Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo and In Vitro Analysis of Factor Binding Sites in Jaagsiekte Sheep Retrovirus Long Terminal Repeat Enhancer Sequences: Roles of HNF-3, NF-I, and C/EBP for Activity in Lung Epithelial Cells

ABSTRACT Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, a contagious lung cancer of sheep that arises from type II pneumocytes and Clara cells of the lung epithelium. Studies of the tropism of this virus have been hindered by the lack of an efficient system for viral replication in tissue culture. To map regulatory regions important for transcriptional activation, an in vivo footprinting method that couples dimethyl sulfate treatment and ligation-mediated PCR was performed in murine type II pneumocyte-derived MLE-15 cells infected with a chimeric Moloney murine leukemia virus driven by the JSRV enhancers (ΔMo+JS Mo-MuLV). In vivo footprints were found in the JSRV enhancers in two regions previously shown to be important for JSRV long terminal repeat (LTR) activity: a binding site for the lung-specific transcription factor HNF-3β and an E-box element in the distal enhancer adjacent to an NF-κB-like binding site. In addition, in vivo footprints were detected in two downstream motifs likely to bind C/EBP and NF-I. Mutational analysis of a JSRV LTR reporter construct (pJS21luc) revealed that the C/EBP binding site is critical for LTR activity, while the putative NF-I binding element is less important; elimination of these sites resulted in 70% and 40% drops in LTR activity, respectively. Electrophoretic mobility shift assays using nuclear extracts from MLE-15 murine Clara cell-derived mtCC1-2 cells with probes corresponding to the NF-I or C/EBP sites revealed several complexes. Antiserum directed against NF-IA, C/EBPα, or C/EBPβ supershifted the corresponding protein-DNA complexes, indicating that these isoforms, which are also important for the expression of several cellular lung-specific genes, may be important for JSRV expression in lung epithelial cells.
Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to first-pass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 23 factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q24) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.
Analysing the Performance Instability Correlation with Various Workflow and Cloud Parameters

Cloud is an eco-system in which virtual machine instances are starting and terminating asynchronously on user demand or automatically when the load is rapidly increased or decreased. Although this dynamic environment allows to rent computing or storage resources cheaper rather than buying them, still it does not guarantee the stable execution during a period of time as the traditional physical environment. This is emphasised even more for workflows execution, since they consist of many data and control dependencies, which cause the makespan to be instable when a workflow is being executed in different periods of time in Cloud. In this paper we analyse several parameters of workflow and the cloud environment that are expected to impact the workflow execution instability and investigate the correlation between them. The cloud parameters include the number of instances and their type, as well as the correlation with the efficient or inefficient execution of workflow parallel sections. We conduct a series of experiments, repeating each experiment by 30 test cases in order to evaluate instability for different cloud and workflow parameters. The results show a neglectful correlation between each pair of parameters, as well as the tasks and file transfers within the workflow. Oppose to the expectations, the distribution of the makespan per experiment does not always comply with the normal distribution, which is also not correlated to a particular cloud or workflow parameter.
Molecular mechanisms of glutamine action

Glutamine is the most abundant free amino acid in the body and is known to play a regulatory role in several cell specific processes including metabolism (e.g., oxidative fuel, gluconeogenic precursor, and lipogenic precursor), cell integrity (apoptosis, cell proliferation), protein synthesis, and degradation, contractile protein mass, redox potential, respiratory burst, insulin resistance, insulin secretion, and extracellular matrix (ECM) synthesis. Glutamine has been shown to regulate the expression of many genes related to metabolism, signal transduction, cell defense and repair, and to activate intracellular signaling pathways. Thus, the function of glutamine goes beyond that of a simple metabolic fuel or protein precursor as previously assumed. In this review, we have attempted to identify some of the common mechanisms underlying the regulation of glutamine dependent cellular functions. © 2005 Wiley‐Liss, Inc.
Pulsed-Field Gel Electrophoresis of Genomic Digests Demonstrates Linkages among Food, Food Handlers, and Patrons in a Food-Borne Salmonella javiana Outbreak in Massachusetts

ABSTRACT A total of 66 isolates of Salmonella javiana isolated from food, food handlers, and patrons that were epidemiologically linked to an outbreak of gastroenteritis were analyzed by pulsed-field gel electrophoresis. Analysis with restriction endonucleasesXbaI and SpeI supported the epidemiologic association and suggested a pathway of transmission among food, food handlers, and patrons.
Isolation of protoplasts, and culture and regeneration into plants in Alstroemeria

SummaryAn efficient system for the regeneration of plants from protoplasts was developed in Alstroemeria. Friable embryogenic callus (FEC) proved to be the best source for protoplast isolation and culture when compared with leaf tissue and compact embryogenic callus. Protoplast isolation was most efficient when FEC was cultured under vacuum for 5 min in an enzyme solution consisting of 4% cellulase, 0.5% Driselase and 0.2% Macerozyme, followed by culture for 12–16h in the dark at 24°C. Cell wall formation and colony formation were better in a liquid medium than on a semi-solid agarose medium. Micro-calluses were formed after 4 wk of culture. Ninety percent of the micro-calluses developed into FEC after 12wk of culture on proliferation medium. FEC cultures produced somatic embryos on a regeneration medium and half of these somatic embryos developed shoots. Protoplast-derived plants showed more somaclonal variation than vegetatively propagated control plants.
Representativeness of a National Heart Failure Quality-of-Care Registry: Comparison of OPTIMIZE-HF and Non–OPTIMIZE-HF Medicare Patients

Background—Participation in clinical registries is nonrandom, so participants may differ in important ways from nonparticipants. The extent to which findings from clinical registries can be generalized to broader populations is unclear. Methods and Results—We linked data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) registry with 100% inpatient Medicare fee-for-service claims to identify matched and unmatched patients with heart failure. We evaluated differences in baseline characteristics and mortality, all-cause readmission, and cardiovascular readmission rates. We used Cox proportional hazards models to examine relationships between registry enrollment and outcomes, controlling for baseline characteristics. There were 25 245 OPTIMIZE-HF patients in the Medicare claims data and 929 161 Medicare beneficiaries with heart failure who were not enrolled in OPTIMIZE-HF. Although hospital characteristics differed, patient demographic characteristics and comorbid conditions were similar. In-hospital mortality for OPTIMIZE-HF and non–OPTIMIZE-HF patients was not significantly different (4.7% versus 4.5%; P=0.37); however, OPTIMIZE-HF patients had slightly higher 30-day (11.9% versus 11.2%; P<0.001) and 1-year unadjusted mortality (37.2% versus 35.7%; P<0.001). Controlling for other variables, OPTIMIZE-HF patients were similar to non–OPTIMIZE-HF patients for the hazard of mortality (hazard ratio, 1.02; 95% confidence interval, 0.98 to 1.06). There were small but significant decreases in all-cause (hazard ratio, 0.94; 95% CI, 0.92 to 0.97) and cardiovascular readmission (hazard ratio, 0.94; 95% CI, 0.91 to 0.98). Conclusions—Characteristics and outcomes of Medicare beneficiaries enrolled in OPTIMIZE-HF are similar to the broader Medicare population with heart failure, suggesting that findings from this clinical registry may be generalized.
Title and Subtitle The Use of Major Risk Factors for Computer-Based Distinction of Diabetic Patients with Ischemic Stroke and Without Stroke Contract Number Grant Number Program Element Number

This study proposes a computer-based decision support system to investigate the distinctive factors of diabetes mellitus (DM) with ischemic (non-embolic type) stroke and without stroke. Database consists of a total of 16 features that are collected from 44 diabetic patients. Features include age, gender, duration of diabetes, cholesterol, higher density lipoprotein (HDL), triglicerit levels, neuropathy, nephropathy, retinopathy, peripheral vascular disease (PVD), myocard infarction (MI) rate, glucose levels, taking medicine, blood pressure. Metric and non-metric features are distinguished. First, the statistics, mean and covariance, of data are estimated and the correlated components are observed. Second, principal component analysis (PCA) is used for major components. Finally, decision making approaches, k-nearest neighbor (k-NN) and MLP, are employed for classification of all the components and major components case. Macrovascular changes emerged as principal distinctive factors of ischemic-stroke in DM. Microvascular changes were generally ineffective discriminators. Recommendations were made according to the rules of evidence-based medicine. Briefly, this case study supports theories of stroke in DM and also concludes that the use of intelligent data analysis improves personalized prevention.
Renal fibrogenesis and platinum compounds in a rat model: a novel Pt (II) complex vs. cisplatin.

BACKGROUND/AIM A new platinum compound, (Pt(O,O'-acac)(γ-acac)(DMS)) (PtAcacDMS), has been shown to possess higher cytotoxic activity than cisplatin on several cancer and chemoresistant cell lines. The aim of the present study was to compare the nephrotoxic effects - particularly renal fibrogenesis- of PtAcacDMS and cisplatin in rats after the subcutaneous administration of a single dose (5 mg/Kg b.w., s.c.) of either compound to ten-day-old rats. MATERIALS AND METHODS Control and treated rats were killed 1 day (PD11), 7 days (PD17), 21 days (PD31) and 40 days (PD50) after the injection. Kidneys were processed for light and electron microscopy, and platinum determination. Antibodies against E-cadherin (E-cad), vimentin (VIM) and α-smooth muscle actin (αSMA) were used to identify epithelial and mesenchymal cells. RESULTS AND CONCLUSION Cisplatin produced progressive cortical fibrotic lesions displaying a variable number of VIM-positive tubules and interstitial αSMA-positive cells around. By contrast, PtAcacDMS induced a minimal number of histopathological changes, which declined in the adult samples, while the renal platinum content was generally higher after PtAcacDMS than after cisplatin. The present experimental model was proven suitable to investigate the occurrence of epithelial-mesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.
Transplantation of Human Umbilical Cord Blood Mesenchymal Stem Cells Improves Survival Rates in a Rat Model of Acute Hepatic Necrosis

Introduction:Stem cell-based therapies are emerging as important and promising methods in the treatment of end-stage liver disease. This study is aimed to evaluate the effects of human umbilical cord blood mesenchymal stem cell (HUCBMSC) transplantation in acute hepatic necrosis (AHN). Methods:Green fluorescent protein (GFP)-labeled HUCBMSCs were injected into the liver of rats in which AHN was induced by carbon tetrachloride, and the migration of these cells in liver slices was evaluated from 48 hours to 4 weeks post-transplantation. The transdifferentiation status of the HUCBMSCs was evaluated using immunohistochemistry and real-time reverse transcription-polymerase chain reaction, and survival rates were statistically analyzed. Results:Dispersed GFP fluorescence was observed along the portal area 48 hours after transplantation. One week post-transplantation, GFP-positive cells were found in necrotic liver areas, and GFP-positive cells persisted after 4 weeks. Immunohistochemistry and real-time polymerase chain reaction analysis showed that transplanted HUCBMSCs expressed several human liver tissue-specific markers in rats with AHN. Statistical analysis revealed that rats with AHN that were transplanted with HUCBMSCs had significantly lower death rates after 48 hours than those receiving no HUCBMSCs. Conclusion:HUCBMSC transplantation can significantly improve the survival of rats with AHN. The underlying mechanisms involved may include the transdifferentiation of HUCBMSCs into hepatocyte-like cells and targeted migration of these cells to liver lesion sites.
Sequence of the Genome of SalmonellaBacteriophage P22

ABSTRACT The sequence of the nonredundant region of the Salmonella enterica serovar Typhimurium temperate, serotype-converting bacteriophage P22 has been completed. The genome is 41,724 bp with an overall moles percent GC content of 47.1%. Numerous examples of potential integration host factor and C1-binding sites were identified in the sequence. In addition, five potential rho-independent terminators were discovered. Sixty-five genes were identified and annotated. While many of these had been described previously, we have added several new ones, including the genes involved in serotype conversion and late control. Two of the serotype conversion gene products show considerable sequence relatedness to GtrA and -B from Shigella phages SfII, SfV, and SfX. We have cloned the serotype-converting cassette (gtrABC) and demonstrated that it results in Salmonella serovar Typhimurium LT2 cells which express antigen O1. Many of the putative proteins show sequence relatedness to proteins from a great variety of other phages, supporting the hypothesis that this phage has evolved through the recombinational exchange of genetic information with other viruses.
Precise missense and silent point mutations are fixed in the genomes of poliovirus mutants from persistently infected cells

Poliovirus mutants selected in persistently infected human neuroblastoma cells have a modified cell tropism and can establish a secondary persistent infection in nonneural cells, such as HEp-2c cells. Nucleotide sequence analysis revealed that the genome of a persistent mutant, S11, differed from that of the parental lytic Sabin 1 poliovirus strain by 31 point mutations. Three mutations occurred in the noncoding regions. The other mutations resulted in 12 amino acid substitutions; 1 substitution occurred in a nonstructural protein (3A), while the other 11 substitutions were clustered in the capsid proteins VP2 and VP1. The same missense mutations, as well as many of the silent mutations that we observed in mutant S11, also accumulated in the genome of two other persistent viruses isolated from independent infections. This finding indicates that both missense and silent mutations are selected during the persistent infection of neuroblastoma cells and suggests that the secondary structure of RNA in the coding region may play a role in viral infection.
Adaptive Interventions in Child and Adolescent Mental Health

The treatment or prevention of child and adolescent mental health (CAMH) disorders often requires an individualized, sequential approach to intervention, whereby treatments (or prevention efforts) are adapted over time based on the youth’s evolving status (e.g., early response, adherence). Adaptive interventions are intended to provide a replicable guide for the provision of individualized sequences of interventions in actual clinical practice. Recently, there has been great interest in the development of adaptive intervenions by investigators working in CAMH. The development of such replicable, real-world, individualized sequences of decision rules to guide the treatment or prevention of CAMH disorders represents an important “next step” in interventions research. The primary purpose of this special issue is to showcase some recent work on the science of adaptive interventions in CAMH. In this overview article, we review why individualized sequences of interventions are needed in CAMH, provide an introduction to adaptive interventions, briefly describe each of the articles included in this special issue, and describe some exciting areas of ongoing and future research. A hopeful outcome of this special issue is that it encourages other researchers in CAMH to pursue creative and significant research on adaptive interventions.
REMODELLING UNIVERSITY GOVERNANCE IN PUBLIC UNIVERSITIES TO RESPOND TO THE DUAL CHALLENGES OF ACADEMIC RESEARCH AND COMMERCIALIZATION

Using an in-depth case study, this paper examines how the governance of a public university responds to the dual challenges of academic research and commercialization. Our findings indicate that the stakeholder model of institutional governance for academic research strongly underpinned by new public management ideologies conflicted with the research commercialization mission dominated by a profit seeking objective. To be governed responsibly, commercialization requires some degree of corporatization, and the corporate governance model seems to offer many advantages to public universities. The study demonstrated that the best way forward for public universities may be to adopt „dual‟ stakeholder and corporate governance models and utilize complementary and collaborative governance strategies to meet the challenges of academic research development and commercialization.
Frontal Cerebral Perfusion Dysfunction in Elderly Late-Onset Major Depression Assessed by 99MTC-HMPAO Spect

Baseline regional cerebral blood flow of thirty unmedicated late-onset unipolar major depressed patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls was imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. To avoid errors of diagnosis--in particular, confusion between major depression and organic cognitive impairment--only treatment responders were included in the final sample. Statistically significant differences were observed in both left and right anterior frontal regions, with reduced uptake in depressed patients; these differences were more pronounced in the left hemisphere. Among patients, there was no correlation between regional cerebral blood flow and the severity of baseline symptoms. Our results support the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally involved in elderly unipolar major depression, particularly in the late-onset subgroup.
When workplace ostracism leads to burnout: the roles of job self-determination and future time orientation

Abstract Given that ostracism is a common occurrence in the workplace, scholars and practitioners alike have identified its range of negative effects. This study aims to examine the association between workplace ostracism and burnout level as well as the moderating effects of job self-determination and employees’ future time orientation, using a survey questionnaire. This was completed by a total of 248 employees from a hotel group. We hypothesized that: (a) workplace ostracism was positively associated with burnout; (b) this positive relationship was contingent upon job self-determination such that the relationship was weaker for higher, rather than lower, job self-determination; and (c) the positive relationship was also contingent upon employees’ future time orientation such that the relationship was weaker for employees who have higher, rather than lower future time orientation. Results confirm all three hypotheses.
WIDER Working Paper 2017/32 Party system institutionalization and reliance on personal income tax

: This paper explores the effect of party system institutionalization on the reliance of tax systems on the personal income tax. As a first step, the paper re-examines the relationship between party system institutionalization and taxation patterns employing the recently launched Government Revenue Dataset. In a second step, the relationship in tested in different country subgroups, based on governance structures, availability of alternative sources of revenue, and geographical location. The main results remain fairly robust using the Government Revenue Dataset: where bureaucratic capacity is low, the effect of party system institutionalization is large and highly significant, whereas where bureaucratic capacity is high this effect disappears. Furthermore, the analysis using the Government Revenue Dataset provides additional insights into the large variance between groups of countries. The results indicate that the effect is particularly strong and robust in democratic regimes and where alternative sources of revenue are abundant. Overall, the findings can be considered to provide additional support for two claims: first, that taxation is best understood as a problem of credible commitment, particularly where bureaucratic capacity tends to be limited, and second, that institutionalized collective actors, such as political parties, play a key role in solving this problem.
Spillovers from United States Monetary Policy on Emerging Markets

The impact of monetary policy in large advanced countries on emerging market economies— dubbed spillovers—is hotly debated in global and national policy circles. When the U.S. resorted to unconventional monetary policy, spillovers on asset prices and capital flows were significant, though remained smaller in countries with better fundamentals. This was not because monetary policy shocks changed (in size, sign or impact on stance). In fact, the traditional signaling channel of monetary policy continued to play the leading role in transmitting shocks, relative to other channels, affecting longer-term bond yields. Instead, we find that larger spillovers stem more from structural factors, such as the use of new instruments (asset purchases). We obtain these results by developing a new methodology to extract, separate, and interpret U.S. monetary policy shocks. JEL Classification Numbers:E4, E5, F3