Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulator of G Protein Signaling 6 (RGS6) Induces Apoptosis via a Mitochondrial-dependent Pathway Not Involving Its GTPase-activating Protein Activity*

Regulator of G protein signaling 6 (RGS6) is a member of a family of proteins called RGS proteins, which function as GTPase-activating proteins (GAPs) for Gα subunits. Given the role of RGS6 as a G protein GAP, the link between G protein activation and cancer, and a reduction of cancer risk in humans expressing a RGS6 SNP leading to its increased translation, we hypothesized that RGS6 might function to inhibit growth of cancer cells. Here, we show a marked down-regulation of RGS6 in human mammary ductal epithelial cells that correlates with the progression of their transformation. RGS6 exhibited impressive antiproliferative actions in breast cancer cells, including inhibition of cell growth and colony formation and induction of cell cycle arrest and apoptosis by mechanisms independent of p53. RGS6 activated the intrinsic pathway of apoptosis involving regulation of Bax/Bcl-2, mitochondrial outer membrane permeabilization (MOMP), cytochrome c release, activation of caspases-3 and -9, and poly(ADP-ribose) polymerase cleavage. RGS6 promoted loss of mitochondrial membrane potential (ΔΨm) and increases in reactive oxygen species (ROS). RGS6-induced caspase activation and loss of ΔΨm was mediated by ROS, suggesting an amplification loop in which ROS provided a feed forward signal to induce MOMP, caspase activation, and cell death. Loss of RGS6 in mouse embryonic fibroblasts dramatically impaired doxorubicin-induced growth suppression and apoptosis. Surprisingly, RGS6-induced apoptosis in both breast cancer cells and mouse embryonic fibroblasts does not require its GAP activity toward G proteins. This work demonstrates a novel signaling action of RGS6 in cell death pathways and identifies it as a possible therapeutic target for treatment of breast cancer.
Hyperresponsivity to threat stimuli in domestic violence offenders: a functional magnetic resonance imaging study.

OBJECTIVE While spouse abuse research has almost exclusively adopted a social perspective, an increasing body of imaging research is documenting neural contributions to violence. METHOD To test the hypothesis that wife batterers are hyperresponsive to threatening stimuli, echo-planar functional magnetic resonance imaging was employed to assess brain function of 10 male batterers and 13 male matched controls during viewing of 4 types of visual stimuli: neutral, positive affect, aggressive-threat, and aggression against women. The study was conducted from September 2005 to August 2006. RESULTS Compared to controls, batterers showed significantly higher neural hyperresponsivity to the threat stimuli in the hippocampus, fusiform gyrus, posterior cingulate gyrus, thalamus, and occipital cortex (p < .001). To a lesser extent, they also showed increased activation to the aggression against women stimuli, particularly in the precuneus bilaterally (p < .001), and also increased activation to positive affect stimuli in right hemisphere orbitofrontal, anterior cingulate, and inferior parietal cortical regions (p < .001). CONCLUSIONS Findings indicate an affect-processing abnormality in wife batterers and suggest that hypersensitivity to mildly threatening affective provocations by their spouses may represent a neurobiological predisposition to spouse abuse in some men.
Health Coaching Integration Into Primary Care for the Treatment of Obesity

Obesity (and its related comorbidities) is one of the fastest-growing health concerns facing the United States and shows no sign of abating.1 The Centers for Disease Control and Prevention calculated that nearly 36% of American adults were obese in 2010 and estimates that this number will reach 44% by 2018. The current standard of care for the management of patients with obesity in primary care is often a general recommendation by the physician to lose weight through improved nutrition and increased physical activity. Educational materials may be provided along with a referral to a dietician, nutritionist, or weight management program. Health coaching as an obesity intervention has yet to be fully integrated into primary care practice but has proven to be effective in corporate wellness and behavioral weight loss programs.2–5
Degradation Mechanism Decoupling of Mid-Power White-Light LEDs by SPD Simulation

A degradation mechanism analysis methodology is proposed for the mid-power white-light LED packages in this paper. Based on the degradation data obtained from a series of aging tests that are performed on the individual packaging material, the degradation kinetics of lumen output and spectral power distribution of the LED packages are investigated using optical simulation. As a result, although the reflectivity of the packaging materials decreased severely for the blue lights (i.e., 450 nm), the simulation showed that lights at this wavelength were little absorbed in the LED package. More specifically, it is found that: 1) the degradation of the blue lights is mainly due to blue chip deterioration, while rarely affected by the degradation of the silicone encapsulant and other packaging materials; 2) the degradation of the down-converted lights is significantly attributed to the degradation of the blue chips, the phosphors, the lead frames, and the package housing; and 3) the degradation of the silicone encapsulant contributes about 1.35% to the total lumen degradation within 168 h, while has no more contribution to the lumen degradation with further aging duration. The simulation results have been validated by experiments and successfully applied to the degradation mechanism analysis of LED packages in LM-80-08 tests.
Interpreting and Implementing the 2006 CDC Recommendations for HIV Testing in Health-Care Settings

On September 22, 2006, the Centers for Disease Control and Prevention (CDC) announced recommendations to expand the role of health-care providers in human immunodeficiency virus (HIV) testing. These clearlyjustified guidelines aim to remove traditional testing barriers, and thereby increase the rate of earlier diagnosis. This overarching strategy to increase testing in all health-care settings also includes less traditional sites such as emergency departments and correctional health-care facilities. The motivation for the guidelines is intuitive, as the need for augmented testing is well supported. Of those infected with HIV in the U.S., approximately one-quarter are unaware of their disease status. People who are unaware of their infection disproportionately account for new transmissions and are unable to benefit from treatment. The HIV incidence has not fallen below approximately 40,000 new diagnoses per year, of which approximately 40% are diagnosed late in the course of infection. Universal screening, even in populations with a disease prevalence of 0.1%, has been shown to be cost-effective. While the guidelines have been reviewed in depth, current interpretations do not adequately outline a structure for further debate or facilitate incremental or partial implementation of the recommendations. This must be remedied, as comprehensive implementation of the guidelines will be controversial or logistically impossible in many settings for the foreseeable future. Herein, we provide a clarified interpretation by outlining the core guideline elements individually and within the context of current barriers to implementation. We then discuss potential combinations of the core elements that would enable increased testing in settings where comprehensive guideline implementation is not possible.
New Techniques for the Analysis of Fine-Scaled Clustering Phenomena within Atom Probe Tomography (APT) Data

Nanoscale atomic clusters in atom probe tomographic data are not universally defined but instead are characterized by the clustering algorithm used and the parameter values controlling the algorithmic process. A new core-linkage clustering algorithm is developed, combining fundamental elements of the conventional maximum separation method with density-based analyses. A key improvement to the algorithm is the independence of algorithmic parameters inherently unified in previous techniques, enabling a more accurate analysis to be applied across a wider range of material systems. Further, an objective procedure for the selection of parameters based on approximating the data with a model of complete spatial randomness is developed and applied. The use of higher nearest neighbor distributions is highlighted to give insight into the nature of the clustering phenomena present in a system and to generalize the clustering algorithms used to analyze it. Maximum separation, density-based scanning, and the core linkage algorithm, developed within this study, were separately applied to the investigation of fine solute clustering of solute atoms in an Al-1.9Zn-1.7Mg (at.%) at two distinct states of early phase decomposition and the results of these analyses were evaluated.
Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides.

Since triglycerides (TG) are a major independent risk factor for coronary heart disease, understanding their genetic and environmental determinants is of major importance. Mouse models indicate an inverse relationship between levels of the newly identified apolipoprotein AV (APOAV) and TG concentrations. We have examined the relative influence of human APOA5 variants on plasma lipids, compared to the impact of variation in APOC3 and APOA4 which lie in the same cluster. Single nucleotide polymorphisms (SNPs) in APOA5 (S19W, -1131T>C) and APOA4 (T347S, Q360H) and an APOA4/A5 intergenic T>C SNP were examined in a large study of healthy middle-aged men (n=2808). APOA5 19WW and -1131CC men had 52% and 40% higher TG (P<0.003) compared to common allele homozygotes, respectively, effects which were independent and additive. APOA4 347SS men had 23% lower TG compared to TT men (P<0.002). Haplotype analysis was carried out to identify TG-raising alleles and included, in addition, four previously genotyped APOC3 SNPs (-2845T>G, -482C>T, 1100C>T, and 3238C>G). The major TG-raising alleles were defined by APOA5 W19 and APOC3 -482T. This suggests that the TG-lowering effect of APOA4 S347 might merely reflect the strong negative linkage disequilibrium with the common alleles of these variants. Thus variation in APOA5 is associated with differences in TGs in healthy men, independent of those previously reported for APOC3, while association between APOA4 and TG reflects linkage disequilibrium with these sites. The molecular mechanisms for these effects remain to be determined.
Negative Cross-talk between Calcium-sensing Receptor and β-Catenin Signaling Systems in Colonic Epithelium*

Here, we examined the role of the extracellular Ca2+-sensing receptor (CaSR) in the control of colonic epithelial cell proliferation in vivo and changes in β-catenin triggered by CaSR stimulation in human colonic epithelial cells in vitro. The in vivo studies, using a novel Casr intestinal-specific knock-out mouse, indicate that the genetic ablation of the Casr leads to hyperproliferation of colonic epithelial cells, expansion of the proliferative zone, changes in crypt structure, and enhanced β-catenin nuclear localization. The in vitro results indicate that stimulation of the CaSR, by Ca2+ or by the calcimimetic R-568, produced a striking and time-dependent decrease in the phosphorylation of β-catenin at Ser-552 and Ser-675, two amino acid residues that promote β-catenin transcriptional activity. The reduced phosphorylation of β-catenin coincided with a decline in its nuclear localization and a marked redistribution to the plasma membrane. Furthermore, CaSR stimulation promoted a down-regulation of β-catenin-mediated transcriptional activation. These studies demonstrate that signaling pathways emanating from the CaSR control colonic epithelial cell proliferation in vivo and suggest that the mechanism involves regulation of β-catenin phosphorylation.
CONVERGENCE OF GLUCOSE‐ AND FATTY ACID‐INDUCED ABNORMAL MYOCARDIAL EXCITATION–CONTRACTION COUPLING AND INSULIN SIGNALLING

1 Myocardial insulin resistance and abnormal Ca2+ regulation are hallmarks of hypertrophic and diabetic hearts, but deprivation of energetic substrates does not tell the whole story. Is there a link between the aetiology of these dysfunctions? 2 Diabetic cardiomyopathy is defined as phenotypic changes in the heart muscle cell independent of associated coronary vascular disease. The cellular consequences of diabetes on excitation–contraction (E‐C) coupling and insulin signalling are presented in various models of diabetes in order to set the stage for exploring the pathogenesis of heart disease. 3 Excess glucose or fatty acids can lead to augmented flux through the hexosamine biosynthesis pathway (HBP). The formation of uridine 5¢‐diphosphate‐hexosamines has been shown to be involved in abnormal E‐C coupling and myocardial insulin resistance. 4 There is growing evidence that O‐linked glycosylation (downstream of HBP) may regulate the function of cytosolic and nuclear proteins in a dynamic manner, similar to phosphorylation and perhaps involving reciprocal or synergistic modification of serine/threonine sites. 5 This review focuses on the question of whether there is a role for HBP and dynamic O‐linked glycosylation in the development of myocardial insulin resistance and abnormal E‐C coupling. The emerging concept that O‐linked glycosylation is a regulatory, post‐translational modification of cytosolic/nuclear proteins that interacts with phosphorylation in the heart is explored.
Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma.

RATIONALE Chronic obstructive pulmonary disease (COPD) and asthma can exhibit overlapping clinical features. Exhaled air contains volatile organic compounds (VOCs) that may qualify as noninvasive biomarkers. VOC profiles can be assessed using integrative analysis by electronic nose, resulting in exhaled molecular fingerprints (breathprints). OBJECTIVES We hypothesized that breathprints by electronic nose can discriminate patients with COPD and asthma. METHODS Ninety subjects participated in a cross-sectional study: 30 patients with COPD (age, 61.6 +/- 9.3 years; FEV(1), 1.72 +/- 0.69 L), 20 patients with asthma (age, 35.4 +/- 15.1 years; FEV(1) 3.32 +/- 0.86 L), 20 nonsmoking control subjects (age, 56.7 +/- 9.3 years; FEV(1), 3.44 +/- 0.76 L), and 20 smoking control subjects (age, 56.1 +/- 5.9 years; FEV(1), 3.58 +/- 0.78). After 5 minutes of tidal breathing through an inspiratory VOC filter, an expiratory vital capacity was collected in a Tedlar bag and sampled by electronic nose. Breathprints were analyzed by discriminant analysis on principal component reduction resulting in cross-validated accuracy values (accuracy). Repeatability and reproducibility were assessed by measuring samples in duplicate by two devices. MEASUREMENTS AND MAIN RESULTS Breathprints from patients with asthma were separated from patients with COPD (accuracy 96%; P < 0.001), from nonsmoking control subjects (accuracy, 95%; P < 0.001), and from smoking control subjects (accuracy, 92.5%; P < 0.001). Exhaled breath profiles of patients with COPD partially overlapped with those of asymptomatic smokers (accuracy, 66%; P = 0.006). Measurements were repeatable and reproducible. CONCLUSIONS Molecular profiling of exhaled air can distinguish patients with COPD and asthma and control subjects. Our data demonstrate a potential of electronic noses in the differential diagnosis of obstructive airway diseases and in the risk assessment in asymptomatic smokers. Clinical trial registered with www.trialregister. nl (NTR 1282).
Power walk: revisiting the random surfer

Measurement of graph centrality provides us with an indication of the importance or popularity of each vertex in a graph. When dealing with graphs that are not centrally controlled (such as the Web, social networks and academic citation graphs), centrality measure must 1) correlate with vertex importance/popularity, 2) scale well in terms of computation, and 3) be difficult to manipulate by individuals. The Random Surfer probability transition model, combined with Eigenvalue Centrality produced PageRank, which has shown to satisfy the required properties. Existing centrality measures (including PageRank) make the assumption that all directed edges are positive, implying an endorsement. Recent work on sentiment analysis has shown that this assumption is not valid. In this article, we introduce a new method of transitioning a graph, called Power Walk, that can successfully compute centrality scores for graphs with real weighted edges. We show that it satisfies the desired properties, and that its computation time and centrality ranking is similar to when using the Random Surfer model for non-negative matrices. Finally, stability and convergence analysis shows us that both stability and convergence when using the power method, are dependent on the Power Walk parameter β.
Back Pain and Vertebral Changes Simulating Scheuermann's Disease

Summary Nineteen adolescent patients who presented with mechanical-type back pain and vertebral changes consisting of intravertebral disc herniation, disc space narrowing, and minimal wedge deformity are described. The symptoms and signs were primarily located at the dorsolumbar junction. A specific strenuous activity or traumatic event was clearly associated with the onset of symptoms in 16 of the 19 patients. Spondylolysis or spondylolisthesis (grade I or II) at L5-S1 was also found in 32% of the patients. Most patients responded well to a program of rest, exercises, salicylates, and temporary avoidance of the particular activity involved. Some required orthoses to obtain relief. No patient had a progressive kyphotic deformity during the follow-up period. The relationship of this condition to increased stresses applied to the immature spine, particularly in a preflexed posture, is emphasized.
Predictors of drug treatment response in obsessive-compulsive disorder.

BACKGROUND Although a large body of evidence indicates the efficacy of pharmacotherapy in the treatment of obsessive-compulsive disorder (OCD), a considerable percentage of these patients do not respond. Very few studies focus on factors related to treatment response of OCD. The purpose of this study was to investigate which clinical factors are related to drug treatment response in OCD. METHOD We examined 53 OCD patients treated with either clomipramine or fluoxetine for a period of 6 months, dividing the sample into "responders" and "nonresponders" to treatment. At admission, patients were evaluated using a semistructured clinical interview, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety. We then compared acute-phase patient characteristics and response to drug treatment. Response was defined as a decrease of at least 40% in the Y-BOCS total score and a rating of "improved" or "very improved" on the Clinical Global Impressions scale within 16 weeks of treatment and maintained over three consecutive evaluations. RESULTS By the sixth month of treatment, 31 patients (58.5%) responded to either clomipramine or fluoxetine. Nonresponders had lower age at onset and longer duration of the disorder; in addition, they showed higher frequency of compulsions, washing rituals, chronic course, concomitant schizotypal personality disorder, and previous hospitalizations. A worse response to drug treatment was predicted in a stepwise multiple regression by (1) concomitant schizotypal personality disorder, (2) presence of compulsions, and (3) longer illness length. CONCLUSION Our findings suggest that there are distinct types of OCD with respect to drug treatment response. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.
Leading Ethically in a Culturally Diverse Global Environment

Globalization has amplified interdependence among nations, creating an increasing need for leaders to function in a variety of cultures. Leaders face ever-expanding complexities and challenges, many of which include ethical dimensions. Lapses in ethical leadership in recent decades have resulted in the destruction of companies and harm to individuals, societies, and economies. Although many leadership theories have been offered to date, scholars and practitioners still search for answers to failed leadership. A recent theoretical construct of ethical leadership has been proposed that may offer a solution (Brown, Trevino, & Harrison, 2004; Trevino, Brown, & Hartman, 2003). This chapter addressed these issues by exploring ethical leadership as a viable theory that may be considered for use across cultures. Research consisted of interviews with experienced international managers who also held MBA degrees. The results led to recommendations for international managers in leadership positions as well as directions for future research.
Robust Color Choice for Small-size League RoboCup Competition

In this paper, the problem of choosing a set of most separable colors in a given environment is discussed. The proposed method models the process of generating theoretically computed best colors, printing of these colors through a color printer, and imaging the printed colors through a camera into an integrated framework. Thus, it provides a feasible way to generate practically best separable colors for a given environment with a set of given equipment. A real world application (robust color choice for small-size league RoboCup competition) is used as an example to illustrate the proposed method. Experimental results on this example show the competitiveness of the colors learned from our algorithm compared to the colors adopted by other teams which are chosen via an extensive trial and error process using standard color papers.
Tourism and Natural World Heritage: A Complicated Relationship

There are legal, political, economic, social, and environmental links between tourism and World Heritage Areas, some straightforward but others controversial. These are examined here as aspects of a long-term, stable, but complicated, relationship. Management of small-scale mobile tourism operations is well established. It includes activities, equipment, timing, numbers, group size, marketing, fees, and permit latency. Management of large-scale fixed-site tourism infrastructure and accommodation involving private equity or operational control is more controversial. It includes legal structure of partnership arrangements, and allocation of revenues, costs, and risks. The relationship framework shows the importance of picking partners carefully and establishing mechanisms for external counseling. Research opportunities include: the marketing value of World Heritage Area (WHA) controversies; the tourism effects of In Danger declarations; funding models; and impact assessment, stakeholder roles, and co-management mechanisms, in different jurisdictions. Quantifying these effects needs large-scale compilation and comparison of case studies.
Kabini: An AMD Accelerated Processing Unit System on A Chip

The AMD accelerated processing unit (APU) code-named "Kabini" integrates a quad-core CPU and a fully featured GPU. It is the first APU generation to incorporate a complete system-on-a-chip (SoC) IP to provide power efficiency and a small footprint. The device family includes the ultra-low-power optimized SoC codenamed "Temash," which is targeted for tablet and two-in-one detachable PC use. Kabini incorporates four high-performance x86 processor cores code-named "Jaguar"; an AMD Radeon HD 8000 Series DirectX11-capable GPU; next-generation media acceleration technology; a 64-bit memory channel; and integrated system I/O. Kabini improves on AMD's Turbo Core technology by actively managing collaborative CPU and GPU workloads and maximizing system responsiveness and performance per watt within the system cooling infrastructure.