Miracle-dz/UniFAR-FTUs huggingface dataset:
Bromodomain and Extraterminal Protein Inhibitor JQ1 Suppresses Thyroid Tumor Growth in a Mouse Model

Purpose: New therapeutic approaches are needed for patients with thyroid cancer refractory to radioiodine treatment. An inhibitor of bromodomain and extraterminal domain (BET) proteins, JQ1, shows potent antitumor effects in hematological cancers and solid tumors. To evaluate whether JQ1 is effective against thyroid cancer, we examined antitumor efficacy of JQ1 using the ThrbPV/PVKrasG12D mouse, a model of anaplastic thyroid cancer. Experimental Design: We treated ThrbPV/PVKrasG12D mice with vehicle or JQ1 at a dose of 50 mg/kg body weight/day starting at the age of 8 weeks for a 10-week period and monitored thyroid tumor progression. Results: JQ1 markedly inhibited thyroid tumor growth and prolonged survival of these mice. Global differential gene expression analysis showed that JQ1 suppressed the cMyc (hereafter referred to as Myc) transcription program by inhibiting mRNA expression of Myc, ccnd1, and other related genes. JQ1-suppressed Myc expression was accompanied by chromatin remodeling as evidenced by increased expression of histones and hexamethylene bis-acetamide inducible 1, a suppressor of RNA polymerase II transcription elongation. Analyses showed that JQ1 decreased MYC abundance in thyroid tumors and attenuated the cyclin D1–CDK4–Rb–E2F3 signaling to decrease tumor growth. Further analysis indicated that JQ1 inhibited the recruitment of BDR4 to the promoter complex of the Myc and Ccnd1 genes in rat thyroid follicular PCCL3 cells, resulting in decreased MYC expression at the mRNA and protein levels to inhibit tumor cell proliferation. Conclusions: These preclinical findings suggest that BET inhibitors may be an effective agent to reduce thyroid tumor burden for the treatment of refractory thyroid cancer. Clin Cancer Res; 23(2); 430–40. ©2016 AACR.
Risk Factors for Childhood Stunting in 137 Developing Countries: A Comparative Risk Assessment Analysis at Global, Regional, and Country Levels

Background Stunting affects one-third of children under 5 y old in developing countries, and 14% of childhood deaths are attributable to it. A large number of risk factors for stunting have been identified in epidemiological studies. However, the relative contribution of these risk factors to stunting has not been examined across countries. We estimated the number of stunting cases among children aged 24–35 mo (i.e., at the end of the 1,000 days’ period of vulnerability) that are attributable to 18 risk factors in 137 developing countries. Methods and Findings We classified risk factors into five clusters: maternal nutrition and infection, teenage motherhood and short birth intervals, fetal growth restriction (FGR) and preterm birth, child nutrition and infection, and environmental factors. We combined published estimates and individual-level data from population-based surveys to derive risk factor prevalence in each country in 2010 and identified the most recent meta-analysis or conducted de novo reviews to derive effect sizes. We estimated the prevalence of stunting and the number of stunting cases that were attributable to each risk factor and cluster of risk factors by country and region. The leading risk worldwide was FGR, defined as being term and small for gestational age, and 10.8 million cases (95% CI 9.1 million–12.6 million) of stunting (out of 44.1 million) were attributable to it, followed by unimproved sanitation, with 7.2 million (95% CI 6.3 million–8.2 million), and diarrhea with 5.8 million (95% CI 2.4 million–9.2 million). FGR and preterm birth was the leading risk factor cluster in all regions. Environmental risks had the second largest estimated impact on stunting globally and in the South Asia, sub-Saharan Africa, and East Asia and Pacific regions, whereas child nutrition and infection was the second leading cluster of risk factors in other regions. Although extensive, our analysis is limited to risk factors for which effect sizes and country-level exposure data were available. The global nature of the study required approximations (e.g., using exposures estimated among women of reproductive age as a proxy for maternal exposures, or estimating the impact of risk factors on stunting through a mediator rather than directly on stunting). Finally, as is standard in global risk factor analyses, we used the effect size of risk factors on stunting from meta-analyses of epidemiological studies and assumed that proportional effects were fairly similar across countries. Conclusions FGR and unimproved sanitation are the leading risk factors for stunting in developing countries. Reducing the burden of stunting requires a paradigm shift from interventions focusing solely on children and infants to those that reach mothers and families and improve their living environment and nutrition.
Seroprevalence of Measles , Rubella , Mumps and Varicella Specific Antibodies in Primary School Children

Measles, mumps, rubella and varicella are diseases that are tracked by the World Health Organization (WHO) as common and serious vaccine-preventable diseases. Aim of the Work: To evaluate the immune status and susceptibility against measles, mumps, rubella, and varicella in primary school children and to study the effects of some sociodemographic factors on the seroprevalence. Subjects and methods: This is a crosssectional study conducted on 180 children. All children included in this study were subjected to thorough history taking and laboratory investigations; to measure serum levels of specific measles, rubella, mumps and varicella immunoglobulins (IgG) Results: (88.9%) of the surveyed children were seropositive to measles, (77.8%) to mumps, (86.7%) to rubella and (38.9%) to varicella. Seropositivity was higher in males than in females for measles (57.7%), mumps (60.7%), rubella (62.2%) and varicella (68.6%) with significant difference for measles. Younger age groups were less seropositive than older age groups for measles (32.5% vs 35%), mumps (34.4 % vs 37.9%), rubella ( 30.8 % vs 39.7 %) and for varicella (21.4%) vs 48.6%). The highest level of seronegativity was seen with regard to varicella specific antibodies (61.1%). Conclusion and recommendations: There is an urgent need for a planned program with different strategies to prevent and control these diseases .
Cancer burden attributable to cigarette smoking among HIV-infected people in North America

Objective: With combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to ever smoking cigarettes. Design: Observational cohort of HIV-infected participants with 270 136 person-years of follow-up in the North American AIDS Cohort Collaboration on Research and Design consortium. Among 52 441 participants, 2306 were diagnosed with cancer during 2000–2015. Main outcome measures: Estimated hazard ratios and population-attributable fractions (PAF) associated with ever cigarette smoking for all cancers combined, smoking-related cancers, and cancers that were not attributed to smoking. Results: People with cancer were more frequently ever smokers (79%) compared with people without cancer (73%). Adjusting for demographic and clinical factors, cigarette smoking was associated with increased risk of cancer overall [hazard ratios = 1.33 (95% confidence interval: 1.18–1.49)]; smoking-related cancers [hazard ratios = 2.31 (1.80–2.98)]; lung cancer [hazard ratios = 17.80 (5.60–56.63)]; but not nonsmoking-related cancers [hazard ratios = 1.12 (0.98–1.28)]. Adjusted PAFs associated with ever cigarette smoking were as follows: all cancers combined, PAF = 19% (95% confidence interval: 13–25%); smoking-related cancers, PAF = 50% (39–59%); lung cancer, PAF = 94% (82–98%); and nonsmoking-related cancers, PAF = 9% (1–16%). Conclusion: Among HIV-infected persons, approximately one-fifth of all incident cancer, including half of smoking-related cancer, and 94% of lung cancer diagnoses could potentially be prevented by eliminating cigarette smoking. Cigarette smoking could contribute to some cancers that were classified as nonsmoking-related cancers in this report. Enhanced smoking cessation efforts targeted to HIV-infected individuals are needed.
First Draft Business Cycles and Fiscal Policies : The Role of Institutions and Financial Markets

Macroeconomic policies are designed to stabilize business cycle fluctuations. Usually, fiscal and monetary policies in industrial countries have been expansionary in response to weak domestic conditions. However, the cyclical properties of fiscal policies are a much more disputed issue among emerging market economies. Several researchers have attributed these differences in cyclical behavior to: (a) factors associated to a weak institutional framework that play a key role in explaining sub-optimal policy decisions, and (b) factors associated to weak integration (or access) to either domestic or international financial markets. The goal of the present paper is to empirically evaluate whether the ability of countries to conduct counter-cyclical fiscal policy is affected by the quality of their institutions and/or by the availability of financial resources either in domestic or international capital markets. Our empirical evaluation yields a more nuanced interpretation to the existing evidence: (1) countries are unable to conduct counter-cyclical fiscal policies if they have poor institutions or lack wide access to credit markets at home and abroad, and (2) institutional factors have a larger weight than financial variables in explaining the differences in cyclical behavior of fiscal policy between industrial and developing countries. JEL Classification: E32, E62, C23
DWT and TSVQ-based Semi-fragile Watermarking Scheme for Tampering Detection in Remote Sensing Images

A semi fragile watermarking scheme for remote sensing images is presented. The suggested scheme uses the signature of the multispectral or hyper spectral image to embed the mark and detects a forgery of the marked image, e.g. a tampered region. The original image is segmented in three-dimensional blocks and, for each block, a discrete Wavelet transform (DWT) and a tree structured vector quantizer is built. These trees are manipulated using an iterative algorithm until the resulting image satisfies some selected conditions. Each tree is partially modified accordingly to a secret key in order to avoid tampering attacks. This key determines the internal structure of the tree and, also, the resulting distortion. In order to make the marked image robust against near-loss less compression, the trees are built using only the LL sub-band of the DWT. The results show that the method works correctly with remote sensing images and detects copy-and-replace attacks from segments of the same image, whilst allowing for JPEG2000 compression.
The electrical resistivity log as an aid in determining some reservoir characteristics

THE usefulness of the electrical resistivity log in determining reservoir characteristics is governed largely by: (I) the accuracy with which the true resistivity of the formation can be determined; (2) the scope of detailed data concerning the relation of resistivity measurements to formation characteristics; (3) the available information concerning the conductivity of connate or formation waters; (4) the extent of geologic knowledge regarding probable changes in facies within given horizons, both vertically and laterally, particularly in relation to the resultant effect on the electrical properties of the reservoir. Simple examples are given in the following pages to illustrate the use of resistivity logs in the solution of some problems dealing with oil and gas reservoirs. From the available information, it is apparent that much care must be exercised in applying to more complicated cases the methods suggested. It should be remembered that the equations given are not precise and represent only approximate relationships. It is believed, however, that under favorable conditions their application falls within useful limits of accuracy.
Nitrophorin 2, a factor IX(a)-directed anticoagulant, inhibits arterial thrombosis without impairing haemostasis

Summary Nitrophorin 2 (NP2) is a 20 kDa lipocalin identified in the salivary gland of the blood sucking insect, Rhodnius prolixus. It functions as a potent inhibitor of the intrinsic pathway of coagulation upon binding to factor IX (FIX) or FIXa. Herein we have investigated the in vivo antithrombotic properties of NP2. Surface plasmon resonance assays demonstrated that NP2 binds to rat FIX and FIXa with high affinities (KD = 43 and 47 nM, respectively), and prolongs the aPTT without affecting the PT. In order to evaluate NP2 antithrombotic effects in vivo two distinct models of thrombosis in rats were carried out. In the rose Bengal/laser induced injury model of arterial thrombosis, NP2 increased the carotid artery occlusion time by ≈35 and ≈155%, at doses of 8 and 80 μg/kg, respectively. NP2 also inhibited thrombus formation in an arterio-venous shunt model, showing ≈60% reduction at 400 μg/kg (i.v. administration). The antithrombotic effect lasted for up to 48 hours after a single i.v. dose. Notably, effective doses of NP2 did not increase the blood loss as evaluated by tail-transection model. In conclusion, NP2 is a potent and long-lasting inhibitor of arterial thrombosis with minor effects on haemostasis. It might be regarded as a potential agent for the treatment of human cardiovascular diseases.
Hybrid Nanomaterials of Magnetic Iron Nanoparticles and Graphene Oxide as Matrices for the Immobilization of β-Glucosidase: Synthesis, Characterization, and Biocatalytic Properties

Hybrid nanostructures of magnetic iron nanoparticles and graphene oxide were synthesized and used as nanosupports for the covalent immobilization of β-glucosidase. This study revealed that the immobilization efficiency depends on the structure and the surface chemistry of nanostructures employed. The hybrid nanostructure-based biocatalysts formed exhibited a 2 to 4-fold higher thermostability as compared to the free enzyme, as well as an enhanced performance at higher temperatures (up to 70 °C) and in a wider pH range. Moreover, these biocatalysts retained a significant part of their bioactivity (up to 40 %) after 12 repeated reaction cycles.
Subcellular Profiling Reveals Distinct and Developmentally Regulated Repertoire of Growth Cone mRNAs

Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons, yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones. Here laser capture microdissection (LCM) was used to isolate the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus, coupled with unbiased genomewide microarray profiling. An unexpectedly large pool of mRNAs defined predominant pathways in protein synthesis, oxidative phosphorylation, cancer, neurological disease, and signaling. Comparative profiling of “young” (pathfinding) versus “old” (target-arriving) Xenopus growth cones revealed that the number and complexity of transcripts increases dramatically with age. Many presynaptic protein mRNAs are present exclusively in old growth cones, suggesting that functionally related sets of mRNAs are targeted to growth cones in a developmentally regulated way. Remarkably, a subset of mRNAs was significantly enriched in the growth cone compared with the axon compartment, indicating that mechanisms exist to localize mRNAs selectively to the growth cone. Furthermore, some receptor transcripts (e.g., EphB4), present exclusively in old growth cones, were equally abundant in young and old cell bodies, indicating that RNA trafficking from the soma is developmentally regulated. Our findings show that the mRNA repertoire in growth cones is regulated dynamically with age and suggest that mRNA localization is tailored to match the functional demands of the growing axon tip as it transforms into the presynaptic terminal.
Single and Dual Amino Acid Substitutions in TCR CDRs Can Enhance Antigen-Specific T Cell Functions

Single and dual amino acid substitution variants were generated in the TCR CDRs of three TCRs that recognize tumor-associated Ags. Substitutions that enhance the reactivity of TCR gene-modified T cells to the cognate Ag complex were identified using a rapid RNA-based transfection system. The screening of a panel of variants of the 1G4 TCR, that recognizes a peptide corresponding to amino acid residues 157–165 of the human cancer testis Ag NY-ESO-1 (SLLMWITQC) in the context of the HLA-A*02 class I allele, resulted in the identification of single and dual CDR3α and CDR2β amino acid substitutions that dramatically enhanced the specific recognition of NY-ESO-1+/HLA-A*02+ tumor cell lines by TCR gene-modified CD4+ T cells. Within this group of improved TCRs, a dual substitution in the 1G4 TCR CDR3α chain was identified that enhanced Ag-specific reactivity in gene-modified CD4+ and CD8+ T cells. Separate experiments on two distinct TCRs that recognize the MART-1 27–35 (AAGIGILTV) peptide/HLA-A*02 Ag complex characterized single amino acid substitutions in both TCRs that enhanced CD4+ T cell Ag-specific reactivity. These results indicate that simple TCR substitution variants that enhance T cell function can be identified by rapid transfection and assay techniques, providing the means for generating potent Ag complex-specific TCR genes for use in the study of T cell interactions and in T cell adoptive immunotherapy.
Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of AIDS virus suppression, residual virus, and curative strategies

Purpose of reviewAnimal models will be critical for preclinical evaluations of novel HIV eradication and/or functional cure strategies in the setting of suppressive combination antiretroviral therapy (cART). Here, the strengths, limitations, and challenges of recent efforts to develop nonhuman primate (NHP) models of cART-mediated suppression for use in studies of persistent virus and curative approaches are discussed. Recent findingsSeveral combinations of NHP species and viruses that recapitulate key aspects of human HIV infection have been adapted for cART-mediated suppression studies. Different cART regimens incorporating drugs targeting multiple different steps of the viral replication cycle have provided varying levels of virologic suppression, dependent in part upon the host species, virus, drug regimen and timing, and virologic monitoring assay sensitivity. New, increasingly sensitive virologic monitoring approaches for measurements of plasma viral RNA, cell-associated and tissue-associated viral RNA and DNA, and the replication-competent residual viral pool in the setting of cART in NHP models are being developed to allow for the assessment of persistent virus on cART and to evaluate the impact of viral induction/eradication strategies in vivo. SummaryGiven the vagaries of each specific virus and host species, and cART regimen, each model will require further development and analysis to determine their appropriate application for addressing specific experimental questions.
Coping and its Correlates: What the Adolescent Coping Scale Tells us

ABSTRACTThis paper on the coping actions of Australian adolescents reporls on research spanning a 5-year period. The central indicator of coping in this work is the Adolescent Coping Scale (ACS), an 80-item checklist that identifies 18 coping strategies commonly used by adolescents. There are clear indications that age, gender, and family of origin are concomitants of coping. Furthermore, coping varies according to adolescent perceptions of the self, perception of the adolescent's ability by others, family climate, and the experience of stress in the family. Positive family climate is generally associated with the use of functional styles of coping. Adolescents who are identified as highly able or gifted use a different coping repertoire in comparison to their nongifted peers. Young people in intact or separated households use similar strategies to manage their general concerns. Moreover, those dealing with separation of parents were generally as adaptive in their use of coping strategies.
Temporal Evolution of Pattern Disparity Processing in Humans

Stereo matching, i.e., the matching by the visual system of corresponding parts of the images seen by the two eyes, is inherently a 2D problem. To gain insights into how this operation is carried out by the visual system, we measured, in human subjects, the reflexive vergence eye movements elicited by the sudden presentation of stereo plaids. We found compelling evidence that the 2D pattern disparity is computed by combining disparities first extracted within orientation selective channels. This neural computation takes 10–15 ms, and is carried out even when subjects perceive not a single plaid but rather two gratings in different depth planes (transparency). However, we found that 1D disparities are not always effectively combined: When spatial frequency and contrast of the gratings are sufficiently different pattern disparity is not computed, a result that cannot be simply attributed to the transparency of such stimuli. Based on our results, we propose that a narrow-band implementation of the IOC (Intersection of Constraints) rule (Fennema and Thompson, 1979; Adelson and Movshon, 1982), preceded by cross-orientation suppression, underlies the extraction of pattern disparity.
A role for XRCC2 gene polymorphisms in breast cancer risk and survival

Background The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer. Methods The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC). Results The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10−4, minor allele frequency (MAF)=0.23). This SNP yielded an ORrec of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-ORrec of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01). Conclusions These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.