Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane Perturbation-Associated Ca2+ Signaling and Incoming Genome Sensing Are Required for the Host Response to Low-Level Enveloped Virus Particle Entry

ABSTRACT The type I interferon (IFN) response is an important aspect of innate antiviral defense, and the transcription factor IRF3 plays an important role in its induction. Membrane perturbation during fusion, a necessary step for enveloped virus particle entry, appears sufficient to induce transcription of a subset of IFN-stimulated genes (ISGs) in an IRF3-dependent, IFN-independent fashion. IRF3 is emerging as a central node in host cell stress responses, although it remains unclear how different forms of stress activate IRF3. Here, we investigated the minimum number of Sendai virus (SeV) and human cytomegalovirus (HCMV) particles required to activate IRF3 and trigger an antiviral response. We found that Ca2+ signaling associated with membrane perturbation and recognition of incoming viral genomes by cytosolic nucleic acid receptors are required to activate IRF3 in response to fewer than 13 particles of SeV and 84 particles of HCMV per cell. Moreover, it appears that Ca2+ signaling is important for activation of STING and IRF3 following HCMV particle entry, suggesting that Ca2+ signaling sensitizes cells to recognize genomes within incoming virus particles. To our knowledge, this is the first evidence that cytosolic nucleic acid sensors recognize genomes within incoming virus particles prior to virus replication. These studies highlight the exquisite sensitivity of the cellular response to low-level stimuli and suggest that virus particle entry is sensed as a stress signal. IMPORTANCE The mechanism by which replicating viruses trigger IRF3 activation and type I IFN induction through the generation and accumulation of viral pathogen-associated molecular patterns has been well characterized. However, the mechanism by which enveloped virus particle entry mediates a stress response, leading to IRF3 activation and the IFN-independent response, remained elusive. Here, we find that Ca2+ signaling associated with membrane perturbation appears to sensitize cells to recognize genomes within incoming virus particles. To our knowledge, this is the first study to show that cytosolic receptors recognize genomes within incoming virus particles prior to virus replication. These findings not only highlight the sensitivity of cellular responses to low-level virus particle stimulation, but provide important insights into how nonreplicating virus vectors or synthetic lipid-based carriers used as clinical delivery vehicles activate innate immune responses.
EXPERIENCES IN THE CONSTRUCTION OF RESEARCH INSTRUMENTS FOR MATHEMATICS TEACHER PROFESSIONAL DEVELOPMENT

The “Analyses of Mathematics Teacher Professional Development Programmes (MTPDP) in selected developed and developing countries: Insights for quality mathematics instruction in subSaharan African countries”, is a caption given to a cross-continental collaborative study initiated by the Department of Mathematics Education, at the University of South Africa. The study aims to investigate the impact of MTPDP initiatives on the quality of teacher pedagogy and students’ performance. The study is an exploratory mixed-methods design involving 11 countries to facilitate the sharing of ideas and a collective reflection on MTPDP activities. The development of data collection instruments was a collaborative effort to probe high school mathematics teachers, school principals, service providers, district officials and subject advisers on MTPDP-related issues. The MTPDP pilot study, which is reported in this paper, aimed: (1) to assess the efficiency of MTPDP data collection instruments; and, (2) to address logistical and methodological issues relating to the MTPDP study. The pilot study highlighted the value of gathering information prior to a larger study to enhance the research design of the latter. Specific lessons acquired from the pilot experience will help to construct effective operational conditions for the main study.
Location of M13 coat protein in sodium dodecyl sulfate micelles as determined by NMR.

The major coat protein (gVIIIp) of bacteriophage M13 solubilized in sodium dodecyl sulfate (SDS) detergent micelles was used as a model system to study this protein in the lipid-bound form. In order to probe the position of gVIIIp relative to the SDS micelles, stearate was added, spin-labeled at the 5- or 16-position with a doxyl group containing a stable nitroxide radical. The average position of the spin-labels in the micelles was derived from the line broadening of the resonances in the 13C spectrum of SDS. Subsequently, we derived a model of the relative position of gVIIIp in the SDS micelle from the effect of the spin-labels on the gVIIIp resonances, monitored via 1H-15N HSQC and TOCSY experiments. The results are consistent with the structure of gVIIIp having two helical strands. One strand is a long hydrophobic helix that spans the micelle, and the other is a shorter amphipathic helix on the surface of the micelle. These results are in good agreement with the structure of gVIIIp in membranes proposed by McDonnell et al. on the basis of solid state NMR data [McDonnell, P. A. , Shon, K. , Kim, Y. , & Opella, S. J. (1993) J. Mol. Biol. 233, 447-463]. This study indicates that high-resolution NMR on this membrane protein, solubilized in detergent micelles, is a very suitable technique for mimicking these proteins in their natural environment. Furthermore, the data indicate that the structure of the micelle near the C-terminus of the major coat protein is distorted. (ABSTRACT TRUNCATED AT 250 WORDS)
Glucagon-like Peptide-1 Analogues Inhibit Proliferation and Increase Apoptosis of Human Prostate Cancer Cells in vitro.

Background: Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) 1. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release. Method: Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2. Also the kinase pathways maybe involved and the expression of GLP-1 receptor (GLP-1 R) in LNCap cells was detected. Results: In our experiments, exenatide and liraglutide significantly inhibited the proliferation of the LNCap cell lines and induced the cell apoptosis. Exenatide (1-100 nmol/L) increased the ratio of Bax/Bcl-2 in a dose-dependent manner, whereas liraglutide increased Bax/Bcl-2 ratio only at concentrations of 10 nmol/L. And we found that GLP-1 analogues activate p38 but not ERK1/2 or AKT in LNCap cells. And classical GLP-1 receptor was detected in LNCap cells. Conclusion: These data suggest that exenatide and liraglutide attenuate prostate cancer growth through regulating P38 pathway by binding with GLP-1R.
Source Apportionment: Findings from the U.S. Supersites Program

Abstract Receptor models are used to identify and quantify source contributions to particulate matter and volatile organic compounds based on measurements of many chemical components at receptor sites. These components are selected based on their consistent appearance in some source types and their absence in others. UNMIX, positive matrix factorization (PMF), and effective variance are different solutions to the chemical mass balance (CMB) receptor model equations and are implemented on available software. In their more general form, the CMB equations allow spatial, temporal, transport, and particle size profiles to be combined with chemical source profiles for improved source resolution. Although UNMIX and PMF do not use source profiles explicitly as input data, they still require measured profiles to justify their derived source factors. The U.S. Supersites Program provided advanced datasets to apply these CMB solutions in different urban areas. Still lacking are better characterization of source emissions, new methods to estimate profile changes between source and receptor, and systematic sensitivity tests of deviations from receptor model assumptions.
Use of Sentiment Analysis for Capturing Patient Experience From Free-Text Comments Posted Online

Background There are large amounts of unstructured, free-text information about quality of health care available on the Internet in blogs, social networks, and on physician rating websites that are not captured in a systematic way. New analytical techniques, such as sentiment analysis, may allow us to understand and use this information more effectively to improve the quality of health care. Objective We attempted to use machine learning to understand patients’ unstructured comments about their care. We used sentiment analysis techniques to categorize online free-text comments by patients as either positive or negative descriptions of their health care. We tried to automatically predict whether a patient would recommend a hospital, whether the hospital was clean, and whether they were treated with dignity from their free-text description, compared to the patient’s own quantitative rating of their care. Methods We applied machine learning techniques to all 6412 online comments about hospitals on the English National Health Service website in 2010 using Weka data-mining software. We also compared the results obtained from sentiment analysis with the paper-based national inpatient survey results at the hospital level using Spearman rank correlation for all 161 acute adult hospital trusts in England. Results There was 81%, 84%, and 89% agreement between quantitative ratings of care and those derived from free-text comments using sentiment analysis for cleanliness, being treated with dignity, and overall recommendation of hospital respectively (kappa scores: .40–.74, P<.001 for all). We observed mild to moderate associations between our machine learning predictions and responses to the large patient survey for the three categories examined (Spearman rho 0.37-0.51, P<.001 for all). Conclusions The prediction accuracy that we have achieved using this machine learning process suggests that we are able to predict, from free-text, a reasonably accurate assessment of patients’ opinion about different performance aspects of a hospital and that these machine learning predictions are associated with results of more conventional surveys.
Wage theft, underpayment and unpaid work in marketised social care

Marketised models of social care provision in Australia are placing pressures on service providers and driving changes in work organisation and employer practices, with potential to degrade social care jobs. While international experience of marketised social care has demonstrated the vulnerability of social care workers to wage theft and other violations of employment laws, Australia’s relatively strong industrial relations safety net might be expected to be better able to protect these low-paid workers. Nevertheless, there is emerging evidence of negative impacts on the pay and entitlements of frontline workers in the expanding community support and homecare workforce. This study investigates the paid and unpaid work time of disability support workers under Australia’s new National Disability Insurance Scheme. The research takes a novel approach combining analysis of working day diaries and qualitative interviews with employees to expose how jobs are being fragmented and work is being organised into periods of paid and unpaid time, leaving employees paid below their minimum entitlement. The article highlights the role of social care policy along with inadequate employment regulation. JEL Codes: J390, J81, J88
Human Shugoshin Mediates Kinetochore-Driven Formation of Kinetochore Microtubules

The conserved protein Shugoshin (Sgo) plays a role in the maintenance of centromeric cohesion in mitosis and meiosis. Human Shugoshin (hSgo) was first identified as an overexpressed protein in breast cancers. Here we demonstrate that hSgo mediates kinetochore-driven formation of kinetochore microtubules (MTs) during bipolar spindle assembly. The regulated overexpression of full-length hSgo, or of truncated proteins containing both the conserved N-terminal coiled-coil domain and C-terminal basic domain, resulted in hSgo localization at centromere at early mitosis and was associated with aberrant nucleation and formation of bundles of kinetochore MTs. The mid-portion of hSgo, between the N- and C-terminal domains, includes both a functional domain for centromeric cohesion and a regulatory domain for spindle assembly. The cells overexpressing natural alternative splicing isoforms, which are almost completely defective for the mid-portion of the hSgo protein, showed premature centromere separation (PCS) and aberrant MT connections. These isoforms are mildly overexpressed in HEK293 cells. On the other hand, cells expressing a truncated protein, defective in the lysine-rich region of the mid-portion, arrested at mitosis due to persistent abnormal MT connections and not because of PCS. Aberrant MT connections were predominantly observed in spindle regions where chromosomes were clustered. Interestingly, we also found that hSgo is rapidly exchanged at kinetochores at early mitosis. Based on these results, we conclude that hSgo may be diffusible and have a role in proper kinetochores-MTs attachment.
Perceptions of Risk Factors for Female Gang Involvement among African American and Hispanic Women

This study examines ethnic minority girls' perceptions of risk factors for female gang involvement. Thirty-one female students at an alternative school in a high-crime, urban environment were interviewed with regard to their beliefs about why adolescents join gangs. Peer pressure was believed to be the largest influence on female gang involvement. In addition, it was thought that girls might turn to gangs for protection from neighborhood crime, abusive families, and other gangs. Family characteristics linked to gang involvement included lack of parental warmth and family conflict. Furthermore, gangs, through their participation in illegal activities, were viewed as providing access to excitement and moneymaking opportunities not available through more legitimate societal institutions. Finally, adolescents may view gang membership as a way of obtaining respect. Implications for intervention programs and future research are discussed.
Predicting potential impacts of China’s retaliatory tariffs on the U.S. farm sector

In April 2018, China proposed import tariffs up to 25% on hundreds of U.S. products, including soybeans, cotton, sorghum, and pork. We analyze the potential impact of these tariffs on U.S. domestic prices, production, and economic welfare. U.S. exports to China could decrease as much as 83%.
Effect of aqueous leaves extract of Ocimum gratissimum on hematological parameters in rats

Objective: This study aims to elucidate the effect of Ocimum gratissimum on hematological parameters in rats. Materials and Methods: Thirty male albino Wistar rats were randomly assigned into three groups of ten rats each. Group 1 was control, while groups 2 (LD) and 3 (HD) received 500 mg/kg and 1000 mg/kg body weight, respectively, of the extract orally once daily. Rats in all three groups received normal rat chow and drinking water ad libitum for 28 days. Complete blood count was done using an automatic counter. Results: The HD group had significantly (P<.05) higher red blood cell (RBC) counts, packed cell volume (PCV), hemoglobin (Hb), and platelet counts as compared with the control and LD groups. No significant changes were observed in the total white blood cell (WBC) count of the three groups, but significantly (P<.05) lower lymphocyte and higher neutrophil counts were observed in the HD group compared with the LD group. The mean platelet volume (MPV), platelet–large cell ratio (P–LCR), and platelet distribution width (PDW) were significantly (P<.05) reduced in the HD compared with the LD group. The mean corpuscular volume (MCV) and RBC distribution width–standard deviation were significantly (P<.05) lower in the HD group than in control. No significant changes were observed in levels of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width–coefficient of variation among the groups. Conclusion: We conclude that oral administration of O gratissimum increases RBC, PCV, Hb, platelet count, and neutrophils and also leads to a decrease in platelet indices (i.e., MPV, P–LCR, and PDW).
'PUTTING THE HORSE BEFORE THE CART': A PRE-CRISIS PANEL DATA INVESTIGATION OF GREEK BANK'S CREDIT GROWTH

The economic crisis that was ignited in 2009 has ushered in an era of economic stagnation and social misery across much of the EU region that could last for a generation or more. As a result, governments in the recession-stricken Eurozone are struggling to find a viable way out of what is perceived to be the worst economic turmoil since the establishment of the EU. In Greece, the rippling effects of the crisis manifested themselves in a sovereign debt crisis accompanied by practically a collapse of its banking sector. This paper by using panel data analysis purports to explore and effectively shed some light on the key factors that determined the lending behavior of the banking sector in the pre-crisis period. To the best of our knowledge, there are hardly any empirical studies conducted on the role of banks over the period 2004-2010. The evidence yielded, relates credit growth to deposit growth and rising housing prices as well as banks’ capital strength. In so far as the business cycle affects lending growth, our results confirm that an ever increasing public debt results in curtailed lending while rising real private consumption kept Greek lenders’ volumes at high levels. Given the current banking sector restructuring that is taking place in Greece the evidence that is generated can be invaluable as it suggests alternative channels through which the battered banking sector could resume its main intermediation role.
Serum ionized magnesium levels and ionized calcium‐to‐magnesium ratios in adult patients with sickle cell anemia

Low levels of total magnesium in sickle cell erythrocytes have been linked to increased sickling due to cell dehydration. We tested the null hypothesis that adult sickle cell anemia (SCA) patients have the same serum level of ionized Mg (Mg2+) and Ca2+/Mg2+ ratio as healthy African Americans (AA) and healthy Caucasians (CAUC). We measured serum Mg2+ and ionized calcium (Ca2+) with ion‐selective electrodes and calculated the serum Ca2+/Mg2+ ratios in patients with SCA and control groups (AA and CAUC). Seventy‐four SCA patients and 61 controls were compared. SCA patients had significantly (P < 0.001) lower levels of serum Mg2+ (0.52 ± 0.05) compared to healthy AA (0.57 ± 0.04) and CAUC (0.62 ± 0.03). Eighty‐six percent of the adult SCA patients had serum Mg2+ levels below the mean for the AA group, and 96% of SCA patients were above the AA group's mean serum Ca2+/Mg2+. Of the SCA patients studied, 25.6% (95% CI, 16.2–37.2%) had serum Mg2+ levels below the racially adjusted lower limit of normal and 50% (95% CI, 38.1–61.9%) were above the upper limit of serum Ca2+/Mg2+ for AA controls. By measuring serum Mg2+ and Ca2+, we were able to define a subset of SCA patients with hypomagnesemia and elevated Ca2+/Mg2+ ratios, who may benefit from magnesium supplementation. Am. J. Hematol. 77:215–222, 2004. © 2004 Wiley‐Liss, Inc.
Tyrosine‐derived polycarbonates: Backbone‐modified “pseudo”‐poly(amino acids) designed for biomedical applications

Starting from L‐tyrosine (Tyr) and its metabolites desaminotyrosine (Dat) and tyramine (Tym), four structurally related model dipeptides were prepared: Dat‐Tym (neither N‐ or C‐terminus present), Z‐Tyr‐Tym (N‐terminus protected by benzyloxycarbonyl), Dat‐Tyr‐Hex (C‐terminus protected by a hexyl ester group), and Z‐Tyr‐Tyr‐Hex (both N‐ and C‐termini present, protected by benzyloxycarbonyl and hexyl ester, respectively). The model dipeptides were used as monomers in the synthesis of polycarbonates. The polymerization reaction in the presence of either phosgene or triphosgene proceeded via the phenolic hydroxyl groups. Polymers with molecular weights of 105,000–400,000 da (by gel permeation chromatography, relative to polystyrene standards) were obtained. The physicomechanical properties (solubility, mechanical strength, glass transition and decomposition temperature, processibility) of the polymers were determined, and an attempt was made to correlate the polymer properties with the nature of the N‐ and C‐terminus protecting groups. The presence of the urethane bond at the N‐terminus protecting group was found to reduce solubility, ductility, and processibility, probably due to interchain hydrogen bonding. The presence of a C‐terminus alkyl ester group increased solubility and processibility. Thus, the most promising candidate polymer for biomedical applications was obtained from Dat‐Tyr‐Hex, the monomer carrying a C‐terminus protecting group only. Since very similar results had recently been obtained for a series of structurally related polyiminocarbonates, the structure property correlations seem to be generally valid.
TOLERANCE TO PENTYLENTETRAZOL-INDUCED CONVULSIONS AND PROTECTION OF CEREBROVASCULAR INTEGRITY BY CHRONIC NICOTINE

The authors' previous studies have shown that in nicotine-induced seizures sensitivity was decreased and blood-brain barrier (BBB) disruption was prevented as a consequence of nicotine pretreatment. This study aimed to investigate the possible protective actions of nicotine on cerebrovascular permeability and seizures induced by pentylentetrazol (PTZ) injection. Cerebrovascular effects of nicotine were evaluated by measuring the permeability changes of BBB using Evans-Blue (EB) dye and specific gravity (SG), which indicates brain water and protein content. The experiments were carried out on Wistar rats. Animals were randomly divided into two groups. Convulsions were induced by injection of PTZ (80 mg/kg i.v.) in rats either pretreated with nicotine daily with a low dose of 0.8 mg/kg day for 21 days or injected with a single dose of 6 mg/kg mecamylamine. The same procedures were followed in control rats with the exception that they were injected only with saline. PTZ injection caused tonic-clonic convulsions and increased the EB dye leakage and specific gravity values in saline-injected control rat brains. Daily injection of nicotine lessened the intensity of seizures. These were accompanied by marked decreases in both the leakage of EB and brain water content. Acute administration of a nAChR antagonist mecamylamine significantly increased seizure latency and decreased the duration of seizures. Thereby, mecamylamine reduced the EB leakage and water content in most brain regions. These results indicate that development of tolerance to PTZ convulsions can be produced by chronic nicotine administration in rats. The mechanism for this effect currently needs clarification. Moreover, the data also suggest that cholinergic activity may account for occurrence of PTZ-induced convulsions.