Miracle-dz/UniFAR-FTUs huggingface dataset:
The Basic Helix-Loop-Helix Genes Hesr1/Hey1 and Hesr2/Hey2 Regulate Maintenance of Neural Precursor Cells in the Brain*

Neural precursor cells proliferate in the ventricular zone while giving rise to neurons of deep layers first, then those of the superficial layers, and lastly, glial cells in the brain. Thus, it is essential to maintain neural precursor cells until late stages of neural development for generation of a wide variety of cell types. Here, we found that the Hes-related basic helix-loop-helix (bHLH) genes Hesr1/Hey1 and Hesr2/Hey2 are expressed in the ventricular zone, which contains neural precursor cells. Misexpression of Hesr1 and Hesr2 by electroporation in mouse brain at embryonic day 13.5 transiently maintains neural precursor cells and thereby increases late-born neurons, which are located in the superficial layers. In contrast, misexpression of the genes at later stages inhibits neurogenesis and promotes generation of astroglial cells. In transient transfection assay with cultured cells, both Hesr1 and Hesr2 inhibit transcription induced by the neuronal bHLH genes Mash1 and Math3. These results indicate that Hesr1 and Hesr2 negatively regulate neuronal bHLH genes, promote maintenance of neural precursor cells, and increase late-born cell types in the developing brain.
Influence of Difference in Timing of Perioperative Administration of Low-dose Ketamine on Postoperative Analgesia

Background: Preemptive analgesia is a part of multimodal regime for effective postoperative analgesia. Ketamine is said to possess preemptive effects, which has been simultaneously refuted by other studies. Hence, we designed this randomized, double-blinded trial to establish the influence of timing of perioperative ketamine administration for superior postoperative analgesia. Methods: Ninety patients undergoing infraumbilical surgeries under spinal anesthesia were randomized to receive ketamine either preincision (Group KI), preincision and during skin closure (Group KII), or only during skin closure (Group KIII). Outcomes studied were postoperative pain, sedation, and incidence of side effects. Results: Analysis of variance statistics for postoperative visual analog scales (VAS) for pain showed no significant difference in three groups. However, there was a significant difference between Groups KII and KIII in the immediate postoperative period (95% confidence interval [CI] of mean VAS for Group KI = 0.9249–1.4889; 95% CI for Group KII = 1.4406–1.8260; P = 0.043). Sedation scores in the immediate, 4 h and 8 h postoperative showed a significant difference between Group KI and Group KII (P = 0.007, 0.008, 0.001, respectively) and between Group KI and KIII (KI: KIII - P = 0.0008, 0.0006, 0.02, respectively). Although the incidence of psychotomimetic effect was more in Groups KIII, it was not statistically significant. Conclusion: Ketamine possesses postoperative analgesic effects in the immediate postoperative period only when its preemptive administration is supplemented with repeat administration during closure. Incidences of side effects were comparable in all groups.
Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review.

BACKGROUND Little is known about the prevalence of antimicrobial resistance (AMR) amongst bacterial pathogens in sub-Saharan Africa (sSA), despite calls for continent-wide surveillance to inform empirical treatment guidelines. METHODS We searched PubMed and additional databases for susceptibility data of key pathogens for surveillance, published between 1990 and 2013. Extracted data were standardized to a prevalence of resistance in populations of isolates and reported by clinical syndrome, microorganism, relevant antimicrobial drugs and region. RESULTS We identified 2005 publications, of which 190 were analysed. Studies predominantly originated from east sSA (61%), were hospital based (60%), were from an urban setting (73%) and reported on isolates from patients with a febrile illness (42%). Quality procedures for susceptibility testing were described in <50% of studies. Median prevalence (MP) of resistance to chloramphenicol in Enterobacteriaceae, isolated from patients with a febrile illness, ranged between 31.0% and 94.2%, whilst MP of resistance to third-generation cephalosporins ranged between 0.0% and 46.5%. MP of resistance to nalidixic acid in Salmonella enterica Typhi ranged between 15.4% and 43.2%. The limited number of studies providing prevalence data on AMR in Gram-positive pathogens or in pathogens isolated from patients with a respiratory tract infection, meningitis, urinary tract infection or hospital-acquired infection suggested high prevalence of resistance to chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline and low prevalence to third-generation cephalosporins and fluoroquinolones. CONCLUSIONS Our results indicate high prevalence of AMR in clinical bacterial isolates to antimicrobial drugs commonly used in sSA. Enhanced approaches for AMR surveillance are needed to support empirical therapy in sSA.
Private Information, Overconfidence and Trader Returns in Prediction Markets

In lab experiments on the value of information in financial markets, groups of “insiders” are randomly chosen to receive perfect information. However, in typical (non-experimental) financial markets, investors often engage in extensive fundamental analysis, a process which may result in over-confidence in one’s private information. In this study, we examine trading volume, prices and trader returns in a set of four real money prediction markets where the values of securities are tied to a movie’s box office performance. Before the markets opened, every trader submitted a detailed forecast of the movie’s future performance. Therefore, all traders have self-generated private information, the accuracy of which can only be known ex-post . As expected, the volume and timing of trading were consistent with over-confidence. In three of the four markets, contract prices were consistent with the prior information equilibrium. In those three markets, traders whose forecast was associated with the winning contract had significantly higher returns than traders whose forecasts suggested that another contract would pay off. In the other market, there were no significant differences in returns across trader groups. This research suggests that when traders are overconfident and trade accordingly, there can value to being better informed if the information is accurate.
An Empirical Study of Configuration Mismatches in Linux

Ideally the variability of a product line is represented completely and correctly by its variability model. However, in practice additional variability is often represented on the level of the build system or in the code. Such a situation may lead to inconsistencies, where the actually realized variability does not fully correspond to the one described by the variability model. In this paper we focus on configuration mismatches, i.e., cases where the effective variability differs from the variability as it is represented by the variability model. While previous research has already shown that these situations still exist even today in well-analyzed product lines like Linux, so far it was unclear under what circumstances such issues occur in reality. In particular, it is open what types of configuration mismatches occur and how severe they are. Here, our contribution is to close this gap by presenting a detailed manual analysis of 80 configuration mismatches in the Linux 4.4. 1 kernel and assess their criticality. We identify various categories of configuration issues and show that about two-thirds of the configuration mismatches may actually lead to kernel misconfigurations.
Systolic 3D first‐pass myocardial perfusion MRI: Comparison with diastolic imaging in healthy subjects

Three‐dimensional (3D) first‐pass myocardial perfusion imaging (MPI) is a promising alternative to conventional two‐dimensional multislice MPI due to its contiguous spatial coverage that is beneficial for estimating the size of perfusion defects. Data acquisition at mid‐diastole is a typical choice for 3D MPI yet is sensitive to arrhythmia and variations in R‐R interval that are common in cardiac patients. End systole is the second longest quiescent cardiac phase and is known to be less sensitive to the R‐R variability. Therefore, 3D MPI with systolic acquisition may be advantageous in patients with severe arrhythmia once it is proven to be comparable to diastolic MPI in subjects with negligible R‐R variation. In this work, we demonstrate the feasibility of 3D MPI with systolic data acquisition in five healthy subjects. We performed 3D MPI experiments in which 3D perfusion data were acquired at both end‐systole and mid‐diastole of every R‐R interval and analyzed the similarity between resulting time intensity curves (TIC) from the two data sets. The correlation between systolic and diastolic TICs was extremely high (mean = 0.9841; standard deviation = 0.0166), and there was a significant linear correlation between the two time intensity curve upslopes and peak enhancements (P < 0.001). Magn Reson Med 63:858–864, 2010. © 2010 Wiley‐Liss, Inc.
Cloned Mice Derived from Embryonic Stem Cell Karyoplasts and Activated Cytoplasts Prepared by Induced Enucleation

Abstract Our objective was to induce enucleation (IE) of activated mouse oocytes to yield cytoplasts capable of supporting development following nuclear transfer. Fluorescence microscopy for microtubules, microfilaments, and DNA was used to evaluate meiotic resumption after ethanol activation and the effect of subsequent transient treatments with 0.4 μg/ml of demecolcine. Using oocytes from B6D2F1 (C57BL/6 × DBA/2) donors, the success of IE of chromatin into polar bodies (PBs) was dependent on the duration of demecolcine treatment and the time that such treatment was initiated after activation. Similarly, variations in demecolcine treatment altered the proportions of oocytes exhibiting a reversible compartmentalization of chromatin into PBs. Treatment for 15 min begun immediately after activation yielded an optimized IE rate of 21% (n = 80) when oocytes were evaluated after overnight recovery in culture. With this protocol, 30–50% of oocytes were routinely scored as compartmentalized when assessed 90 min postactivation. No oocytes could be scored as such following overnight recovery, with 66% of treated oocytes cleaving to the 2-cell stage (n = 80). Activated cytoplasts were prepared by mechanical removal of PBs from oocytes whose chromatin had undergone IE or compartmentalization. These cytoplasts were compared with mechanically enucleated, metaphase (M) II cytoplasts whose activation was delayed in nuclear transfer experiments using HM-1 embryonic stem cells. Using oocytes from either B6D2F1 or B6CBAF1 (C57BL/6 × CBA) donors, the in vitro development of cloned embryos using activated cytoplasts was consistently inferior to that observed using MII cytoplasts. Live offspring were derived from both oocyte strains using the latter, whereas a single living mouse was cloned from activated B6CBAF1 cytoplasts.
The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index.

PURPOSE The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) markedly potentiates the efficacy of many cytotoxic agents against several human cancer xenografts, irrespective of tumor EGFR expression levels. We subsequently investigated the extent to which ZD1839 might improve radiation therapy (RT) in similar animal models of human cancer within the limits of tolerance at a relevant organ site. EXPERIMENTAL DESIGN We carried out studies of ZD1839 in in vivo models of human non-small cell lung (A549 and SK-LC-16) and breast (MDA-MB468) cancers and human mesothelioma (JMN). The tumors were implanted s.c. over the rib cage or on the most proximate breast and RT given ventral dorsally to the chest only, with mediastinal protection. After the tumor reached a palpable size (0.4-0.6 mm), treatment was initiated with the maximum-tolerated dose (MTD) of ZD1839 (150 mg/kg once daily x 5 for 2 successive weeks), RT (a total of 40 Gy given fractionally at 4 Gy once daily x 5 for 2 successive weeks), or both ZD1839 and RT. RESULTS This level of RT induced no untoward effects in the mice and was effective (18-72%) in bringing about regression of the tumors with a few complete regressions. ZD1839 alone, given p.o. on the same schedule at its MTD (150 mg/kg), was modestly inhibitory (35-40%) to tumor growth. RT and ZD1839 could be given together at the same doses on the same schedule, resulting in marked regression (50-99%) and a large number of complete regressions of each of the tumors studied. In these studies, the MTD of ZD1839 could be combined with the MTD of RT with no change in schedule or increase toxicity over ZD1839 or RT alone. CONCLUSIONS ZD1839 significantly enhanced the antitumor action of RT against the test tumors without significant adverse effects, increasing the therapeutic selectively of ionizing radiation in these model systems. These results predict substantial benefits for this multimodality regimen of therapy in patients.
Predicting Alcohol, Cigarette, and Marijuana Use From Preferential Music Consumption

This study investigated whether use of alcohol, cigarettes, and marijuana may be predicted from preferential consumption of particular music genres. Undergraduates (257 women and 78 men) completed a questionnaire assessing these variables. Partial correlation analyses, controlling for sensation-seeking tendencies and behaviors, revealed that listening to conventional music (pop, country, and religious genres) was negatively correlated with cigarette smoking (p = .001) and marijuana use (p < .001). Additionally, listening to energetic music (rap or hip-hop and soul or funk genres) was positively correlated with marijuana use (p = .004). The only significant predictor of alcohol use was country music, with which it was positively correlated (p = .04). This research suggests an especially harmful influence of energetic music on marijuana use.
Lack of Longitudinal Intrapatient Correlation between p24 Antigenemia and Levels of Human Immunodeficiency Virus (HIV) Type 1 RNA in Patients with Chronic HIV Infection during Structured Treatment Interruptions

ABSTRACT Structured treatment interruptions (STIs) have been proposed as a potential treatment strategy during human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy. This still-experimental intervention requires a close monitoring of patients' plasma viremia and CD4+-T-cell counts during the treatment interruption phase. By using signal amplification of a heat-dissociated p24 antigen (p24Ag) assay, we compared p24Ag levels with levels of HIV RNA in plasma. One hundred seventy-four plasma samples were obtained from 51 chronically HIV-infected patients: 117 from patients who underwent STIs and 57 from patients who did not. Partial immune complex dissociation and clearance of those complexes by the erythrocytes were also investigated. A significant association between the two assays was observed (β = 0.23, 95% confidence interval = 0.18, 0.28; P < 0.0001), but the association was smaller in the subset of samples from patients undergoing STIs. Moreover, discordant results and lack of longitudinal intrapatient correlation between levels of p24Ag and HIV-1 RNA were higher in this group. Incomplete immune complex dissociation and binding of those complexes to erythrocytes could be contributing factors involved in the diminished detection of p24Ag. Therefore, signal amplification of a heat-dissociated p24Ag had a positive association with current HIV RNA assays in a population-based analysis. However, it might not be sensitive enough to monitor longitudinal intrapatient viremia during STIs in patients with high CD4+-T-cell counts potentially due to the production of high-affinity anti-p24 antibodies and clearance of immune complexes by erythrocytes.
Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan

A combination of diclofenac and glucan administered repeatedly in a protective regimen in the course of repeated gamma irradiation of mice (6 × 2 Gy during 3 weeks) enhanced granulopoiesis and other indices of hematopoietic recovery investigated from 3 to 7 days after the last radiation exposure. Repeated administration of diclofenac or glucan alone or treatment of the mice with the didofenac‐glucan combination given once before the first or the last radiation exposure did not induce such effects. The protective effect of the repeatedly administered combination of the drugs was realized despite the fact that the response of the serum colony‐stimulating activity to the repeated combined drug administration was decreased at the end of the treatment regimen compared to that of mice given this drug combination only once. The combined treatment is supposed to act via increased proliferation of the hematopoietic stem or progenitor cells. Additivity or even synergism of the hematostimulatory action of glucan and of the strengthening of positive control of cell proliferation achieved by removing negatively acting prostaglandins (diclofenac action) may account for the radioprotective effects observed.
The appraisal of positive life changes following cancer diagnosis: An interview study

Objective: This research examines positive life changes that cancer patients may experience following their diagnosis. Although cancer is often believed to have negative impacts on the life of patients, positive impacts have been also discussed empirically. This study focuses on cancer patients' appraisal of positive life changes following their diagnosis and examines how and in which fields they recognize their lives as positively changed based on the study of Petrie et al. (1999). Methods: A total of eight cancer patients in a cancer support group participated in this research. A group discussion and semistructured interviews were conducted. Content analysis was applied. Results: The content analysis produced insights into the seven types of cancer-related life changes: improved empathy, greater knowledge about health, renewed recognition of life, change in personal life priorities, greater appreciation of health and life, improved close relationships, and healthy lifestyle change. Negative life changes were also reported. Significance of the research: This research showed that cancer patients tended to find and appraise their own positive life changes following cancer. The categorization of positive life changes basically supported that of Petrie et al. (1999), but produced an original category: renewed recognition of life. Positive life changes might be seen as a natural process that encourages patients' adjustment to cancer. Understanding positive impacts of cancer could be important in capturing the life-sized features of cancer patients. Future research could expand the view of the impacts of cancer and demonstrate how people recognize them as benefits.
Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation

Malignant rhabdoid tumors (MRT) exhibit a very poor prognosis because of their resistance to chemotherapeutic agents and new therapies are needed for the treatment of this cancer. Here, we show that the histone deacetylase (HDAC) inhibitor FK228 (depsipeptide) has an antitumor effect on MRT cells both in vitro and in vivo. FK228 is a unique cyclic peptide and is among the most potent inhibitors of both Class I and Class II HDACs. FK228 inhibited proliferation and induced apoptosis in all MRT cell lines tested. Preincubation with the pancaspase inhibitor zVAD‐fmk did not completely rescue FK228‐induced cell death, although it did inhibit apoptosis. Transmission electron microscopy (TEM) showed that FK228 could stimulate MRT cells to undergo apoptosis, necrosis or autophagy. FK228 converted unconjugated microtubule‐associated protein light chain 3 (LC3‐I) to conjugated light chain 3 (LC3‐II) and induced localization of LC3 to autophagosomes. Apoptosis inducing factor (AIF), which plays a role in caspase‐independent cell death, translocated to the nucleus in response to FK228 treatment. Moreover, small interfering RNA (siRNA) targeting of AIF prevented the morphological changes associated with autophagy and redistribution of LC3 to autophagosomes. Disrupting autophagy with chloroquine treatment enhanced FK228‐induced cell death. In vivo, FK228 caused a reduction in tumor size and induced autophagy in tumor tissues. Using immunoelectron microscopy, we confirmed AIF translocation into the nucleus of FK228‐induced autophagic cells in vivo. Thus, FK228 is a novel candidate for an antitumor agent for MRT cells. © 2008 Wiley‐Liss, Inc.
Comparison of fecal microflora of elderly persons in rural and urban areas of Japan

The Fecal microflora of 15 healthy elderly persons with a median age of 84 years in a rural area whose inhabitants tend to be long-lived (Yuzurihara-area, Uenohara, Yamanashi Prefecture) was compared with the microflora of individuals with a median age of 68 years in an urban area (Tokyo). The diet of the elderly persons in the Yuzurihara area is characterized by a high intake of dietary fiber. Total numbers of anaerobic bacteria were significantly smaller in the elderly persons in the Yuzurihara area than those in the Tokyo area. A significantly large number of bifidobacteria, but not of lecithinase-negative clostridia, was observed in the elderly persons in the Yuzurihara area. Large numbers and high incidences of bacilli and lecithinase-positive clostridia (mainly Clostridium perfringens) were found in the elderly persons in the Tokyo area. Twenty-five genera and over 81 species were isolated from the elderly persons in the Yuzurihara area, and 25 genera and over 92 species were isolated from the elderly persons in the Tokyo area. Furthermore, significantly larger numbers of Bifidobacterium adolescentis and Fusobacterium mortiferum strains were found in the Yuzurihara group, but significant reductions in the Bacteroides buccae-oris group, B. thetaiotaomicron, Bacteroides spp. , C. coccoides, C. paraputrificum, and Clostridium spp. were observed in the same group. A significantly higher isolation rate of Bacillus subtilis was observed in the elderly persons in the Tokyo area. The difference in the fecal microflora between elderly persons in Yuzurihara and those in the Tokyo area might be due to a difference in the intake of dietary fiber.
Regulation of connexin‐ and pannexin‐based channels by post‐translational modifications

Connexin (Cx) and pannexin (Panx) proteins form large conductance channels, which function as regulators of communication between neighbouring cells via gap junctions and/or hemichannels. Intercellular communication is essential to coordinate cellular responses in tissues and organs, thereby fulfilling an essential role in the spreading of signalling, survival and death processes. The functional properties of gap junctions and hemichannels are modulated by different physiological and pathophysiological stimuli. At the molecular level, Cxs and Panxs function as multi‐protein channel complexes, regulating their channel localisation and activity. In addition to this, gap junctional channels and hemichannels are modulated by different post‐translational modifications (PTMs), including phosphorylation, glycosylation, proteolysis, N‐acetylation, S‐nitrosylation, ubiquitination, lipidation, hydroxylation, methylation and deamidation. These PTMs influence almost all aspects of communicating junctional channels in normal cell biology and pathophysiology. In this review, we will provide a systematic overview of PTMs of communicating junction proteins and discuss their effects on Cx and Panx‐channel activity and localisation.