Miracle-dz/UniFAR-FTUs huggingface dataset:
ymoA, a Yersinia enterocolitica chromosomal gene modulating the expression of virulence functions

The virulence functions of Yersinia enterocolitica include the pYV‐encoded Yop proteins and YadA adhesin as well as the chromosome‐encoded enterotoxin, Yst. The yop and yadA genes form a temperature‐activated regulon controlled by the transcriptional activator VirF. Gene virF, also localized on pYV, is itself thermoinduced in the absence of other pYV genes. The enterotoxin ysf gene is silent in some collection strains including strain W22703. This paper describes two Tn5‐Tc1 chromosomal insertion mutants of W22703 transcribing virF, and hence the yop and yadA genes, at low temperature. These mutants also resumed their production of Yst, with its typical temperature dependence. Both mutations were insertions in the same gene called ymoA for‘Yersinia modulator’The cloned ymoA gene fully complemented the two mutations. Several properties of the mutants suggest that ymoA encodes a histone‐like protein. According to the nucleic acid sequence, the product of ymoA is an 8064 Da protein rich in aspartic acid (9%), glutamic acid (9%) and lysine (10.5%), but the predicted amino acid sequence shows no similarity with any described histone‐like protein. This work supports recent reports which propose a role for DNA topology and bacterial chromatin structure in thermoregulation of virulence functions.
In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques

ABSTRACT Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies of NNRTI resistance, we examined whether a SIV that causes immunopathogenesis in pigtail macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIVmne: SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIVmne contains the entire HIV-1 RT coding region. Both mutant viruses grew to high titers in vitro but had reduced fitness relative to wild-type SIVmne. Although the HIV-1 RT was properly processed into p66 and p51 subunits in RT-SHIVmne particles, the RT-SHIVmne virions had lower levels of RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT activity in RT-SHIVmne and SIV-RT-YY particles. HIV-1 and RT-SHIVmne were similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However, SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIVmne. Classical NNRTI resis tance mutations were selected in RT-SHIVmne after in vitro drug treatment and were monitored in a sensitive allele-specific real-time RT-PCR assay. Collectively, these results indicate that RT-SHIVmne may be a useful model in macaques for the preclinical evaluation of NNRTIs and for studies of the development of drug resistance in vivo.
Genetic polymorphisms of drug-metabolizing enzymes and the susceptibility to antituberculosis drug-induced liver injury

Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury ranges from a mild to severe form, and the associated mortality cases are not rare. The major drug-metabolizing enzyme of isoniazid is N-acetyltransferase. Other possible enzymes are CYP2E1 and glutathione S-transferase. There is evidence that polymorphisms of the genes that encode these enzymes may influence the activity of the corresponding drug-metabolizing enzymes. Recent studies demonstrated that these genetic polymorphisms may be associated with the susceptibility to antituberculosis drug-induced liver injury. The proposed risk-associated genotypes are NAT2 slow acetylator (without wild-type NAT2*4 allele), CYP2E1 *1A/*1A (homozygous wild type) and homozygous null GSTM1 genotype. Although the available data in the field are still limited and warrants further confirmation in different ethnic populations with larger sample sizes, it still cast some light on the application of these pharmacogenetic or pharmacogenomic approaches to prevent grave antituberculosis drug-induced liver injury in the near future.
Ferromagnetic resonance characterization of greigite (Fe3S4), monoclinic pyrrhotite (Fe7S8), and non‐interacting titanomagnetite (Fe3‐xTixO4)

Ferromagnetic resonance (FMR) spectroscopy has become an increasingly useful tool for studying the magnetic properties of natural samples. Magnetite (Fe3O4) is the only magnetic mineral that has been well characterized using FMR. This limits the wider use of FMR in rock magnetism and paleomagnetism. In this study, we applied FMR analysis to a range of magnetic minerals, including greigite (Fe3S4), monoclinic pyrrhotite (Fe7S8), magnetically non‐interacting titanomagnetite (Fe3‐xTixO4), and synthetic magnetite chains to constrain interpretation of FMR analysis of natural samples and to explore applications of FMR spectroscopy. We measured the FMR signatures of a wide range of well‐characterized samples at the X‐ and Q‐bands. FMR spectra were also simulated numerically to compare with experimental results. The effects of magnetic anisotropy, mineralogy, domain state, and magnetostatic interactions on the FMR spectra are discussed for all studied minerals. Our experimental and theoretical analyses of magnetically non‐interacting tuff samples and magnetically interacting chains enable quantitative assessment of contributions of magnetostatic interactions and magnetic anisotropy to the FMR spectra. Our results also indicate that intact magnetosomes are a unique system with distinct FMR signatures. While FMR analysis is useful for characterizing magnetic properties of natural samples, care is needed when making interpretations because of overlaps in a range of FMR signatures of different magnetic minerals with different magnetic properties. Our analyses will help to constrain such interpretations in rock magnetic studies.
Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review

Objective: To determine the accuracy of assessing cardiovascular disease (CVD) risk in the primary prevention of CVD and its impact on clinical outcomes. Design: Systematic review. Data sources: Published studies retrieved from Medline and other databases. Reference lists of identified articles were inspected for further relevant articles. Selection of studies: Any study that compared the predicted risk of coronary heart disease (CHD) or CVD, with observed 10-year risk based on the widely recommended Framingham methods (review A). Randomised controlled trials examining the effect on clinical outcomes of a healthcare professional assigning a cardiovascular risk score to people predominantly without CVD (review B). Review methods: Data were extracted on the ratio of the predicted to the observed 10-year risk of CVD and CHD (review A), and on cardiovascular or coronary fatal or non-fatal events, risk factor levels, absolute cardiovascular or coronary risk, prescription of risk-reducing drugs and changes in health-related behaviour (review B). Results: 27 studies with data from 71 727 participants on predicted and observed risk for either CHD or CVD were identified. For CHD, the predicted to observed ratios ranged from an underprediction of 0.43 (95% CI 0.27 to 0.67) in a high-risk population to an overprediction of 2.87 (95% CI 1.91 to 4.31) in a lower-risk population. In review B, four randomised controlled trials confined to people with hypertension or diabetes found no strong evidence that a cardiovascular risk assessment performed by a clinician improves health outcomes. Conclusion: The performance of the Framingham risk scores varies considerably between populations and evidence supporting the use of cardiovascular risk scores for primary prevention is scarce.
Implementation and Analysis of Ring Oscillator PUFs on 60 nm Altera Cyclone FPGAs

ABSTRACT Ring Oscillator (RO) physically unclonable functions (PUFs) on field programmable gate arrays (FPGAs) have drawn much attention in recent years. Making each FPGA uniquely identifiable, they allow for protection of intellectual property (IP) or generation of secret encryption keys. Their implementation has been widely discussed, but most experiments have been conducted on Xilinx platforms. In this paper, we report the statistical results from an analysis spanning 20 Cyclone IV FPGAs with 60 nm technology. We parameterize the RO length, placement, ambient temperature, and non-PUF switching activity and discuss the observed effects on PUF quality.
Eye Disease, the Fertility Decline, and the Emergence of Global Income Differences*

This research advances and empirically establishes the hypothesis that regional variation in the historical incidence of eye disease has influenced the current global distribution of per capita income. By reducing work life expectancy, high historical eye disease incidence has served to diminish the incentive to accumulate skills, thereby delaying the fertility transition and the take-off to sustained economic growth. As a consequence of a differential timing of the take-off to growth, prompted by differences in the inherent return to skill formation, global income disparities have emerged.
Promoting Breastfeeding-Friendly Hospital Practices

Background: Hospital breastfeeding support practices can affect breastfeeding outcomes. Learning collaboratives are an increasingly common strategy to improve practices in health care and have been applied to breastfeeding in many cases. Objectives: The aims of this study of the Evidence-Based Hospital Breastfeeding Support Learning Collaborative (EBBS LC) were to describe the perceptions of participants regarding the process and effectiveness of the EBBS LC, describe perceived barriers and facilitators to implementing the Ten Steps to Successful Breastfeeding, and identify additional actions and resources needed in future learning collaboratives. Methods: Qualitative, semistructured telephone interviews were conducted with 13 key staff who represented 16 of the 18 participating hospitals. Results: The learning collaborative was perceived positively by participants, meeting the expectations of 9 and exceeding the expectations of 4 persons interviewed. The most beneficial aspect of the program was its collaborative nature, and the most difficult aspect was the time required to participate as well as technological difficulties. The key barriers were staff time, staff changes, cost, and the difficulty of changing the existing practices of hospitals and communities. The key facilitating factors were supportive management, participation in multiple breastfeeding quality improvement projects, collecting data on breastfeeding outcomes, tangible resources regarding the Ten Steps, and positive community response. Participants in the EBBS LC stated that they would like to see the Washington State Department of Health create a resource-rich, centralized source of information for participants. Conclusion: This learning collaborative approach was valued by participants. Future efforts can be guided by these evaluation findings.
A spatiotemporal quantile regression model for emergency department expenditures

Motivated by a recent study of geographic and temporal trends in emergency department care, we develop a spatiotemporal quantile regression model for the analysis of emergency department‐related medical expenditures. The model yields distinct spatial patterns across time for each quantile of the response distribution, which is important in the spatial analysis of expenditures, as there is often little spatiotemporal variation in mean expenditures but more pronounced variation in the extremes. The model has a hierarchical structure incorporating patient‐level and region‐level predictors as well as spatiotemporal random effects. We model the random effects via intrinsic conditionally autoregressive priors, improving small‐area estimation through maximum spatiotemporal smoothing. We adopt a Bayesian modeling approach based on an asymmetric Laplace distribution and develop an efficient posterior sampling scheme that relies solely on conjugate full conditionals. We apply our model to data from the Duke support repository, a large georeferenced database containing health and financial data for Duke Health System patients residing in Durham County, North Carolina. Copyright © 2015 John Wiley & Sons, Ltd.
Extension of the critical period for developmental plasticity of the corticospinal pathway

The corticospinal tract (CST) of the rat undergoes a prolonged period of postnatal development. Lesions of the presumptive CST pathway at birth are followed by the aberrant rerouting of the developing corticospinal axons around the lesion site through adjacent undamaged CNS tissue. This developmental plasticity becomes severely restricted by 5‐6 days of age, so the axons are no longer capable of growth around the site of injury. The aim of the current study was to determine whether altering the environment at the site of injury by filling the lesion with transplanted fetal spinal cord tissue could prolong the critical period for developmental plasticity of the corticospinal pathway. The spinal cord was damaged (overhemisection) at three stages in the development of the corticospinal (CS) pathway: 1) prior to the arrival of CS axons, 2) after the axons elongated through the cord but prior to synaptogenesis, and 3) after both axonal elongation and synaptogenesis were completed. One to 9 months later, anterograde neuronal tracing with horseradish peroxidase was used to assess the growth of the corticospinal pathway with or without a fetal transplant at the site of injury, and the pattern of labeling was compared with that observed in adult nonlesioned control animals. Our results indicate that the presence of a transplant prolongs the critical period for developmental plasticity of the CST. Transplants elicited growth of CST axons throughout the postnatal period examined. CST axons damaged prior to synaptogenesis exhibited more robust growth than those lesioned after synaptogenesis had been completed. These results suggest that both environmental and neuronal factors interact to regulate the response of immature CS neurons to injury.
Late Pregnancy Suppresses Relapses in Experimental Autoimmune Encephalomyelitis: Evidence for a Suppressive Pregancy-Related Serum Factor1

Women with multiple sclerosis have significantly diminished disease activity during pregnancy. The purpose of our study was to identify the underlying mechanism for the diminished disease activity. We found that during the period of late pregnancy there is protection against paralysis, during both the induction and effector phases of relapsing experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. We did not find any changes in the cytokine secretion profiles or the proliferative activity of autoreactive T cells from mice induced during late pregnancy compared with virgin controls. In mice mated after disease onset, the inflammatory histologic lesions did not clear, despite marked clinical improvement during pregnancy. We found evidence for a serum factor present in late pregnancy that suppresses T cell activation. In the presence of sera taken from mice late in pregnancy, the proliferative response and IL-2 production of proteolipid protein p139–151-specific T cells were significantly diminished as compared with stimulation in the presence of normal mouse sera. In conclusion, serum from late pregnancy has the capacity to down-regulate T cell responses and might be associated with the amelioration of disease activity in experimental autoimmune encephalomyelitis.
Antibody persistence after primary immunization with trivalent oral poliovirus vaccine.

Five years after primary infant immunization with trivalent oral poliovirus vaccine, employing either a three-dose primary series as recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP) or a four-dose series as recommended by the Committee on Infectious Diseases of the American Academy of Pediatrics. 115 children were serologically tested for persistence of neutralizing antibodies by the microneutralization test. Of the 57 individuals immunized according to the ACIP recommendation, antibody persistence was demonstrated in 92% for type 1 poliovirus, 98% for type 2, and 84% for type 3. Of those 58 individuals originally receiving a four-dose primary infant immunization series, the persistence of antibody was 98% to type 1, 98% to type 2, and 87% to type 3. Twenty-one of 24 negative sera showed neutralizing ability when tested by a more sensitive plaque reduction test. Thus, individuals completing either immunization schedule demonstrated satisfactory persistence of neutralizing antibody to all three poliovirus types over a five-year period.
Evaluating E-Learning System Use by CBAM-Stages of Concern Methodology in Jordanian Universities

This paper presents the use of a new approach towards evaluating the use of e-learning system by faculty members in Jordanian universities. Evaluating the use of any system is aimed towards providing a better understanding for the needs, challenges and opportunities that are expected from using such systems. E-learning as a supportive method for education in Jordanian universities has been available since 2003 [1]. Different studies have provided an assessment for the use of e-learning in Jordan using different tools many of which have been found unstandardized tool for performing the evaluation. Some of those tools managed to give significant results, while others lacked the systematic approach and the use of appropriate methodology. The Concern Based Adoption Model (CBAM) Framework has been created in order to provide 3 different tools to assess the use of innovation tools used within educational context. CBAM framework is widely used in America, Canada and parts of Europe, and this tool has not been used in any research related to Jordan or e-learning in Jordanian universities. This study is the first study to use and provide valuable outputs for assessing the use of e-learning in Jordanian Universities. Keywords-component; CBAM, Evaluation, E-learning, Jordanian Universities, Stages of Concern.
Electrical transport properties of Ge-doped GaN nanowires

The conductivity and charge carrier concentration of single GaN nanowires (NWs) doped with different concentrations of Ge were determined by four-point resistivity and temperature-dependent Seebeck coefficient measurements. We observed high carrier concentrations ranging from 9.1 × 1018 to 5.5 × 1019 cm−3, well above the Mott density of 1.6 × 1018 cm−3, and conductivities up to 625 S cm−1 almost independent of the NW diameter. The weak temperature dependence of the conductivity between 2 and 10 K could be assigned to the formation of an impurity band. For the sample with the highest conductivity metallic behaviour was found, indicated by a positive temperature coefficient of the resistivity. The near band edge emission analyzed by micro-photoluminescence spectroscopy showed only a small increase of the peak width up to 70 meV and no spectral shift for carrier concentrations up to 5.5 × 1019 cm−3. The latter was attributed to the simultaneous influence of band filling, band gap renormalization, and strain.
Gamma irradiation of human leukaemic cells HL-60 and MOLT-4 induces decrease in Mcl-1 and Bid, release of cytochrome c, and activation of caspase-8 and caspase-9

Purpose: Apoptosis is significantly controlled by proteins of Bcl-2 (B-cell lymphoma 2) family promoting cell death or maintaining cell survival. We selected two representatives of Bcl-2 family (anti-apoptotic Mcl-1 – myeloid cell line-1 and pro-apoptotic Bid – Bcl-2 homology domain 3 interacting death agonist), cytochrome c (cyt-c), and two initial caspases (-8 and -9) to evaluate their function in ionizing radiation (IR)-induced apoptosis in human leukaemic cell lines diverging in p53 (TP53 tumor suppressor gene) status. Materials and methods: A total of 30 μg of proteins of whole-cell lysates or 10 μg of mitochondrial protein fractions were electrophoretically separated and analyzed by Western-blotting. Results: Here we show that in both HL-60 (p53 null) and MOLT-4 (p53 wild type) leukaemic cells the amount of Mcl-1 initially increased after irradiation by sublethal but not by lethal dose and later (when apoptosis occurred) it decreased in a dose-dependent manner. Caspase-8 was cleaved and afterwards the amount of Bid decreased as it was truncated. We also found cyt-c release from the inner mitochondrial membrane space into cytoplasm to be dose-dependent and it was followed by induction of apoptosis. In the p53-null cells caspase-8 was activated prior caspase-9, whereas the cells harboring p53 exhibited a simultaneous activation of both initial caspases. Conclusion: IR induced a decrease in Mcl-1, activation of Bid, caspase-8, and -9, and release of cyt-c. Presented data indicate that both extrinsic and intrinsic apoptosis signalling pathways were activated in HL-60 and MOLT-4 cells upon exposure to IR regardless to the p53 status.
Postulated Role of Interdomain Interaction within the Ryanodine Receptor in Ca2+ Channel Regulation*

Localized distribution of malignant hyperthermia (MH) and central core disease (CCD) mutations in N-terminal and central domains of the ryanodine receptor suggests that the interaction between these domains may be involved in Ca2+ channel regulation. To test this hypothesis, we investigated the effects of a new synthetic domain peptide DP4 corresponding to the Leu2442–Pro2477 region of the central domain. DP4 enhanced ryanodine binding and induced a rapid Ca2+release. The concentration for half-maximal activation by agonists was considerably reduced in the presence of DP4. These effects of DP4 are analogous to the functional modifications of the ryanodine receptor caused by MH/CCD mutations (viz. hyperactivation of the channel and hypersensitization of the channel to agonists). Replacement of Arg of DP4 with Cys, mimicking the in vivoArg2458-to-Cys2458 mutation, abolished the activating effects of DP4. An N-terminal domain peptide DP1 (El-Hayek, R., Saiki, Y., Yamamoto, T., and Ikemoto, N. (1999) J. Biol. Chem. 274, 33341–33347) shows similar activation/sensitization effects. The addition of both DP4 and DP1 produced mutual interference of their activating functions. We tentatively propose that contact between the two (N-terminal and central) domains closes the channel, whereas removal of the contact by these domain peptides or by MH/CCD mutations de-blocks the channel, resulting in hyperactivation/hyper-sensitization effects.