Miracle-dz/UniFAR-FTUs huggingface dataset:
Ser386 phosphorylation of transcription factor IRF‐3 induces dimerization and association with CBP/p300 without overall conformational change

The transcription factor IRF‐3 is activated by microbial invasions and produces a variety of cytokines including type‐I interferon. Upon microbial infection, IRF‐3 is phosphorylated at its C‐terminal regulatory domain, then oligomerized, translocated into the nucleus, and here it binds to CBP/p300. Although a number of studies have been reported investigating the activation mechanism of IRF‐3, there are a number of unresolved issues, especially on the phosphorylation sites, the oligomerization process and the binding mechanism with CBP/p300. In this report, the phosphorylated IRF‐3 regulatory domain (IRF‐3 RD) was prepared using the kinase IKK‐i, and the active form of phosphorylated IRF‐3 RD was identified. The paper also reports the crystal structure of the active form of the phosphorylated IRF‐3 RD. Furthermore, the phosphorylation of Ser386 was found to be essential for its dimerization and binding with CBP/p300 using mutational analysis and mass spectrometry. Thus, we conclude that the phosphorylation of Ser386 is essential for activation of IRF‐3.
Gene Expression Profiling for Breast Cancer Prognosis in Chinese Populations

Abstract: To investigate a quantitative reverse transcription polymerase chain reaction (QRT‐PCR) assay different from 21‐gene assay which can be used to prognosticate the risk of recurrence in patients with estrogen receptor (ER) positive, lymph node (LN) negative breast cancer. To accurately determine the relationship between the Recurrence Score (RS) derived from our assay and the risk of distant recurrence in Chinese patients with LN negative and positive breast cancer through the analysis of paraffin tissues. We obtained archival paraffin‐embedded tissues from patients with invasive breast cancer and varying axillary lymph node involvement. QRT‐PCR reaction was performed by using the method of SYBR Green I dye with primers. Expression of the 21‐genes was converted to RS by a prespecified algorithm. We then assessed the probability of the test to accurately predict distant recurrence‐free survival in this retrospective cohort. Ninety‐three patients were eligible based on gene expression profiles. In our population, most breast cancer patients were premenopausal (82.6%), at early stage (93.6%) and ER positive (91.4%). Median follow‐up was 65.9 months. The 5‐year recurrence‐free survival rate for the group was 58.8%. The concordance between the reverse transcription‐PCR and immunohistochemical (IHC) measurement for ER, progesterone receptor (PgR), and HER‐2 determinations was high and comparable. High RS was predictive of an elevated risk of relapse (p < 0.001). In subgroups of patients, RS had significantly predictive performance both in node‐negative (p = 0.009) and node‐positive patients (p = 0.038). Multivariable analysis showed that nodal status, adjuvant hormonal therapy and RS were significantly related to prognosis. RS category is a better predictor than the other risk assessment criteria or clinicopatholic features, with which we can determine more accurately the risks for recurrence of various patients. We have established an easy and economical QRT‐PCR assay and validated in concordance with IHC measurements for ER, PgR, and HER‐2. RS was associated with distant recurrence among Chinese patients with hormone receptor (HR) positive breast cancer. This study may promote the use of RS estimated from the expression of the 21‐gene set for prognostication and routine clinical diagnostic application in Chinese populations.
Relative Effectiveness of Inquiry and Expository Methods of Teaching Social Studies on Academic Performance of Secondary Students in Akwa Ibom State, Nigeria

The aim of this work was to find out the relative effectiveness of inquiry and expository methods of teaching social studies on the academic achievement of secondary school students in Akwa Ibom State. Related literature was reviewed. The research design was pretest-post-test experimental design. Two hypotheses were raised to guide the study. The independent t-test statistical instrument was used in analyzing the data at . 05 level of significance. The sample of the study was made up of 300 randomly sampled students from six public secondary schools in the state. The result revealed that students taught with the expository method. Based on this finding, it was recommended that inquiry method of teaching social studies be encouraged in the secondary school setting. Keywords : Inquiry, Expository, Social Studies, Performance.
"The Story of Zosimus" or "the History of the Rechabites"?

L'analyse et critique redactionnelle du pseudepigraphe de l'Ancien Testament Le recit de Zosime (StorZos) concerne surtout le noyau ancien du document, les chapitres 8-10 (l'histoire des Rechabites). L'A. pose la question suivante: StorZos 8-10 peut-il etre lu comme texte complet dans la version grecque ou syriaque? Il examine ensuite la relation avec Jeremie 35
Efficient Ordered Combinatorial Semi-Bandits for Whole-Page Recommendation

Multi-Armed Bandit (MAB) framework has been successfully applied in many web applications. However, many complex real-world applications that involve multiple content recommendations cannot fit into the traditional MAB setting. To address this issue, we consider an ordered combinatorial semi-bandit problem where the learner recommends S actions from a base set of K actions, and displays the results in S (out of M) different positions. The aim is to maximize the cumulative reward with respect to the best possible subset and positions in hindsight. By the adaptation of a minimum-cost maximum-flow network, a practical algorithm based on Thompson sampling is derived for the (contextual) combinatorial problem, thus resolving the problem of computational intractability.With its potential to work with whole-page recommendation and any probabilistic models, to illustrate the effectiveness of our method, we focus on Gaussian process optimization and a contextual setting where click-through rate is predicted using logistic regression. We demonstrate the algorithms’ performance on synthetic Gaussian process problems and on large-scale news article recommendation datasets from Yahoo! Front Page Today Module.
FK506 attenuates early ischemic neuronal death in a monkey model of stroke.

UNLABELLED FK506 is an immunosuppressive agent that has been reported to have neuroprotective effects in several kinds of rodent models of stroke. The purpose of this study was to evaluate the neuroprotective effects of FK506 in a monkey model of stroke. METHODS Cynomolgus monkeys underwent 3 h of occlusion followed by 5 h of reperfusion of the right middle cerebral artery (MCA) through a transorbital approach. A single bolus dose of FK506 (0.1 mg/kg) was injected intravenously 5 or 175 min after MCA occlusion. Eight hours after ischemia, a neuropathologic study was performed and the volume of ischemic damage was determined. To measure local cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO(2)), and the oxygen extraction fraction during the experiments, PET scans were obtained using a steady-state (15)O continuous-inhalation method. Four consecutive PET scans (before and 2 h after ischemia and immediately and 3 h after reperfusion) were obtained on each monkey. RESULTS Treatment with FK506 (0.1 mg/kg) 5 or 175 min after ischemia significantly reduced cortical damage 8 h after ischemia by 82% (P < 0.05) and 73% (P < 0.05), respectively. In PET studies, FK506 did not affect CBF or physiologic parameters in any treatments. In the FK506-treated group, a volume of >40% CMRO(2) reduction 3 h after reperfusion decreased significantly (P < 0.05). CONCLUSION This study showed that FK506 showed a powerful neuroprotective effect in a nonhuman primate model of stroke. The therapeutic time window of FK506 was at least 3 h after onset. PET studies detected neuroprotective effects only in areas with >40% CMRO(2) reduction 3 h after reperfusion.
Ogimah Ikwe: Native Women and Their Path to Leadership

F A L L 2 0 1 1 W I C A Z O S A R E V I E W Much documentation gathered on Native American women’s activities originated in the journals of European male missionaries and explorers. These fi rst visitors observed Native societies through the eyes of their own culture, a culture in which male activities were the only happenings of note.1 This bias led to indirect and distorted descriptions of Native American women’s activities and beliefs.2 Scholars who study Native American women today have made signifi cant inroads into their histories; however, many interpretations remain incorrect and undeveloped. Devon Mihesuah states, “Because many authors write from a patriarchal or white feminist perspective, the value of Indian women is vastly underrated. ”3 Gretchen Bataille and Kathleen Sands address this shortcoming, saying, “The portrayal of American Indian women in North America over the last four centuries offers an uneven body of documentary evidence about the lives of Native women as individuals and members of their group. ”4 This study’s purpose is to increase the visibility of Native American women in leadership roles by recording the voices and histories of nine Native American women leaders. It focuses on the experiences, perceptions, and beliefs of the women interviewed, giving a voice to nine of today’s Native American female leaders, nine Ogimah Ikwe (leader women). Centuries of silence surround Native American women’s leadership roles following European contact.5 The best information on what it was like to be a Native American woman in early America would have Ogimah Ikwe Native Women and Their Path to Leadership
Determinants of Secretion and Intracellular Localization of Human Herpesvirus 8 Interleukin-6

ABSTRACT Human herpesvirus 8 (HHV-8) interleukin-6 (vIL-6) is distinct from human and other cellular IL-6 proteins in that it does not require the nonsignaling α-receptor subunit for the formation of gp130-based signal transducing complexes and also is largely retained intracellularly rather than being secreted. We and others have reported that vIL-6 is retained and is active in the endoplasmic reticulum (ER) compartment, and data from our laboratory have demonstrated that intracellular vIL-6 is functional in the autocrine promotion of proliferation and survival of HHV-8 latently infected primary effusion lymphoma cells. It has also been reported that vIL-6 secretion in gp130-deficient cells can be enhanced by introduced gp130, thereby implicating the signal transducer in vIL-6 trafficking to the cell surface. We examine here the requirements for intracellular retention and localization of vIL-6. Using vIL-6-hIL-6 chimeric and point-mutated vIL-6 proteins, we identified regions and residues of vIL-6 influencing vIL-6 secretion. However, there was no correlation between vIL-6 secretion and gp130 interaction. We found that vIL-6, but not hIL-6, could associate stably with ER-resident chaperone protein calnexin. Glycosylation-dependent interaction of vIL-6 with calnexin correlated with proper protein folding, but there was no direct relationship between vIL-6-calnexin interaction and intracellular retention. While calnexin depletion had little influence on absolute amounts of secreted vIL-6, it led to markedly reduced levels of intracellular cytokine. This was reversed by gp130 transduction, which had no detectable effect on vIL-6 secretion, but redistributed vIL-6 into ER-distinct locations in calnexin-depleted cells, specifically. Our data reveal that calnexin plays a role in ER localization of vIL-6 and that gp130 promotes ER exit, but not secretion, of the viral cytokine.
Relationship between sociometric types and academic achievement in a sample of compulsory secondary education students / Relación entre tipos sociométricos y rendimiento académico en una muestra de estudiantes de Educación Secundaria Obligatoria

Abstract The aim of this study was to analyse the relationship between sociometric types, behavioural categories and academic achievement in a sample of 1,349 compulsory secondary education students (51.7% boys), ranging in age from 12 to 16 years. The students’ sociometric identification was performed by using the Programa Socio and academic performance was measured by school marks provided by teachers in the subjects of Spanish language, mathematics and average academic performance. The results show that sociometric types were significant predictors of academic achievement, as students who were rated positively by their peers (popular, leaders, collaborators and good students) were more likely to have high academic achievement (in mathematics, Spanish language and average academic achievement) than students rated negatively by peers (rejected-aggressive, rejected-shy, neglected and bullies).
Multiparametric comparison of thermal welding versus cold knife tonsillectomy with tonsil size * Thermal welding tonsillektomi ile so ¤ uk

Bulgular: Ameliyat süresinin TWT grubunda SBT grubuna göre daha k›sa oldu¤u saptand› (P<0.01). SBT grubunda 1. 3 ve 7. gün a¤r› skorlar› ortalamas›, TWT grubu ortalamas›ndan anlaml› flekilde yüksek bulundu (p<0.01). So¤uk b›çak tonsillektomi grubunda bademcik büyüklü¤ü 1 ve 2 olan olgular›n 7. gün a¤r› skorlar› ortalamas›, 3 olan olgulara göre anlaml› flekilde yüksek bulundu (p<0.01). Thermal welding tonsillektomi grubunda bademcik büyüklü¤ü 1 ve 2 olan olgular›n 3. gün, 7. gün ve 14. gün a¤r› skorlar› ortalamas›, 3 olan olgulara göre anlaml› flekilde yüksek bulundu (p<0.01). So¤uk b›çak tonsillektomi grubunda kanama miktar› ortalamas›, TWT grubundan anlaml› flekilde yüksek bulundu (p<0.01). Her iki grupta da bademcik büyüklü¤üne göre olgular›n kanama durumlar› aras›nda anlaml› farkl›l›k bulunmad› (p>0.05).
Role of methotrexate exposure in apoptosis and proliferation during early neurulation

Apoptosis and proliferation play important roles in embryonic development and are required for neural tube closure. The antifolate drug methotrexate (MTX) induces folate dysmetabolism by inhibition of dihydrofolate reductase and causes abnormal apoptosis and proliferation. In this study, we established an animal model of neural tube defects (NTDs) using MTX to investigate the role of apoptosis and proliferation in NTDs caused by folate deficiency. Differential gene expressions were studied by microarray and reverse transcription–polymerase chain reaction in the NTD animal model. Results showed that 30.8% of NTDs were caused by using MTX in treatment regimens. Microarray indicated that 166 genes were significantly different between the control and NTD mice, including four apoptosis‐related genes (Endog, Trp53, Casp3, Bax) and three proliferation‐related genes (Ptch1, Pla2g4a, Foxg1). Levels of Endog, Trp53, Casp3, Bax (fold change > 1.5) were upregulated but Ptch1, Pla2g4a, Foxg1 (fold change < 0.67) were downregulated (P < 0.05). These results were confirmed by reverse transcription–polymerase chain reaction. TUNEL, immunohistochemical assays and Western blot were further used to detect apoptosis and proliferation in the NTD animal model. It was found that apoptosis in neuroepithelial cells was increased as determined by TUNEL (P < 0.05). Expressions of caspase‐3 were significantly enhanced (P < 0.05) but expressions of phosphohistone H3 were greatly decreased (P < 0.05). These results concluded that MTX caused a folate and folate‐associated dysmetabolism, and further induced abnormal apoptosis and proliferation, which may play a critical role in the occurrence of NTDs caused by folate deficiency. Copyright © 2013 John Wiley & Sons, Ltd.
Prevalence of intestinal parasitic infections in military personnel and military dogs, Thailand.

OBJECTIVE To determine the prevalence of intestinal parasitic infections and risk factors among military personnel and military dogs at the Military Dog Center, Veterinary and Remount Department, Royal Thai Army, Thailand. MATERIAL AND METHOD A cross-sectional study was conducted in January 2006 to examine intestinal parasitic infections using wet preparation and, formalin-ethyl acetate concentration. Modified acid fast and gram-chromotrope stains were used to identify Cryptosporidium spp. and microsporidia, respectively. Culture for Blastocystis was performed using Jone's medium. Genotypic characterization of Blastocystis and Giardia duodenalis were also determined using PCR-RFLP. To determine the risk factors and outcomes of intestinal parasitic infections, standardized questionnaires were used in the present study. RESULTS Of 317 military personnel, the prevalence of intestinal parasitic infections was 22.4%. Blastocystis was the most predominant intestinal protozoa infection of 14.5% while G. duodenalis was only 1.3%. The prevalence of other helminthic infections were 4.8% which were Strongyloides stercoralis (2.5%), Hookworm (1.0%), Opisthorchis viverrini (1.0%), and Taenia spp. (0.3%), respectively. Blastocystis subtype 1 was identified in 25 positive culture specimens while all 4 positive of G. duodenalis were analyzed as Assemblage B, subgenotype IV. The presented data could not indicate that intestinal parasitic infections and blastocystosis in this army population were significantly linked to risk association among groups with regard to rank, age group, working unit, area of residence, animal contact, source and treatment of drinking water. Of 189 military dogs, the prevalence of intestinal parasitic infections was only 3.7% which was Blastocystis sp. (2.6%), S. stercoralis (0.5%), and Entamoeba coli (0.5%), respectively. CONCLUSION The predominant intestinal parasites found in this population, such as Blastocystis sp. and G duodenalis transmit to humans via fecal-oral route so that improvement of sanitation and personal hygiene should be emphasized.
American Orthopaedic Foot and Ankle Society Women's Shoe Survey

Shoes have been implicated as being responsible for the majority of foot deformities and problems that physicians encounter in women. A total of 356 women were studied in this investigation to evaluate trends in women's shoe wear and their effect on the development of foot deformities and pain. The majority of women in this study wore shoes that were too small for their feet, had foot pain and deformity, and had increased shoe size since the age of 20. Few women had their feet measured in over 5 years. The women without foot pain or deformities also wore shoes that were smaller than their feet but to a lesser degree.
Etude de l’efficacité et de la tolérance d’une tisane à base de Artemisia annua L. (Asteraceae) cultivée au Bénin pour la prise en charge du paludisme simple

Artemisia annua L. est une plante annuelle, glabre, de la famille des Asteraceae et originaire de la Chine. Cette plante contient plusieurs sesquiterpenes dont l’artemisinine (0,01% a 1,4% du poids des feuilles seches) et d’autres composes comme les flavonoides, les coumarines, les triterpenes, les steroides, les composes phenoliques, les purines, les lipides et les composes aliphatiques. Cette plante a ete acclimatee et cultivee au Benin. Elle a ensuite ete testee pour la prise en charge du paludisme simple par un essai clinique. La concentration en artemisinine de cette plante etait d’environ 0,30%. Il ressort de notre etude que la tisane de Artemisia annua L. (Asteraceae ) obtenue au Benin a une capacite d’action sur Plasmodium falciparum avec un taux d’efficacite superieur a 95%, taux retenu par l’OMS pour valider un traitement. Mots cles : Malaria, Artemisia annua , clairance thermique, parasitemie, essais cliniques.
Identification of a Novel Class of Endoperoxides from Arachidonate Autoxidation*

Free radical-initiated lipid autoxidation in low density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis. Oxidation of the lipid components of LDL leads to a complex mixture of hydroperoxides, bicyclic endoperoxides, monocyclic peroxides, and serial cyclic peroxides. The oxidation compounds and/or their decomposition products can modify protein components, which may lead to various diseases. A novel class of peroxides (termed dioxolane-isoprostanes) having a bicyclic endoperoxide moiety characteristic of the isoprostanes and a dioxolane peroxide functionality in the same molecule was identified in the product mixture formed from in vitro autoxidation of cholesteryl arachidonate. The same products are also detected in in vitro oxidized LDL. Various mass spectrometric techniques have been applied to characterize these new peroxides. The structure of these compounds has also been confirmed by independent synthesis. We reason, based on the free radical mechanism of the transformation, that only the 12- and 8-peroxyl radicals (those leading to 12-HPETE and 8-HPETE) of arachidonate can form these new peroxides. We also suggest that the formation of these peroxides provides a rationale to explain the fact that 5- and 15-series isoprostanes are formed in preference to 8- and 12-series. Furthermore, series of other isoprostanes, such as dioxolane A2, D2, E2, etc., can be derived from the dioxolane-isoprostane peroxides. These findings offer further insights into the oxidation products of arachidonate and the opportunity to study their potential biological relevance.
Intravenous Anesthetic Propofol Inhibits Multiple Human Cardiac Potassium Channels

Background:Propofol is widely used clinically for the induction and maintenance of anesthesia. Clinical case reports have shown that propofol has an antiatrial tachycardia/fibrillation effect; however, the related ionic mechanisms are not fully understood. The current study investigates the effects of propofol on human cardiac potassium channels. Methods:The whole cell patch voltage clamp technique was used to record transient outward potassium current (Ito) and ultrarapidly activating delayed rectifier potassium current (IKur) in human atrial myocytes and hKv1.5, human ether-à-go-go-related gene (hERG), and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells. Current clamp mode was used to record action potentials in human atrial myocytes. Results:In human atrial myocytes, propofol inhibited Ito in a concentration-dependent manner (IC50 = 33.5 ± 2.0 &mgr;M for peak current, n = 6) by blocking open channels without affecting the voltage-dependent kinetics or the recovery time constant; propofol decreased IKur (IC50 = 35.3 ± 1.9 &mgr;M, n = 6) in human atrial myocytes and inhibited hKv1.5 current expressed in HEK 293 cells by preferentially binding to the open channels. Action potential duration at 90% repolarization was slightly prolonged by 30 &mgr;M propofol in human atrial myocytes. In addition, propofol also suppressed hERG and hKCNQ1/hKCNE1 channels expressed in HEK 293 cells. Conclusion:Propofol inhibits multiple human cardiac potassium channels, including human atrial Ito and IKur, as well as hKv1.5, hERG, and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, and slightly prolongs human atrial action potential duration, which may contribute to the antiatrial tachycardia/fibrillation effects observed in patients who receive propofol.
Penicillin-binding proteins of Haemophilus ducreyi

The penicillin-binding protein (PBP) profile of Haemophilus ducreyi was determined by a whole-cell-labeling assay. Only two major PBPs, of molecular weights 90,000 (PBP 1) and 38,500 (PBP 2), were detected in six of eight strains studied. Competition binding experiments and the attendant morphological effects suggested that PBP 1 was either a functional amalgamation or a lack of resolution of two proteins equivalent to PBPs 1 and 3 of Escherichia coli.