Miracle-dz/UniFAR-FTUs huggingface dataset:
Intercellular signaling of reproductive development by the C. elegans DAF-9 cytochrome P450

Parallel pathways control C. elegans reproductive development in response to environmental cues. Attenuation of daf-2 insulin-like or daf-7 TGFβ-like signaling pathways cause developmental arrest at the stress resistant and long-lived dauer stage. Loss-of-function mutations in the cytochrome P450 gene daf-9 also cause dauer arrest and defects in cell migration. A rescuing daf-9::GFP fusion gene driven by the daf-9 promoter is expressed in two head cells at all stages, in the hypodermis from mid-second larval stage (L2) to the fourth larval stage (L4), and in the spermatheca of the adult hermaphrodite. Although the level of daf-9::GFP expression in the head cells and spermatheca is constant, hypodermal daf-9::GFP expression is modulated by multiple inputs. In particular, daf-9::GFP expression in the hypodermis is absolutely dependent on daf-12, the nuclear receptor that is negatively regulated by daf-9 gene activity, suggesting feedback control between daf-9 and daf-12 in this tissue. daf-9 expression exclusively in the hypodermis is sufficient to restore reproductive development in daf-9 mutant animals, suggesting that daf-9 functions in a cell nonautonomous manner. Furthermore, constitutive expression of daf-9 in the hypodermis suppresses dauer arrest of daf-7 mutant animals and inhibits dauer remodelling of some tissues in daf-2 mutant animals. Thus, daf-9 may integrate outputs from daf-2 and daf-7 signaling pathways to relay neuroendocrine signals through synthesis of a lipophilic hormone.
An Intelligent Droop Control for Simultaneous Voltage and Frequency Regulation in Islanded Microgrids

Voltage and frequency of microgrids (MGs) are strongly impressionable from the active and reactive load fluctuations. Often, there are several voltage source inverters (VSIs) based distributed generations (DGs) with a specific local droop characteristic for each DG in a MG. A load change in a MG may lead to imbalance between generation and consumption and it changes the output voltage and frequency of the VSIs according to the droop characteristics. If the load change is adequately large, the DGs may be unable to stabilize the MG. In the present paper, following a brief survey on the conventional voltage/frequency droop control, a generalized droop control (GDC) scheme for a wide range of load change scenarios is developed. Then to remove its dependency to the line parameters and to propose a model-free based GDC, a new framework based on adaptive neuro-fuzzy inference system (ANFIS) is developed. It is shown that the proposed intelligent control structure carefully tracks the GDC dynamic behavior, and exhibits high performance and desirable response for different load change scenarios. It is also shown that the ANFIS controller can be effectively used instead of the GDC. The proposed methodology is examined on several MG test systems.
Effect of Ag Addition on the Microstructural and Mechanical Properties of Sn-Cu Eutectic Solder

The effect of adding Ag up to 1 mass% on the microstructural and mechanical properties of Sn–Cu eutectic solder alloy was examined. Without Ag, primary β–Sn grains are surrounded by the eutectic network band of Cu6Sn5 needle precipitates/β–Sn. With increasing Ag content, the primary β–Sn grain size and the eutectic network size become finer. In the eutectic band fine Ag3Sn particles appear in addition to Cu6Sn5 precipitates. The DSC experiment revealed the presence of four endothermic reactions on heating for Sn–Cu–Ag alloys; the two peaks near 217°C correspond to the Sn–Cu–Ag ternary eutectic melting reaction and those at 223–225°C/224–226°C are for Sn–Cu binary melting. The 0.2% proof stress and tensile strength decrease with the addition of 0.1 mass%Ag and then gradually increase up to 1 mass%Ag. Even with 1% Ag, they are less than the values for a Sn–0.7Cu binary alloy. In contrast, elongation increases with increasing Ag content up to 1%. Thus, the addition of Ag to Sn–0.7Cu alloy can effectively improve its ductility. The strain rate dependence of 0.2% proof stress of Sn–0.7Cu–0.5Ag is similar to that of Sn–Ag eutectic alloy but is different from that of Sn–Cu eutectic alloy. A small amount of added Ag results in a change of the deformation mechanism of Sn–Cu alloy.
Le opinioni sul lavoro imprenditoriale: una ricerca su studenti e genitori

La scelta occupazionale e i comportamenti lavorativi dipendono da un insieme di fattori sia individuali che contestuali. I giovani intraprendono carriere di lavoro dipendente, autonomo o imprenditoriale sulla base delle proprie aspirazioni ma anche delle opinioni sul lavoro che si formano prevalentemente all’interno del contesto familiare e socio-economico di appartenenza. La presente ricerca mette in evidenza la coerenza degli atteggiamenti e delle opinioni sull’imprenditore e sul lavoro imprenditoriale di un gruppo di 287 giovani diplomandi e dei loro rispettivi 542 genitori. Tale coerenza si rileva sia nelle opinioni che negli atteggiamenti che i giovani esprimono verso il lavoro autonomo e imprenditoriale e porta a ipotizzare che le opinioni e gli atteggiamenti verso il lavoro si formino in prevalenza nella cultura familiare e del contesto sociale di riferimento.
The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults: a Cochrane Systematic Review with trial sequential analysis

Acute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all‐cause mortality. We performed several subgroup and sensitivity analyses to assess the effect of inhaled nitric oxide. There was no statistically significant effect of inhaled nitric oxide on longest follow‐up mortality (inhaled nitric oxide group 250/654 deaths (38.2%) vs. control group 221/589 deaths (37.5%; relative risk (95% CI) 1.04 (0.9–1.19)). We found a significant improvement in PaO2/FIO2 ratio at 24 h (mean difference (95% CI) 15.91 (8.25–23.56)), but not at 48 h or 72 h, while four trials indicated improved oxygenation in the inhaled nitric oxide group at 96 h (mean difference (95% CI) 14.51 (3.64–25.38)). There were no statistically significant differences in ventilator‐free days, duration of mechanical ventilation, resolution of multi‐organ failure, quality of life, length of stay in intensive care unit or hospital, cost‐benefit analysis and methaemoglobin and nitrogen dioxide levels. There was an increased risk of renal impairment (risk ratio (95% CI) 1.59 (1.17–2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may induce renal impairment.
Opium withdrawal and some blood biochemical factors in addicts' individuals

Objective: One of the common misinterpretation be- liefs in some societies (especially eastern communities) is the using of opium can reduce serum glucose and lipids. Opium is a derivative from a plant family called Papaveracea and contains almost 80 types of alkaloids. Drug addiction causes physiological dependency and its withdrawal lead to some disorders. The aim of this study was to determine the effects of opium consumption and its withdrawal on some blood biochemical factors in addicted people. Methods: We enrolled fifty-six opium addicted people according to the especial criteria to this study. Biochemical blood parameter levels such as fasting blood sugar (FBS), urea, Creatinine (Cr), Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline phosphatase (ALP) enzymes levels were measured and urine analysis was also performed before and 3 months after withdrawal. Data were analyzed by using SPSS software version 18 and a P < 0.05 was considered as significant. Results: our finding showed that opium withdrawal reduces FBS and increases AST but these changes were not significant. Nevertheless opium withdrawal significantly increased blood urea level (P < 0.0001). We didn’t find any significant difference in Cr, ALP, AST and Urea specific gravity (SG). Conclusion: According to the results of the current study we can concluded that opium increases FBS, which is in contrast to the most previous studies and withdrawal has opposite effects.
Preparing Clinical Pharmacy Scientists for Careers in Clinical/Translational Research: Can We Meet the Challenge?

Developing clinical pharmacists' research skills and their ability to compete for extramural funding is an important component of the American College of Clinical Pharmacy's (ACCP) vision for pharmacists to play a prominent role in generating the new knowledge used to guide patient pharmacotherapy. Given the recent emphasis on clinical/translational research at the National Institutes of Health (NIH) and the key role of drug therapy in the management of many diseases, there is an unprecedented opportunity for the profession to contribute to this enterprise. A crucial question facing the profession is whether we can generate enough appropriately trained scientists to take advantage of these opportunities to generate the new knowledge to advance drug therapy. Since the 2009 publication of the ACCP Research Affairs Committee editorial recommending the Ph.D. degree (as opposed to fellowship training) as the optimal method for preparing pharmacists as clinical/translational scientists, significant changes have occurred in the economic, professional, political, and research environments. As a result, the 2012 ACCP Research Affairs Committee was charged with reexamining the college's position on training clinical pharmacy scientists in the context of these substantial environmental changes. In this commentary, the potential impact of these changes on opportunities for pharmacists in clinical/translational research are discussed as are strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. Failure of our profession to take advantage of these opportunities risks our ability to contribute substantively to the biomedical research enterprise and ultimately improve the pharmacotherapy of our patients.
Taste sensitivity to phenylthiocarbamide in Turkey.

The ability to taste phenylthiocarbamide (PTC) has been investigated in a group of 366 Turkish medical students. The incidence of non-tasters was 7.78% (t gene frequency = .279) and 12.9% (t gene frequency = .359) for females and males respectively. The frequency of non-tasters for both sexes combined was 11.2% (t gene frequency = .335).
Using multi-agent systems to explore information sharing in arborescent supply chain networks

The impact of information sharing in supply chains has been traditionally restricted to classical serially-linked echelon structures, an assumption which does not often correspond to reality. In this paper, the potential benefits of information sharing in a divergent supply chain are analyzed. To do so, a Java-based multi-agent simulation is developed to compare the performance of a serial supply chain with that of a divergent supply chain, both under non information sharing and information sharing conditions. Results show that the traditional (i.e. without information exchange) arborescent supply chain structure performs worse than the serial supply chain when the market demand suffers violent and unexpected changes. On the contrary, a significant reduction of the discrepancy between both SCNs can be noted when implementing information sharing strategies.
Hepatic Temporal Gene Expression Profiling in Helicobacter hepaticus-Infected A/JCr Mice

Helicobacter hepaticus infection of A/JCr mice is a model of infectious liver cancer. We monitored hepatic global gene expression profiles in H. hepaticus infected and control male A/JCr mice at 3 months, 6 months, and 1 year of age using an Affymetrix-based oligonucleotide microarray platform on the premise that a specific genetic expression signature at isolated time points would be indicative of disease status. Model based expression index comparisons generated by dChip yielded consistent profiles of differential gene expression for H. hepaticus infected male mice with progressive liver disease versus uninfected control mice within each age group. Linear discriminant analysis and principal component analysis allowed segregation of mice based on combined age and lesion status, or age alone. Up-regulation of putative tumor markers correlated with advancing hepatocellular dysplasia. Transcriptionally down-regulated genes in mice with liver lesions included those related to peroxisome proliferator, fatty acid, and steroid metabolism pathways. In conclusion, transcriptional profiling of hepatic genes documented gene expression signatures in the livers of H. hepaticus infected male A/JCr mice with chronic progressive hepatitis and preneoplastic liver lesions, complemented the histopathological diagnosis, and suggested molecular targets for the monitoring and intervention of disease progression prior to the onset of hepatocellular neoplasia.
Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy

ABSTRACT A major limitation of highly active antiretroviral therapy is that it fails to eradicate human immunodeficiency virus (HIV) infection due to its limited effects on viral reservoirs carrying replication-competent HIV, including monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting HIV-infected M/M may prove useful in the clinical management of HIV-infected patients. In previous studies, we have shown that administration of fludarabine-loaded red blood cells (RBC) in vitro selectively induces cell death in HIV-infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of this novel therapeutic strategy, we treated six naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or PMPA in association with fludarabine-loaded RBC. The rationale of this treatment was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is suppressing viral replication taking place in activated CD4+ T cells. In vivo administration of fludarabine-loaded RBC was well tolerated and did not induce any discernible side effect. Importantly, addition of fludarabine-loaded RBC to PMPA delayed the rebound of viral replication after suspension of therapy, thus suggesting a reduction in the size of SIV reservoirs. While administrations of fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell compartments, we observed, in chronically SIV-infected SMs, a selective depletion of M/M expressing pSTAT1. This study suggests that therapeutic strategies based on the administration of fludarabine-loaded RBC may be further explored as interventions aimed at reducing the size of the M/M reservoirs during chronic HIV infection.
Multilocus phylogeographic assessment of the California Mountain Kingsnake (Lampropeltis zonata) suggests alternative patterns of diversification for the California Floristic Province

Phylogeographic inference can determine the timing of population divergence, historical demographic processes, patterns of migration, and when extended to multiple species, the history of communities. Single‐locus analyses can mislead interpretations of the evolutionary history of taxa and comparative analyses. It is therefore important to revisit previous single‐locus phylogeographic studies, particularly those that have been used to propose general patterns for regional biotas and the processes responsible for generating inferred patterns. Here, we employ a multilocus statistical approach to re‐examine the phylogeography of Lampropeltis zonata. Using nonparametic and Bayesian species delimitation, we determined that there are two well‐supported species within L. zonata. Ecological niche modelling supports the delimitation of these taxa, suggesting that the two species inhabit distinct climatic environments. Gene flow between the two taxa is low and appears to occur unidirectionally. Further, our data suggest that gene flow was mediated by females, a rare pattern in snakes. In contrast to previous analyses, we determined that the divergence between the two lineages occurred in the late Pliocene (c. 2.07 Ma). Spatially and temporally, the divergence of these lineages is associated with the inundation of central California by the Monterey Bay. The effective population sizes of the two species appear to have been unaffected by Pleistocene glaciation. Our increased sampling of loci for L. zonata, combined with previously published multilocus analyses of other sympatric species, suggests that previous conclusions reached by comparative phylogeographic studies conducted within the California Floristic Province should be reassessed.
Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy

Background: Reduction in peripheral blood lymphocytes is an expected pharmacodynamic outcome of fingolimod therapy. Objective: The objective of this article is to evaluate lymphocyte dynamics during and after fingolimod therapy and assess the relationship between lymphocyte counts and infections. Methods: Lymphocyte counts and their relationship with infections were evaluated in three multiple sclerosis (MS) populations: (Group A) FREEDOMS phase 3 core study group (n = 1272); (Group B) All Studies group (one phase 2 and two phase 3 studies, plus their extensions; n = 2315); and (Group C) Follow-up group (after fingolimod discontinuation; n = 538). Results: Administration of fingolimod 0.5 mg led to reductions in lymphocyte counts to a steady-state of 24%–30% of baseline values within two weeks, which remained stable while on therapy. Following fingolimod discontinuation, average counts exceeded the lower limit of normal range within six to eight weeks, and were 80% of baseline values by three months. In Group A, infection rates per patient-year were 1.4 with placebo and 1.0 in fingolimod-treated patients who had the lowest lymphocyte counts (< 0.2 × 109/l). No evidence was seen for an increase in serious or opportunistic infections. Conclusions: Fingolimod induces a rapid and reversible reduction in lymphocyte counts without an increase in infections relative to placebo. Because fingolimod reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be utilized to evaluate the lymphocyte subset status of a patient.
Intestinal stem cells – types and markers

Intestinal epithelium is a rapidly cycling tissue, always renewing every 4–5 days under normal conditions, which is maintained by intestinal stem cells (ISCs). Using the fluorescence labelling trace, ISCs can be divided into two different types: active intestinal stem cells (A‐ISCs) located in bottom of the intestinal crypt and the quiescent intestinal stem cells (Q‐ISCs) in the +4 position of the crypt. There is a complex signal regulation net between the ISCs and other intestinal cells, such as Wnt and Notch pathways. ISCs have an intimate relationship with the colorectal cancer (CRC). However, a deficiency of stem cells markers severely limits research on the biological characteristics of ISCs. We have reviewed several ISCs markers, including Lgr5, PHLDA1, Bmi1 and Lrig1. These markers have widely different biological functions, but also have a close relationship with cancers, especially CRC. Our hypothesis concerns the reasons for ISCs having two distinct types and why endless ISCs markers have emerged.
Presynaptic size of associational/commissural CA3 synapses is controlled by fibroblast growth factor 22 in adult mice

Associational/commissural CA3–CA3 synapses define the recurrent CA3 network that generates the input to CA1 pyramidal neurons. We quantified the fine structure of excitatory synapses in the stratum radiatum of the CA3d area in adult wild type (WT) and fibroblast growth factor 22 knock‐out (FGF22KO) mice by using serial 3D electron microscopy. WT excitatory CA3 synapses are rather small yet range 10 fold in size. Spine size, however, was small and uniform and did not correlate with the size of the synaptic junction. To reveal mechanisms that regulate presynaptic structure, we investigated the role of FGF22, a target‐derived signal specific for the distal part of area CA3 (CA3d). In adult FGF22KO mice, postsynaptic properties of associational CA3 synapses were unaltered. Presynaptically, the number of synaptic vesicles (SVs), the bouton volume, and the number of vesicles in axonal regions (the super pool) were reduced. This concurrent decrease suggests concerted control by FGF22 of presynaptic size. This hypothesis is supported by the finding that WT presynapses in the proximal part of area CA3 (CA3p) that do not receive FGF22 signaling in WT mice were smaller than presynapses in CA3d in WT but of comparable size in CA3d of FGF22KO mice. Docked SV density was decreased in CA1, CA3d, and CA3p in FGF22KO mice. Because CA1 and CA3p are not directly affected by the loss of FGF22, the smaller docked SV density may be an adaptation to activity changes in the CA3 network. Thus, docked SV density potentially is a long‐term regulator for the synaptic release probability and/or the strength of short‐term depression in vivo. © 2015 Wiley Periodicals, Inc.