Miracle-dz/UniFAR-FTUs huggingface dataset:
Viral Activation of Interleukin-15 (IL-15): Characterization of a Virus-Inducible Element in the IL-15 Promoter Region

We identified an interferon regulatory factor motif (IRF-E) upstream of an NF-kappaB binding site in the interleukin-15 (IL-15) promoter. Since these two motifs are part of the virus-inducible enhancer region of the beta interferon promoter, we speculated that there might be similar responses of these two genes to stimuli such as viruses. To test this hypothesis, L929 cells were infected with Newcastle disease virus (NDV), which led to the induction of IL-15 mRNA and protein expression. Using IL-15 promoter-reporter deletion constructs, a virus-inducible region, encompassing IRF-E, NF-kappaB, and a 13-nucleotide sequence flanked by these two motifs, was mapped to the -295-to--243 position relative to the transcription initiation site. Using cotransfection studies, it was demonstrated that all three motifs were essential to achieve the maximum promoter activity induced by IRF-1 and NF-kappaB expression plasmids. The presence of a virus-inducible region in the IL-15 promoter suggests a role for IL-15 as a component of host antiviral defense mechanisms.
Regulation of Kinase Cascade Activation and Heat Shock Protein Expression by Poly(ADP-ribose) Polymerase Inhibition in Doxorubicin-induced Heart Failure

Cardiomyopathy is one of the most severe side effects of the chemotherapeutic agent doxorubicin (DOX). The formation of reactive oxygen species plays a critical role in the development of cardiomyopathies, and the pathophysiological cascade activates nuclear enzyme poly(ADP-ribose) polymerase (PARP), and kinase pathways. We characterized the effects of the PARP-inhibitor and kinase-modulator compound L-2286 in DOX-induced cardiac injury models. We studied the effect of the established superoxide dismutase–mimic Tempol and compared the effects of this agent with those of the PARP inhibitor. In the rat H9C2 cardiomyocytes, in which DOX-induced poly(ADP-ribosyl)ation, L-2286 protected them from the DOX-induced injury in a concentration-dependent manner. In the in vivo studies, mice were pretreated (for 1 week) with L-2286 or Tempol before the DOX treatment. Both the agents improved the activation of cytoprotective kinases, Akt, phospho-specific protein kinase C ϵ, ζ/λ and suppressed the activity of cell death promoting kinases glycogen synthase kinase-3β, JNK, and p38 mitogen-activated protein kinase, but the effect of PARP inhibitor was more pronounced and improved the survival as well. L-2286 activated the phosphorylation of proapoptotic transcription factor FKHR1 and promoted the expression of Hsp72 and Hsp90. These data suggest that the mode of the cytoprotective action of the PARP inhibitor may include the modulation of kinase pathways and heat shock protein expression.
Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of human papillomavirus infections, smoking and alcohol

Tobacco and alcohol consumption are the main risk factors for head and neck squamous cell carcinoma (HNSCC). In addition, human papillomavirus (HPV) infection plays a causal role in oropharyngeal cancer (OPC), a subset of HNSCC. We assessed the independent effects of tobacco, alcohol and HPV infection on OPC risk in the head and neck cancer (HeNCe) Life study, a hospital-based case-control study of HNSCC with frequency-matched controls by age and sex from four Montreal hospitals. Interviewers collected information on socio-demographic and behavioural factors. We tested exfoliated oral cells for HPV DNA by polymerase chain reaction (PCR). We included only OPC cases (n = 188) and controls (n = 427) without missing values for HPV, smoking or alcohol. We examined associations by estimating odds ratios (ORs) and corresponding 95% confidence intervals (CI) using unconditional logistic regression. Smoking (OR = 1.90, 95% CI: 1.04-3.45) and alcohol (OR = 2.74, 95% CI: 1.45-5.15) were associated with an increased risk of OPC independent of HPV status. Positivity for HPV 16 among heavy smokers and heavy alcohol users was associated with a 30.4-fold (95% CI: 8.94-103.26) and 18.6-fold (95% CI: 5.75-60.13) elevation in risk of OPC relative to participants who were HPV negative, respectively. Moreover, the combined effect of heavy smoking and alcohol comsumption with HPV 16 infection substantially increased OPC risk (OR = 48.76, 95% CI: 15.83-150.17) and (OR = 50.60, 95% CI: 15.96-160.40), respectively. Our results support the independent roles of smoking, alcohol and HPV infection in OPC risk and a possible combined effect. Efforts should be made to tackle these major risk factors simultaneously.
The Validity of Peer Review in a General Medicine Journal

All the opinions in this article are those of the authors and should not be construed to reflect, in any way, those of the Department of Veterans Affairs. Background Our study purpose was to assess the predictive validity of reviewer quality ratings and editorial decisions in a general medicine journal. Methods Submissions to the Journal of General Internal Medicine (JGIM) between July 2004 and June 2005 were included. We abstracted JGIM peer review quality ratings, verified the publication status of all articles and calculated an impact factor for published articles (Rw) by dividing the 3-year citation rate by the average for this group of papers; an Rw>1 indicates a greater than average impact. Results Of 507 submissions, 128 (25%) were published in JGIM, 331 rejected (128 with review) and 48 were either not resubmitted after revision was requested or were withdrawn by the author. Of 331 rejections, 243 were published elsewhere. Articles published in JGIM had a higher citation rate than those published elsewhere (Rw: 1.6 vs. 1.1, p = 0.002). Reviewer quality ratings of article quality had good internal consistency and reviewer recommendations markedly influenced publication decisions. There was no quality rating cutpoint that accurately distinguished high from low impact articles. There was a stepwise increase in Rw for articles rejected without review, rejected after review or accepted by JGIM (Rw 0.60 vs. 0.87 vs. 1.56, p<0.0005). However, there was low agreement between reviewers for quality ratings and publication recommendations. The editorial publication decision accurately discriminated high and low impact articles in 68% of submissions. We found evidence of better accuracy with a greater number of reviewers. Conclusions The peer review process largely succeeds in selecting high impact articles and dispatching lower impact ones, but the process is far from perfect. While the inter-rater reliability between individual reviewers is low, the accuracy of sorting is improved with a greater number of reviewers.
A spatial model of the ef fi ciency of T cell search in the in fl uenza-infected lung

Emerging strains of influenza, such as avian H5N1 and 2009 pandemic H1N1, are more virulent than seasonal H1N1 influenza, yet the underlying mechanisms for these differences are not well understood. Subtle differences in how a given strain interacts with the immune system are likely a key factor in determining virulence. One aspect of the interaction is the ability of T cells to locate the foci of the infection in time to prevent uncontrolled expansion. Here, we develop an agent based spatial model to focus on T cell migration from lymph nodes through the vascular system to sites of infection. We use our model to investigate whether different strains of influenza modulate this process. We calibrate the model using viral and chemokine secretion rates we measure in vitro together with values taken from literature. The spatial nature of the model reveals unique challenges for T cell recruitment that are not apparent in standard differential equation models. In this model comparing three influenza viruses, plaque expansion is governed primarily by the replication rate of the virus strain, and the efficiency of the T cell search-and-kill is limited by the density of infected epithelial cells in each plaque. Thus for each virus there is a different threshold of T cell search time above which recruited T cells are unable to control further expansion. Future models could use this relationship to more accurately predict control of the infection. & 2016 Elsevier Ltd. All rights reserved.
Vildagliptin: an anti‐diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin‐induced Alzheimer's disease

Adults who develop type 2 diabetes (T2D) at later stages are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents such as dipeptidyl peptidase‐4 (DPP‐4) inhibitors that increase the levels of glucagon‐like peptide‐1 (GLP‐1) and ameliorate T2D have also become promising candidates as disease‐modifying agents in the treatment of AD. The present study investigates the efficacy of vildagliptin, a DPP‐4 inhibitor in a streptozotocin (STZ)‐induced rat model of AD.
Non-negative graph embedding

We introduce a general formulation, called non-negative graph embedding, for non-negative data decomposition by integrating the characteristics of both intrinsic and penalty graphs [17]. In the past, such a decomposition was obtained mostly in an unsupervised manner, such as Non-negative Matrix Factorization (NMF) and its variants, and hence unnecessary to be powerful at classification. In this work, the non-negative data decomposition is studied in a unified way applicable for both unsupervised and supervised/semi-supervised configurations. The ultimate data decomposition is separated into two parts, which separatively preserve the similarities measured by the intrinsic and penalty graphs, and together minimize the data reconstruction error. An iterative procedure is derived for such a purpose, and the algorithmic non-negativity is guaranteed by the non-negative property of the inverse of any M-matrix. Extensive experiments compared with NMF and conventional solutions for graph embedding demonstrate the algorithmic properties in sparsity, classification power, and robustness to image occlusions.
Theories of Stress and Its Relationship to Health

C onceptualizations of stress and the stress response have varied in form and context throughout the centuries. In watching disease, both in private houses and in public hospitals, the thing which strikes the experienced observer most forcibly is this, that the symptoms or the sufferings generally considered to be inevitable and incidental to the disease are very often not symptoms of disease at all, but of something quite different—of the want of fresh air, or of light, or of warmth, or of quiet, or of cleanliness, or of punctuality and care in the administration of diet, of each or of all of these. (p. 8) Nightingale believed that all patients were experiencing some stress (as it was later to be called) regardless of their illness. She wrote to nursing, " If you knew how unreasonably sick people suffer from reasonable causes of distress, you would take more pains about these things " (p. 104). Nursing's challenge is to facilitate the " reparative process " (p. 9). More than 70 years later, Hans Selye (1936), a young medical student at the University of Prague, wrote, Whether a man suffers from a loss of blood, an infectious disease, or advanced cancer, he loses his appetite, his muscle strength, and his ambition to accomplish anything; usually the patient also loses weight and even his facial expression betrays that he is ill. (p. 19) He labeled this phenomenon the " syndrome of just being sick " and pursued the catalysts and processes of this syndrome in the laboratory and in his medical practice for more than 50 years. He described it as " stress-response theory " and systematically examined its relationship with health. Other researchers of the stress-response phenomenon include Mason (1971), McEwen (1998), and McEwen and Wingfield (2003). This chapter examines, in depth, the development of stress-response theory and the wealth of research, theory development, and clinical implications that have been derived from the work. Selye (1976a) initially proposed a triadic model as the basis for the stress-response pattern. The elements included adrenal cortex hypertrophy, thy-micolymphatic (e.g., the thymus, the lymph nodes, and the spleen) atrophy, and gastrointesti-nal ulcers. These three, he reasoned, were closely interdependent; they seemed to accompany most illnesses and were provoked no matter what the stimulus or illness. Selye could evoke the response in laboratory rats with agents such as formalin,
Chronic Inhibition, Self-Control and Eating Behavior: Test of a ‘Resource Depletion’ Model

The current research tested the hypothesis that individuals engaged in long-term efforts to limit food intake (e.g., individuals with high eating restraint) would have reduced capacity to regulate eating when self-control resources are limited. In the current research, body mass index (BMI) was used as a proxy for eating restraint based on the assumption that individuals with high BMI would have elevated levels of chronic eating restraint. A preliminary study (Study 1) aimed to provide evidence for the assumed relationship between eating restraint and BMI. Participants (N = 72) categorized into high or normal-range BMI groups completed the eating restraint scale. Consistent with the hypothesis, results revealed significantly higher scores on the weight fluctuation and concern for dieting subscales of the restraint scale among participants in the high BMI group compared to the normal-range BMI group. The main study (Study 2) aimed to test the hypothesized interactive effect of BMI and diminished self-control resources on eating behavior. Participants (N = 83) classified as having high or normal-range BMI were randomly allocated to receive a challenging counting task that depleted self-control resources (ego-depletion condition) or a non-depleting control task (no depletion condition). Participants then engaged in a second task in which required tasting and rating tempting cookies and candies. Amount of food consumed during the taste-and-rate task constituted the behavioral dependent measure. Regression analyses revealed a significant interaction effect of these variables on amount of food eaten in the taste-and-rate task. Individuals with high BMI had reduced capacity to regulate eating under conditions of self-control resource depletion as predicted. The interactive effects of BMI and self-control resource depletion on eating behavior were independent of trait self-control. Results extend knowledge of the role of self-control in regulating eating behavior and provide support for a limited-resource model of self-control.
Ira Tabas , Kevin Jon Williams and Jan Borén and Therapeutic Implications Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis : Update

The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B–containing lipoproteins. Local biological responses to these retained lipoproteins, including a chronic and maladaptive macrophageand T-cell–dominated inflammatory response, promote subsequent lesion development. The most effective therapy against atherothrombotic cardiovascular disease to date—low density lipoprotein–lowering drugs—is based on the principle that decreasing circulating apolipoprotein B lipoproteins decreases the probability that they will enter and be retained in the subendothelium. Ongoing improvements in this area include more aggressive lowering of low-density lipoprotein and other atherogenic lipoproteins in the plasma and initiation of low-density lipoprotein–lowering therapy at an earlier age in at-risk individuals. Potential future therapeutic approaches include attempts to block the interaction of apolipoprotein B lipoproteins with the specific subendothelial matrix molecules that mediate retention and to interfere with accessory molecules within the arterial wall that promote retention such as lipoprotein lipase, secretory sphingomyelinase, and secretory phospholipase A2. Although not the primary focus of this review, therapeutic strategies that target the proatherogenic responses to retained lipoproteins and that promote the removal of atherogenic components of retained lipoproteins also hold promise. The finding that certain human populations of individuals who maintain lifelong low plasma levels of apolipoprotein B lipoproteins have an 90% decreased risk of coronary artery disease gives hope that our further understanding of the pathogenesis of this leading killer could lead to its eradication. (Circulation. 2007;116:1832-1844.)
Molecular mechanisms of experience-dependent plasticity in visual cortex

A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.
Coping strategies of adolescents living with HIV: disease-specific stressors and responses

Abstract This study examined disease-specific stressors and coping responses employed by youth with HIV. Data were analyzed from Adolescent Impact, a multi-site study of 166 adolescents infected with HIV in three major US cities. Participants identified HIV-related stressors during a face-to-face interview. Coping strategies were measured using the adolescent version of the Kidcope. Emotional and behavioral functioning were assessed with the Youth or Adult Self Report symptom checklists. Medication-related stressors were most common (30%) and reported more often by perinatally infected youth, whereas youth infected through risk behaviors reported more disclosure-related stressors. Passive emotional regulation was perceived as the most used and most helpful coping strategy overall. Youth reporting medication adherence-related stressors used resignation most frequently. A two-factor model (Passive and Active Coping) emerged. The Passive Coping factor included strategies that do not directly approach the problem, whereas Active Coping included strategies that involve an active approach. Youth with moderately advanced disease (CD4 200–500 cells/mm3) used a Passive Coping style more often than healthier youth (CD4 > 500 cells/mm3). Additionally, Passive Coping was associated with greater emotional and behavioral problems. Youth infected with HIV may benefit from interventions promoting adaptive coping responses to HIV-specific stressors, particularly medication adherence.
On the Relation between Associative Strength and Automatic Behavior

In two experiments the relation between past contact, stereotypic associative strength, and stereotype activation effects on memory performance was investigated. It was hypothesized that, for some stereotypes, contact can lead to the development of stronger stereotypical associations. Associative strength, in turn, was expected to determine stereotype activation effects on behavior (in this case, memory performance). In Experiment 1, it was shown that people who reported to have had much previous contact with elderly people performed worse on a memory (free recall) test after being primed with the stereotype of the elderly. People who reported to have had little previous contact did not show any effects of priming. In Experiment 2, we confirmed that this effect is mediated by associative strength. People who reported to have had a lot of contact with the elderly had developed an association between the category elderly and the attribute “forgetfulness. ” The strength of this association, in turn, predicted the degree of memory impairment after activation of the category elderly.
Politics and banking in Russia: the rise of Putin

ABSTRACT We investigate whether lending by the dominant Russian state bank, Sberbank, contributed to Vladimir Putin’s ascent to power during the presidential elections of March2000. Our hypothesis is that Sberbank corporate loans were used as incentives for managers at private firms to mobilize employees to vote for Putin. In line with our proposed voter mobilization mechanism, we find that the growth of regional corporate Sberbank loans in the months before the presidential election is related to the regional increase in votes for Putin and to the regional increase in voter turnout between the Duma election of December1999 and the presidential election of March2000. The effect is pronounced in regions where the governor is affiliated with the regime and in regions with extensive private employment, and less apparent in regions bequeathed with single-company towns, where voter intimidation suffices to get the required result. The results are highly robust.
A comparison of 3 lasers and liquid nitrogen in the treatment of solar lentigines: a randomized, controlled, comparative trial.

OBJECTIVE To determine if laser therapy is superior to liquid nitrogen for the treatment of solar lentigines and if so, to determine if one laser is superior to the other lasers that were tested. DESIGN Randomized, controlled, comparative study with blinded observers. SETTING University-based dermatology clinic. PARTICIPANTS Twenty-seven patients with multiple solar lentigines on the backs of both hands. INTERVENTIONS Liquid nitrogen cryotherapy, the Medlite II frequency-doubled Q-switched Nd:YAG laser (Continuum Biomedical, Livermore, Calif), the HGM K1 krypton laser (HGM Medical Laser Systems Inc, Salt Lake City, Utah), and the DioLite 532-nm diode-pumped vanadate laser (Iridex Corp, Mountain View, Calif). MAIN OUTCOME MEASURES Photographs of the hands were taken prior to and 6 and 12 weeks following treatment. Blinded observers and patients evaluated each treatment on its ability to lighten pigmented lesions without causing unwanted adverse effects. RESULTS Many new laser systems claim an advantage for treating pigmented lesions by selectively destroying melanin. In this study, the frequency-doubled Q-switched Nd:YAG laser was most likely to provide significant lightening (P<.05), followed by the HGM K1 krypton laser, the 532-nm diode-pumped vanadate laser, and liquid nitrogen. The frequency-doubled Q-switched Nd:YAG laser also had the fewest adverse effects (P<.05), while the HGM K1 krypton laser had the most (P<.05). Of the 27 patients, 25 preferred laser therapy to cryotherapy, with the frequency-doubled Q-switched Nd:YAG laser being the most popular. CONCLUSIONS Laser therapy is superior to liquid nitrogen for the treatment of solar lentigines. Of the laser systems tested in this study, the frequency-doubled Q-switched Nd:YAG laser is the most effective.