Miracle-dz/UniFAR-FTUs huggingface dataset:
Human leucocyte antigen‐identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft‐versus‐host disease and pre‐existing viral infections

Major histocompatibility complex class II deficiency, a rare autosomal recessive primary immunodeficiency, is caused by the defective expression of human leucocyte antigen (HLA) class II molecules due to mutated trans‐acting elements of any one of four regulatory genes (CIITA, RFXANK, RFX5, RFXAP). The impaired CD4 T‐cell differentiation and antigen presentation in the periphery results in a severe defect of cellular and humoral response consistent with severe recurrent infections, leading to a poor prognosis. Currently, allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative approach, but the overall cure rate is lower than in other immunodeficiencies. We report a single centre experience of 17 HSCTs with 15 HLA‐identical donors between 1981 and 2004. Eight patients survived, while the occurrence of acute graft‐versus‐host disease (GVHD) was 50%. This study aimed to identify potential risk factors for GVHD and outcome within pre‐HSCT complications related to the immunodeficiency. Five of seven patients with pre‐existing viral infections developed acute GVHD ≥ grade II, of whom four died. Two of seven patients without detectable pre‐existing viral infection developed GVHD ≥ grade II, and one died. The difference was significant (P < 0·05). A plausible link with other factors potentially associated with the development of GVHD could not be found. We suggest that the reduced survival after HLA‐identical HSCT may be caused by the high incidence of pre‐existing viral infections and associated with the onset of severe acute GVHD.
Empirical Patterns of Time Value Decay in Options

Purpose - The purpose of this paper is to conduct an empirical analysis of the pattern of time value decay in listed equity options, considering both call and put options and different moneyness and maturity levels. Design/methodology/approach - The research design is empirical, with great attention paid to creating a standardized measure of time value that can be both tracked over time for an individual option contract and meaningfully compared across two or more different option contracts. Findings - The author finds that moneyness classification at the beginning of the holding period is the key determinant of the pattern of subsequent time decay. The type of option, call or put, and the maturity of the contract have surprisingly little relevance to the pattern of time decay “out-the-money contracts having similar patterns on average, regardless of whether they are calls or puts, 30-day or 60-day contracts. ” More detailed analysis reveals that In-the-money and out-the-money contracts have slow time decay for most of the contract life, with a significant percentage of the time decay concentrated on the final day of the option. At-the-money contracts experience strong decay early in the life of the option. Research limitations/implications - The study is limited by not having intra-day data included to analyze more frequent price movements. Practical implications - The results reported in the paper provide insight into issues of active management facing options traders, specifically choices such as the initial maturity of the option contract and rollover frequency. Originality/value - Very few studies examine the important issue of how option time value behaves. Time value is the subjective part of the option contract value, and therefore very difficult to predict and understand. This paper provides insight into typical empirical patterns of time value behavior.
Role of p21waf1/cip1 in effects of oxaliplatin in colorectal cancer cells

Clinical studies have shown that oxaliplatin, a novel platinum derivative, is a potent chemotherapeutic agent for colorectal cancer when combined with 5-fluorouracil and leucovorin. Although the toxic activity is based on covalent adducts between platinum and DNA, its actual biological behavior is mostly unknown. In an effort to explore the mechanism of tumor susceptibility to oxaliplatin, we examined the cytotoxic effects of oxaliplatin in colorectal cancer cell lines in reference to p53 gene status. Although p53 gene status did not clearly predict sensitivity to oxaliplatin, p53 wild-type cells including HCT116 were sensitive but HCT116 p53−/− were found to be resistant to oxaliplatin. Oxaliplatin caused strong p21waf1/cip1 induction and G0-G1 arrest in p53 wild-type cells, whereas cisplatin did not induce G0-G1 arrest. Assays using p53 wild but p21waf1/cip1 null HCT116 cells revealed that oxaliplatin did not show G0-G1 arrest and reduced growth-inhibitory effects, suggesting that p21waf1/cip1 may be a key element in oxaliplatin-treated p53 wild-type cells. Although HCT116 is DNA mismatch repair–deficient, a mismatch repair–proficient HCT116+ch3 cell line displayed similar responses with regard to p21waf1/cip1-mediated growth inhibition and G0-G1 arrest. In p53 mutant cells, on the other hand, oxaliplatin caused an abrupt transition from G1 to S phase and eventually resulted in G2-M arrest. This abrupt entry into S phase was associated with loss of the p21waf1/cip1 protein via proteasome-mediated degradation. These findings suggest that p21waf1/cip1 plays a role in oxaliplatin-mediated cell cycle and growth control in p53-dependent and -independent pathways.
Effects of Metal Micro and Nano-Particles on hASCs: An In Vitro Model

As the knowledge about the interferences of nanomaterials on human staminal cells are scarce and contradictory, we undertook a comparative multidisciplinary study based on the size effect of zero-valent iron, cobalt, and nickel microparticles (MPs) and nanoparticles (NPs) using human adipose stem cells (hASCs) as a model, and evaluating cytotoxicity, morphology, cellular uptake, and gene expression. Our results suggested that the medium did not influence the cell sensitivity but, surprisingly, the iron microparticles (FeMPs) resulted in being toxic. These data were supported by modifications in mRNA expression of some genes implicated in the inflammatory response. Microscopic analysis confirmed that NPs, mainly internalized by endocytosis, persist in the vesicles without any apparent cell damage. Conversely, MPs are not internalized, and the effects on hASCs have to be ascribed to the release of ions in the culture medium, or to the reduced oxygen and nutrient exchange efficiency due to the presence of MP agglomerating around the cells. Notwithstanding the results depicting a heterogeneous scene that does not allow drawing a general conclusion, this work reiterates the importance of comparative investigations on MPs, NPs, and corresponding ions, and the need to continue the thorough verification of NP and MP innocuousness to ensure unaffected stem cell physiology and differentiation.
Oversight and Inspection of Auditing

One of the major changes in audit regulation of the past decade relates to the system of audit oversight. In response to high-profile corporate financial reporting scandals, the US set the tone by creating the Public Company Accounting Oversight Board (PCAOB) in 2002 and thereby putting an end to self-regulation of the auditing profession, which had been the dominant model for many decades. Subsequently, many other countries followed the US example of installing independent public oversight in varying forms and stages of development. The central aim of independent audit regulators is to enhance protection of investors and the public interest through audit oversight, enforcement and improvements in audit quality. Despite the potential merits of public oversight, it cannot be denied that corporate scandals continue to occur across the globe and that regulators continue to be under pressure especially in the aftermath of the financial crisis and the current economic downturn. Hence, the core mission of oversight bodies seems far from completed. In this chapter, we introduce public oversight by providing an overview of the development and current challenges, a summary of research findings and outstanding issues for future research.
Study on testicular response to prolong artemisinin‐based combination therapy treatments in guinea pigs

Artemisinin‐based combination therapies (ACTs) are first‐line agents in malaria chemotherapy, but often abused in malaria endemic countries including Nigeria. This study investigated the effects of prolong treatment of artesunate–amodiaquine (ATS–Amod), artesunate‐sulfadoxine‐pyrimethamine (ATS–SP) and artemether–lumefantrine (ATM–Lum) on testicular indices in guinea pigs. Sixty‐five pigs were grouped into 13 (n = 5 per group). Six groups were given standard or double therapeutic dose equivalents of ATS–Amod, ATS‐SP or ATM–Lum daily for 14 day and sacrificed 24 hr after treatments. Six other groups (recovery groups) received similar drug treatments but allowed to recover for 14 day before sacrificed. Control group received distilled water. ATS–Amod, ATS–SP and ATM–Lum, respectively, decreased (p < .01) sperm count (17.7%, 37.7% and 33.8%), motility (48.6%, 50% and 51.4%), viability (32.7%, 43.7% and 35.9%) and morphology (123.5%, 0% and 0%), compared to control. These effects were reversed in recovery animals. Also, they decreased (p < .01) luteinising hormone and testosterone serum levels, without affecting follicle‐stimulating hormone. Testicular malondialdehyde level was elevated, and glutathione was decreased, while catalase and superoxide dismutase enzymes were unaffected by the drugs. The alterations were all reversed in recovery animals. The study reveals that prolong administration of ACTs results in reversible alteration of sperm parameters and reduction of testosterone which is partly attributable to oxidative stress.
Bacterial Na+-translocating ferredoxin:NAD+ oxidoreductase

The anaerobic acetogenic bacterium Acetobacterium woodii carries out a unique type of Na+-motive, anaerobic respiration with caffeate as electron acceptor, termed “caffeate respiration. ” Central, and so far the only identified membrane-bound reaction in this respiration pathway, is a ferredoxin:NAD+ oxidoreductase (Fno) activity. Here we show that inverted membrane vesicles of A. woodii couple electron transfer from reduced ferredoxin to NAD+ with the transport of Na+ from the outside into the lumen of the vesicles. Na+ transport was electrogenic, and accumulation was inhibited by sodium ionophores but not protonophores, demonstrating a direct coupling of Fno activity to Na+ transport. Results from inhibitor studies are consistent with the hypothesis that Fno activity coupled to Na+ translocation is catalyzed by the Rnf complex, a membrane-bound, iron–sulfur and flavin-containing electron transport complex encoded by many bacterial and some archaeal genomes. Fno is a unique type of primary Na+ pump and represents an early evolutionary mechanism of energy conservation that expands the redox range known to support life. In addition, it explains the lifestyle of many anaerobic bacteria and gives a mechanistic explanation for the enigma of the energetic driving force for the endergonic reduction of ferredoxin with NADH plus H+ as reductant in a number of aerobic bacteria.
Meta-analysis of Grade Retention Research: Implications for Practice in the 21st Century

Abstract Retaining a child at grade level has become increasingly popular, consistent with the emphasis on accountability and standards in elementary education. This article provides a comprehensive review of the research examining the academic and socioemotional outcomes associated with grade retention. Following a brief historical overview of previously published literature reviews, a summary of studies published between 1990 and 1999 is provided. A systematic review and meta-analysis of 20 recent studies includes: outcome variables (i.e., achievement and socioemotional adjustment), age or grade of retained population, matched or controlled for variables in analyses with comparison groups, and the overall conclusion regarding the efficacy of grade retention. Results of recent studies and this meta-analysis are consistent with past literature reviews from the 1970s and 1980s. In addition to a summary of the results, the discussion addresses the disparity between educational practice and converging research regarding grade retention and suggests directions for practice. This review encourages researchers, educational professionals, and legislators to abandon the debate regarding social promotion and grade retention in favor of a more productive course of action in the new millennium.
Cleaved antitrypsin polymers at atomic resolution

α1‐Antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of α1 antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that α1‐antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the β‐sheet of another. However, this long‐standing hypothesis has not been confirmed by direct structural evidence. Here, we describe the first crystallographic evidence of a β‐strand linked polymer form of α1‐antitrypsin: the crystal structure of a cleaved α1‐antitrypsin polymer.
ROS stimulate reorganization of mesangial cell-collagen gels by tyrosine kinase signaling

Zent, Roy, Menachem Ailenberg, Gregory P. Downey, and Melvin Silverman. ROS stimulate reorganization of mesangial cell-collagen gels by inducing tyrosine kinase signaling. Am. J. Physiol. 276 (Renal Physiol. 45): F278– F287, 1999. —Reactive oxygen species (ROS) initiate multiple pathological and physiological cellular responses, including tyrosine phosphorylation of proteins. In this study, we investigated the effects of ROS on cell-extracellular matrix interactions utilizing the floating three-dimensional collagen gel assay. Exposure of mesangial cells grown in three-dimensional culture to H2O2, 3-amino-1,2,4-triazole (a catalase inhibitor), or puromycin is associated with gel reorganization accompanied by tyrosine phosphorylation of multiple proteins, including focal adhesion kinase (FAK). Neutrophils cocultured with mesangial cells in three-dimensional culture also induce mesangial cell-collagen gel reorganization and initiate tyrosine phosphorylation of a similar set of proteins. Collectively, these results show that ROS of either endogenous or exogenous origin can modulate mesangial cellextracellular matrix interactions through initiation of a phosphotyrosine kinase signaling cascade. Consequently, ROS may play a role as signaling molecules that regulate mesangial cell-extracellular matrix interactions in both physiological and pathological conditions.
Knock‐In of the Recurrent R368X Mutation of PRKAR1A that Represses cAMP‐Dependent Protein Kinase A Activation: A Model of Type 1 Acrodysostosis

In humans, activating mutations in the PRKAR1A gene cause acrodysostosis 1 (ACRDYS1). These mutations result in a reduction in PKA activation caused by an impaired ability of cAMP to dissociate mutant PRKAR1A from catalytic PKA subunits. Two striking features of this rare developmental disease are renal resistance to PTH and chondrodysplasia resulting from the constitutive inhibition of PTHR1/Gsa/AC/cAMP/PKA signaling. We developed a knock‐in of the recurrent ACRDYS1 R368X PRKAR1A mutation in the mouse. No litters were obtained from [R368X]/[+] females (thus no homozygous [R368X]/[R368X] mice). In [R368X]/[+] mice, Western blot analysis confirmed mutant allele heterozygous expression. Growth retardation, peripheral acrodysostosis (including brachydactyly affecting all digits), and facial dysostosis were shown in [R368X]/[+] mice by weight curves and skeletal measurements (μCT scan) as a function of time. [R368X]/[+] male and female mice were similarly affected. Unexpected, however, whole‐mount skeletal preparations revealed a striking delay in mineralization in newborn mutant mice, accompanied by a decrease in the height of terminal hypertrophic chondrocyte layer, an increase in the height of columnar proliferative prehypertrophic chondrocyte layer, and changes in the number and spatial arrangement of proliferating cell nuclear antigen (PCNA)‐positive chondrocytes. Plasma PTH and basal urinary cAMP were significantly higher in [R368X]/[+] compared to WT mice. PTH injection increased urinary cAMP similarly in [R368X]/[+] and WT mice. PRKACA expression was regulated in a tissue (kidney not bone and liver) manner. This model, the first describing the germline expression of a PRKAR1A mutation causing dominant repression of cAMP‐dependent PKA, reproduced the main features of ACRDYS1 in humans. It should help decipher the specificity of the cAMP/PKA signaling pathway, crucial for numerous stimuli. In addition, our results indicate that PRKAR1A, by tempering intracellular cAMP levels, is a molecular switch at the crossroads of signaling pathways regulating chondrocyte proliferation and differentiation. © 2016 American Society for Bone and Mineral Research.
Stress as a Risk Factor for Seizures Among Adults with Epilepsy

Summary: This study examines the effects of major life events, daily hassles and uplifts, and daily stress levels as they increase or decrease the risks of having seizures and estimates risk ratios for specific stressors and perceived stress levels. Utilizing a prospective design, 12 adults with severe epilepsy monitored the occurrence of seizures, stressors, and stress levels over a 3‐month period. In within‐individual analyses, high stress levels and stressful events were associated with more frequent seizures for most participants. The association between higher stress levels and increased seizures was confirmed in group analyses. This study provides empirical evidence of the association between stress and seizures and describes the use of a statistical model that is useful for investigating risk factors as they influence physical and mental illness.
Lean Six Sigma in higher education institutions

Purpose This paper aims to illustrate the application of Lean Six Sigma (LSS) in higher education institutions (HEIs). A real-time case study presented as part of the paper highlights the value which LSS can bring to the higher education system. Design/methodology/approach The paper commences with an overview and the success of the LSS methodology. The uniqueness of the higher education system for imbibing quality excellence is elaborated, comparing it with the manufacturing industry. Various opportunities for LSS projects in HEIs are then discussed as part of the paper. The last section of the paper elaborates a real-time case study, explaining how LSS was leveraged to improve a university library process. Findings The study identified the key attributes of the higher education system, which need to be understood for imbibing quality excellence. The study also provided an insight into the upcoming application of LSS and the benefits it can bring to HEIs. Practical implications The introduction of LSS into the higher education setup could bring multifold organizational and social benefits Originality/value LSS has been successful in the past few decades in the manufacturing and service sector. However, its application in HEIs was very nascent. This study illustrates its importance and application to a highly responsible area of the service sector, for imbibing quality excellence, serving as an excellent resource for researchers and higher education professionals.
Biomembranes from slaughterhouse blood erythrocytes as prolonged release systems for dexamethasone sodium phosphate

The present study investigated preparation of bovine and porcine erythrocyte membranes from slaughterhouse blood as bio‐derived materials for delivery of dexamethasone‐sodium phosphate (DexP). The obtained biomembranes, i.e., ghosts were characterized in vitro in terms of morphological properties, loading parameters, and release behavior. For the last two, an UHPLC/–HESI–MS/MS based analytical procedure for absolute drug identification and quantification was developed. The results revealed that loading of DexP into both type of ghosts was directly proportional to the increase of drug concentration in the incubation medium, while incubation at 37°C had statistically significant effect on loaded amount of DexP (P < 0.05). The encapsulation efficiency was about fivefold higher in porcine compared to bovine ghosts. Insight into ghosts’ surface morphology by field emission‐scanning electron microscopy and atomic force microscopy confirmed that besides inevitable effects of osmosis, DexP inclusion itself had no observable additional effect on the morphology of the ghosts carriers. DexP release profiles were dependent on erythrocyte ghost type and amount of residual hemoglobin. However, sustained DexP release was achieved and shown over 3 days from porcine ghosts and 5 days from bovine erythrocyte ghosts. © 2016 American Institute of Chemical Engineers Biotechnol. Prog. , 32:1046–1055, 2016
Bacteria isolated from the duodenum, ileum, and cecum of young chicks

Facultatively anaerobic and strictly anaerobic bacteria colonizing the intestinal tracts of 14-day-old chicks fed a corn-based diet were enumerated, isolated, and identified. Colony counts from anaerobic roll tubes (rumen fluid medium) or aerobic plates (brain heart infusion agar) recovered from homogenates of the duodenum, upper and lower ileum, and cecum varied appreciably among samples from individual birds. Anaerobic and aerobic counts from the duodenum and ileum were similar. Anaerobic counts were highest from the cecum (0.7 X 10(11) to 1.6 X 10(11)/g of dry tissue) and exceeded aerobic plate counts by a factor of at least 10(2). Facultatively anaerobic groups (Streptococcus, Staphylococcus, Lactobacillus, and Escherichia coli) comprised the predominant flora of the duodenum and ileum, although large numbers of anaerobes (9 to 39% of the small intestine isolates), represented by species of Eubacterium, Propionibacterium, Clostridium, Gemmiger, and Fusobacterium, were also recovered. Strict anaerobes (anaerobic gram-positive cocci, Eubacterium, Clostridium Gemmiger, Fusobacterium, and Bacteriodes) made up nearly the entire microbial population of the cecum. Scanning electron microscopy of the intestinal epithelia of chicks revealed populations of microbes on the duodenal, ileal, and cecal mucosal surfaces.