Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance to tamoxifen‐induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer

Overexpression of Her2/neu is implicated in the development of resistance to the antiestrogen tamoxifen (TAM) that exerts its inhibitory effect through interaction with estrogen receptor (ER). Whereas Her2/neu and ER are believed to be important cell survival/death factors in human breast cancer cells, if and how they interact to confer resistance to hormone therapy is not known. This prompted us to investigate whether modulation of the effect of TAM occurs via the Her2/neu pathway and whether targeting the interaction between the Her2/neu pathway and the ER pathway is beneficial. There are 2 forms of ER that are localized to the cell membrane and to the nucleus. For the first time, we found that Her2/neu directly interacts with ER at the cell membrane. We then investigated the role of Her2/neu overexpression in the regulation of the cell membrane ER pathway in TAM‐resistant breast cancer cells and the nature of this interaction in apoptotic signaling. Relief of TAM resistance was associated with Her2/neu downregulation and ER upregulation. TAM‐induced apoptosis occurred immediately after dissociation of Her2/neu from cell membrane ER. These results demonstrate a novel mechanism by which Her2/neu regulates the cell membrane ER‐coupled apoptosis and the possible involvement of the Her2/neu in TAM resistance of breast cancer cells. Moreover, the antiproliferative activity of TAM should rely on the integration between the signal transduction from the cell membrane ER and the gene regulation by the nuclear ER. Coordinated modulation on the cell membrane ER/Her2/neu pathway and the nuclear ER/RAR pathway may provide a new approach for treatment of ER‐positive, Her2/neu overexpressing breast cancer. © 2001 Wiley‐Liss, Inc.
Age- and Sex-Related Differences in Spontaneous Hemorrhage and Fibrosis of the Pancreatic Islets in Sprague–Dawley Rats

To elucidate the spontaneous occurrence of hemorrhage in the pancreatic islet, naïve Crj:CD(SD)IGS rats were given a commercially available standard diet ad libitum over 20 weeks, and were sequentially examined. Islet hemorrhage was morphologically observed from 12 weeks of age, and its incidence was significantly higher in males than in females, with a wide distribution in all pancreatic lobes. The incidence (%) of affected islets to examined islets was increased with age. Hemorrhage was accompanied by brownish pigmentation, and reacted positively for iron by Prussian/Berlin blue staining. In 26 weeks old, most of the islets were dissected by dense fibrous tissue into small nests, and disarranged β cells were detected by insulin immunostaining. Ultrastructurally, no apparent morphological change was seen in any islet endothelial cell, although blood leakage with migrated macrophages and dense collagen fibers was observed around the capillaries. In serum biochemistry of rats aged 26 weeks, the estradiol level in males with hemorrhage was significantly lower than that in males with non-hemorrhage, presumably suggesting the lack of capillary protective ability. Next, when rats were given a high fat/protein diet over 20 weeks to clarify whether it accelerated the frequency or timing of hemorrhage, its occurrence was essentially identical to that of the animals fed the standard diet. In conclusion, the onset of spontaneous islet hemorrhage was observed predominantly in aged males, resulting from the low estradiol level in serum.
Climatic stability and genetic divergence in the tropical insular lizard Anolis krugi, the Puerto Rican ‘Lagartijo Jardinero de la Montaña’

Two factors that can lead to geographic structuring in conspecific populations are barriers to dispersal and climatic stability. Populations that occur in different physiographic regions may be restricted to those areas by physical and/or ecological barriers, which may facilitate the formation of phylogeographic clades. Long‐term climatic stability can also promote genetic diversification, because new clades are more likely to evolve in areas that experience lesser climatic shifts. We conducted a phylogeographic study of the Puerto Rican lizard Anolis krugi to assess whether populations of this anole show genetic discontinuities across the species’ range, and if they do, whether these breaks coincide with the boundaries of the five physiographic regions of Puerto Rico. We also assessed whether interpopulation genetic distances in A. krugi are positively correlated with relative climatic stability in the island. Anolis krugi exhibits genetic structuring, but the phylogroups do not correspond to the physiographic regions of Puerto Rico. We used climatic reconstructions of two environmental extremes of the Quaternary period, the present conditions and those during the last glacial maximum (LGM), to quantify the degree of climatic stability between sampling locations. We documented positive correlations between genetic distances and relative climatic stability, although these associations were not significant when corrected for autocorrelation. Principal component analyses indicated the existence of climatic niche differences between some phylogeographic clades of A. krugi. The approach that we employed to assess the relationship between climatic stability and the genetic architecture of A. krugi can also be used to investigate the impact of factors such as the spatial distribution of food sources, parasites, predators or competitors on the genetic landscape of a species.
Mutations on a random binary tree with measured boundary

Consider a random real tree whose leaf set, or boundary, is endowed with a finite mass measure. Each element of the tree is further given a type, or allele, inherited from the most recent atom of a random point measure (infinitely-many-allele model) on the skeleton of the tree. The partition of the boundary into distinct alleles is the so-called allelic partition. In this paper, we are interested in the infinite trees generated by super-critical, possibly time-inhomogeneous, binary branching processes, and in their boundary, which is the set of particles 'co-existing at infinity'. We prove that any such tree can be mapped to a random, compact ultrametric tree called coalescent point process, endowed with a 'uniform' measure on its boundary which is the limit as t → ∞ of the properly rescaled counting measure of the population at time t. We prove that the clonal (i.e., carrying the same allele as the root) part of the boundary is a regenerative set that we characterize. We then study the allelic partition of the boundary through the measures of its blocks. We also study the dynamics of the clonal subtree, which is a Markovian increasing tree process as mutations are removed.
The effect of neighborhood disadvantage, social ties, and genetic variation on the antisocial behavior of African American women: A multilevel analysis

Abstract Social disorganization theory posits that individuals who live in disadvantaged neighborhoods are more likely to engage in antisocial behavior than are those who live in advantaged neighborhoods and that neighborhood disadvantage asserts this effect through its disruptive impact on social ties. Past research on this framework has been limited in two respects. First, most studies have concentrated on adolescent males. In contrast, the present study focused on a sample of adult African American females. Second, past research has largely ignored individual-level factors that might explain why people who grow up in disadvantaged neighborhoods often do not engage in antisocial behavior. We investigated the extent to which genetic variation contributes to heterogeneity of response to neighborhood conditions. We found that the impact of neighborhood disadvantage on antisocial behavior was mediated by neighborhood social ties. Further, the analysis indicated that the effects of neighborhood disadvantage and social ties on antisocial behavior were moderated by genetic polymorphisms. Examination of these moderating effects provided support for the differential susceptibility model of Gene × Environment. The effect of Gene × Neighborhood Disadvantage on antisocial behavior was mediated by the effect of Gene × Neighborhood Social Ties, providing support for an expanded view of social disorganization theory.
Apoptosis of Bovine Granulosa Cells After Serum Withdrawal Is Mediated by Fas Antigen (CD95) and Fas Ligand1

Abstract Ovarian follicular atresia occurs by apoptosis of granulosa and theca cells. The Fas antigen (Fas), a cell surface receptor that triggers apoptosis when activated by Fas ligand (FasL), may be involved in this process. A possible role of the Fas pathway in mediating serum withdrawal-induced apoptosis of granulosa cells was examined. Granulosa cells collected from 5- to 10-mm bovine follicles were cultured in DMEM-F12 containing serum for 3 days, deprived of serum, and live cells were counted at various times after serum withdrawal. Cell death increased significantly 6 h after serum withdrawal (21% ± 7%; P < 0.05 vs. 0 h) and continued to increase until 24 h (43% ± 6%). No further increases in cell death were observed through 72 h. Detection of the translocation of phosphatidylserine to the outer surface of the cell membrane by annexin V binding indicated that cells died by apoptosis. Quantitative reverse transcriptase-polymerase chain reaction assays showed no changes in Fas mRNA levels but a 4.7-fold increase in FasL mRNA 3 h after serum withdrawal (P < 0.05 vs. 0 h). FasL mRNA remained elevated through 24 h and returned to basal levels at 48 h. Immunohistochemical staining showed that both Fas and FasL protein increased on the cell surface within 3 h and remained elevated through 12 h (the last time point tested). Binding of FasL to Fas was blocked with two reagents that bind to the extracellular domain of FasL: an anti-FasL antibody and Fas:Fc, a chimeric protein consisting of the Fc portion of human immunoglobulin G and the extracellular domain of human Fas. Cell death 24 h after serum withdrawal was reduced 55% ± 10% and 34% ± 12% by anti-FasL antibody and Fas:Fc, respectively (P < 0.05 vs. no blocking protein). In conclusion, serum withdrawal-induced apoptosis of bovine granulosa cells is mediated at least partially by Fas/FasL interactions. These results are consistent with a potential role of Fas in an autocrine or paracrine pathway to trigger ovarian follicular atresia.
Corporate Social Responsibility Beyond Law, Through Law, for Law

The adoption of Corporate Social Responsibility (CSR) policies is no longer a matter of voluntary practice on the part of business. In one sense it was never really voluntary, being in most cases a response to market pressures and reputational risk. But increasingly CSR is also subject to legal pressure and legal enforcement, not necessarily in the form of conventional state regulation but rather through indirect state pressure and through the use of private law by private actors, sometimes through highly innovative uses of law. This paper analyses and critically assesses the market forces pressing for CSR. It then demonstrates the range of mechanisms being used to foster and enforce 'voluntary' CSR through law. However it also shows a two way relationship between CSR and law with market pressures being used to press for a new sense of responsibility in how business approaches legal compliance, with the emphasis on compliance with the spirit, not just the letter of the law. The paper demonstrates a widening range of governance methods being brought into play to form a new corporate accountability.
Photonic-Crystal-Slab-Type Guided Mode Resonance Filters in Infrared Range

Transmission characteristics of photonic crystal (PhC)-slab-type guided mode resonance (GMR) filters in the infrared range (4-10 mum) are studied numerically and experimentally. Using a finite-difference time-domain method, the dependencies of the spectral response with the depth and size of holes are investigated and analyzed. The GMR filters were fabricated on a silicon-on-insulator wafer and the experimental transmission spectra were compared with the simulations. In this context, we identified a list of conditions for the realization of PhC-slab-type GMR filters in the infrared range.
Corporate Accountability in Disclosing Carbon Information: Evidence from a Developing Nation

The issue of climate change has been a significant concern globally both in the developed and developing economies. This study aims to uncover the quality of carbon information disclosed in a developing country i.e. Malaysia. A content analysis of the annual and sustainability reports of Top 100 companies in environmentally-sensitive industries in Malaysia over a two-year period in 2011 and 2014 was undertaken. The results revealed that the quality of carbon information provided by companies improved over the two-year period and the changes were significant. The companies were also beginning to translate quantitative details into monetary amounts. The dimension Carbon reduction and costs had the highest mean score for both years. The findings revealed that the construction industry had the lowest mean score for all dimensions in both years and this finding is a concern as activities of the construction industry are generally known to have numerous effects on the environment. The findings from the study revealed that companies are taking the initiatives to set carbon reduction targets to be achieved in the future, hence, a signal of enhanced corporate environmental accountability. Nevertheless, the overall low disclosure of carbon information may require the intervention from stakeholders to improve the quality of the report.
Mutations simultaneously affecting endonuclease II and exonuclease III in Escherichia coli.

We studied mutants of E. coli originally identified as being deficient in either endonuclease II (deoxyribonucleate oligonucleotidohydrolase, EC 3.1.4.30) or exonuclease III [deoxyribonucleate (double-stranded) 5'-nucleotidohydrolase, EC 3.1. 4.27] activity. Twelve independently derived mutants were tested, including three new endonuclease II mutants. Deficiency of one enzyme was always accompanied by deficiency of the other. Furthermore, temperature-sensitivity of one activity was always accompanied by temperature-sensitivity of the other, and the enzymes were co-purified. The results suggested a physical association between exonuclease III and endonuclease II, which may be of advantage in the excision-repair of DNA. A thermolabile endonuclease II was purified from one of the new mutants, indicating that it had an altered structural gene. This mutation, and all similar ones mapped by genetic transduction, was located between the pncA and aroD genes on the E. coli chromosome. One mutant had a prolonged generation time, an increased sensitivity to the alkylating agents methyl-methanesulfonate and mitomycin C, and a decreased plating efficiency for bacteriophage lambda, but no marked sensitivity to ultraviolet or gamma-irradiation. Its enzymatic and biological abnormalities were simultaneously revertible, suggesting they were caused by a single mutation. These results suggested a role for these enzymes in normal cell growth processes and in the repair of alkylation damage.
Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p < 0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p < 0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG.
'I could have just done with a little more help': an analysis of women's help-seeking from health visitors in the context of domestic violence.

Domestic violence is a serious issue that adversely affects large numbers of women and children. Despite having an adverse impact upon health and welfare, women experiencing domestic violence face a number of difficulties seeking help about their situation from statutory health and welfare agencies. The present paper is based upon a study of British health visiting in relation to women experiencing domestic violence. Drawing upon interview data from 16 women who experienced domestic violence and were the mothers of small children, this paper explores their accounts of contact with the health visiting service. All of the 16 women who participated in this research described difficulties in seeking help about domestic violence. These included practical concerns such as fears for their own safety, lack of knowledge regarding appropriate sources of support and protection, and concerns about losing custody of their children. Given these concerns, some women concealed their experiences of domestic violence from their health visitors. For those who disclosed the domestic violence to their health visitors, they did not always receive appropriate support or protection. Of particular concern was the absence of information about accessing more specialist services. The research findings suggest that there is considerable scope for practice development in order to ensure that women experiencing domestic violence are able to receive safe and appropriate responses from health visitors.
Improving Mouse-Based Computer Interaction in Users With Weak Upper Limb Motion Control Using a Haptic Assistive System

Computer-assisted therapy is one of the most promising new techniques for those suffering from physical and neurological dysfunction. Yet, impairments to physical movement arising from a central nervous system dysfunction or from muscle spasms generated through other neurological damage or dysfunction can often make it difficult or impossible for individuals to interact with computer-generated environments using a conventional mouse interface. This paper investigates the use of a 2-D haptic device as an assistive robotic aid to minimize the effects of the pathological absence of motor control in the upper limb in impaired users when using a mouse. The assistive functionality is evaluated in 2-D tracking tasks using a human subject with failure of the gross coordination of the upper limb muscle movements-“Muscle Ataxia. ” The results demonstrate that with this system the capability of the impaired subject to track predefined trajectories within a computer generated 2D is significantly improved. The average of the means of the error distance for the trajectories performed under the assistive mode was significantly lower (more than 40%) than that of the trajectories without assistance. In addition, when using the assistive device, the impaired subject was able to complete the tracking tasks in less time.
The Necessity for Post-Maneuver Restrictions in the Treatment of Benign Paroxysmal Positional Vertigo: An Updated Meta-Analysis of the Literature.

OBJECTIVE Many studies have published conflicting results regarding the necessity of post-maneuver postural restrictions following treatment of benign paroxysmal positional vertigo (BPPV). The purpose of this meta-analysis is to complete an updated, comprehensive review to determine best practice following a repositioning maneuver (RM). DATA SOURCES PubMed, CINAHL, and Embase were searched through July 2016. The reference lists of the selected studies were searched for studies that were not identified in the electronic database searches. STUDY SELECTION Studies investigating the effect of post-maneuver postural restrictions on RM treatment efficacy were included. DATA EXTRACTION The methodology, number of participants, type of RM administered, post-maneuver restrictions implemented, outcome measures, and results for each study were recorded. DATA SYNTHESIS Following data extraction, heterogeneity and homogeneity values of included studies were determined. Risk ratios and random effects values were obtained to determine effect size. RESULTS Eleven studies were included in the meta-analysis. The results of 739 total subjects were analyzed, 362 of which received post-maneuver postural restrictions and 377 of which did not. Meta-analysis revealed that there was not a statistically significant difference in treatment success rates between patients who received post-maneuver postural restrictions (90.3%) and those who did not (81.7%) (p = 0.095). CONCLUSIONS There was no statistically significant difference found in treatment efficacy between subjects who received post-maneuver postural restrictions and those who did not. Based on the results of this meta-analysis, if there is any benefit from prescribing the postural restrictions, it is likely to be a small marginal improvement in outcomes.
Long-term Mortality After Acute Kidney Injury in the Pediatric ICU.

OBJECTIVES (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)-defined AKI alters the association. METHODS A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46-6.57] and 3.38 [1.63-7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships.