Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of Gag-Specific CD8+ T-Cell Function in Mucosal and Systemic Compartments of Simian Immunodeficiency Virus mac251- and Simian-Human Immunodeficiency Virus KU2-Infected Macaques

ABSTRACT The identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8+ T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8+ T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8+ and CD4+ T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIVmac251 and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4+ T cells. The frequency of the Gag 181 (p11C, C→M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8+ T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIVmac251 that were progressing to disease. Overall, the functionality of CD8+ tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIVmac251-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8+ T-cell function.
A few seedlings of research

Graduate students sometimes ask. or fail to ask: "How does one do research in mathematical statistics? It is a reasonable question because the fruits of research, lectures and published papers bear little witness to the ways and means of their germination and ripening. How did that author ever come to state this theorem so aptly, to snatch this neat proof from the thin air: surely it never sprang fully armed like Pallas Athene from the brow of Zeus? No, indeed not. rest reassured. But still the question is a hard one. The answer depends much upon the field of statistics. and even more upon the tastes and skills anld prejudices of the researcher. The only means of appraisal is case study. and no author has the data for any case study but his own. Without more ado or apology. I shall speak of some of my own work and how it came about: and it will have to be a personal story. with all natural drawbacks, and of course to get a proper view of things at large, you will, nay must, look elsewhere for other accounts by other men of their own work. The Committee on Support of Research in the Mathematical Sciences, in the introduction to a volume of essays [21]. wrote:
oncordance of mother – daughter diurnal cortisol production : nderstanding the intergenerational transmission of risk for epression

A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across 2 days from mothers with (remitted; RMD) and without (CTL) ntergenerational transmission of risk PA axis
Shedding light on prion disease

ABSTRACT Proteolytic processing regulates key processes in health and disease. The cellular prion protein (PrPC) is subject to at least 3 cleavage events, α-cleavage, β-cleavage and shedding. In contrast to α- and β-cleavage where there is an ongoing controversy on the identity of relevant proteases, the metalloprotease ADAM10 represents the only relevant PrP sheddase. Here we focus on the roles that ADAM10-mediated shedding of PrPC and its pathogenic isoform (PrPSc) might play in regulating their physiological and pathogenic functions, respectively. As revealed by our recent study using conditional ADAM10 knockout mice (Altmeppen et al., 2015), shedding of PrP seems to be involved in key processes of prion diseases. These aspects and several open questions arising from them are discussed. Increased knowledge on this topic can shed new light on prion diseases and other neurodegenerative conditions as well.
The Relationship between Transparency & Disclosure and Firm Performance in the ISE: Does IFRS Adoption Make a Difference?

There has been a proliferation of firm-specific research on the effect of compliance with high corporate governance (CG) standards on the cost of capital and financial performance. As a result of the observed positive link and the recent CG and accounting scandals, most countries are upgrading their laws and regulations to include compliance with best CG and transparency and disclosure (T&D) standards and firms are voluntarily having their CG and T&D practices rated, to signal their quality and to improve their current practices. In this study, we use a database of T&D scores in three categories for 52 large and liquid Turkish firms, previously created by S&P and Sabanci University CG Forum researchers. The creation of this database and the T&D scores are described in detail in S&P’s newsletter dated 6/6/2005 and in Aksu and Kosedag, 2005 which compares the T&D scores of Turkish public firms with those in other countries where the same survey had been conducted by S&P and also explores the firm-specific determinants of the T&D scores. Using the same database, we first associate the T&D scores of 52 public Turkish firms with accounting based (return on assets and return on equity) and market based (excess returns) performance measures. We investigate the relationship for the overall T&D scores and the scores in the three sub-categories of T&D. The results show significant differences in financial performance of sample firms in the two extreme T&D score quartiles while the relationship is not strong in multivariate tests run with the addition of control variables. Second, we use early voluntary adoption of IFRS in 2003 as an observable indicator of and commitment to better disclosure and transparency, and test if the T&D scores themselves and their relationship with performance are higher in these early adaptors. Finally, we create a parsimonious Commitment to Better Disclosure (CBD) Index which includes early voluntary adoption of IFRS, existence of a CG Charter, and presentation of the annual report on the company website as the only three attributes out of our 106 attribute T&D index. As of 2003, these attributes of good T&D were all voluntary and costly steps taken by the sample firms and, as such, indicate a strong commitment to transparency and full disclosure. Observing the high correlation between the two indices, we repeat our tests of the relationship between firm performance and T&D scores by using this new CBD index. The results support the previous studies that use factor analysis to come up with a few significant variables rather than using an index with many heterogeneous, perhaps offsetting, attributes. The study should be of interest to T&D researchers, managers, analysts, boards, and especially to international and local policy makers and regulators at a time when debate on convergence to IFRS has become intense.
Asymptotic trust algorithm: extension for reputation systems in online auctions

Online auctions have become a big business and the number of auction site users is growing rapidly. These virtual mar- ketplaces give traders a lot of opportunities to find a contracting party. However, lack of physical contact between users decreases the degree of trust. Auction portals require an efficient mechanism for building trust between participants, whereas most of them provide simple participation counts for reputation rating. Moreover, a single opinion has virtually no effect on a big online store that already has many reputation points, so buyers are very hesitant to give negative feedback for fear of retaliation. Consequently, almost no negative feedback is provided 1 . In this paper we introduce a new trust system called Asymp- totic Trust Algorithm (ATA) which prevents many fraud attempts and still is both simple and easy to understand for most users. Our new method can be applied in addition to the participation counts systems currently used by Allegro, eBay and most of other online auction sites because it does not require any additional information other than positive, negative or neutral feedback on transactions. Most importantly, ATA encourages users to submit unbiased com- ments, regardless of the number of previous transactions.
Exponential dynamic output feedback controller design for stochastic neutral systems with distributed delays

This paper investigates the problem of stochastic stabilization for stochastic neutral systems with distributed delays. The time delay is assumed to appear in both the state and measurement equations. Attention is focused on the design of linear dynamic output feedback controllers such that the resulting closed-loop system is exponentially mean-square stable. A sufficient condition for the solvability of the problem is obtained in terms of a linear matrix inequality (LMI). When this LMI is feasible, an explicit expression of a desired dynamic output feedback controller is also given. The theory developed in this paper is demonstrated via a numerical example
Co-Occurrence of 12-Month Alcohol and Drug Use Disorders and Personality Disorders in the United States

Background Very little information is available on the co-occurrence of different personality disorders (PDs) and alcohol and drug use disorders in the U.S. population. Objective To present national data on sex differences in the co-occurrence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM–IV) alcohol and drug use disorders and 7 of the 10 DSM–IV PDs. Design Face-to-face interviews conducted in the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Setting The United States and the District of Columbia, including Alaska and Hawaii. Participants Household and group-quarters residents, age 18 and older. Results Among individuals with a current alcohol use disorder, 28.6 percent (95 percent confidence interval [CI], 26.7–30.6) had at least one PD, whereas 47.7 percent (95 percent CI, 43.9–51.6) of those with a current drug use disorder had at least one PD. Further, 16.4 percent (95 percent CI, 15.1–17.6) of individuals with at least one PD had a current alcohol use disorder, and 6.5 percent (95 percent CI, 5.7–7.3) had a current drug use disorder. Associations between PDs and alcohol and drug use disorders were overwhelmingly positive and significant (P < .05). Overall, alcohol use disorders were most strongly related to antisocial (odds ratio [OR], 4.8; 95 percent CI, 4.1–5.6), histrionic (OR, 4.7; 95 percent CI 3.8–5.8), and dependent (OR, 3.0; 95 percent CI, 1.9–4.8) PDs. Drug use disorders also were more highly associated with antisocial (OR, 11.8; 95 percent CI, 9.7–14.3), histrionic (OR, 8.0; 95 percent CI, 6.0–10.7), and dependent (OR, 11.6; 95 percent CI, 7.1–19.1) PDs. Associations between obsessive-compulsive, histrionic, schizoid, and antisocial PDs and specific alcohol and drug use disorders were significantly stronger (P < .04) among women than men, whereas the association between dependent PD and drug dependence was significantly greater (P < .04) among men than women. Conclusions The co-occurrence of PDs with alcohol and drug use disorders is pervasive in the U.S. population. Results highlight the need for further research on the underlying structure of these disorders and the treatment implications of these disorders when comorbid.
Emotional dissonance and the information technology professional

The information technology professional is regularly expected to work with colleagues in both IT and other areas of the organization. During these interactions, the IT employee is expected to conform to occupational or organizational norms regarding the display of emotion. How do these display norms affect the IT professional? This study examines an IT professional's emotional dissonance, the conflict between norms of emotional display and an employee's felt emotion. Emotional dissonance is studied as a factor of IT professionals' work exhaustion, job satisfaction, and turnover intention, modeled as an extension to the work of Moore (2000a). The results indicate emotional dissonance predicts work exhaustion better than do perceived workload, role conflict, or role ambiguity, constructs which have long been associated with work exhaustion. Job satisfaction is influenced directly by role ambiguity and work exhaustion. In turn, job satisfaction influences employee turnover intention. We discuss implications of these findings for both IT management and future research.
Extra‐pair fertilizations contribute to selection on secondary male ornamentation in a socially monogamous passerine

Despite considerable research effort, it remains unclear whether extra‐pair fertilizations (EPF) drive the evolution of male secondary ornamentation in socially monogamous systems. In this study, we test the hypothesis that EPF contribute to the evolution or maintenance of male feather ornamentation in a sexually dichromatic passerine, the Scarlet Rosefinch, Carpodacus erythrinus. We show that the colouration of ornamental breast feathers is a good predictor of basic sources of variation in male annual reproductive output in rosefinches and that the annual realized reproductive success of males is positively associated with measures of ornamental colouration only when gains and losses because of EPF are considered. The results indicate that EPF in rosefinches may rely on absolute (good genes) rather than self referential (genetic complementarity) criteria of mate choice. Our study corroborates the potentially important role of EPF in the evolution and/or maintenance of elaborate male ornaments in socially monogamous taxa.
Percutaneous irreversible electroporation (IRE) of hepatic malignant tumours: contrast-enhanced ultrasound (CEUS) findings.

PURPOSE The aim of this study is to describe the image findings of contrast-enhanced ultrasound (CEUS) after irreversible electroporation (IRE), and to assess its usefulness in relation to the evaluation of the ablation status using a dynamic recording of the microvascularisation. MATERIAL AND METHOD In this prospectively designed study, a percutaneous IRE was performed for the treatment of malignant hepatic lesions in a total of 15 patients following the interdisciplinary diagnosis. The lesions were documented using CEUS before, immediately after and 20 minutes after the ablation. The acquired CEUS image data was subsequently independently retrospectively evaluated by 2 experienced radiologists and assessed in relation to microvascularisation using a 5 point scale. RESULTS Using CEUS, a significant reduction in the microcirculation of the lesions, both centrally and marginally, could be detected following IRE (p < 0.001 and p < 0.001). The mean evaluation of the central microcirculation was reduced from 3.13 ± 1.38 to 0.47 ± 0.64 (p < 0.01). For the peripheral area of the lesion and the ablation margin, there was a reduction of 3.37 ± 1.13 to 1.57 ± 0.46 (p = 0.001). There was no significant reduction in the macrocirculation. CONCLUSION Within the framework of this study, it could be demonstrated that, in the course of IRE, a rapid significant reduction of the microcirculation in the ablation area occurred.
A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage response independent of telomere length in mice

Telomeres are nucleoprotein structures that cap the ends of chromosomes, protecting them from exonucleases and distinguishing them from double-stranded breaks. Their integrity is maintained by telomerase, an enzyme consisting of a reverse transcriptase, TERT and an RNA template, TERC, and other components, including the pseudouridine synthase, dyskerin, the product of the DKC1 gene. When telomeres become critically short, a p53-dependent pathway causing cell cycle arrest is induced that can lead to senescence, apoptosis, or, rarely to genomic instability and transformation. The same pathway is induced in response to DNA damage. DKC1 mutations in the disease dyskeratosis congenita are thought to act via this mechanism, causing growth defects in proliferative tissues through telomere shortening. Here, we show that pathogenic mutations in mouse Dkc1 cause a growth disadvantage and an enhanced DNA damage response in the context of telomeres of normal length. We show by genetic experiments that the growth disadvantage, detected by disparities in X-inactivation patterns in female heterozygotes, depends on telomerase. Hemizygous male mutant cells showed a strikingly enhanced DNA damage response via the ATM/p53 pathway after treatment with etoposide with a significant number of DNA damage foci colocalizing with telomeres in cytological preparations. We conclude that dyskerin mutations cause slow growth independently of telomere shortening and that this slow growth is the result of the induction of DNA damage. Thus, dyskerin interacts with telomerase and affects telomere maintenance independently of telomere length.
Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection

In experimental Chagas’ disease, lymphocytes from mice infected with Trypanosoma cruzi show increased apoptosis in vivo and in vitro. Treatment with a pan‐caspase blocker peptide inhibited expression of the active form of effector caspase‐3 in vitro and rescued both B and T cells from cell death. Injection of the caspase inhibitor benzyloxycarbonyl‐Val‐Ala‐Asp(OMe)‐fluoromethyl ketone, but not a control peptide, reduced parasitemia and lymphocyte apoptosis in T. cruzi‐infected mice. Moreover, treatment with caspase inhibitor throughout acute infection increased the absolute numbers of B and T cells in the spleen and lymph nodes, without affecting cell infiltrates in the heart. Following treatment, we found increased accumulation of memory/activated CD4 and CD8 T cells, and secretion of IFN‐γ by splenocytes stimulated with T. cruzi antigens. Caspase inhibition in the course of infection reduced the intracellular load of parasites in peritoneal macrophages, and increased the production of TNF‐α and nitric oxide upon activation in vitro. Our results indicate that inhibition of caspases with a pan‐caspase blocker peptide improves protective type‐1 immune responses to T. cruzi infection. We suggest that mechanisms of apoptosis are potential therapeutic targets in Chagas’ disease.
GSTP1 and MDR1 Genotypes and Central Nervous System Relapse in Childhood Acute Lymphoblastic Leukemia

The probability of event-free survival of childhood acute lymphoblastic leukemia (ALL) approaches 80% or more with the use of modern multiagent chemotherapeutic regimens. One major contribution to this success has been reduction of the rate of central nervous system (CNS) relapses to less than 5%. However, heterogeneity is observed with regard to the incidence of CNS relapse in homogenously treated patient populations. One potential explanation for this heterogeneity is variation in the genetic background of these populations. Glutathione S-transferase P1 and P-glycoprotein are implicated in resistance to a variety of chemotherapeutic agents and have been localized to the blood-brain barrier. In a matched case-control study, we investigated the associations between CNS relapse in childhood ALL and the presence of phenotypically relevant single nucleotide polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding for Pgp; exon 26, C3435T). Significant reductions in risk of CNS relapse were observed for patients homozygous for the GSTP1 Val105 allele as well as for patients with the MDR1 3435T/T or C/T genotype. For both genotypes, the effect was restricted to patients at intermediate or high risk of treatment failure.These results suggested a modulating role for host genetic variation in the development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt-Münster protocols.
Do community interventions targeting licensed venues reduce alcohol-related emergency department presentations?

INTRODUCTION AND AIMS Excessive alcohol consumption is related to substantial health and social order costs. Many of the harms have been identified as coming from licensed venues. Most communities struggle to find interventions that are effective, particularly in an environment of little federal government action. Furthermore, most interventions are based on little or no empirical evidence. This study aims to investigate the effect of a suite of interventions on emergency department (ED) attendances in Geelong, Australia. DESIGN AND METHODS This paper reports stage one findings from the Dealing with Alcohol-Related Problems in the Night-time Economy project (DANTE) and specifically examines all alcohol-related injury frequencies before to after intervention in the City of Greater Geelong of Victoria, Australia, from 2005 to 2009. Auto-regressive integrated moving average time-series were used to determine the effect of the interventions on ED attendances in Geelong. RESULTS There were 3934 triage presentations involving alcohol. Over two-thirds (68.9%) of triage presentations were male and over half (58.5%) of alcohol-related attendances occurred on the weekend. The time-series analyses indicated that ID scanners (z = 2.66, P < 0.001) and the Just Think awareness campaign (z = 4.21, P < 0.001) were significant predictors of increases in alcohol-related injury presentation rates to the ED. DISCUSSION AND CONCLUSIONS Overall, the community interventions implemented have not been associated with reduced alcohol-related attendances at the ED. The findings raise questions about whether targeting the night-time economy is effective and whether interventions should instead be targeted at reducing whole-of-community alcohol consumption.