Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive Density and Conditional Confidence Interval Accuracy Tests

This paper outlines testing procedures for assessing the relative out-of-sample predictive accuracy of multiple conditional distribution models. The tests that are discussed are based on either the comparison of entire conditional distributions or the comparison of predictive confidence intervals. We also briefly survey existing related methods in the area of predictive density evaluation, including methods based on the probability integral transform and the Kullback-Leibler Information Criterion. The procedures proposed in this paper are similar in many ways to Andrews' (1997) conditional Kolmogorov test and to White's (2000) reality check. In particular, a predictive density test is outlined that involves comparing square (approximation) errors associated with models I, i=1,. ,n, by constructing weighted averages over U of E[( F_{i}(u|Z^{t},theta _{i}^\dagger )-F_{0}(u|Z^{t}, theta _{0})) ^{2}] , where F_{0}(. |. ) and F_{i}(.|.)$ are true and model-i distributions, u belongs to U, and U is a possibly unbounded set on the real line. A conditional confidence interval version of this test is also outlined, and appropriate bootstrap procedures for obtaining critical values when predictions used in the formation of the test statistics are obtained via rolling and recursive estimation schemes are developed. An empirical illustration comparing alternative predictive models for U.S. inflation is given for the predictive confidence interval test.
Copula Methods and the Analysis of Credit Risk

Banks' internal credit risk assessment may take into account not only publicly available ratings but also internal measures of credit risk. We present a credit rating model of credit risk that permits banks to employ their own risk assessment in addition to public rating information. Banks need to evaluate the credit risk of portfolios of risky assets. Ordinary correlation techniques fail to capture dependency relationships between marginal distribution functions. The copula can describe these relationships exactly. To model the credit risk of baskets of securities we examine dependency using copula methods paired with EVT techniques. We empirically estimate the dependency between different credit classes, and discuss the application of the empirical copula to valuation problems.
Encapsulation of nystatin in nanoliposomal formulation: characterization, stability study and antifungal activity against Candida albicans

Polyene antibiotics are a group of macrolide lactones that have antifungal activity against a wide variety of fungi. Administration of this group of antibiotics have recently increased due to the use of immunosuppressive drugs and increasing incidence of AIDS (1,2). Nystatin, the first polyene drug to be identified, is active against a wide variety of fungal pathogens including Candida, Aspergillus, Histoplasma and Coccidioides spp. (4,5,6). Nystatin has a similar structure to amphotericin B, but has a broader spectrum of action than amphotericin B and is used for the treatment of cutaneous, vaginal and oral candidiases by oral, pleural inhalation and topical administration (7-9). Nystatin, has a broad spectrum of activity, but due to its low solubility in injectable solvents and toxicity, its use in the treatment of systemic fungal infections is limited (7,8). Unfortunately its clinical use, other than by topical application, has been Abstract In this study, nystatin liposomal formulation was prepared and characterized. The physicochemical properties of formulations including vesicle size, drug entrapment stability and in vitro release were studied. The highest entrapment efficiency of nystatin into liposomes was obtained about 70% when cholesterol (CHO) was added to the formulations prepared with dipalmitoylphosphatidylcholine. In addition, the drug entrapment efficiency was decreased when distearoylphosphatidylcholine was used but it was improved by addition of CHO and hydration with 9% sucrose solution. Liposomes with uniform size distribution and average size of 100 nm were produced. Long term stability study indicated that the lyophilized liposomal nystatin was physically stable for at least 6 months at 4 C. In vitro anti-fungal activity of liposomal nystatin was found to be more effective than free nystatin against Candida albicans.
To understand the current user profile of Leeds City Credit Union and examine the reasons for usage

The aim of this thesis is to understand, using detailed modelling, the users and their reasons for use of Leeds City Credit Union (LCCU) with implied application for other UK credit unions. With the initial aims resulting from a Knowledge Transfer Programme (KTP) between LCCU and the University of Leeds, this study has been performed using a case-study (LCCU) with the intention that the findings can be adapted to suit the needs and understanding of other UK credit unions, thus answer the broader research questions around credit union usage. The original contribution to knowledge is therefore the modelling relating to the users and usage of LCCU so that a detailed understanding of the user profile can be tailored and applied to other UK credit unions as niche financial service providers. The main source of data for this thesis was the analysis of a user and non-user questionnaire and this was supported by the use of focus groups. This data was then analysed using a range of techniques: qualitative analysis through the focus groups; descriptive analysis; factor analysis; and regression. From this analysis it was discovered that users are motivated to join LCCU for three key reasons. There are those who: use providers offering the best rates of return; support the ethical stance that the credit union movement offers; and who are financially excluded and unable to access credit elsewhere. Each of these three segments displayed unique profiling characteristics. In addition responses between users and non-users were also compared to identify the significant characteristics of users. These findings were contrary to the expectation that credit unions are just for the poorest sectors of society. This provides not only a unique academic insight in this niche financial services provider but also practically, in the development of a marketing strategy as defined by the KTP programme.
The composition and role of cross links in mechanoelectrical transduction in vertebrate sensory hair cells

Summary The key components of acousticolateralis systems (lateral line, hearing and balance) are sensory hair cells. At their apex, these cells have a bundle of specialized cellular protrusions, which are modified actin-containing microvilli, connected together by extracellular filaments called cross links. Stereociliary deflections open nonselective cation channels allowing ions from the extracellular environment into the cell, a process called mechanoelectrical transduction. This produces a receptor potential that causes the release of the excitatory neurotransmitter glutamate onto the terminals of the sensory nerve fibres, which connect to the cell base, causing nerve signals to be sent to the brain. Identification of the cellular mechanisms underlying mechanoelectrical transduction and of some of the proteins involved has been assisted by research into the genetics of deafness, molecular biology and mechanical measurements of function. It is thought that one type of cross link, the tip link, is composed of cadherin 23 and protocadherin 15, and gates the transduction channel when the bundle is deflected. Another type of link, called lateral (or horizontal) links, maintains optimal bundle cohesion and stiffness for transduction. This Commentary summarizes the information currently available about the structure, function and composition of the links and how they might be relevant to human hearing impairment.
Persistence, Immune Response, and Antigenic Variation of Mycoplasma genitalium in an Experimentally Infected Pig-Tailed Macaque (Macaca nemestrina)

ABSTRACT Mycoplasma genitalium is a sexually transmitted pathogen associated with several acute and chronic reproductive tract disease syndromes in men and women. To evaluate the suitability of a pig-tailed macaque model of M. genitalium infection, we inoculated a pilot animal with M. genitalium strain G37 in the uterine cervix and in salpingeal pockets generated by transplanting autologous Fallopian tube tissue subcutaneously. Viable organisms were recovered throughout the 8-week experiment in cervicovaginal specimens and up to 2 weeks postinfection in salpingeal pockets. Humoral and cervicovaginal antibodies reacting to MgpB were induced postinoculation and persisted throughout the infection. The immunodominance of the MgpB adhesin and the accumulation of mgpB sequence diversity previously observed in persistent human infections prompted us to evaluate sequence variation in this animal model. We found that after 8 weeks of infection, sequences within mgpB variable region B were replaced by novel sequences generated by reciprocal recombination with an archived variant sequence located elsewhere on the chromosome. In contrast, mgpB region B of the same inoculum propagated for 8 weeks in vitro remained unchanged. Notably, serum IgG reacted strongly with a recombinant protein spanning MgpB region B of the inoculum, while reactivity to a recombinant protein representing the week 8 variant was reduced, suggesting that antibodies were involved in the clearance of bacteria expressing the original infecting sequence. Together these results suggest that the pig-tailed macaque is a suitable model to study M. genitalium pathogenesis, antibody-mediated selection of antigenic variants in vivo, and immune escape.
CD 4 T Lymphocytes Play a Critical Role in Antibody Production and Tumor Immunity against Simian Virus 40 Large Tumor Antigen 1

The role of CD4 T lymphocytes in antitumor immunity has been largely attributed to providing signals required for the priming of MHC class I-restricted CD8 cytotoxic T lymphocytes, and CD8 cytotoxic T lymphocytes are thought to serve as the predominant mediators of tumor killing in vivo. We decided to evaluate the role of T lymphocyte subsets in tumor immunity induced by recombinant SV40 large tumor antigen (Tag) within an experimental murine pulmonary metastasis model of SV40 Tag-expressing tumors. Studies in BALB/c mice used in vivo depletion of either CD4 or CD8 T cells in the induction phase of the immune response to SV40 Tag. These studies indicate that CD4 T cells but not CD8 T cells were critical in the production of antibodies to SV40 Tag and in tumor immunity as the result of recombinant SV40 Tag immunization. On the basis of the predominance of the IgG1 isotype in the antibody response to SV40 Tag immunization, Th2 type CD4 T cells appeared to be involved. SV40 Tag immunization was not as effective in the induction of tumor immunity in therapeutic modalities when compared with the prophylactic setting. Our results suggest that CD4 T cells, along with antibody responses, play a role in the induction of tumor immunity to a viral-encoded tumor antigen.
GC-MS ANALYSIS OF CASSIA ITALICA LEAF METHANOL EXTRACT

Plants have been an important source of medicine with qualities for thousands of years. Mainly on traditional remedies such as herbs for their history it has been used as a popular folk medicine. Cassia italica has medicinal values; methanol leaf extract of this plant was analyzed using Gas Chromatography–Mass Spectrometry, while the mass spectra of the compounds found in the extract was matched with the National Institute of Standards and Technology (NIST) library. Gas chromatography mass spectrometry (GC-MS) analysis revealed the presence of 17 compounds. In GCMS analysis, some of the phytocomponents screened were Phytol, Squalene and n-Hexadecanoic acid. The compounds were identified by comparing their retention time and peak area with that of literature and by interpretation of mass spectra. Many of them are used in industry for various applications like flavor, antioxidant, anti-inflammatory, antimicrobial, pesticide and cancer preventive.
Differential expression of microRNAs and their possible roles in patients with chronic idiopathic urticaria and active hives

Background Chronic idiopathic urticaria (CIU) is a complicated skin disease with unknown pathophysiology. MicroRNAs (miRNA) have been shown to be active in cellular regulation. The goal of this pilot study was to examine whether miRNAs may be involved in the regulation of CIU or as biomarkers for CIU. Methods Four groups of three patients each were selected: patients with either active hives or no hives and with positive or negative chronic urticaria (CU) index results. MiRNAs were isolated from patient plasma and analyzed by using miRNA microarray technology to determine the amount of each of the 2567 known human miRNAs. Results A total of 16 miRNAs were found to be differentially expressed in patients with active hives. Among them, five (2355–3p, 4264, 2355–5p, 29c-5p, and 361–3p) were significantly increased in samples with positive CU index results, which could be useful biomarkers for patients with chronic autoimmune urticaria. The miRNA data bases were used to find the targets of these selected miRNA sequences. These potential targets were then compared against a list of 154 urticaria-related genes. Twenty-five genes were found to match. These included eight that were significantly downregulated and eight that were significantly upregulated; however, seven of the eight downregulated genes (FBXL20, OPHN1, YPEL2, STARD9, EZH1, KLHL24, ING4) and five of the eight upregulated genes (BYSL, PNO1, ADAMTS9, STEAP4, SRGN) have no reported roles in signaling. For the 13 genes with reported roles in signaling, the following pathways were found: transforming growth factor beta signaling pathway (NRC31, KITLG, THBS1, CCL2), glucocorticoid receptor signaling pathway (NR3C1, SELE, CCL2), p53 signaling pathway (CCNG2, THBS1, CCL2), p21-activated kinase pathway (PAK1IP1, KITLG, CCL2), phosphoinositide-3 kinase protein kinase B signaling pathway (KITLG, CHRM, THBS1), and neuroactive ligand-receptor interaction (NRC31, HRH1, CHRM), which could play important roles in CIU. Conclusion A better understanding of those genes with undefined function and simultaneous quantitation of both miRNAs and messenger RNAs are needed to fully understand CIU disease.
On the Managerial Skills of Mutual Fund Managers (Manipulation-Proof Performance Measure)

The on-going debate over whether fund managers have skills and whether those skills are short-lived is still inconclusive. Using the performance measure that can’t be manipulated with respect to the underlying distribution, time variation, nor estimation error, (the manipulation-proof performance measure (MPPM, Goetzmann et al. (2007)), we rank all U.S. domestic equity mutual funds from 1980 to 2013 on a quarterly basis and analyze their portfolio holdings to generate few insights. First, fund managers in the higher ranked MPPM deciles persistently outperform lower ranked managers by posting higher gross and net fund returns, higher holding-based returns, and generating positive return gap. Second, the characteristic of the holdings indicates higher ranked fund managers would hold younger, smaller, growth, and particularly stocks with lower liquidity and higher information asymmetry. Based on the five-factor (Fama and French (2014)) analysis, our results show that higher ranked managers could generate 15 to 29 basis points while lower ranked managers would loss 20 to 26 basis points on their risk-adjusted ex-post monthly holding returns (alphas) based on their ex-ante constructed holdings. Fourth, the differences on managers of the highest rank and the lowest rank result in monthly risk-adjusted returns (alphas) up to 49 to 52 basis points. Even though the managerial skills are identified at the higher ranked managers, the persistent and the predictability of their superior holding-based returns and fund returns are merely limited to up to six months. We conclude that even though higher ranked managers have better stock picking skills, their net fund returns are not large enough to offset their expenses to warrant positive alphas.
Circulating endotoxin during initial antibiotic treatment of severe gram-negative bacteremic infections.

The impact of antibiotics on total endotoxemia and circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe bacteremic sepsis or septic shock due to gram-negative species was investigated. Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and 4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0 (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL; interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4 (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that endotoxemia is not increased by antibiotherapy of severe gram-negative bacteremia.
Effect of Chronic Statin Pretreatment on Hospital Outcome in Patients With Acute Non-ST-Elevation Myocardial Infarction

Purpose: We sought to investigate the impact of prior statin therapy on in-hospital outcome in patients presenting with acute non-ST-elevation myocardial infarction. Methods and Results: We analyzed the data of consecutive patients with non-ST-elevation myocardial infarction who were prospectively enrolled in the German Acute Coronary Syndrome Registry between July 2000 and November 2002. Overall, 6358 patients were included, and we compared the patients who received statins before hospital admission (n = 1247, 19.6%) with those who did not (n = 5111, 80.4%). There was no age difference between the two groups; however, pretreated patients had a higher incidence of prior atherothrombotic events diabetes mellitus and renal insufficiency. The percentage of patients undergoing percutaneous coronary intervention and coronary artery bypass grafting was similar. Infarct size measured by peak creatine kinase level was lower in statin users (238 vs. 283U/L, P < 0.0001). After adjustment for confounding variables, a significant reduction of in-hospital death could be observed in patients on statins (odds ratio 0.65, 95% confidence interval 0.46-0.90). Conclusions: In clinical practice, pretreatment with statins was associated with smaller myocardial infarction size (peak creatine kinase level) and a significant reduction of hospital mortality. However, the data were obtained from an observational study, and the results need further prospective confirmation.
Contribution of adenosine A2 receptors and cyclic adenosine monophosphate to protective ischemic preconditioning of sinusoidal endothelial cells against storage/reperfusion injury in rat livers

A brief period of liver ischemia decreases sinusoidal endothelial cell killing after cold liver storage and improves graft survival after liver transplantation, a phenomenon called ischemic preconditioning. In this study, we investigated the mechanism of sinusoidal endothelial cell protection after ischemic preconditioning. Livers were preconditioned by 5 minutes of ischemia and 5 minutes of reperfusion. Subsequently, livers were stored for 30 hours in cold University of Wisconsin (UW) solution and reperfused briefly with physiological buffer containing Trypan blue. Ischemic preconditioning decreased sinusoidal endothelial cell killing after storage/reperfusion, as assessed by Trypan blue staining of nonparenchymal cells. Adenosine A2 receptor blockade prevented the protective effect of ischemic preconditioning. By contrast, adenosine A1 receptor blockade did not prevent protective ischemic preconditioning. Other rat livers were treated with adenosine A1 and A2 receptor agonists or dibutyryl–cyclic adenosine monophosphate (DB‐cAMP) before storage. The adenosine A2 receptor agonist, CGS‐21680, and DB‐cAMP decreased sinusoidal endothelial cell killing to the same extent as ischemic preconditioning, but the adenosine A1 receptor agonist, 2‐chloro‐N6‐cyclopentyladenosine (CCPA), had no effect. The adenosine A2 agonist and prostaglandin E2 , another agent that preconditions sinusoidal endothelial cells against storage/reperfusion injury, but not the adenosine A1 agonist, increased cAMP levels in cultured sinusoidal endothelial cells. In conclusion, an adenosine A2 receptor pathway coupled to increased cAMP mediates sinusoidal endothelial cell protection by ischemic preconditioning.
Logistic Regression Models for Polymorphic and Antagonistic Pleiotropic Gene Action on Human Aging and Longevity

In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic situation. Genotype and allele‐based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture the age‐dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age‐dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important gene variations that contribute to human aging and longevity.
Confocal Microscopy and Corneal Sensitivity in a Patient with Corneal Manifestations of Tangier Disease

Purpose: Tangier disease is an autosomal recessive disorder in which cholesterol-rich lipids are deposited at various tissues of the body including the cornea. In this case report, the corneal changes in a patient with Tangier disease are described. Methods: A 72-year-old patient who was diagnosed with Tangier disease 25 years before received a complete eye examination including confocal microscopy and Cochet-Bonnet esthesiometry. Results: Slit-lamp biomicroscopy and confocal microscopy showed bilateral corneal opacifications caused by lipid accumulation. Confocal microscopy showed that pathologic changes in the cornea in Tangier disease are limited to the stroma. Neither a reduced corneal sensation nor lid abnormalities as previously described in Tangier disease were found. Conclusion: Confocal microscopy helps to identify corneal changes in the stroma caused by Tangier disease easily missed in a slit-lamp examination. The ocular manifestations of Tangier disease do not necessarily include a reduced corneal sensitivity and lid abnormalities.
Attitudinal Explanation on Virtual Shopping Intention

Virtual stores provide great efficiency in the retail value chain, and their existence has tremendously paved the way for electronic commerce. Understanding the intention of consumers to shop online in attitudinal perspective will provide important contribution to the area of e-commerce. This research proposes Task Technology Fit, Perceived Ease of Use (PEoU), and Perceived Usefulness (PU) as the factors that drive consumers' intention. The results from our survey study of 310 online consumers in Indonesia indicate that TTF affects PEoU and PU significantly. Our hierarchical model also reports that PEoU is the mediating effect on the relationship between TTF and Intention. The resulting model explains a large portion of the factors that lead a user's behavioural intention to use a virtual shop.
Activation of TRKB receptor in murine hematopoietic stem/progenitor cells induced mastocytosis.

To the editor: Dysregulation of tropomyosin-related kinase (TRK) receptors has been reported to be involved in many human diseases, including cancer and neurological diseases. Recently, Peng et al[1][1] demonstrated that patients with mastocytosis had enhanced neurotrophin levels and elevated