Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibiting STAT5 by the BET Bromodomain Inhibitor JQ1 Disrupts Human Dendritic Cell Maturation

Maturation of dendritic cells (DCs) is required to induce T cell immunity, whereas immature DCs can induce immune tolerance. Although the transcription factor STAT5 is suggested to participate in DC maturation, its role in this process remains unclear. In this study, we investigated the effect of STAT5 inhibition on LPS-induced maturation of human monocyte-derived DCs (Mo-DCs). We inhibited STAT5 by treating Mo-DCs with JQ1, a selective inhibitor of BET epigenetic readers, which can suppress STAT5 function. We found that JQ1 inhibits LPS-induced STAT5 phosphorylation and nuclear accumulation, thereby attenuating its transcriptional activity in Mo-DCs. The diminished STAT5 activity results in impaired maturation of Mo-DCs, as indicated by defective upregulation of costimulatory molecules and CD83, as well as reduced secretion of IL-12p70. Expression of constitutively activated STAT5 in JQ1-treated Mo-DCs overcomes the effects of JQ1 and enhances the expression of CD86, CD83, and IL-12. The activation of STAT5 in Mo-DCs is mediated by GM-CSF produced following LPS stimulation. Activated STAT5 then leads to increased expression of both GM-CSF and GM-CSFR, triggering an autocrine loop that further enhances STAT5 signaling and enabling Mo-DCs to acquire a more mature phenotype. JQ1 decreases the ability of Mo-DCs to induce allogeneic CD4+ and CD8+ T cell proliferation and production of proinflammatory cytokines. Furthermore, JQ1 leads to a reduced generation of inflammatory CD8+ T cells and decreased Th1 differentiation. Thus, JQ1 impairs LPS-induced Mo-DC maturation by inhibiting STAT5 activity, thereby generating cells that can only weakly stimulate an adaptive-immune response. Therefore, JQ1 could have beneficial effects in treating T cell–mediated inflammatory diseases.
Pilot study of the immunologic effects of recombinant human growth hormone and recombinant insulin‐like growth factor in HIV‐infected patients

Objective:To study the immunologic effects of recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor type 1 (rhIGF-1), or the combination, in patients with moderately advanced HIV infection. Design:Randomized but not blinded trial. Setting:Government medical research center. Patients:Twenty-four HIV-infected patients with CD4 cell counts of 100–400 × 106/l who were receiving nucleoside antiretroviral therapy. Interventions:Either rhGH, rhIGF-1, or the combination was administered subcutaneously for 12 weeks. Main outcome measures:Immunologic parameters, including T-cell subsets and assays of in vitro interleukin (IL)-2 production in response to antigens and mitogens, and safety profile. Results:Plasma IGF-1 levels were low or low-normal prior to treatment and increased with all three therapies. There were no significant changes in CD4 cell counts, RA/RO CD4 cell subsets, natural killer cell function, immunoglobulin levels, or in vitro IL-2 production in response to mitogen or alloantigens. However, there was an upward trend (and for p18IIIB a statistically significant increase) in the in vitro IL-2 production in response to each of five HIV envelope peptides. Potential toxic effects included fatigue, arthralgia, edema, myalgia, and headache. Patients also were noted to have weight gain averaging 4 kg early in the course of treatment. Conclusions:These results suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that modest improvement in HIV-specific immune function was attained. Further studies will help clarify the therapeutic potential of rhGH/rhIGF-1 as an immunostimulator in the setting of HIV infection.
Should Unconventional Monetary Policies Become Conventional?

The large recession that followed the Global Financial Crisis of 2008–09 triggered unprecedented monetary policy easing around the world. Most central banks in advanced economies deployed new instruments to affect credit conditions and to provide liquidity at a large scale after short-term policy rates reached their effective lower bound. In this paper, we study if this new set of tools, commonly labeled as unconventional monetary policies (UMP), should still be used when economic conditions and interest rates normalize. We study the optimality of UMP by using an estimated non-linear DSGE model with a banking sector and long-term private and public debt for the United States. We find that the benefits of using UMP in normal times are substantial, equivalent to 1.45 percent of consumption. However, the benefits from using UMP are shock-dependent and mostly arise when the economy is hit by financial shocks. When more traditional business cycle shocks (such as supply and demand shocks) hit the economy, the benefits of using UMP are negligible or zero.
Meta-analysis of randomized controlled trials of simplified versus continued protease inhibitor-based antiretroviral therapy in HIV-1-infected patients

Objective: To evaluate the efficacy and safety of simplified maintenance therapy (SMT) compared with continued protease inhibitor (PI) therapy. Design: Meta-analysis of nine randomized controlled trials in which 833 patients were switched to SMT (abacavir, efavirenz or nevirapine) and 616 continued PI, assessing virologic failure (primary outcome), discontinuation of therapy for reasons other than virologic failure, CD4 cell count, total plasma cholesterol and triglycerides. Results: The risk ratio for virologic failure for SMT compared to continued PI was 1.06 [95% confidence interval (CI) 0.58–1.92; test for homogeneity P = 0.01] for SMT, 2.56, (95% CI, 1.17–5.64) for abacavir, 0.83 (95% CI, 0.36–1.91) for efavirenz and 0.54 (95% CI, 0.29–1.02) for nevirapine. The risk ratio for premature discontinuation of therapy with SMT was 0.61 (95% CI, 0.48–0.77; test for homogeneity P < 0.10). The difference in absolute mean cholesterol for SMT compared to continued PI was −0.15 mmol/l, (95% CI, −0.40 to 0.09; test for homogeneity P < 0.01) for SMT, −0.51 mmol/l (95% CI, −0.70 to −0.33) for abacavir, 0.22 mmol/l (95% CI, 0 to 0.43) for efavirenz and −0.19 mmol/l (95% CI, −0.48 to 0.09) for nevirapine. Conclusions: Current evidence suggests that SMT with abacavir rather than continued PI increases the risk of virologic failure, this increased risk may be confined to patients with prior mono or dual therapy with reverse transcriptase inhibitors. There is not enough evidence on whether SMT with efavirenz and nevirapine influences the risk of virologic failure. SMT with any of the three drugs reduces the risk of discontinuation of therapy, and SMT with abacavir reduces plasma cholesterol.
The Impact of STEM Outreach Programs in Addressing Teacher Efficacy and Broader Issues in STEM Education

This study explores the potential of the Outreach Workshops in STEM (OWS) to affect Science, Technology, Engineering, and Mathematics (STEM) teachers’ content knowledge, self-efficacy, and pedagogical approaches, as well as its viability as a potential form of professional development (PD). The data for the thesis is taken from a larger longitudinal study looking at the potential of OWS to influence middle school students’ and teachers’ attitudes and beliefs around STEM. The study employs a mixed-methods design, utilizing surveys, open-ended questions, interviews, and observations. The findings show that there were no significant changes in teachers’ content knowledge, confidence, or pedagogical approaches. However, the majority of participants reported that they learned new teaching ideas and considered the workshops to be an effective PD opportunity.
Do sex and ethnic differences in smoking initiation mask similarities in cessation behavior?

OBJECTIVES This study compared success in smoking cessation by sex, ethnic status, and birth cohort. METHODS African and European American respondents to the 1996 Current Population Survey (tobacco supplement) and the 1987 National Health Interview Survey (cancer control and cancer epidemiology supplements) constituted the study population. Elapsed time from smoking initiation to cessation was compared via nonparametric tests and survival analysis techniques. RESULTS Findings showed that success in quitting was independent of ethnic status and sex and that population differences in smoking initiation age (assuming no differences in quitting behavior) could produce statistical associations between sex/ethnicity and smoking cessation. CONCLUSIONS Population differences in smoking initiation patterns can mask similarities in cessation rates.
Cross-Cultural Leadership: Best Practices In Multinational Graduate Education

The international security environment depends in part on professional military leaders with the knowledge, skills and attributes to execute a broad range of leadership communication, collaboration and negotiations with counterparts in complex international and intercultural settings. If higher education is the path to cognition, metacognition, motivation and behavior, then it may be an effective instrument for developing leadership readiness for a range of international/inter-cultural tasks. This study explores US military leaders’ perceptions about graduate-level, senior professional military education alongside foreign military officers at the U.S. Army War College as an influence on readiness for decision-making, cultural adaptation, and task performance in a cross-cultural leadership context. Five findings suggest the influence of a collaborative multinational graduate education setting on US leaders’ cross-cultural competence. Best practices based on theory-based analysis of graduate interviews include institutional guidance linking cultural agility and professional purpose; direct and meaningful engagements; skillful faculty facilitation; cultural immersion-like effects through multiple crosscultural experiences; and experiential learning that challenges and reframes mental models.
Board characteristics, ownership structure and audit report lag in the Middle East

Timeliness of corporate annual financial reports has a significant importance for users of financial statements. Timeliness of financial reporting of companies is considered to be a critical factor that affects the usefulness of information that helps the external users. This paper goes beyond the standard audit report lag studies by incorporating board characteristics and ownership structure variables into the determinants of financial reporting timeliness. The sample of this study comprises of 201 companies for the period from 2009 to 2013 that cover 11 countries of S%P Pan Arab index. Ordinary Least Square (OLS) and Ridge regression analysis are performed to test the audit report timeliness determinants. This study examines the effect of board characteristics, ownership structure, audit type, firm size, firm age, leverage and firm profitability on audit report timeliness. The results reveal that the higher percentage of companies releasing their audit report in less than 60 days and are audited by big four firms shows that big four firms are characterized by a higher audit quality. A regression analysis indicates that CEO duality, board size, board independence, ownership concentration, institutional ownership, foreign ownership, auditor type, return on assets, and firm age significantly affect audit report lag.
Identification of MUP1 as a Regulator for Glucose and Lipid Metabolism in Mice*

Major urinary protein (MUP) 1 is a lipocalin family member abundantly secreted into the circulation by the liver. MUP1 binds to lipophilic pheromones and is excreted in urine. Urinary MUP1/pheromone complexes mediate chemical communication in rodents. However, it is unclear whether circulatory MUP1 has additional physiological functions. Here we show that MUP1 regulates glucose and lipid metabolism. MUP1 expression was markedly reduced in both genetic and dietary fat-induced obesity and diabetes. Mice were infected with MUP1 adenoviruses via tail vein injection, and recombinant MUP1 was overexpressed in the liver and secreted into the bloodstream. Recombinant MUP1 markedly attenuated hyperglycemia and glucose intolerance in genetic (db/db) and dietary fat-induced type 2 diabetic mice as well as in streptozotocin-induced type 1 diabetic mice. MUP1 inhibited the expression of both gluconeogenic genes and lipogenic genes in the liver. Moreover, recombinant MUP1 directly decreased glucose production in primary hepatocyte cultures by inhibiting the expression of gluconeogenic genes. These data suggest that MUP1 regulates systemic glucose and/or lipid metabolism through the paracrine/autocrine regulation of the hepatic gluconeogenic and/or lipogenic programs, respectively.
One currency, one price? Euro Changeover related inflation in Estonia

This paper studies euro changeover-related inflation using disaggregated price level data. The difference-in-differences approach is used and the control group for the treatment country, Estonia, is built from 12 euro area countries. The Nielsen Company disaggregated price data are employed at product, brand and shop-type level. The results indicate that while the overall inflationary effect of euro adoption was modest, the effects were significantly different across various market segments. Changeoverrelated inflation was higher for products that were relatively cheaper than the euro area average. Inflationary effects were stronger in smaller shops.
Molecular Markers of Multiple Drug Resistance in Breast Cancer

Breast cancer is a significant health problem in terms of both morbidity and mortality, with approximately 12% of women directly affected by this disease. Chemotherapy, given to patients with earlier stage disease, has a good survival impact and may contribute to cure. The failure of chemotherapeutic drugs to eradicate cancer cells in more advanced disease states may be due to intrinsic or acquired drug resistance, including multiple drug resistance. The drug resistance observed in breast cancer patients is likely to be multifactorial, involving mechanisms such as altered expression and/or activity of drug efflux pumps, nuclear DNA-binding enzymes, metabolizing and conjugating enzymes, and mismatch repair deficiency. More extensive transcriptomic and proteomic analyses of breast tumour and normal biopsies, followed by functional genomic studies in relevant cell line models, should increase our understanding of this phenomenon and lead to therapies being individualized for identifiable subgroups of breast cancer patients.
A Method for the Immunohistochemical Identification and Localization of Osterix in Periosteum-Wrapped Constructs for Tissue Engineering of Bone

A novel immunohistochemistry (IHC) approach has been developed to label and localize osterix, a bone-specific transcription factor, within formalin-fixed, paraffin-embedded, tissue-engineered constructs uniquely containing synthetic polymers and human periosteal tissue. Generally, such specimens consisting in part of polymeric materials and mineral are particularly difficult for IHC identification of proteins. Samples here were fabricated from human periosteum, electrospun poly-l-lactic acid (PLLA) nanofibers, and polycaprolactone/poly-l-lactic acid (PCL/PLLA, 75/25) scaffolds and harvested following 10 weeks of implantation in athymic mice. Heat-induced and protease-induced epitope retrieval methods from selected existing protocols were examined to identify osterix. All such protease-induced techniques were unsuccessful. Heat-induced retrieval gave positive results for osterix immunohistochemical staining in sodium citrate/EDTA/Tween 20 with high heat (120C) and pressure (~30 psi) for 10 min, but the heat and pressure levels resulted in tissue damage and section delamination from slides that limited protocol effectiveness. Heat-induced epitope retrieval led to other osterix-positive staining results achieved with minimal impact on structural integrity of the tissue and polymers in sodium citrate/EDTA/Tween 20 buffer at 60C and normal pressure (14.5 psi) for 72 hr. The latter approach identified osterix-positive cells by IHC within periosteal tissue, layers of electrospun PLLA nanofibers, and underlying PCL/PLLA scaffolds of the tissue-engineered constructs.
Insights from Accounting Practitioners on China's Convergence with IFRS

This study provides insights from accounting practitioners on China's convergence with International Financial Reporting Standards (IFRS). Through a survey of 33 senior financial executives of Chinese listed companies in 2014, the study reports their perceptions on the following issues: first, the degree of convergence between IFRS and Chinese Accounting Standards (CAS); second, the choice between fair value and historical cost accounting, and the usefulness of fair value accounting for Chinese companiesâ€™ financial reporting; third, challenges in the process of China's harmonisation with IFRS; and finally, essential capabilities of Chinese accounting professionals in the process of China's harmonisation with IFRS. Multivariate regression was used for further analysis. The survey findings reveal that in general CAS have converged with IFRS, with a few exceptions that reflect the unique Chinese context. Historical cost accounting is the preferred measurement base to fair value accounting. Exercising professional judgement was identified as a challenge for China's full convergence with IFRS. Ownership structure and the expertise of accounting practitioners were found to affect respondentsâ€™ judgements on China's convergence with IFRS. This study has policy implications for international accounting standard setters and accounting educators to consider the contextual issues of implementing IFRS in an emerging economy.
Antibiotic prophylaxis in cataract surgery – An evidence-based approach

Various protocols are being followed for endophthalmitis prophylaxis in cataract surgery, and this subject continues to be a matter of debate. We summarize the most recent evidence-based studies on this topic with additional stress on intracameral (IC) antibiotic prophylaxis. Here, we discuss several large, international clinical studies which discuss the efficacy, adoption, safety, cost, and newer trends in antibiotic prophylaxis. Majority of these studies report a significant reduction in endophthalmitis rates with IC antibiotic prophylaxis. Efficacy data have been reported for IC cefuroxime, vancomycin, and moxifloxacin. Surgeons are now looking for alternatives to vancomycin for IC prophylaxis because of its association with the rare but sight-threatening complication of hemorrhagic occlusive retinal vasculitis. A recent large clinical study shows convincing efficacy with IC moxifloxacin prophylaxis. Two large studies have also reported significant endophthalmitis reduction following use of IC antibiotic prophylaxis, in eyes with posterior capsule tear which are at highest risk for infection. Except for one randomized controlled trial, there is a lack of prospective data on this subject; however, considering the complexity of performing such studies, surgeons have to rely on the mounting evidence from other recent big data studies. Availability of approved intraocular antibiotic formulations will see a much higher adoption in the future.
A Method for Automatic Fall Detection of Elderly People Using Floor Vibrations and Sound—Proof of Concept on Human Mimicking Doll Falls

Falls are a major risk for the elderly people living independently. Rapid detection of fall events can reduce the rate of mortality and raise the chances to survive the event and return to independent living. In the last two decades, several technological solutions for detection of falls were published, but most of them suffer from critical limitations. In this paper, we present a proof of concept to an automatic fall detection system for elderly people. The system is based on floor vibration and sound sensing, and uses signal processing and pattern recognition algorithm to discriminate between fall events and other events. The classification is based on special features like shock response spectrum and mel frequency ceptral coefficients. For the simulation of human falls, we have used a human mimicking doll: ldquoRescue Randy.rdquo The proposed solution is unique, reliable, and does not require the person to wear anything. It is designed to detect fall events in critical cases in which the person is unconscious or in a stress condition. From the preliminary research, the proposed system can detect human mimicking dolls falls with a sensitivity of 97.5% and specificity of 98.6%.
Members of the JAK/STAT proteins are expressed and regulated during development in the mammalian forebrain

The presence and activation of members of the Janus Kinases/ Signal Transducers and Activator of Transcription proteins in response to specific cytokines is currently the focus of intense investigation in the hematopoietic system. Although some evidence suggests that cytokines might play an important role in brain development and brain pathologies, very limited information is available on the presence of the JAK/ STAT proteins in the Central Nervous System. Here we provide Western blot and immunohystochemistry data on the presence of Jak2 in vivo in the immature brain, its expression being greater in early stages of the embryonic life and gradually diminishing towards adulthood. Conversely, Jak1 was found expressed at a lower level compared to Jak2 and not modulated during brain maturation. Western blot data also show that specific members of the STAT family, the cytoplasmic substrates of the Janus Kinases, are present in vivo and that the extent of their expression is modulated differently at various stages. In particular, Stat6 protein levels were markedly attenuated at advanced stages of differentiation, as well as in the adult brain, with respect to early embryonic life. On the contrary, Stat3 levels did not vary. Analysis of Stat1 and Stat5 proteins showed a more complex expression pattern. These data indicate that members of the JAK/ STAT proteins are present and modulated in vivo in the embryonic and postnatal brain, therefore supporting their role in the modulation of gene expression during the different stages of brain maturation. J. Neurosci. Res. 54:320–330, 1998. © 1998 Wiley‐Liss, Inc.
Who Married How? Modeling Marital Decisions in Early-Twentieth Century Taiwan

Marriage in Taiwan in the early twentieth century was a very diverse phenomenon. Marriages could be in the “minor” fashion, in which the bride was adopted at an early age by her parents-in-law. They could also be of the virilocal “major” type, in which young adults married and lived in the household of the husband's parents. Finally, they could be “uxorilocal,” in which the husband came to live with his in-laws. The diversity of types reflects a complex mixture of motives on behalf of parents, who aimed to secure the patrilineage, but in the meantime were motivated to save on wedding expenses, safeguard their hold on the younger generation, forge alliances between clans, and bring in additional labor. In our paper, we assess the relative importance of these parental motives by applying a competing risks analysis on household registry data from nine Taiwanese communities. By combining data on the levels of the individuals, the composition of their households, the characteristics of their communities, and economic fluctuations, we demonstrate the remarkable flexibility and adaptability of Taiwanese marriage within the overriding constraint of producing male offspring.