Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct regulation of interleukin-17 in human T helper lymphocytes.

OBJECTIVE Interleukin-17 (IL-17)-producing T helper cells have been proposed to represent a separate lineage of CD4+ cells, designated Th17 cells, which are regulated by the transcription factor retinoic acid-related orphan receptor gammat (RORgammat). However, despite advances in understanding murine Th17 differentiation, a systematic assessment of factors that promote the differentiation of naive human T cells to Th17 cells has not been reported. The present study was undertaken to assess the effects on naive human CD4+ T cells of cytokines known to promote murine Th17 cells. METHODS Human naive and memory CD4+ T cells isolated from peripheral blood were activated and cultured with various cytokines. Cytokine production was measured by enzyme-linked immunosorbent assay and flow cytometry. Messenger RNA was measured by quantitative polymerase chain reaction. RESULTS In response to anti-CD3/anti-CD28 stimulation alone, human memory T cells rapidly produced IL-17, whereas naive T cells expressed low levels. Transforming growth factor beta1 and IL-6 up-regulated RORgammat expression but did not induce Th17 differentiation of naive CD4+ T cells. However, IL-23 up-regulated its own receptor and was an important inducer of IL-17 and IL-22. CONCLUSION The present data demonstrate the differential regulation of IL-17 and RORgammat expression in human CD4+ T cells compared with murine cells. Optimal conditions for the development of IL-17-producing T cells from murine naive precursors are ineffective in human T cells. Conversely, IL-23 promoted the generation of human Th17 cells but was also a very potent inducer of other proinflammatory cytokines. These findings may have important implications in the pathogenesis of human autoimmunity as compared with mouse models.
Forecasting of Realised Volatility with the Random Forests Algorithm

The paper addresses the forecasting of realised volatility for financial time series using the heterogeneous autoregressive model (HAR) and machine learning techniques. We consider an extended version of the existing HAR model with included purified implied volatility. For this extended model, we apply the random forests algorithm for the forecasting of the direction and the magnitude of the realised volatility. In experiments with historical high frequency data, we demonstrate improvements of forecast accuracy for the proposed model.
Distinct roles for the two cGATA-1 finger domains

We have generated and analyzed by functional assays mutations of the chicken erythroid transcription factor GATA-1. The cGATA-1 protein contains two related finger domains highly conserved across species and characteristic of the family of GATA-binding factors. We find that mutations in the C-terminal finger or adjacent basic region abolish sequence-specific DNA binding, confirming that this region constitutes a novel DNA-binding domain sufficient to recognize the consensus WGATAR motif. At least three separate regions outside of this finger II domain contribute in a cooperative manner to the trans-activation potential of the protein. As expected from previous results analyzing the mouse homolog, we find that the N-terminal finger plays a role in DNA binding by affecting the stability of the DNA-protein complex. In addition, we find mutations of finger I subtly altered in DNA-binding function which greatly diminish trans-activation. Our results support the notion that the GATA-1 protein must be positioned precisely on the GATA cis element to enable the activation of target genes.
Regulation of PTEN by CK2 and Notch1 in primary T-cell acute lymphoblastic leukemia: rationale for combined use of CK2- and γ-secretase inhibitors

T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN. However, it is not clear whether NOTCH1 mutations associate with decreased PTEN expression in primary T-ALL. Here, we compared patients with or without NOTCH1 mutations and report that the former presented higher MYC transcript levels and decreased PTEN mRNA expression. We recently showed that T-ALL cells frequently display CK2-mediated PTEN phosphorylation, resulting in PTEN protein stabilization and concomitant functional inactivation. Accordingly, the T-ALL samples analyzed, irrespectively of their NOTCH1 mutational status, expressed significantly higher PTEN protein levels than normal controls. To evaluate the integrated functional impact of Notch transcriptional and CK2 post-translational inactivation of PTEN, we treated T-ALL cells with both the gamma-secretase inhibitor DAPT and the CK2 inhibitors DRB/TBB. Our data suggest that combined use of gamma-secretase and CK2 inhibitors may have therapeutic potential in T-ALL.
Taming cronyism!: the role of Public Private Dialogues

Purpose The purpose of this paper is to explore the effect of Public Private Dialogues (PPD) on cronyism accounting for various cultural and governance institutions. Design/methodology/approach It proposes a number of hypotheses on: whether PPD characterized by high official representation and business representation, through mainly building trust, succeed in minimizing cronyism; whether certain cultural and governance institutions help PPD in achieving this; and in cultural settings which are originally inducing cronyism whether PPD help in minimizing cronyism. These are tested empirically using an ordinary least squares multivariate panel regression. Findings High official representation and high business people’s participation in PPD were found to help in minimizing cronyism in different cultures. This is arguably attributed to building trust in cultures characterized by having low general trust and low trust in governments. Accountability and transparency are significantly assisting PPD in this regard. Yet, PPD do not always succeed in taming cronyism, and in particular in ethnic fractionalized societies and societies having high collective cultures. Research limitations/implications The biggest challenge this research faced was estimating a proxy for PPD. Better data on business associations’ participation worldwide are needed to construct a more developed proxy. Practical implications PPD with high business participation and government representation should be encouraged. The same is true for reform leading to higher levels of transparency and accountability. Originality/value Constructing a proxy for PPD that allowed meta-analysis; and investigating theoretically and empirically the effect of the interaction of PPD with various institutions on cronyism.
Do Precious Metals Act As Hedges and Safe Heavens against G-7 Stock Markets?: A Vine Copula Approach

This paper investigates the role of precious metals (Gold, Silver and Platinum) as hedge and/or safe haven assets against the G-7 stock markets that represents the most developed economies, by characterizing the multivariate dependence structure using vine copulas, mainly the C-vine and the D-vine, to capture more flexibly the dependencies between the three precious metals and each stock market index. Therefore, by the information about the dependence on average and the dependence in extreme market conditions provided by the vine copula, we find that all precious metals under study serve as hedge and safe haven assets in almost all countries with different degrees. On one hand, our hedge analysis results indicate that only gold may serve as a strong hedge on average while silver and platinum may be good diversifier assets. On the other hand, our safe haven analysis results show that both of gold and silver may be strong safe haven assets in almost all the G-7 countries.
How to Study DNA and Proteins by Linear Dichroism Spectroscopy

The technique of linear dichroism (LD) is a simple absorbance technique that uses two polarised light beams. Since only oriented molecules show different absorbances for different polarisations, LD detects only oriented molecules. In aqueous solutions, flow orientation is an attractive orientation methodology as it selects long molecules or molecular assemblies. LD thus is selective for molecules that are particularly challenging to study by more standard biophysical techniques. In this article, a brief review of the application of LD to DNA, DNA–drug systems, DNA–protein enzymatic complexes, fibrous proteins and membrane peptides and proteins is given.
Corticosterone Response as an Age-Specific Mediator of Nestling Body Mass in a Wild Passerine

The environment can affect individual performance directly via resource availability or indirectly through resource allocation among competing fitness components, such as body growth and maintenance activities related to short-term survival. Corticosterone (CORT), the main glucocorticoid in birds, may be an important mediator of energy allocation to different organismal functions, but its effect on the plasticity of fitness-related traits has rarely been investigated at different ontogenetic stages. Here, we evaluated the role of baseline and stress-induced CORT on nestling development of wild great tits (Parus major) under different growth conditions and at different developmental stages. We found that nestling mass and condition were positively related to stress-induced levels of total CORT and free CORT in the middle of nestling stage but negatively related at the prefledging stage. Our results also showed that stress-induced levels of total CORT can be used as a proxy for bioavailable free CORT. No significant relationship of body mass or condition in either stage was shown with levels of baseline CORT or stress-induced CORT-binding globulin capacity. None of these age-specific relationships depend on brood size manipulation. We conclude that the effects of glucocorticoids on nestling performance are stage specific. The ability to secrete CORT may have beneficial effects on nestling development in the middle of the nestling stage, while it can be adaptive to keep CORT levels at optimal ranges before fledging to give priority to growth-related processes that are important for long-term fitness.
Old-age dependency: is it really increasing in aging populations?

ABSTRACT To account for economic dependency we propose an adjustment to the old-age dependency ratio based on savings of the elderly. Computations are simple and the adjusted ratio is aimed at retaining the exogenous character of the conventional demographic ratio. Data from an economy with stagnating incomes and a fast growing elderly population (Japan) and an economy with fast growing incomes (Singapore) highlight that the conventional dependency ratio substantially exaggerates the burden of the elderly.
Biopolymers and biodegradable smart implants for tissue regeneration after spinal cord injury

Purpose of reviewThis article reviews recent experimental advances in the development of biosynthetic implants for repair of spinal cord injury. Recent findingsVarious important advances in the development of biosynthetic conduits for spinal cord repair have recently been reported. It was found that implantation of freeze dried alginate sponge into completely transected spinal cord supports axonal regeneration across the lesion site. A poly(lactic-co-glycolic acid) scaffold seeded with neural stem cells has been developed that promotes axonal regeneration across the gap. It was found that polyethylene glycol can reseal damaged spinal cord axons and restore impulse conduction. Findings have been reported that poly-β-hydroxybutyrate conduits in combination with alginate and fibronectin provide neuroprotection for axotomized descending neurones. It has been reported that conduits made of fibronectin mats or fibrin in combination with neurotrophic growth factors promote axonal growth into the grafts. Finally, magnetic resonance imaging after experimental spinal cord injury has been used to monitor regeneration in biosynthetic conduits in vivo over time. SummaryBiosynthetic conduits carrying extracellular matrix molecules and different cell lines, and supplemented with neurotrophic growth factors have yielded encouraging results in the treatment of experimental spinal cord injury. These findings provide a basis for further development of techniques aimed at spinal cord repair in humans.
A cost-effectiveness evaluation of enamel matrix derivatives alone or in conjunction with regenerative devices in the treatment of periodontal intra-osseous defects.

PURPOSE To identify the most cost-effective approach to treatment of infrabony lesions with enamel matrix derivatives (EMD). METHODS We incorporated costs and clinical outcomes of 12 different treatment techniques (including flap operation, EMD alone, and EMD in association with other reconstructive devices) within a decision tree model in which costs were based on insurance regulations in Germany and health outcomes followed a recent meta-analysis. The most cost-effective treatment option was identified on the basis of the maximum net benefit criterion. RESULTS Treatment techniques using EMD were cost-efficient if the decision maker's willingness-to-pay (WTP) was at least €150-175 per incremental mm of pocket probing depth reduction and clinical attachment level gain, respectively (1-year perspective). When EMD was affordable, the maximum net benefit was achieved by treatment with EMD in conjunction with bioactive glass or bovine bone substitutes. Additional application of platelet-rich plasma (PRP) or a resorbable membrane came at relatively high costs. CONCLUSIONS If EMD use is indicated, EMD in conjunction with either bioactive glass or bovine bone substitutes is more cost-effective than EMD alone. The additional use of PRP or a resorbable membrane may only be justifiable when monetary resources for treatment are very generous.
QUALITY PERCEPTIONS OF ONLINE LEARNERS ABOUT THEIR EDUCATION SYSTEMS

Online learning (OL) has become an important part of university education. In the past OL was applied in different universities with different forms. With rapid technological developments OL gains a new format through Internet. Students can take courses online wherever they are geographically. Therefore working people and adults can enroll in a higher education institution without time and space barriers. Like many other countries, Turkey adapted its education system to this new form. Beginning from 1980s, this system was applied through open education faculties in state universities. However as the number of foundation universities increase, OL became more common application in many programs at different levels. In this study, quality perception of online learners that enrolled in a university in Turkey will be determined and analyzed through statistical analyses.
Island Rule, quantitative genetics and brain–body size evolution in Homo floresiensis

Colonization of islands often activate a complex chain of adaptive events that, over a relatively short evolutionary time, may drive strong shifts in body size, a pattern known as the Island Rule. It is arguably difficult to perform a direct analysis of the natural selection forces behind such a change in body size. Here, we used quantitative evolutionary genetic models, coupled with simulations and pattern-oriented modelling, to analyse the evolution of brain and body size in Homo floresiensis, a diminutive hominin species that appeared around 700 kya and survived up to relatively recent times (60–90 kya) on Flores Island, Indonesia. The hypothesis of neutral evolution was rejected in 97% of the simulations, and estimated selection gradients are within the range found in living natural populations. We showed that insularity may have triggered slightly different evolutionary trajectories for body and brain size, which means explaining the exceedingly small cranial volume of H. floresiensis requires additional selective forces acting on brain size alone. Our analyses also support previous conclusions that H. floresiensis may be most likely derived from an early Indonesian H. erectus, which is coherent with currently accepted biogeographical scenario for Homo expansion out of Africa.
Effects of 2 ankle fatigue models on the duration of postural stability dysfunction.

CONTEXT Muscle fatigue is generally categorized in 2 ways: that caused by peripheral weakness (peripheral fatigue) and that caused by a progressive failure of voluntary neural drive (central fatigue). Numerous variables have been studied in conjunction with fatigue protocols, including postural stability, maximum voluntary contraction force, and reaction time. When torque recordings fall below 50% of a maximum voluntary contraction, the muscle is described as fatigued, but whether this value is a good indicator of fatigue has not been studied. OBJECTIVE To compare the effects of 2 ankle musculature fatigue protocols (30% and 50%) on the duration of postural stability dysfunction. DESIGN To assess differences between the 30% and 50% fatigue protocols, we calculated a 1 between-groups factor (subjects) and 2 within-groups factors (fatigue, test) analysis of variance. SETTING E.J. Nutter Athletic Training Facility. PATIENTS OR OTHER PARTICIPANTS Twenty subjects (10 men, 10 women; age = 21.15 +/- 2.23 years; height = 172.97 +/- 9.86 cm; mass = 70.62 +/- 14.60 kg) volunteered for this study. Subjects had no history of lower extremity injury, vestibular or balance disorders, functional ankle instability, or head injury in the past 6 months. INTERVENTION(S) On separate days, subjects performed isokinetic fatiguing contractions of the plantar flexors and dorsiflexors in a 30% protocol (70% decrease in strength) and a 50% protocol (50% decrease in strength). MAIN OUTCOME MEASURE(S) Baseline and postfatigue postural stability scores were determined before and after the isokinetic fatiguing contractions. Plantar-flexion peak-torque measurements were obtained for the 2 fatiguing protocols. Three prefatigue and 12 postfatigue postural stability trials were recorded. Velocities for testing were 60 degrees /s for plantar flexion and 120 degrees /s for dorsiflexion. RESULTS Sway velocity was significantly greater when the ankle was fatigued to 30% (1.56 degrees /s) than in the 50% condition (1.36 degrees /s). For the 30% protocol, sway was significantly impaired when the pretest condition (1.19 degrees /s) was compared with posttest trial 1 (2.34 degrees /s), trial 2 (2.37 degrees /s), and trial 3 (1.71 degrees /s). For the 50% protocol, sway was significantly impaired when the pretest condition (1.27 degrees /s) was compared with posttest trial 1 (2.02 degrees /s). CONCLUSIONS The 30% fatigue protocol resulted in significantly longer impairment of postural stability than the 50% protocol. Because the 30% protocol resulted in a greater effect but was relatively short-lived (approximately 75 to 90 s), it is more useful for research purposes.
Evidence of Behavioural Compensation in Internal Replication Study of Male Circumcision Trial to Reduce HIV Acquisition in Kisumu, Kenya

Abstract We replicated the study ‘Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial’ using an epidemiological approach as well as an econometric approach. Both approaches confirmed the 60 per cent protective effect of circumcision reported in the original paper. Similar to the original paper, we found no evidence of heterogeneous treatment effects by age. Contrary to the original study, we found evidence of risk compensation, with circumcised men less likely to stay abstinent (odds ratio 0.79 [95% CI: 0.64, 0.99]) and more likely to have had unprotected intercourse (OR 1.2 [1.1, 1.4]). These findings reinforce the impact of circumcision but highlight behavioural risk.
Genetic variation in CXCL12 and risk of cervical carcinoma: a population‐based case–control study

CXCL12 provides a chemotactic signal‐directing leucocyte migration and regulates metastatic behaviour of tumour cells. We conducted a population‐based case–control study to test the hypothesis that common genetic variation in CXCL12 individual single nucleotide polymorphism (SNP) alleles and haplotypes] is associated with the risk of cervical carcinoma. Cases (n = 917) were residents of western Washington State diagnosed with invasive squamous cell cervical carcinoma (SCC), invasive adenocarcinoma or adenosquamous carcinoma, or adenocarcinoma in situ of the cervix. Control participants (n = 849) were identified from the source population by random digit telephone dialling and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR = 0.74, 95% CI: 0.56–0.98). Among the ten common haplotypes inferred from the nine tagSNPs, one haplotype defined by minor alleles at 5′‐flanking SNP rs17885289 and rs266085, and common alleles at the other seven SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR = 0.72, 95% CI: 0.56–0.93; recessive model OR = 0.35, 95% CI: 0.12–0.97; and log‐additive model OR = 0.72, 95% CI: 0.57–0.90). A stepwise procedure identified rs17885289, rs266085 and 3′‐untranslated region (UTR) SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3′‐UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population‐based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.
Shorting Leveraged ETF Pairs

This article examines the strategy of shorting a pair of leveraged ETFs and inverse leveraged ETFs of the same index. The profitability of this strategy does not depend on the direction of the underlying benchmark. The authors derive an approximation formula to show that the expected return is high when the weighted sum of various orders of autocorrelations is negative and the volatility of the underlying index is high. They then study the trading strategy in six markets and show that it can generate mean monthly returns of over 1% in four markets. The returns can be further enhanced if they exploit the persistence of the volatility and start the shorting pair strategy when the observed volatility is high.
Vitamin D Toxicity, Policy, and Science

The serum 25‐hydroxyvitamin D [25(OH)D] concentration that is the threshold for vitamin D toxicity has not been established. Hypercalcemia is the hazard criterion for vitamin D. Past policy of the Institute of Medicine has set the tolerable upper intake level (UL) for vitamin D at 50 μg (2000 IU)/d, defining this as “the highest level of daily nutrient intake that is likely to pose no risks of adverse health effects to almost all individuals in the general population. ” However, because sunshine can provide an adult with vitamin D in an amount equivalent to daily oral consumption of 250 μg (10,000 IU)/d, this is intuitively a safe dose. The incremental consumption of 1 μg (40 IU)/day of vitamin D3 raises serum 25(OH)D by ∼1 nM (0.4 ng/ml). Therefore, if sun‐deprived adults are to maintain serum 25(OH)D concentrations >75 nM (30 ng/ml), they will require an intake of more than the UL for vitamin D. The mechanisms that limit vitamin D safety are the capacity of circulating vitamin D–binding protein and the ability to suppress 25(OH)D‐1‐α‐hydroxylase. Vitamin D causes hypercalcemia when the “free” concentration of 1,25‐dihydroxyvitamin D is inappropriately high. This displacement of 1,25(OH)2D becomes excessive as plasma 25(OH)D concentrations become higher than at least 600 nM (240 ng/ml). Plasma concentrations of unmetabolized vitamin D during the first days after an acute, large dose of vitamin D can reach the micromolar range and cause acute symptoms. The clinical trial evidence shows that a prolonged intake of 250 μg (10,000 IU)/d of vitamin D3 is likely to pose no risk of adverse effects in almost all individuals in the general population; this meets the criteria for a tolerable upper intake level.