Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence on Ergogenic Action of Glucocorticoids as a Doping Agent Risk

Abstract Systemic administration of glucocorticoids (GCs) is banned by the World Anti-Doping Agency (WADA) during competition. Few studies have examined the effects of GCs on exercise performance, but increasing evidence has shown that short-term GC intake enhances performance in animals and humans. However, there are many health risks associated with GC use. Based on the available evidence, as presented in this article, I conclude that GCs are doping agents and should remain on the WADA's list of banned products. Because of the complexity of GCs, however, determining the boundaries between their medical use and abuse (eg, in sports) is a constant challenge for the WADA.
MeCP2-Chromatin Interactions Include the Formation of Chromatosome-like Structures and Are Altered in Mutations Causing Rett Syndrome*

hMeCP2 (human methylated DNA-binding protein 2), mutations of which cause most cases of Rett syndrome (RTT), is involved in the transmission of repressive epigenetic signals encoded by DNA methylation. The present work focuses on the modifications of chromatin architecture induced by MeCP2 and the effects of RTT-causing mutants. hMeCP2 binds to nucleosomes close to the linker DNA entry-exit site and protects ∼11 bp of linker DNA from micrococcal nuclease. MeCP2 mutants differ in this property; the R106W mutant gives very little extra protection beyond the ∼146-bp nucleosome core, whereas the large C-terminal truncation R294X reveals wild type behavior. Gel mobility assays show that linker DNA is essential for proper MeCP2 binding to nucleosomes, and electron microscopy visualization shows that the protein induces distinct conformational changes in the linker DNA. When bound to nucleosomes, MeCP2 is in close proximity to histone H3, which exits the nucleosome core close to the proposed MeCP2-binding site. These findings firmly establish nucleosomal linker DNA as a crucial binding partner of MeCP2 and show that different RTT-causing mutations of MeCP2 are correspondingly defective in different aspects of the interactions that alter chromatin architecture.
Computational strategies for understanding the nature of interaction in dioxin imprinted nanoporous trappers

A new computational model capable of understanding the nature of interactions in signature complexes formed between the template (2,3,7,8‐tetrachlorodibenzo‐p dioxin (TCDD)) and the functional monomers (methacrylic acid (MAA)) using density functional theory (DFT) has been designed. The polymer precursors were optimized for geometries in polymerization media, computing the interaction energies between template molecules and functional monomers of transient pre‐polymerized complexes (PPC), and structural and vibrational properties reference to theoretical infrared spectra were computed using DFT of B3LYP/6 311+G(d,p) hybrid functional method. Atom in molecule theory was used to analyze the hydrogen‐bonding characteristics of PPC of MAA–TCDD. Considering the theoretical titrations conducted in a virtual solvent box, it was found that the 1:4 molar ratio was required to form the most stable PPC in a given solvent system. The electron density plots indicate strong hydrogen bonding as shown by the 2pz dominant highest occupied molecular orbital (HOMO) character that could be the preferable sites of binding for target molecule, TCDD. Considering HOMO approach, the active adsorption sites in molecularly imprinted polymer was modeled to get insight on molecular recognition property for targeted molecule, TCDD. The proposed computational protocol is simple, accurate, and novel to design the polymer and is useful to predict the properties of polymer systems than the conventional theoretical analysis of template–monomer interactions. Copyright © 2015 John Wiley & Sons, Ltd.
Gads/Grb2-Mediated Association with LAT Is Critical for the Inhibitory Function of Gab2 in T Cells

ABSTRACT A docking protein, Gab2, is recruited to the vicinity of the TCR complex and inhibits downstream signaling by interaction with negative regulators. However, the molecular mechanisms of this recruitment remain unclear. We have found that Gab2 associates with LAT upon TCR stimulation and that LAT is essential for Gab2 phosphorylation. By analysis of several Gab2 mutants, the c-Met binding domain (MBD) of Gab2 was found to be both necessary and sufficient for stimulation-induced LAT binding. Within the MBD domain, a novel Grb2 SH3 binding motif, PXXXR, is critical for constitutive association with Gads/Grb2. Through this association, Gab2 is recruited to the lipid raft after TCR ligation and exerts inhibitory function. The in vivo significance of this association is illustrated by the fact that T-cell responses are impaired in transgenic mice expressing wild-type Gab2 but not in mice expressing mutant Gab2 lacking the motif. Furthermore, T cells from Gab2-deficient mice showed enhanced proliferative responses upon TCR stimulation. These results indicate that Gads/Grb2-mediated LAT association is critical for the inhibitory function of Gab2, implying that Gab2 induced in stimulated T cells may exert an efficient negative feedback loop by recruiting inhibitory molecules to the lipid raft and competing with SLP-76 through Gads binding.
A game theoretic model for enabling honeypots in IoT networks

Honeypots have been considered as one of the methods to ensure security for networks in the Internet of Things (IoT) realm. In this paper, we study the problem of defending against attacks in honeypot-enabled networks by looking at a game-theoretic model of deception involving an attacker and a defender. The attacker may try to deceive the defender by employing different types of attacks ranging from a suspicious to a seemingly normal activity, while the defender in turn can make use of honeypots as a tool of deception to trap attackers. The problem is modeled as a Bayesian game of incomplete information, where equilibria are identified for both the one-shot game and the repeated game versions. Our results showed that there is a threshold for the frequency of active attackers, above which both players will take deceptive actions and below which the defender can mix up his/her strategy while keeping the attackers success rate low.
On the Performance of the Intel SR30 Depth Camera: Metrological and Critical Characterization

Specifically conceived for applications related to face analytics and tracking, scene segmentation, hand/finger tracking, gaming, augmented reality, and RGB-D cameras are nowadays used even as 3-D scanners. Despite depth cameras’ accuracy and precision are not comparable with professional 3-D scanners, they still constitute a promising device for reverse engineering (RE) applications in the close range, due to their low cost. This is particularly true for more recent devices, such as, for instance, the RealSense SR300, which promises to be among the best performing close range depth cameras in the market. Given the potentiality of this new device, and since to date a deep investigation on its performances has not been assessed in scientific literature, the main aim of this paper is to characterize and to provide metrological considerations on the Intel RealSense SR300 depth sensor when this is used as a 3-D scanner. To this end, the device sensor performances are first assessed by applying the existing normative guidelines (i.e. the one published by the Association of German Engineers - Verein Deutscher Ingenieure - VDI/VDE 2634) both to a set of raw captured depth data and to a set acquired with optimized setting of the camera. Then, further assessment of the device performances is carried out by applying some strategies proposed in the literature using optimized sensor setting, to reproduce “real life” conditions for the use as a 3-D scanner. Finally, the performance of the device is critically compared against the performance of latest short-range sensors, thus providing a useful guide, for researchers and practitioners, in an informed choice of the optimal device for their own RE application.
Quantification of the impact of enzyme‐inducing antiepileptic drugs on irinotecan pharmacokinetics and SN‐38 exposure

The population pharmacokinetic model reported here was developed using data from 2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the impact of concomitant therapy with enzyme‐inducing antiepileptic drugs (EIAEDs) on irinotecan pharmacokinetics. Patients received weekly irinotecan doses of 100 to 400 mg/m2, and plasma samples were collected and analyzed for irinotecan and its APC, SN‐38, and SN‐38G metabolites. Nonlinear mixed‐effects modeling was employed for population pharmacokinetic analysis. Concomitant therapy with phenytoin, phenobarbital, or carbamazepine increased the clearances of irinotecan, SN‐38, and SN‐38G but not APC. SN‐38 clearance was 2‐fold higher with concomitant EIAED use, resulting in 40% lower SN‐38 exposure. Evaluation of additional covariates revealed no clinically relevant effects of sex or concomitant corticosteroid use. The population pharmacokinetic model suggests that a 1.7‐fold increase in irinotecan dose may compensate for decreases in SN‐38 exposure in the presence of concomitant EIAEDs. Although slightly more conservative, this dose adjustment is consistent with those recommended based on increases in the maximally tolerated dose for malignant glioma patients receiving EIAEDs and may be an appropriate starting point for further investigation when extrapolating to other cancer types or alternative regimens.
Ruling out learning and change? Lessons from urban flood mitigation

Abstract This article shows how particular rule configurations can create conditions for learning from experimentation on an operation level. It does so by using the IAD framework in a diagnostic analysis of decisions to fund the development of drainage in the Denver Metropolitan Area before and after the 2013 Colorado Flood. The discussion first synthesizes recent developments in this research area. Then, it demonstrates how formal institutional analysis can be used to address existing gaps. To conclude, recommendations for further research to develop our understanding of the link between learning and change are presented.
Oral Tongue Squamous Cell Carcinoma in Never-Smokers

Objectives (1) To compare clinical characteristics, survival, and recurrence between never-smokers and ever-smokers with oral tongue squamous cell carcinoma (OTSCC). (2) To assess the relationship between clinicopathologic characteristics and survival/recurrence in OTSCC. Study Design Historical cohort study. Setting Academic university medical center. Subjects and Methods This is a study of 120 patients with OTSCC who were treated from January 1999 to February 2010. Clinicopathologic factors were compared between never-smokers and ever-smokers using t tests and χ2 tests. Cox regression analyses examined their association with survival and recurrence. Results Of 120 subjects, 66 (55%) were prior or current smokers. There were no significant differences in clinicopathologic factors between ever-smokers and never-smokers. After adjustment for clinicopathologic factors, multivariate Cox regression analysis demonstrated decreased overall survival for never-smokers, but this difference was not significant (hazard ratio [HR], 2.84; P = .056). Increased depth of tumor invasion (HR per millimter invasion, 1.09; P = .005), nodal metastasis (HR, 7.1; P = .025), and stage III or IV disease (HR, 9.45 and 7.31; P = .026 and .029, respectively) were associated with decreased overall survival. Perineural invasion (HR, 8.56; P = .005) and lymphovascular invasion (HR, 6.01; P = .011) were associated with disease recurrence. Conclusion Overall survival may be decreased in never-smokers with OTSCC. Greater depth of tumor invasion and more advanced stage disease are associated with decreased survival. Perineural invasion and lymphovascular invasion are associated with disease recurrence.
Antioxidant potential of thyme extract: alleviation of N-nitrosodiethylamine-induced oxidative stress

Protective role of thyme extract against N-nitrosodiethylamine (NDEA)-induced oxidative stress has been evaluated in albino rats. For this, one group of rats were fed diet supplemented with thyme extract (0.5%) and served as the test group, whereas animals of the other group fed on normal diet served as the control group. The rats were fed on respective diets for a period of 2 weeks after which stress was induced to half the animals of each group by i.p. administration of NDEA at 200 mg/kg body weight. Animals were killed 48 h post stress-induction period. Feed intake and body weight decreased significantly in both test and control groups, the effect being less in test group. Increase in osmotic fragility and in-vitro lipid peroxidation (LPO) on stress induction was of lower degree in the test group. NDEA toxicity was mainly reflected in liver as evidenced by increased activities of plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. The effect was of lower degree in test group as compared with that in the control group. Increase in urea levels observed following NDEA administration was also of lower degree in test groups. Blood glutathione (GSH) levels increased more so in test group compared with control group on stress induction. The activities of superoxide dismutase (SOD), peroxidase (Px), and catalase (CAT) activities decreased significantly on stress induction in erythrocytes. LPO increased in all the tissues through varying degree, and the increase was appreciably of lower degree in test group. The activity of SOD increased significantly in both test and control group on stress induction, whereas activities of Px and CAT decreased following NDEA treatment, and the effects were of lower degree in test group. Thus, supplementation of diet with thyme extract can improve antioxygenic potential and hence help to prevent oxidative stress.
Innate immunity to virus infection

Summary: The innate immune system is essential for the initial detection of invading viruses and subsequent activation of adaptive immunity. Three classes of receptors, designated retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs), Toll‐like receptors (TLRs), and nucleotide oligomerization domain (NOD)‐like receptors (NLRs), sense viral components, such as double‐stranded RNA (dsRNA), single‐stranded RNA, and DNA. RLRs and TLRs play essential roles in the production of type I interferons (IFNs) and proinflammatory cytokines in cell type‐specific manners. While the RLRs play essential roles in the recognition of RNA viruses in various cells, plasmacytoid dendritic cells utilize TLRs for detecting virus invasion. NLRs play a role in the production of mature interleukin‐1β to dsRNA stimulation. Activation of innate immune cells is critical for mounting adaptive immune responses. In this review, we discuss recent advances in our understanding of the mechanisms of viral RNA recognition by these different types of receptors and its relation to acquired immune responses.
Uncertainty, information, and disagreement of economic forecasters

ABSTRACT An information framework is proposed for studying uncertainty and disagreement of economic forecasters. This framework builds upon the mixture model of combining density forecasts through a systematic application of the information theory. The framework encompasses the measures used in the literature and leads to their generalizations. The focal measure is the Jensen–Shannon divergence of the mixture which admits Kullback–Leibler and mutual information representations. Illustrations include exploring the dynamics of the individual and aggregate uncertainty about the US inflation rate using the survey of professional forecasters (SPF). We show that the normalized entropy index corrects some of the distortions caused by changes of the design of the SPF over time. Bayesian hierarchical models are used to examine the association of the inflation uncertainty with the anticipated inflation and the dispersion of point forecasts. Implementation of the information framework based on the variance and Dirichlet model for capturing uncertainty about the probability distribution of the economic variable are briefly discussed.
A population-based study of sexual orientation identity and gender differences in adult health.

OBJECTIVES We provide estimates of several leading US adult health indicators by sexual orientation identity and gender to fill gaps in the current literature. METHODS We aggregated data from the 2001-2008 Massachusetts Behavioral Risk Factor Surveillance surveys (N = 67,359) to examine patterns in self-reported health by sexual orientation identity and gender, using multivariable logistic regression. RESULTS Compared with heterosexuals, sexual minorities (i.e., gays/lesbians, 2% of sample; bisexuals, 1%) were more likely to report activity limitation, tension or worry, smoking, drug use, asthma, lifetime sexual victimization, and HIV testing, but did not differ on 3-year Papanicolaou tests, lifetime mammography, diabetes, or heart disease. Compared with heterosexuals, bisexuals reported more barriers to health care, current sadness, past-year suicidal ideation, and cardiovascular disease risk. Gay men were less likely to be overweight or obese and to obtain prostate-specific antigen tests, and lesbians were more likely to be obese and to report multiple risks for cardiovascular disease. Binge drinking and lifetime physical intimate partner victimization were more common among bisexual women. CONCLUSIONS Sexual orientation disparities in chronic disease risk, victimization, health care access, mental health, and smoking merit increased attention. More research on heterogeneity in health and health determinants among sexual minorities is needed.
Religious Affiliation and Open-Mindedness in Binocular Resolution

20 Ss, 10 Jewish and 10 Catholic, were exposed to a stereoscopic task and a test of open-mindedness. The stereoscopic task involved a series of 22 slides pairing Jewish and Catholic symbols, words and pictures, exposed under conditions of conflict thus calling for some form of binocular resolution by Ss. The test of open-mindedness was Rokeach's Dogmatism Scale, Form E. There was a statistically significant tendency to report seeing material related to one's own religion. This may be expressed in the form of a point biserial correlation coefficient of . 95 (p < .001). There was a significant correlation between open-mindedness and the tendency to report seeing material associated with the “other” religion (r = .40, p < .025).
On the homogenized behaviour of reinforced and other Bingham composites

A recently developed (Ponte Castañeda 2002 J. Mech. Phys. Solids 50, 737–757) ‘second–order’ nonlinear homogenization method is used to estimate the constitutive response of reinforced and other Bingham composites. For the special case of rigidly reinforced Bingham composites with overall isotropy (in two dimensions), the results show that the homogenized response of such materials is not strictly Bingham. Thus, instead of a purely linear incremental response beyond the relevant threshold (yield) stress, the response is strongly nonlinear just after yield and asymptotes to a purely linear incremental response only at sufficiently large stress or strain–rate levels. This phenomenon is linked to the presence of strong fluctuations of the strain–rate field in the composite at the onset of yield.
Versatile Nanosystem-Based Cancer Theranostics: Design Inspiration and Predetermined Routing

The relevance of personalized medicine, aimed at a more individualized drug therapy, has inspired research into nano-based concerted diagnosis and therapeutics (theranostics). As the intention is to “kill two birds with one stone”, scientists have already described the emerging concept as a treasured tailor for the future of cancer therapy, wherein the main idea is to design “smart” nanosystems to concurrently discharge both therapeutic and diagnostic roles. These nanosystems are expected to offer a relatively clearer view of the ingenious cellular trafficking pathway, in-situ diagnosis, and therapeutic efficacy. We herein present a detailed review of versatile nanosystems, with prominent examples of recently developed intelligent delivery strategies which have gained attention in the field of theranostics. These nanotheranostics include various mechanisms programmed in novel platforms to enable predetermined delivery of cargo to specific sites, as well as techniques to overcome the notable challenges involved in the efficacy of theranostics.
Interferon-gamma up-regulates expression of cysteinyl leukotriene type 2 receptors on eosinophils in asthmatic patients.

STUDY OBJECTIVES Cysteinyl leukotrienes (cysLTs) are strong bronchoconstrictive mediators that play a key role in asthma inflammation. They act through specific receptors including cysLT type 1 receptor (CysLT1R) and cysLT type 2 receptor (CysLT2R). Although these two receptors are co-expressed on inflammatory cells, little is known about CysLT2R in patients with asthma. The aims of this study were to investigate the changes in cysLT receptors (CysLTRs) during asthma exacerbations and to determine which cytokine modulates CysLTR expression on eosinophils. METHODS We assessed protein expression and messenger RNA of CysLT1R and CysLT2R in peripheral blood eosinophils and measured urinary leukotriene E(4) levels in 36 patients with stable asthma, 23 subjects with asthma exacerbation, and 15 healthy subjects. We also evaluated the modulation of these receptors by interleukin (IL)-1beta, IL-4, IL-5, IL-13, interferon (IFN)-gamma and tumor necrosis factor-alpha in cultured eosinophils. RESULTS Expression of both CysLT1R and CysLT2R on eosinophils during asthma exacerbations was significantly higher (p < 0.05) than in stable asthma and healthy subjects. A greater expression of CysLT2R in exacerbation was found in nonatopic asthmatics. Only IFN-gamma up-regulated cell-surface expression of CysLT2R in a dose-dependent manner and enhanced messenger RNA levels. No cytokine affected CysLT1R expression or messenger RNA level. CONCLUSIONS CysLT2R expression on eosinophils was increased in patients, especially in nonatopic subjects, during asthma exacerbation, and was up-regulated by IFN-gamma; therefore we speculate that a pathway through CysLT2R might modulate exacerbations of asthma.
LRRK2 pathobiology in Parkinson's disease

Mutations in the catalytic Roc‐COR and kinase domains of leucine‐rich repeat kinase 2 (LRRK2) are a common cause of familial Parkinson's disease (PD). LRRK2 mutations cause PD with age‐related penetrance and clinical features identical to late‐onset sporadic PD. Biochemical studies support an increase in LRRK2 kinase activity and a decrease in GTPase activity for kinase domain and Roc‐COR mutations, respectively. Strong evidence exists that LRRK2 toxicity is kinase dependent leading to extensive efforts to identify selective and brain‐permeable LRRK2 kinase inhibitors for clinical development. Cell and animal models of PD indicate that LRRK2 mutations affect vesicular trafficking, autophagy, protein synthesis, and cytoskeletal function. Although some of these biological functions are affected consistently by most disease‐linked mutations, others are not and it remains currently unclear how mutations that produce variable effects on LRRK2 biochemistry and function all commonly result in the degeneration and death of dopamine neurons. LRRK2 is typically present in Lewy bodies and its toxicity in mammalian models appears to be dependent on the presence of α‐synuclein, which is elevated in human iPS‐derived dopamine neurons from patients harboring LRRK2 mutations. Here, we summarize biochemical and functional studies of LRRK2 and its mutations and focus on aberrant vesicular trafficking and protein synthesis as two leading mechanisms underlying LRRK2‐linked disease.