Miracle-dz/UniFAR-FTUs huggingface dataset:
Decreased Anti-Tumor Cytotoxic Immunity among Microsatellite-Stable Colon Cancers from African Americans

Colorectal cancer is a leading cause of cancer related deaths in the U.S., with African-Americans having higher incidence and mortality rates than Caucasian-Americans. Recent studies have demonstrated that anti-tumor cytotoxic T lymphocytes provide protection to patients with colon cancer while patients deficient in these responses have significantly worse prognosis. To determine if differences in cytotoxic immunity might play a role in racial disparities in colorectal cancer 258 microsatellite-stable colon tumors were examined for infiltrating immune biomarkers via immunohistochemistry. Descriptive summary statistics were calculated using two-sample Wilcoxon rank sum tests, while linear regression models with log-transformed data were used to assess differences in race and Pearson and Spearman correlations were used to correlate different biomarkers. The association between different biomarkers was also assessed using linear regression after adjusting for covariates. No significant differences were observed in CD8+ (p = 0.83), CD57+ (p = 0.55), and IL-17-expressing (p = 0.63) cell numbers within the tumor samples tested. When infiltration of granzyme B+ cells was analyzed, however, a significant difference was observed, with African Americans having lower infiltration of cells expressing this cytotoxic marker than Caucasians (p<0.01). Analysis of infiltrating granzyme B+ cells at the invasive borders of the tumor revealed an even greater difference by race (p<0.001). Taken together, the data presented suggest differences in anti-tumor immune cytotoxicity may be a contributing factor in the racial disparities observed in colorectal cancer.
Characterization of Chikungunya Virus Induced Host Response in a Mouse Model of Viral Myositis

While a number of studies have documented the persistent presence of chikungunya virus (CHIKV) in muscle tissue with primary fibroblast as the preferable cell target, little is known regarding the alterations that take place in muscle tissue in response to CHIKV infection. Hence, in the present study a permissive mouse model of CHIKV infection was established and characterized in order to understand the pathophysiology of the disease. The two dimensional electrophoresis of muscle proteome performed for differential analysis indicated a drastic reprogramming of the proteins from various classes like stress, inflammation, cytoskeletal, energy and lipid metabolism. The roles of the affected proteins were explained in relation to virus induced myopathy which was further supported by the histopathological and behavioural experiments proving the lack of hind limb coordination and other loco-motor abnormalities in the infected mice. Also, the level of various pro-inflammatory mediators like IL-6, MCP-1, Rantes and TNF-α was significantly elevated in muscles of infected mice. Altogether this comprehensive study of characterizing CHIKV induced mouse myopathy provides many potential targets for further evaluation and biomarker study.
PROBLEMATIKA GURU DALAM MENGGUNAKAN MEDIA PEMBELAJARAN PADA MATA PELAJARAN IPS DI MADRASAH IBTIDAIYAH DARUSSALAM KOTA BENGKULU

Teachers problematic in using Learning Media in Social Science Education Subject at Madrasah Ibtidaiyah Darussalam Bengkulu City. This research aims to determine what problems are faced by teachers in using learning media and how teachers deal with these problems. This research was conducted in the Islamic Middle School Madrasah of the City of Bengkulu with the social studies teacher as a research subject. This research used descriptive qualitative method. Data collection technique used is in-defth interview and interactive model of Milles and Huberman for the data analysis, which consisted of three stages, namely data reduction, data display, and conclusion drawing. The results in the study are: 1) in using learning media, social studies teachers face several problems, namely problems in planning (making learning media), problems in using media (skills using learning media), and problems in choosing learning media - especially those that are suitable with material and learning methods; 2) in overcoming some problems with the use of instructional media, some of the things that social studies teachers do are like equipping themselves with knowledge about learning media, attending training, and training using various forms of learning media.
Poleward force at the kinetochore in metaphase depends on the number of kinetochore microtubules

To examine the dependence of poleward force at a kinetochore on the number of kinetochore microtubules (kMTs), we altered the normal balance in the number of microtubules at opposing homologous kinetochores in meiosis I grasshopper spermatocytes at metaphase with a focused laser microbeam. Observations were made with light and electron microscopy. Irradiations that partially damaged one homologous kinetochore caused the bivalent chromosome to shift to a new equilibrium position closer to the pole to which the unirradiated kinetochore was tethered; the greater the dose of irradiation, the farther the chromosome moved. The number of kMTs on the irradiated kinetochore decreased with severity of irradiation, while the number of kMTs on the unirradiated kinetochore remained constant and independent of chromosome-to-pole distance. Assuming a balance of forces on the chromosome at congression equilibrium, our results demonstrate that the net poleward force on a chromosome depends on the number of kMTs and the distance from the pole. In contrast, the velocity of chromosome movement showed little dependence on the number of kMTs. Possible mechanisms which explain the relationship between the poleward force at a kinetochore, the number of kinetochore microtubules, and the lengths of the kinetochore fibers at congression equilibrium include a "traction fiber model" in which poleward force producers are distributed along the length of the kinetochore fibers, or a "kinetochore motor-polar ejection model" in which force producers located at or near the kinetochore pull the chromosomes poleward along the kMTs and against an ejection force that is produced by the polar microtubule array and increases in strength toward the pole.
Joule heating in single-walled carbon nanotubes

Joule heating in single-walled carbon nanotubes (CNTs) using a quantum mechanical approach is presented in this paper. The modeling is based on the energy transfer between the electrons and both acoustic and optical phonons. In this formulation, only the knowledge of the full energy dispersion relation, phonon dispersion relation, and the electron-phonon coupling potential is required for the calculations. For verification of the proposed model, the current-voltage relation for extremely long nanotubes is calculated and the results are compared with the experimental data. The electric field dependence of the amount of energy generated by Joule heating is plotted. Moreover the effect of the thermal environment on the behavior of Joule heating is studied. The formulation proposed in this paper can also be used for structures other than CNTs. Computations indicate that, contrary to popular opinion, metallic CNT does not follow Joule’s law of P=IV. Joule heating in CNT is significantly less than what is predi.
Single-Nucleotide Resolution Mapping of Hepatitis B Virus Promoters in Infected Human Livers and Hepatocellular Carcinoma

ABSTRACT Hepatitis B virus (HBV) is a major cause of liver diseases, including hepatocellular carcinoma (HCC), and more than 650,000 people die annually due to HBV-associated liver failure. Extensive studies of individual promoters have revealed that heterogeneous RNA 5′ ends contribute to the complexity of HBV transcriptome and proteome. Here, we provide a comprehensive map of HBV transcription start sites (TSSs) in human liver, HCC, and blood, as well as several experimental replication systems, at a single-nucleotide resolution. Using CAGE (cap analysis of gene expression) analysis of 16 HCC/nontumor liver pairs, we identify 17 robust TSSs, including a novel promoter for the X gene located in the middle of the gene body, which potentially produces a shorter X protein translated from the conserved second start codon, and two minor antisense transcripts that might represent viral noncoding RNAs. Interestingly, transcription profiles were similar in HCC and nontumor livers, although quantitative analysis revealed highly variable patterns of TSS usage among clinical samples, reflecting precise regulation of HBV transcription initiation at each promoter. Unlike the variety of TSSs found in liver and HCC, the vast majority of transcripts detected in HBV-positive blood samples are pregenomic RNA, most likely generated and released from liver. Our quantitative TSS mapping using the CAGE technology will allow better understanding of HBV transcriptional responses in further studies aimed at eradicating HBV in chronic carriers. IMPORTANCE Despite the availability of a safe and effective vaccine, HBV infection remains a global health problem, and current antiviral protocols are not able to eliminate the virus in chronic carriers. Previous studies of the regulation of HBV transcription have described four major promoters and two enhancers, but little is known about their activity in human livers and HCC. We deeply sequenced the HBV RNA 5′ ends in clinical human samples and experimental models by using a new, sensitive and quantitative method termed cap analysis of gene expression (CAGE). Our data provide the first comprehensive map of global TSS distribution over the entire HBV genome in the human liver, validating already known promoters and identifying novel locations. Better knowledge of HBV transcriptional activity in the clinical setting has critical implications in the evaluation of therapeutic approaches that target HBV replication.
Cross-cultural measurement equivalence of the Revised Conflict Tactics Scales ( CTS 2 ) Portuguese version used to identify violence within couples Equivalência transcultural de mensuração da versão em português das Revised Conflict Tactics Scales ( CTS 2 )

Following a previous evaluation of concept, item and semantic equivalences, this paper assesses the measurement equivalence between a Portuguese version of Revised Conflict Tactics Scales (CTS2) and the original instrument conceived in English. The CTS2 has been widely used to tap violence between couples. An intra-observer reliability evaluation involved 165 replications carried out within a 24-48 hour period. Kappa point-estimates were above 0.75 for all scales except sexual coercion. The analysis of internal consistency concerned 768 subjects with complete sets of items. Kuder-Richardson-20 estimates ranged from 0.65 to 0.86. Results were similar to those found in the original instrument in English for the negotiation, psychological aggression and physical violence scales, yet not so for the sexual coercion and injury scales. Factor analysis identified factors with a recognizable correspondence to the underlying dimensions, although a few inconsistencies were detected. For the assessment of construct validity (n = 528) associations between the instrument’s scales were evaluated, as well as the relationships between violence and putative underlying dimensions. Overall, the findings suggest that the version can be used in the Brazilian context, although further investigation should be carried out to unveil some important remaining issues.
Hacia el paradigma del don

La Encíclica de Benedicto XVI Caritas in Veritate propone un nuevo paradigma de pensamiento económico que representa un cambio en el sentido común convencional. Este cambio podría ser sintetizado como el paso de una concepción auto-interesada de las acciones económicas y de mercado hacia otra que, sin negar esta dimensión, considera que estas acciones también están abiertas a una dimensión de gratuidad, relacionalidad y don: “El gran desafío que tenemos, planteado por las dificultades del desarrollo en este tiempo de globalización y agravado por la crisis económico-financiera actual, es mostrar, tanto en el orden de las ideas como de los comportamientos, que no sólo no se pueden olvidar o debilitar los principios tradicionales de la ética social, como la transparencia, la honestidad y la responsabilidad, sino que en las relaciones mercantiles el principio de gratuidad y la lógica del don, como expresiones de fraternidad, pueden y deben tener espacio en la actividad económica ordinaria. ” (CV, 36). Aunque el Papa ha hecho evidentemente un movimiento audaz con la inclusión de este concepto en un documento tan importante, no ha sido, sin embargo, el primero en considerar la importancia del don en las actividades de mercado. De hecho, gran parte de la literatura económica y sociológica actualmente en circulación reconoce la existencia de relaciones de don entrelazadas con los intercambios de equivalentes típicos de la interpretación convencional de las relaciones de mercado. Sin embargo, al mismo tiempo, esta misma literatura con frecuencia interpreta las relaciones de donación de tal manera que es difícil diferenciarlas de los intercambios de equivalentes. En este artículo trataré de presentar una visión rápida de lo que creo que son algunas de las principales cuestiones filosóficas en el debate entre algunas de las propuestas actuales para interpretar las relaciones de donación en las actividades económicas. Por un lado, voy a mostrar algunos de los supuestos en común sobre el don que creo que hay detrás de la economía neoclásica, el estructuralismo antropológico y la desconstrucción. Por el otro, voy a presentar una visión alternativa del don para interpretar las relaciones en entornos de mercado basada en los argumentos ofrecidos por algunos filósofos personalistas y por algunos pensadores económicos contemporáneos que son capaces de dar apoyo, a mi criterio, a la propuesta audaz del Papa Benedicto XVI.
Human Leukocyte/Endothelial Cell Interactions and Mitochondrial Dysfunction in Type 2 Diabetic Patients and Their Association With Silent Myocardial Ischemia

OBJECTIVE Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed. RESEARCH DESIGN AND METHODS Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition– and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed. RESULTS Waist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA1c, high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O2 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist. CONCLUSIONS Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.
Washing away original sin: vulnerability to crisis and the role of local currency bonds in Sub-Saharan Africa

This paper starts from the concept of ‘original sin’ to demonstrate that the development of local currency bond markets remains a priority for Sub-Saharan African countries, both as a prevention mechanism against external shocks and to exploit growth-boosting investment opportunities. We present evidence suggesting that in Sub-Saharan Africa, as in other developing country regions, original sin (at least in its domestic form) is today less prevalent than it used to be. An increasing number of African governments now issue non-indexed local currency bonds with tenors of 10 years and more on a regular basis. This is not to say that all is well. African bond markets often lack liquidity, feature few corporate securities, and have a narrow investor base of commercial banks. Many more hurdles remain to be taken, by African countries themselves and the international community, if we are to further wash away original sin.
Posttranslational Modification of the Androgen Receptor in Prostate Cancer

The androgen receptor (AR) is important in the development of the prostate by regulating transcription, cellular proliferation, and apoptosis. AR undergoes posttranslational modifications that alter its transcription activity, translocation to the nucleus and stability. The posttranslational modifications that regulate these events are of utmost importance to understand the functional role of AR and its activity. The majority of these modifications occur in the activation function-1 (AF1) region of the AR, which contains the transcriptional activation unit 1 (TAU1) and 5 (TAU5). Identification of the modifications that occur to these regions may increase our understanding of AR activation in prostate cancer and the role of AR in the progression from androgen-dependent to castration-resistant prostate cancer (CRPC). Most of the posttranslational modifications identified to date have been determined using the full-length AR in androgen dependent cells. Further investigations into the role of posttranslational modifications in androgen-independent activation of full-length AR and constitutively active splicing variants are warranted, findings from which may provide new therapeutic options for CRPC.
Antigenic comparison of envelope protein E between Japanese encephalitis virus and some other flaviviruses using monoclonal antibodies.

The antigenic relationships between Japanese encephalitis (JE) virus and several other flaviviruses have been investigated using anti-JE virus monoclonal antibodies (MAbs). Seventeen MAbs directed against envelope protein E of JE virus were characterized and divided into eight MAb groups based on reactivity patterns in haemagglutination inhibition test, neutralization (N) test, ELISA and competitive binding assay with JE virus. The results suggest the existence of at least eight epitopes on the E protein of JE viruses. Analysis of cross-reactivity of the antibodies with several other flaviviruses indicated these findings JE virus, belonging to West Nile (WN) subgroup, is antigenically closely related to viruses in the same subgroup, i.e. Murray Valley encephalitis (MVE), WN and St. Louis encephalitis (SLE) viruses. Of these three viruses, JE virus has the closest relationship with MVE virus. WN virus is relatively close to JE virus, whereas SLE virus is the least closely related. Dengue viruses types 1 and 2, which belong to another subgroup of flaviviruses, show markedly less antigenic homology to JE virus. One of the critical N sites on the E protein showed JE virus specificity. Some cross-reactive antibodies which did not neutralize JE virus showed low but significant N activity against several other flaviviruses. Mixtures of several MAbs, which showed different reactivity patterns, potentiated the N activity against not only JE virus but also other members of the WN subgroup of flaviviruses, namely MVE, WN and SLE viruses.
Rapid Signaling of Estrogen in Hypothalamic Neurons Involves a Novel G-Protein-Coupled Estrogen Receptor that Activates Protein Kinase C

Classically, 17β-estradiol (E2) is thought to control homeostatic functions such as reproduction, stress responses, feeding, sleep cycles, temperature regulation, and motivated behaviors through transcriptional events. Although it is increasingly evident that E2 can also rapidly activate kinase pathways to have multiple downstream actions in CNS neurons, the receptor(s) and the signal transduction pathways involved have not been identified. We discovered that E2 can alter μ-opioid and GABA neurotransmission rapidly through nontranscriptional events in hypothalamic GABA, proopiomelanocortin (POMC), and dopamine neurons. Therefore, we examined the effects of E2 in these neurons using whole-cell recording techniques in ovariectomized female guinea pigs. E2 reduced rapidly the potency of the GABAB receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K+ channels in hypothalamic neurons. These effects were mimicked by the membrane impermeant E2-BSA and selective estrogen receptor modulators, including a new diphenylacrylamide compound, STX, that does not bind to intracellular estrogen receptors α or β, suggesting that E2 acts through a unique membrane receptor. We characterized the coupling of this estrogen receptor to a Gαq-mediated activation of phospholipase C, leading to the upregulation of protein kinase Cδ and protein kinase A activity in these neurons. Moreover, using single-cell reverse transcription-PCR, we identified the critical transcripts, PKCδ and its downstream target adenylyl cyclase VII, for rapid, novel signaling of E2 in GABA, POMC, and dopamine neurons. Therefore, this unique Gq-coupled estrogen receptor may be involved in rapid signaling in hypothalamic neurons that are critical for normal homeostatic functions.
WHAT IS THE EVIDENCE ? Management of obesity in primary prevention of CKD Maintenance of a stable weight in the primary prevention of CKD

Weight management a. We suggest the maintenance of a stable (within 5%), healthy weight as it is associated with a lower risk of developing chronic kidney disease (2C) b. We suggest, where weight loss is required, the use of medications such as topiramate (if available) in conjunction with a non-pharmacological weight loss programme to increase weight loss and reduce the risk of developing chronic kidney disease (2B) Dietary modification c. We suggest adherence to a low salt diet (<100 mmol or 2300mg/ day) to reduce the risk of developing chronic kidney disease (2C) d. We suggest a normal dietary protein intake, as the relative benefits versus harms of dietary protein restriction has not been adequately established (2D) Lifestyle modification e. We recommend avoidance or cessation of cigarette smoking to reduce the risk of developing chronic kidney disease (1D) f. We suggest that patients with identified excessive alcohol consumption should receive psychological support and interventions to minimise excessive intake (2D) g. We suggest that patients be encouraged to undertake regular physical exercise to reduce the risk of developing chronic kidney disease. Exercise needs to be appropriate for their physical ability and medical history (2C)