Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cytotoxic and Proapoptotic Activities of Hypnophilin are Associated with Calcium Signaling in UACC‐62 Cells

Hypnophilin (HNP) is a sesquiterpene that is isolated from Lentinus cf. strigosus and has cytotoxic activities. Here, we studied the calcium signaling and cytotoxic effects of HNP in UACC‐62 cells, a human skin melanoma cell line. HNP was able to increase the intracellular calcium concentration in UACC‐62 cells, which was blocked in cells stimulated in Ca2+‐free media. HNP treatment with BAPTA‐AM, an intracellular Ca2+ chelator, caused an increase in calcium signals. HNP showed cytotoxicity against UACC‐62 cells in which it induced DNA fragmentation and morphological alterations, including changes in the nuclear chromatin profile and increased cytoplasmatic vacuolization, but it had no effect on the plasma membrane integrity. These data suggest that cytotoxicity in UACC‐62 cells, after treatment with HNP, is associated with Ca2+ influx. Together, these findings suggest that HNP is a relevant tool for the further investigation of new anticancer approaches. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:479‐485, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21507
Identifying factors affecting utilization of an inpatient palliative care service: a physician survey.

BACKGROUND Little is currently known about physicians': (1) level of involvement in and comfort delivering palliative care in the inpatient setting, (2) perceived barriers to referring patients to an inpatient Palliative Care Consult Service (PCCS), and (3) attitudes regarding palliative care. METHODS Eligible participants included physicians who regularly provide inpatient care at New York Presbyterian Hospital. Two groups of physicians were targeted: those that had referred 1 or more patient to the PCCS and those that had not. Face-to-face interviews were conducted to collect information regarding participants' demographic and practice characteristics, and the outcomes described above. RESULTS A total of 74 physicians were enrolled (50 referring physicians and 24 nonreferring physicians). Most respondents irrespective of referral status reported high levels of involvement in and comfort managing many symptoms that occur commonly in patients with advanced disease, but were less comfortable managing delirium and patients' psychosocial and existential needs. The most commonly endorsed barrier to referral was the patient and/or family's perceived unrealistic expectations regarding disease prognosis (by 70%). Most participants had generally favorable attitudes about palliative care, but nonreferring (versus referring) physicians were significantly more likely to disagree with the statement that a palliative care specialist is the best person to coordinate the palliative care of patients with advanced disease (29% versus 8%, p < 0.05). CONCLUSIONS Our results suggest possible avenues for building more effective partnerships between palliative care consult services and referring physicians and highlight the need for interventions designed to facilitate physician-patient communication about palliative care.
Patient and Surgeon Characteristics Associated With Primary Anterior Cruciate Ligament Reconstruction Graft Selection

Background: It has been suggested that a surgeon’s experience and training are the most important factors associated with graft selection, but no studies have qualified this association. Graft usage prevalence has not been described for large anterior cruciate ligament reconstruction (ACLR) populations in the United States. Purpose: To describe the prevalence of graft usage in a large community-based practice and evaluate the association of patient, surgeon, and site characteristics with choice of primary ACLR graft. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Primary ACLRs performed between February 2005 and June 2010 were selected for the study. A community-based ligament registry was used to identify cases and variables used for analysis. Graft choice (any allograft, hamstring autograft, and bone–patellar tendon–bone [BPTB] autograft) was compared by patient characteristics and surgeon and site characteristics. Associations between independent variables and graft choice were evaluated using a polychotomous regression model. Results: Of the 9849 patients included in the study, 64% were male, and overall median age was 28 years. Of these, 2796 (28.4%) received BPTB autografts, 3013 (30.6%) received hamstring autografts, and 4040 (41.0%) received allografts. The prevalence of graft source by patients’ gender, race, age, body mass index (BMI), as well as surgeons’ fellowship training status, average volume, and site volume were significantly different (all P < .001). Adjusted models showed that patients’ gender (P < .001), race (P = .018), age (P < .001), BMI (P < .001), as well as surgeons’ fellowship training status (P < .001), average volume (P < .001), and site volume (P < .001) are associated with graft selection. Older and female patients with lower BMI were more likely to receive allografts and hamstring autografts than BPTB autografts. Cases performed by non–fellowship-trained surgeons, lower volume sites, and/or lower volume surgeons were also more likely to be performed with allografts or hamstring autografts than BPTB autografts. Conclusion: Gender, age, race, as well as facility and surgeon characteristics such as volume and location are associated with ACL graft choices.
Does the Migration to GitHub Relate to Internal Software Quality?

Software development is more and more influenced by the usage of FLOSS (Free, Libre and Open Source Software) projects. These software projects are developed in web collaborative environments hosted on web platforms, called code forges. Many code forges exist, with different capabilities. GitHub is perhaps the largest code forge available, and many projects have been migrated from different code forges to GitHub. Given its success, we want to understand if its adoption has effect on the projects’ internal quality. To consider objective measures of internal quality, we apply four known tools performing static analysis to extract metrics and code anomalies. These data is extracted on six versions of six FLOSS projects, and compared to understand if the migration to GitHub had any consistent effect over any of the considered measures.
The CLC ‘chloride channel’ family: revelations from prokaryotes (Review)

Members of the CLC ‘chloride channel’ family play vital roles in a wide variety of physiological settings. Research on prokaryotic CLC homologues provided long-anticipated high-resolution structures as well as the unexpected discovery that some CLCs are not chloride channels, but rather are proton-chloride antiporters. Hence, CLCs encompass two functional classes of transport proteins once thought to be fundamentally different from one another. In this review, we discuss the structural features and molecular mechanisms of CLC channels and antiporters. We focus on ClC-0, the most thoroughly studied CLC channel, and ClC-ec1, the prokaryotic antiporter of known structure. We highlight some striking similarities between these CLCs and discuss compelling questions that remain to be addressed. Prokaryotic CLCs will undoubtedly continue to shed light upon this understudied family of proteins.
Localization of the synapsin II (SYN2) gene to human chromosome 3 and mouse chromosome 6.

The synapsins are a family of four synaptic vesicle-associated proteins, synapsins Ia, Ib, IIa, and IIb, that have been implicated in modulation of neurotransmitter release and in synaptogenesis . They are products from alternative splicing of two distinct genes, the synapsin I and synapsin II genes. The synapsin I (SYN1) gene has been mapped to the X chromosome in human and mouse. In this study, we have determined the chromosomal location of the synapsin II (SYN2) gene in both and human and mouse. 10 refs., 1 fig.
Environmental factors influencing larval walleye pollock Theragra chalcogramma feeding in Alaskan waters

This study examines potential interactions among the environmental variables likely to affect larval walleye pollock Theragra chalcogramma feeding in the sea. Walleye pollock larvae were sampled from Shelikof Strait, Gulf of Alaska, and from the eastern Bering Sea, with corresponding environmental data. Variables used in our study were time spent feeding, seawater temperature, light, prey density, wind speed and standard length of the larvae. We applied an additivity test to detect the presence of potential interactions among these variables and adopted an expansion of gen- eralized additive models (GAMs) that allowed the inclusion of interaction terms in a non-parametric regression analysis. After testing all possible 2-way interactions among these variables, we found 4 significant terms: (1) time feeding-standard length, (2) temperature-light, (3) light-wind speed and (4) prey density-standard length. The most influential interaction term was the light-wind speed interaction, which caused a decrease of the model-generalized cross-validation (GCV, whereby lower values indicate more parsimonious models) from 0.0402 (for a model with all variables but no interaction term) to 0.0290 (for a model with all variables and this interaction), and an increase of the model explained variance by 7% (R 2 = 0.89 versus 0.82). This result indicates that the effect of wind speed (turbulence) on larval walleye pollock feeding is dependent upon the amount of light avail- able. This may be due to vertical movements in the water column by both walleye pollock larvae and their prey in response to turbulence.
Putting the public back in public reporting of health care quality.

RECENT EFFORTS TO INCREASE TRANSPARENCY REgarding the quality of health care have been guided, in part, by the notion that this information will help patients make better choices about where to seek care. Despite substantial progress in measure development and dissemination, there is limited evidence that patients are putting such information to use, and only 6% of Americans are familiar with Hospital Compare, the quality reporting Web site maintained by the Centers for Medicare & Medicaid Services (CMS). There are several reasons for this: patients who are acutely ill rarely have the time to compare potential sources of care, clinical knowledge is required to make sense of most hospital process measures, the concept of a risk-standardized outcome is difficult to understand, and patients may not recognize the possibility that quality of care might vary. Additionally, patients may still prefer referrals from trusted family members or physicians over information obtained on the internet; practical matters, such as hospital location, often trump other considerations; and insurance co-payments may instill additional barriers to choice. Another reason for the slow uptake of Hospital Compare and similar quality reporting Web sites is the relatively limited opportunity they provide for patients to take part in the process. With the exception of reporting the results of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS), which surveys between 300 and 1000 randomly selected patients per hospital per year, quality reporting Web sites usually do not offer patients the opportunity to provide subjective feedback about the health care they receive. However, experience from nonmedical industries indicates that consumers are often as interested in the subjective judgments of their peers as they are in more formal measures of quality. Web sites are emerging that allow patients to write reviews of their physicians and hospitals, and although only a limited number of patients appear to be posting information on such Web sites, it seems likely that powerful demographic and cultural forces may lead to increased use of these sites over time.
Transcription-induced mutations: increase in C to T mutations in the nontranscribed strand during transcription in Escherichia coli.

Cytosines in single-stranded DNA deaminate to uracils at 140 times the rate for cytosines in double-stranded DNA. If resulting uracils are not replaced with cytosine, C to T mutations occur. These facts suggest that cellular processes such as transcription that create single-stranded DNA should promote C to T mutations. We tested this hypothesis with the Escherichia coli tac promoter and found that induction of transcription causes approximately 4-fold increase in the frequency of C to U or 5-methylcytosine to T deaminations in the nontranscribed strand. Excess mutations caused by C to U deaminations were reduced, but not eliminated, by uracil-DNA glycosylase. Similarly, mutations caused by 5-methylcytosine to T deaminations were only partially reduced by the very short-patch repair process in E.coli. These effects are unlikely to be caused by differential repair of the two strands, and our results suggest that all actively transcribed genes in E. coli should acquire more C to T mutations in the nontranscribed strand.
Long-term prognosis of 69 patients with dermatomyositis or polymyositis.

OBJECTIVES To assess the long-term prognosis of dermatomyositis and pol myositis. METHODS 69 patients with dermatomyositis or polymyositis were selected according to the diagnostic criteria of Bohan and Peter and were followed up for a minimum of 6.3 years (for surviving patients) (mean 11.6 years). Clinical and biological features, and pulmonary and muscle parameters were considered as prognostic factors for death. Functional disability was assessed using a 4-stage grading system. RESULTS 30 deaths (43.5%) occurred mainly due to cardiovascular (8), pulmonary (8), carcinomatous (5) and iatrogenic complications (5). Survival rates were 82.6% at 1 year, 73.9% at 2.66, 7% at 5 and 55.4% at 9. Significant prognostic factors for death (Cox model with time-dependent covariates) were old age (p < 0.0001), dysphonia (p < 0.001), pulmonary interstitial fibrosis (p < 0.02), absence of dysphagia (p < 0.02) and asthenia-anorexia (p < 0.05). Dermatomyositis and polymyositis subgroups had slightly different significant prognostic factors for death: old age, cancer, pulmonary interstitial fibrosis and asthenia-anorexia for dermatomyositis; old age, failure to improve muscle strength in response to treatment after one month, and the absence of myalgia as presenting symptom for polymyositis. At the end of the follow-up, 33/39 surviving patients (84.6%) had no or insignificant muscular disability, whereas 3 children were bedridden due to generalized calcinosis. CONCLUSIONS High mortality occurred in the first year, and the survival rate decreased continually up to 9 years. The main prognostic factor for death is old age, but dermatomyositis and polymyositis must be considered separately. General features (pulmonary fibrosis, cancer, asthenia-anorexia) are involved in dermatomyositis, whereas muscular symptoms are the most significant in polymyositis. The long-term functional prognosis was fairly good, except for generalized calcinosis, which tended to occur in childhood dermatomyositis.
Precoding in relay networks with frequency selective channels

We consider a wireless network with one source, multiple relays and multiple destinations. The source and the relays are assumed to utilize multiple antennas. To reduce the effects of the frequency selective source-to-relay and relay-to-destination channels, and to compensate for the different delays of the various signal paths in the network and for multi-user interference and noise, the source, the relays and the destinations apply linear filtering to their signals. The proposed scheme generalizes the recently proposed filter-and-forward relaying scheme. We propose an iterative algorithm to solve the problem of maximizing the quality-of-service at the destinations. Simulation results demonstrate the performance improvement achievable due to the precoding at the source.
Two Regulators of Ste12p Inhibit Pheromone-Responsive Transcription by Separate Mechanisms

ABSTRACT The yeast Saccharomyces cerevisiae transcription factor Ste12p is responsible for activating genes in response to MAP kinase cascades controlling mating and filamentous growth. Ste12p is negatively regulated by two inhibitor proteins, Dig1p (also called Rst1p) and Dig2p (also called Rst2p). The expression of a C-terminal Ste12p fragment (residues 216 to 688) [Ste12p(216–688)] from aGAL promoter causes FUS1 induction in a strain expressing wild-type STE12, suggesting that this region can cause the activation of endogenous Ste12p. Residues 262 to 594 are sufficient to cause STE12-dependent FUS1induction when overexpressed, and this region of Ste12p was found to bind Dig1p but not Dig2p in yeast extracts. In contrast, recombinant glutathione S-transferase–Dig2p binds to the Ste12p DNA-binding domain (DBD). Expression of DIG2, but notDIG1, from a GAL promoter inhibits transcriptional activation by an Ste12p DBD-VP16 fusion. Furthermore, disruption of dig1, but not dig2, causes elevated transcriptional activation by a LexA–Ste12p(216–688) fusion. Ste12p has multiple regions within the C terminus (flanking residue 474) that can promote multimerization in vitro, and we demonstrate that these interactions can contribute to the activation of endogenous Ste12p by overproduced C-terminal fragments. These results demonstrate that Dig1p and Dig2p do not function by redundant mechanisms but rather inhibit pheromone-responsive transcription through interactions with separate regions of Ste12p.
Expression and cell localization of brain‐derived neurotrophic factor and TrkB during zebrafish retinal development

Brain‐derived neurotrophic factor (BDNF) signaling through TrkB regulates different aspects of neuronal development, including survival, axonal and dendritic growth, and synapse formation. Despite recent advances in our understanding of the functional significance of BDNF and TrkB in the retina, the cell types in the retina that express BDNF and TrkB, and the variations in their levels of expression during development, remain poorly defined. The goal of the present study is to determine the age‐dependent changes in the levels of expression and localization of BDNF and TrkB in the zebrafish retina. Zebrafish retinas from 10 days post‐fertilization (dpf) to 180 dpf were used to perform PCR, Western blot and immunohistochemistry. Both BDNF and TrkB mRNAs, and BDNF and full‐length TrkB proteins were detected at all ages sampled. The localization of these proteins in the retina was very similar at all time points studied. BDNF immunoreactivity was found in the outer nuclear layer, the outer plexiform layer and the inner plexiform layer, whereas TrkB immunoreactivity was observed in the inner plexiform layer and, to a lesser extent, in the ganglion cell layer. These results demonstrate that the pattern of expression of BDNF and TrkB in the retina of zebrafish remains unchanged during postembryonic development and adult life. Because TrkB expression in retina did not change with age, cells expressing TrkB may potentially be able to respond during the entire lifespan of zebrafish to BDNF either exogenously administered or endogenously produced, acting through paracrine mechanisms.
Expression of Exposure in Negative Carcinogenicity Studies: Dose/Body Weight, Dose/Body Surface Area, or Plasma Concentrations?

Evaluation of positive findings in a rodent carcinogenicity study and the subsequent extrapolation to humans is based on chemical structure, mutagenicity, pharmacology, hormone changes, chronic toxicity, and the nature of the tumors induced. For negative studies, adequacy of exposure may become an issue. The use of plasma concentrations as a metric for exposure assumes that each species responds in a similar manner to a given concentration; data are now available that demonstrate that this is not generally true for carcinogenicity. The use of the body surface area metric (i.e., mg/m2) is a special case of interspecies allometric scaling (i.e., W0.67). For a chemical to be amenable to such scaling in toxicology, it must satisfy 3 criteria: (a) the concentration-time profile of the putative toxicant at the site of action must be governed by a scalable pharmacokinetic process (e.g., glomerular filtration); (b) the mechanism of action and the susceptibility of each species to a given systemic exposure must be the same and, for example, be independent of lifespan, cellular repair mechanism/rate, and so forth; and (c) the biological response must depend only on size (e.g., not on race, strain, gender, age, or parity). Carcinogens rarely, if ever, meet these criteria. An empirical analysis of carcinogenic potency data in rodents and in humans shows that, in general, exposure is best expressed in terms of mg/kg body weight.
Individuals and Organizations as Sources of State Effectiveness

Bureaucrats implement policy. How important are they for a state’s productivity? And do the trade-offs between policies depend on their effectiveness? Using data on 16 million public purchases in Russia, we show that 39 percent of the variation in prices paid for narrowly defined items is due to the individual bureaucrats and organizations who manage procurement. Low-price buyers also display higher spending quality. Theory suggests that such differences in effectiveness can be pivotal for policy design. To illustrate, we show that a common one—bid preferences for domestic suppliers—substantially improves procurement performance, but only when implemented by ineffective bureaucrats. (JEL D73, H57, H83, L14, P26)
Physical properties of monolithically integrated Ga(NAsP)/(BGa)P QW lasers on silicon

This paper reports the lattice matched monolithic integration of novel direct band-gap dilute nitride Ga(NAsP) QW lasers on an (001) silicon substrate using novel (BGa)P strain compensating layer. Lasing operation up to 165K is verified with a threshold current density of 1.6kAcm−2 and a characteristic temperature of 73K for a SQW device, which is a positive step towards a commercial solution for the monolithic integration of long term stable laser diodes on silicon substrates.
Examining Individual Factors According to Health Risk Appraisal Data as Determinants of Absenteeism Among US Utility Employees

Objectives: To investigate predictors of absenteeism and discuss potential implications for policy/program design. Methods: Health Risk Appraisal (HRA) data and self-reported and objective absenteeism (personnel records) were used to develop a structural equation model, controlling for age, sex, and job classification. A Medical Condition Burden Index (MCBI) was created by summing the number of self-reported medical conditions. Results: Higher MCBI and stress were direct predictors of absenteeism. Physical activity was not associated with absenteeism but mediated both stress and MCBI. Conclusions: Because stress impacted both absenteeism and MCBI, organizations may benefit by placing stress management as a priority for wellness program and policy focus. Physical activity was not directly associated with absenteeism but was a mediating variable for stress and MCBI. Measures of stress and physical health may be more meaningful as outcome measures for physical activity programs than absenteeism.