Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Constitutive GPR3 Signaling and Surface Localization by GRK2 and β-arrestin-2 Overexpression in HEK293 Cells

G protein-coupled receptor 3 (GPR3) is a constitutively active receptor that maintains high 3′-5′-cyclic adenosine monophosphate (cAMP) levels required for meiotic arrest in oocytes and CNS function. Ligand-activated G protein-coupled receptors (GPCRs) signal at the cell surface and are silenced by phosphorylation and β-arrestin recruitment upon endocytosis. Some GPCRs can also signal from endosomes following internalization. Little is known about the localization, signaling, and regulation of constitutively active GPCRs. We demonstrate herein that exogenously-expressed GPR3 localizes to the cell membrane and undergoes internalization in HEK293 cells. Inhibition of endocytosis increased cell surface-localized GPR3 and cAMP levels while overexpression of GPCR-Kinase 2 (GRK2) and β-arrestin-2 decreased cell surface-localized GPR3 and cAMP levels. GRK2 by itself is sufficient to decrease cAMP production but both GRK2 and β-arrestin-2 are required to decrease cell surface GPR3. GRK2 regulates GPR3 independently of its kinase activity since a kinase inactive GRK2-K220R mutant significantly decreased cAMP levels. However, GRK2-K220R and β-arrestin-2 do not diminish cell surface GPR3, suggesting that phosphorylation is required to induce GPR3 internalization. To understand which residues are targeted for desensitization, we mutated potential phosphorylation sites in the third intracellular loop and C-terminus and examined the effect on cAMP and receptor surface localization. Mutation of residues in the third intracellular loop dramatically increased cAMP levels whereas mutation of residues in the C-terminus produced cAMP levels comparable to GPR3 wild type. Interestingly, both mutations significantly reduced cell surface expression of GPR3. These results demonstrate that GPR3 signals at the plasma membrane and can be silenced by GRK2/β-arrestin overexpression. These results also strongly implicate the serine and/or threonine residues in the third intracellular loop in the regulation of GPR3 activity.
On the relation of refactorings and software defect prediction

This paper analyzes the influence of evolution activities such as refactoring on software defects. In a case study of five open source projects we used attributes of software evolution to predict defects in time periods of six months. We use versioning and issue tracking systems to extract 110 data mining features, which are separated into refactoring and non-refactoring related features. These features are used as input into classification algorithms that create prediction models for software defects. We found out that refactoring related features as well as non-refactoring related features lead to high quality prediction models. Additionally, we discovered that refactorings and defects have an inverse correlation: The number of software defects decreases, if the number of refactorings increased in the preceding time period. As a result, refactoring should be a significant part of both bug fixes and other evolutionary changes to reduce software defects.
The Differential Impact of the Perceived Motivational Climate in Physical Activity Settings on Adolescents’ Psychophysiological Stress & Motivational Responses

1 The purpose of this research was to investigate whether the leader-driven motivational 2 climate in physical activity settings has a differential impact on adolescent psychological and 3 physiological stress (i.e., salivary cortisol) and motivational responses, as achievement goal 4 theory (Nicholls, 1984, 1989) would suggest. It is important to investigate these relationships, as 5 psychological stress and stress-responsive hormones have been implicated in a variety of 6 biochemical processes that threaten the mental and physical health of youth (McEwen & Stellar, 7 1993), whereas social support and physical activity have been shown to counter stress and 8 enhance health and well-being (Cohen & Wills, 1985; Norris, Carroll, & Cochrane, 1992). It is 9 equally important to recognize that although youth consistently respond more favorably to 10 caring, task-involving motivational climates in physical activity settings, ego-involving climates 11 remain prevalent in youth sport contexts. If physical education and sport are to serve as 12 formidable catalysts for youth to live more physically active, healthier lifestyles, it may be worth 13 understanding how controllable elements within the psychosocial context of sport/physical 14 activity affect these outcomes. Achievement goal theory is a theoretical framework that has 15 provided insight into how leaders can structure activities and provide feedback in order to help 16 foster a continued interest in physical activity and promote more advantageous cognitive, 17 affective, and behavioral responses in youth (Braithwaite, Spray, & Warburton, 2011). 18 In developing achievement goal theory (Nicholls, 1984, 1989), Nicholls sought to 19 understand how we can optimize not just the motivation, but the experience of each child in 20 achievement settings. Decades of research investigating achievement goal theory has revealed 21 that when leaders emphasize and reward high effort and personal improvement, create a fair and 22 cooperative atmosphere, and help youth learn from their mistakes, this reliably elicits more 23
Chapter 1 Decomposition of Space-Time Domains : Accelerated Waveform Methods , with Applicationto Semiconductor Device Simulation

In this paper, we present accelerated waveform methods for solving time-dependent problems from the viewpoint of domain-based paral-lelism. We show that the waveform approach is a methodology for decomposing the space-time computational domain of time-dependent problems and circumventing the serial time-stepping bottleneck that arises when parallelizing standard sequential methods. Experimental results using waveform methods to solve the time-dependent semiconductor drift-diiusion equations are presented and demonstrate that waveform techniques are superior to standard techniques in diierent parallel environments.
Gender is what you look like: Emerging gender identities in young children and preoccupation with appearance

Abstract Our work examining young children’s strong desire to wear gender-stereotypical clothing suggests that physical appearance may be early reflections of developing gender identities. We test implications of this association between gender and appearance with two studies examining young children’s preoccupation with looking pretty or handsome. Findings revealed that being more attuned to gender information was linked to greater appearance preoccupation. Girls were more preoccupied with their appearances compared to boys. Age was associated with greater appearance preoccupation in two of our three measures. These studies suggest that appearances may reflect developing gender identities, and that gender identity development can influence children’s appearance preoccupation. We suggest that future research examine the stability and generalizability of appearance preoccupation.
Attitudes of Physicians Towards Barriers to Evidence-Based Medicine in Ilam, Iran

Background: Evidence based medicine (EBM) is very crucial in physician’s decisions. Several studies have been conducted on EBM in Iran, but none have referred to barriers regarding EBM. Objectives: In order to address this issue, we conducted a study on physicians to determine their attitudes towards the barriers to EBM. Patients and Methods: This study was a cross-sectional analytical study. One-hundred and twenty physicians were selected using stratified random sampling among 200 physicians of Ilam city. The main outcome was the measure of the attitudes of physicians towards barriers to EBM. Results: Of the 120 distributed questionnaires, 94 questionnaires were completed and returned (78.3%). About 56.6% of participants used the internet to answer the questions about their patients. There was a significant relationship between patient-related barriers and manager-related barriers (r = 0.237, P = 0.023). Post hoc tests showed that there is a significant difference between the attitude of general practitioners and the attitude of specialists regarding evidence-related barriers (mean difference = 2.4, Std = 1.1, P = 0.47). Conclusions: This study highlights the barriers encountered by physicians, related to the use of EBM in four sections. Evidence based medicine is now available in Iran and physicians must move towards learning this approach, while health managers should carefully start planning in this field. The recommendations of this study include a review of barriers of EBM in Iran
Stability and Change in Domain–Specific Self–Esteem and Global Self–Esteem

A notable uptick of interest in the stability of self–esteem has been observed over the past few years. Most researchers, however, have focused on unidimensional rather than multidimensional conceptualizations of self–esteem. The paucity of empirical research is surprising given conflicting theoretical perspectives on the stability of self–esteem. The goal of the present study was to thoroughly disentangle different conceptualizations of self–esteem and test opposing classical theories on (i) the stability and (ii) the direction of mutual influence of these different forms of self–esteem. We analysed two–year longitudinal data from participants (N = 644 at T1, N = 241 at T2) with an average age of 47.0 years (SD = 12.4). Analyses using a latent variable approach revealed that the domains of self–esteem were relatively stable in terms of rank order and mean levels. In fact, the size of the stability coefficients was comparable to that of other trait measures that have been reported in the literature and paralleled the stability observed for global self–esteem. Results did not provide support for either top–down or bottom–up effects between domain–specific and global self–esteem. These findings have important theoretical and practical implications regarding the stability and development of self–esteem in adulthood and advance the understanding of self–esteem in personality theory. © 2018 European Association of Personality Psychology
Factors that influence end-of-life care in nursing homes: the physical environment, inadequate staffing, and lack of supervision.

PURPOSE This study investigated the physical environment and organizational factors that influenced the process of providing care to terminally ill nursing home residents. DESIGN AND METHODS Participant observation, interviews, and event analysis were used to obtain data in two proprietary facilities. RESULTS The physical environment was not conducive to end-of-life care. The rooms were crowded, there was little privacy, and the facilities were noisy. Inadequate staffing and lack of supervision were among the most significant organizational factors that influenced care. Often, residents did not receive basic care, such as bathing, oral hygiene, adequate food and fluids, and repositioning. A consequence of inadequate staffing was the development of pressure ulcers; 54% of the residents had pressure ulcers; 82% of these residents died with pressure ulcers. IMPLICATIONS Findings suggest that the nursing home environment in these two facilities, as now structured, is an inappropriate setting for end-of-life care.
Integrin a v b 3-Mediated Endocytosis of Immobilized Fibrinogen by A 549 Lung Alveolar Epithelial Cells

Fibrinogen (FBG), together with its polymerized form fibrin, modulates cellular responses during wound repair and tissue remodeling. Thus, we sought to determine whether A549 lung epithelial type II–like cells would endocytose insoluble, surface-bound FBG as a potential mechanism of alveolar matrix remodeling. Surface-bound FBG was endocytosed into either lysosomes or late endosomes by A549 cells through arg-glyasp–dependent binding to a v b 3 but not a 5 b 1 integrin receptors. Soluble FBG added to confluent monolayers of A549 cells was not endocytosed. Unlike the uptake of the extracellular matrix glycoproteins vitronectin and thrombospondin by other cell types, endocytosis of FBG by A549 cells was neither inhibited by heparin nor dependent on binding to cell-surface heparan sulfate proteoglycans. FBG did not colocalize with endocytosed transferrin, whereas dextran showed partial colocalization with FBG in endocytic vesicles, suggesting nonclathrin-mediated endocytosis. Inhibition of actin filament polymerization blocked endocytosis of both dextran and FBG but not transferrin, providing further support that FBG is endocytosed via a nonclathrin pathway. Disruption of actin polymerization inhibited integrin-mediated cell spreading, which contributed to an overall reduction in FBG clearance that was most likely due to reduced cell migration and associated pericellular proteolysis. Trasylol inhibition of extracellular plasmin activity did not inhibit endocytosis of FBG. The endocytosed FBG was degraded to trichloroacetic acid–soluble fragments that showed an electrophoretic pattern distinctly different from plasmin-degraded FBG. Together, these results suggest that endocytosis of matrix-associated FBG by alveolar epithelial cells may be involved in the processes of alveolar tissue repair and matrix remodeling.
Anisotropic seismic structure of the lithosphere beneath the Adriatic coast of Italy constrained with mode‐converted body waves

PS converted waves observed near Ancona on the Adriatic coast of central Italy, as revealed by teleseismic receiver functions (RFs), vary with earthquake back‐azimuth and epicentral distance in a manner consistent with a 1‐D anisotropic seismic structure. Using reflectivity calculations, we develop a profile of anisotropic seismic velocity through the Adriatic lithosphere at this locality. We infer crustal thickness of ∼45 km. Anisotropy within the crust appears at ∼15‐km depth, suggesting a decollement between the subducting Adriatic lithosphere and the overriding crustal wedge. Lineation of inferred rock fabric is compatible with simple shear in ENE‐WSW direction. In the upper mantle, we infer an anisotropic layer at 80–90 km depth. If caused by olivine crystals alignment, the nearly north‐south lineation of the inferred rock fabric would be consistent with some nearby shear‐wave splitting observations. This anisotropic layer may be related to mantle deformation induced by the rollback of Adriatic lithosphere.
Amyloid-like interactions within nucleoporin FG hydrogels

The 62 kDa FG repeat domain of the nucleoporin Nsp1p forms a hydrogel-based, sieve-like permeability barrier that excludes inert macromolecules but allows rapid entry of nuclear transport receptors (NTRs). We found that the N-terminal part of this domain, which is characterized by Asn-rich inter-FG spacers, forms a tough hydrogel. The C-terminal part comprises charged inter-FG spacers, shows low gelation propensity on its own, but binds the N-terminal part and passivates the FG hydrogel against nonselective interactions. It was previously shown that a hydrophobic collapse involving Phe residues is required for FG hydrogel formation. Using solid-state NMR spectroscopy, we now identified two additional types of intragel interactions, namely, transient hydrophobic interactions between Phe and methyl side chains as well as intermolecular β-sheets between the Asn-rich spacer regions. The latter appear to be the kinetically most stable structures within the FG hydrogel. They are also a central feature of neuronal inclusions formed by Asn/Gln-rich amyloid and prion proteins. The cohesive properties of FG repeats and the Asn/Gln-rich domain from the yeast prion Sup35p appear indeed so similar to each other that these two modules interact in trans. Our data, therefore, suggest a fully unexpected cellular function of such interchain β-structures in maintaining the permeability barrier of nuclear pores. They provide an explanation for how contacts between FG repeats might gain the kinetic stability to suppress passive fluxes through nuclear pores and yet allow rapid NTR passage.
Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential hypertension and left ventricular hypertrophy

Objective To compare the effects of the angiotensin II antagonist, losartan, with those of atenolol on left ventricular hypertrophy (LVH), blood pressure and neurohormone concentrations in hypertensive patients with LVH. Design A multinational, randomized, double-blind trial. Setting Hospital. Patients Hypertensive patients with an echocardiographically documented left ventricular mass index (LVMI) > 120 g/m2 (men) or > 105 g/m2 (women). Interventions Patients allocated randomly to groups received either losartan or atenolol 50 mg/day for 36 weeks, with possible titration to 100 mg/day, and addition of hydrochlorothiazide 12.5 or 25 mg/day. Main outcome measures Changes in LVMI and sitting systolic (SBP) and diastolic (DBP) blood pressures after 36 weeks of treatment (study powered for non-inferiority hypothesis). All echocardiographic data were read in a central laboratory by staff blinded to the treatments and sequence of echocardiographic tapes. Results The estimated treatment difference between the losartan and atenolol regimens (mean change from baseline at week 36) in LVMI was −2.5 g/m2 [95% confidence interval (CI) −7.36 to 2.37 g/m2] in favor of losartan, indicating that losartan was significantly non-inferior (P < 0.001, non-inferiority limit 8 g/m2) and numerically superior to atenolol in reducing LVMI. The losartan-based regimen significantly reduced LVMI after 36 weeks compared with baseline (−6.56 g/m2, 95% CI −10.24 to −2.88 g/m2, P < 0.001), whereas the atenolol-based regimen had no significant effect (−3.71 g/m2, 95% CI −7.75 to 0.32 g/m2, P = NS). In a subset of 82 patients, significant changes in serum concentrations of atrial natriuretic peptide, brain natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic peptide were recorded in losartan-treated (P < 0.01) but not atenolol-treated patients. Losartan and atenolol significantly decreased SBP and DBP from baseline after 6, 12, 24 and 36 weeks. The changes from baseline in DBP were greater in the atenolol group at weeks 6 and 36 [difference −2.6 mmHg (P = 0.016) at week 36]. However, both treatment regimens achieved similar SBP/DBP values at week 36 (141.1 ± 12.8/86.8 ± 8.2 mmHg for losartan and 141.4 ± 17.2/85.0 ± 10.1 mmHg for atenolol, respectively). Overall, losartan treatment was associated with significantly fewer drug-related clinical adverse events, compared with atenolol (10 and 22%, respectively, P = 0.028). Conclusions Both losartan- and atenolol-based regimens effectively decreased blood pressure. Losartan was non-inferior and numerically superior to atenolol in regression of LVH. The reduction in hypertrophy with losartan treatment was accompanied by reductions in circulating concentrations of cardiac natriuretic peptides. Losartan, by specifically blocking angiotensin II, may therefore have effects on the heart beyond those expected from the decrease in blood pressure alone. Losartan was better tolerated than atenolol.
Covariance Control for Bilinear Stochastic Systems via Sliding Mode Control Concept

Based on the concept of sliding mode control, we study the problem of steady state covariance assignment for bilinear stochastic systems. We find that the invariance property of sliding mode control ensures nullity of the matched bilinear term in the system on the sliding mode. By suitably using Ito calculus, the controller u(t) can be designed to force the feedback gain matrix G to achieve the goal of steady state covariance assignment. We also compare our method with other approaches via simulations.
Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects

OBJECTIVE— Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of κB (IκB)/nuclear factor κB (NFκB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IκB/NFκB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS— TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IκB/NFκB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS— Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IκBα content, an indication of elevated IκB/NFκB signaling. The increase in TLR4 and NFκB signaling was accompanied by elevated expression of the NFκB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IκB/NFκB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IκB/NFκB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFκB. CONCLUSIONS— Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.
Design of Compact Reflection-Type Phase Shifters With High Figure-of-Merit

This paper presents reflection-type phase shifters (RTPSs) with very high figure-of-merit (FoM) and low insertion-loss variation, achieving up to 360 ° relative phase shifts. Two compact topologies are proposed. They were implemented at the working frequency of 2 GHz on a printed circuit board technology. The reflection loads are based on the use of one transmission line loaded by varactors, forming L- or π-type networks. An automatic procedure is given to design the electrical length and the characteristic impedance of the transmission line of the reflection loads as well as the output impedance of the 3-dB branch-line coupler in order to get phase shifters with the highest possible FoM. Measurement results of the first L-type network RTPS showed a relative phase shift of 201 ° for only 0.54 dB ± 0.09 dB of insertion loss, leading to a FoM of 319 °/dB. A relative phase shift of 385 ° was achieved for the π-type network RTPS with insertion loss of only 0.98 dB ± 0.58 dB, leading to an FoM of 246 °/dB. In both cases, simulation and measurement results fit very well. Moreover, the return loss over a 10% bandwidth is always better than 10.9 dB for the first RTPS and better than 12.3 dB for the second one, respectively. The comparison with previous works shows more compact reflection loads with electrical performance equal to the state-of-the-art.