exposed landowners and 31 nonexposed controls. Urinary ETU was used to compare exposure between groups. We found an increase in TSH (p = 0.05) among applicators compared to controls, but no decrease in thyroid hormone (T4). We found increases in sister chromatid exchange (p = 0.03) and in chromosome translocations (chromosome aberrations that persist through cell division) for applicators compared to controls (p = 0.05). However, the subset of reciprocal translocations showed a lesser increase (p = 0.24). Our data suggest that EBDCs affect the thyroid gland and the lymphocyte genome among heavily exposed workers. However, our data are limited to subclinical outcomes, are of borderline statistical significance, and should be interpreted with caution. ImagesFigure 1.
Over-Expression of GmGIa-Regulated Soybean miR172a Confers Early Flowering in Transgenic Arabidopsis thaliana

Flowering is a pivotal event in the life cycle of plants. miR172 has been widely confirmed to play critical roles in flowering time control by regulating its target gene expression in Arabidopsis. However, the role of its counterpart in soybean remains largely unclear. In the present study, we found that the gma-miR172a was regulated by a GIGANTEA ortholog, GmGIa, in soybean through miRNA metabolism. The expression analysis revealed that gma-miR172a has a pattern of diurnal rhythm expression and its abundance increased rapidly as plants grew until the initiation of flowering phase in soybean. One target gene of gma-miR172a, Glyma03g33470, was predicted and verified using a modified RLM 5′-RACE (RNA ligase-mediated rapid amplification of 5′ cDNA ends) assay. Overexpression of gma-miR172a exhibited an early flowering phenotype and the expression of FT, AP1 and LFY were simultaneously increased in gma-miR172a-transgenic Arabidopsis plants, suggesting that the early flowering phenotype was associated with up-regulation of these genes. The overexpression of the gma-miR172a-resistant version of Glyma03g33470 weakened early flowering phenotype in the toe1 mutant of Arabidopsis. Taken together, our results suggested that gma-miR172a played an important role in GmGIa-mediated flowering by repressing Glyma03g33470, which in turn increased the expression of FT, AP1 and LFY to promote flowering in soybean.
Evaluation of LED therapy at 945nm on bone repair by micro x-ray fluorescence spectroscopy and scanning electron microscopy

Phototherapy is able to modulate cellular metabolism of bone tissue and consequently accelerate the repair. The aim of this study was to evaluate the effect of this therapy in repair of bone monocortical defects in femurs of thirty male Wistar rats. The animals were divided into six groups (five animals for group), including three controls and three irradiated groups with different experimental times (14, 21, and 28 days after surgery). LED was used for the irradiation, emitting non-coherent light in the spectral range of 945±20 nm and output power of 48 mW, on one point of irradiation for four minutes. Seven treatment sessions were performed with 48 hours between sessions. For analysis on the bone repair, qualitative and quantitative assessments of Ca and P contents were done by micro x-ray fluorescence spectroscopy (μXRF) and the morphological structure was carried out using Scanning Electron Microscopy (SEM). The results showed the efficiency of infrared LED therapy, because the amount of mineral components analyzed by μXRF and the morphological features of cortical and trabecular bones, demonstrated by the SEM images, showed enhanced bone repair in the irradiated groups when compared to their corresponding control groups at all stages.
Legality and Venture Governance Around the World

We analyze governance with a dataset on investments of venture capitalists in 3848 portfolio firms in 39 countries from North and South America, Europe and Asia spanning 1971-2003. We find that cross-country differences in Legality have a significant impact on the governance structure of investments in the VC industry: better laws facilitate faster deal screening and deal origination, a higher probability of syndication and a lower probability of potentially harmful co-investment, and facilitate board representation of the investor. We also show better laws reduce the probability that the investor requires periodic cash flows prior to exit, which is in conjunction with an increased probability of investment in high-tech companies.
Assisted reproduction techniques for HIV serodiscordant couples: 18 months of experience.

BACKGROUND Assisted reproduction techniques can minimize the risk of infection and treat possible sterility associated with serodiscordant couples. METHODS We assessed the efficacy of these techniques in 57 couples in which at least one partner had human immunodeficiency virus (HIV-1) infection that was currently under control (47 men and 10 women). The semen of seropositive men was prepared and tested for viruses. Assisted reproduction techniques included intrauterine insemination (IUI), IVF and especially ICSI, with ovarian stimulation that used a long agonist protocol and recombinant FSH. Embryos were transferred on day 3 after oocyte retrieval. RESULTS For couples with seropositive men, five IUI and 49 IVF or ICSI attempts were perfomed, whilst for seropositive women these numbers were three IUI and 12 IVF or ICSI. No pregnancy occurred following the eight IUI trials. Seroconversion was not observed in any partners of seropositive men. Efficacy of treatment for these couples with ICSI was good, the clinical pregnancy rate per embryo transfer was 48.8%. The results for seropositive women were disappointing, with a clinical pregnancy rate per embryo transfer of 9.1%. Fourteen babies from 47 treated couples have so far been born and no pregnancies from IUI. CONCLUSIONS Assisted reproduction techniques and particularly ICSI provide HIV-1-seropositive men with a safe and highly effective means of fathering children. These techniques may be less effective for seropositive women.
Inactivation of ICa‐L is the major determinant of use‐dependent facilitation in rat cardiomyocytes

Two models have been proposed to explain facilitation of the L‐type calcium current (ICa‐L). A positive feedback model proposes that calcium released during a conditioning pulse (I1) facilitates the subsequent pulse (I2) via calmodulin/calmodulin kinase II (CaMKII) mechanisms. The negative feedback model proposes that the calcium release of each pulse feeds back on itself via calcium‐dependent inactivation. The relative physiological roles were evaluated in rat ventricular myocytes. Paired pulses (450 ms interpulse interval) elicited facilitation (I2 of 872 ± 145 versus I1 of 777 ± 132 pA, P < 0.01). Inactivation time (T0.37) was prolonged for I2versus I1 (22 ± 2 and 16 ± 2 ms, P > 0.01). Evidence for the negative feedback mechanism includes: (a) ryanodine (0.3 mm) eliminated facilitation, surprisingly by increasing the amplitude of I1 more than that of I2 (1039 ± 216 and 977 ± 186 pA) and eliminated the difference in T0.37 between I2 and I1 (33.1 ± 4.5 versus 32.5 ± 4.6 ms); (b) an outward I2, which does not trigger sarcoplasmic reticulum (SR) Ca2+ release, eliminated facilitation even when it was conditioned by an inward I1; (c) facilitation decayed as the I1–I2 interval lengthened (time constant (τ) = 16.9 ± 1.4 s); (d) thapsigargin (0.1 μm) slowed this decay (τ= 43.8 ± 11.7 s) whereas isoproterenol accelerated it (τ> = 5.6 ± 1.4 s, P < 0.01) and T0.37 paralleled this decay; and (e) the magnitude of ICa‐L was negatively correlated with the sodium‐calcium exchange current (INa/Ca) elicited by the SR‐Ca2+ release. In conclusion, Ca2+‐dependent inactivation of ICa‐L is the major mechanism underlying facilitation.
Early life events and their consequences for later disease: A life history and evolutionary perspective

Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk—the “developmental origins of health and disease” (DOHaD) paradigm—have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences—the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy‐dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention. Am. J. Hum. Biol. 19:1–19, 2007. © 2006 Wiley‐Liss, Inc. © 2006 Wiley‐Liss, Inc.
Child Care

clearly in the handbook written by ~ Agatha Bowley,! and the case reports Wbl she quotes are very human stories. It is early yet to offer any serious critJcisJIj of the national schemes for the care children, but the most obvious disadvant~ from which the Children's Committees sU tbt is that they have no functions relating to '0 preventiol1 of unhappiness or delinqueIlcY ~o the home. The Children's Officer haslet! statutory powers unless and until the I1e~~ or disharmony in the home has re? ~f such a pitch that the child is sertoes suffering. It is true that in these early sta~t; the Health Visitors from the Health Dep~1\l ment playa very important part and dur~. the past gener~tion ha~e contribu~e~ en J mously to theIr happllless in mllh.et homes by their timely and friendly ad\~p and by the material and spiritual b to which their organization has been ableti6 give. The greatest danger for the future ot in the possibility that these two importa~ committees will each act without refere~~ h . "blO' to t e other. There are many ways In \ tilt this may be avoided. In BirminghaJ1lbest medical care and supervision of t cC children is provided by the medical otli" of health and his staff, aild in this "'~} cd close degree of co-operation is obtal~~ between the two departments, aIld btf system has been adopted by many O~OOI authorities. The best means of co-oper~cC however, is the small committee at ° 100 level, which most authorities have set ~lP J the advice of the Home Olice, consistlllgJl'1 representative officers from the ChiId;tlll Department, the Health Department all ! Jttl Education Department. Other mp ~ may be co-opted to this committee sUc tioO the N.S. P.C. C. inspector, the prob; tJll officer and the local representative 0 l1all National Assistance Board. In a S~tte' authority the members of this cO l1l1l1\ jn can be the chief officers themselves, ~ttl, IJl larger areas the work must of necesS) \te' delegated to assistants. At such a COI1lIlll~ it is possible, if the way has been prep:J fof beforehand by the necessary dOCUll1eIl~lel1tS the children at risk to have their pro d ~lt examined with sympathy and care, all \,cot most appropriate action taken first to pre l\IEDICINE
Systematic observations of autistic behavior.

IN 1943, Kanner published his first description of early infantile autism in which the characteristic features of the illness consisted of a profound withdrawal from contact with people existing "from the beginning of life," an obsessive desire for the preservation of sameness, a skillful and even affectionate relation to objects, the retention of an intelligent and pensive physiognomy, and either mutism or noncommunicative speech. 1-3 The syndrome has subsequently become one of the most provocative and controversial targets of psychiatric research, with most of the work being focused in the areas of ego development, personal relations, affect, and language development. In only a few recent studies has serious attention been given to the unusual and stereotyped motor and perceptual behaviors frequently seen in these children. It is our conjecture that these behavioral characteristics are indeed significant and may actually provide a key to
PD-L1 Blockade Attenuated Sepsis-Induced Liver Injury in a Mouse Cecal Ligation and Puncture Model

Liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome and it is of vital importance in host defense and bacteria clearance. Our previous studies indicated that programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are crucial modulators of host immune responses during sepsis. Our current study was designed to investigate the role of PD-L1 in sepsis-induced liver injury by a mouse cecal ligation and puncture (CLP) model. Our results indicated that there was a significant increase of PD-L1 expression in liver after CLP challenge compared to sham-operated controls, in terms of levels of mRNA transcription and immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus, anti-PD-L1 antibody might have a therapeutic potential in attenuating liver injury in sepsis.
Multi-Mechanical Approach to Structural Performance Assessment of Corroded RC Members in Shear

A multi-mechanical model that explicitly takes into account corrosion cracks in structural safety performance is presented to deal with materialized corrosive substances around steel bars and equilibrated damage in structural concrete. The multi-mechanics of corrosive product and cracked concrete are integrated with nonlinear multi-directional fixed crack modeling so that corrosion cracks in structural concrete can be simulated in a unified manner. Structural analysis of corroded RC beams is carried out for experimental verification of the multi-mechanical model in terms of shear capacity and ductility. RC beams, which primarily fail in shear or flexure, are discussed and special attention is addressed to the conversion of failure modes and the absolute capacity. Consideration of inherent cracking on corroded RC members is proven to be crucial for structural performance assessment and the anchorage failure of longitudinal reinforcement is found to cause considerable decay of member capacity.
Optimal Distributed Online Prediction Using Mini-Batches

Online prediction methods are typically presented as serial algorithms running on a single processor. However, in the age of web-scale prediction problems, it is increasingly common to encounter situations where a single processor cannot keep up with the high rate at which inputs arrive. In this work, we present the distributed mini-batch algorithm, a method of converting many serial gradient-based online prediction algorithms into distributed algorithms. We prove a regret bound for this method that is asymptotically optimal for smooth convex loss functions and stochastic inputs. Moreover, our analysis explicitly takes into account communication latencies between nodes in the distributed environment. We show how our method can be used to solve the closely-related distributed stochastic optimization problem, achieving an asymptotically linear speed-up over multiple processors. Finally, we demonstrate the merits of our approach on a web-scale online prediction problem.
Hypothetical Intertemporal Consumption Choices

The paper extends and replicates part of the analysis by Barsky, Juster, Kimball, and Shapiro (1997), which exploits hypothetical choices among different consumption streams to infer intertemporal substitution elasticities and rates of time preference.We use a new and much larger dataset than Barsky et al. Furthermore, we estimate structural models of intertemporal choice, while parameterizing the parameters of interest as a function of relevant individual characteristics.We also consider lobehaviorallc extensions, like habit formation.Models with habit formation appear to be superior to models with intertemporally additive preferences.
ABO blood groups and birth weight

We have previously reported a high sex ratio among newborn infants of B group compatible with their mothers. Further analysis of 631 consecutive newborn infants from the population of Rome has shown the following. The proportion of B compatible females is lower than expected on the basis of ABO gene frequencies. The mean birth weight of these infants is about 300 g. below the mean level for females (p.∼0.01). No similar deviation are observed among male newborn infants. The data suggest that XX zygotes of B group compatible with their mothers may experience a relative disantvantage during intrauterine life, resulting in a sex ratio deviation in favour of males. Previous investigations on the relationship between birth weight and blood groups have given contrasting results. The present data indicate that such relationship does indeed exist and it is influenced by the sex of infant and the feto-maternal ABO compatibility.