Miracle-dz/UniFAR-FTUs huggingface dataset:
Granulysin Production and Anticryptococcal Activity Is Dependent upon a Far Upstream Enhancer That Binds STAT5 in Human Peripheral Blood CD4+ T Cells

Previous studies have demonstrated that STAT5 is critical for expression of granulysin and antimicrobial activity. Because the signaling pathway and the resultant microbicidal activity are defective in HIV-infected patients, the mechanism by which STAT5 leads to granulysin expression is of great interest. In the current study, IL-2–stimulated CRL-2105 CD4+ T cells expressed granulysin and killed Cryptococcus neoformans similar to primary CD4+ T cells. The enhancer activity of the upstream element of the granulysin promoter was analyzed in primary CD4+ T cells and CRL-2105 T cells with a luciferase reporter assay, and a STAT5 binding site, 18,302 to 18,177 bp upstream of the transcription start site, was identified as an enhancer. Additionally, the enhancer functioned in the context of heterologous SV40 promoter irrespective of its transcriptional orientation. Chromatin immunoprecipitation and EMSAs demonstrated that the enhancer element bound STAT5 both in vivo and in vitro, and mutation of the STAT5 binding site abrogated its enhancer activity. Furthermore, overexpression of a dominant negative STAT5a abolished the enhancer activity of the STAT5 binding site and abrogated the anticryptococcal activity of IL-2–stimulated primary CD4+ T cells. Taken together, these data provide details about the complex regulation leading to granulysin expression and anticryptococcal activity in primary CD4+ T cells.
Use of reconstituted influenza virus virosomes as an immunopotentiating delivery system for a peptide‐based vaccine

Immunopotentiating reconstituted influenza virosomes (IRIV) were used as a delivery system for the synthetic peptide‐based malaria vaccine SPf66. The reduced SPf66 peptide molecules containing terminal cysteine residues were covalently attached to phosphatidylethanolamine with the heterobifunctional crosslinker γ‐maleimidobutyric acid N‐hydroxysuccinimide ester. The SPf66‐phosphatidylethanolamine was incorporated into IRIV and BALB/c mice were immunized twice by intramuscular injection with peptide‐loaded virosomes. Titres of elicited anti‐SPf66 IgG were determined by ELISA. These titres were significantly higher and the required doses of antigen were lower, when mice had been preimmunized with a commercial whole virus influenza vaccine. After preimmunization with the influenza vaccine, SPf66‐IRIV elicited far more consistently anti‐SPf66 antibody responses than SPf(66)n adsorbed to alum. MoAb produced by four B cell hybridoma clones derived from a SPf66‐IRIV‐immunized mouse cross‐reacted with Plasmodium falciparum blood stage parasites in immunofluorescence assays. All four MoAbs were specific for the merozoite surface protein‐1 (MSP‐1)‐derived 83.1 portion of SPf66. Sequencing of their functionally rearranged κ light chain variable region genes demonstrated that the four hybridomas were generated from clonally related splenic B cells. Biomolecular interaction analyses (BIA) together with these sequencing data provided evidence for the selection of somatically mutated affinity‐matured B cells upon repeated immunization with SPf66‐IRIV. The results indicate that IRIV are a suitable delivery system for synthetic peptide vaccines and thus have a great potential for the design of molecularly defined combined vaccines targeted against multiple antigens and development stages of one parasite, as well as against multiple pathogens.
Metropolitan income inequality and working-age mortality: A cross-sectional analysis using comparable data from five countries

The relationship between income inequality and mortality has come into question as of late from many within-country studies. This article examines the relationship between income inequality and working-age mortality for metropolitan areas (MAs) in Australia, Canada, Great Britain, Sweden, and the United States to provide a fuller understanding of national contexts that produce associations between inequality and mortality. An ecological cross-sectional analysis of income inequality (as measured by median share of income) and working-age (25–64) mortality by using census and vital statistics data for 528 MAs (population >50,000) from five countries in 1990–1991 was used. When data from all countries were pooled, there was a significant relationship between income inequality and mortality in the 528 MAs studied. A hypothetical increase in the share of income to the poorest half of households of 1% was associated with a decline in working-age mortality of over 21 deaths per 100,000. Within each country, however, a significant relationship between inequality and mortality was evident only for MAs in the United States and Great Britain. These two countries had the highest average levels of income inequality and the largest populations of the five countries studied. Although a strong ecological association was found between income inequality and mortality across the 528 MAs, an association between income inequality and mortality was evident only in within-country analyses for the two most unequal countries: the United States and Great Britain. The absence of an effect of metropolitan-scale income inequality on mortality in the more egalitarian countries of Canada. Australia, and Sweden is suggestive of national-scale policies in these countries that buffer hypothetical effects of income inequality as a determinant of population health in industrialized economies.
An adaptive and composite spatio-temporal data compression approach for wireless sensor networks

Wireless Sensor Networks (WSN) are often deployed to sample the desired environmental attributes and deliver the acquired samples to the sink for processing, analysis or simulations as per the application needs. Many applications stipulate high granularity and data accuracy that results in high data volumes. Sensor nodes are battery powered and sending the requested large amount of data rapidly depletes their energy. Fortunately, the environmental attributes (e.g., temperature, pressure) often exhibit spatial and temporal correlations. Moreover, a large class of applications such as scientific measurement and forensics tolerate high latencies for sensor data collection. Accordingly, we develop a fully distributed adaptive technique for spatial and temporal in-network data compression with accuracy guarantees. We exploit the spatio-temporal correlation of sensor readings while benefiting from possible data delivery latency tolerance to further minimize the amount of data to be transported to the sink. Using real data, we demonstrate that our proposed scheme can provide significant communication/energy savings without sacrificing the accuracy of collected data. In our simulations, we achieved data compression of up to 95% on the raw data requiring around 5% of the original data to be transported to the sink.
On Over-fitting in Model Selection and Subsequent Selection Bias in Performance Evaluation

Model selection strategies for machine learning algorithms typically involve the numerical optimisation of an appropriate model selection criterion, often based on an estimator of generalisation performance, such as k-fold cross-validation. The error of such an estimator can be broken down into bias and variance components. While unbiasedness is often cited as a beneficial quality of a model selection criterion, we demonstrate that a low variance is at least as important, as a non-negligible variance introduces the potential for over-fitting in model selection as well as in training the model. While this observation is in hindsight perhaps rather obvious, the degradation in performance due to over-fitting the model selection criterion can be surprisingly large, an observation that appears to have received little attention in the machine learning literature to date. In this paper, we show that the effects of this form of over-fitting are often of comparable magnitude to differences in performance between learning algorithms, and thus cannot be ignored in empirical evaluation. Furthermore, we show that some common performance evaluation practices are susceptible to a form of selection bias as a result of this form of over-fitting and hence are unreliable. We discuss methods to avoid over-fitting in model selection and subsequent selection bias in performance evaluation, which we hope will be incorporated into best practice. While this study concentrates on cross-validation based model selection, the findings are quite general and apply to any model selection practice involving the optimisation of a model selection criterion evaluated over a finite sample of data, including maximisation of the Bayesian evidence and optimisation of performance bounds.
The Relationship between Eating and Lifestyle Habits and Cancer in Van Lake Region: Another Endemic Region for Esophageal and Gastric Cancers

Purpose. To examine the relationship between esophageal and gastric cancers commonly seen in Van Lake region and the traditional eating habits of the geography. Materials and Methods. Esophageal and gastric cancer cases, who underwent surgery between January 1, 2012, and December 31, 2013, were examined. Pathology reports of the patients and presence of Helicobacter pylori (HP) were recorded. Surveys were filled by face to face meeting or telephone call. Control group was created with randomly selected individuals without any cancer diagnosis having age, gender, and socioeconomic characteristics similar to patient group. All data were analyzed using SAS.9. 3 statistical programme. Results. Compared with the control group, herby cheese consumption (a component of eating habits) and smoking were significantly higher in the patient group (P < 0.001). Tandoor exposure is compared in terms of female gender, and significant difference was found between the groups (P = 0.0013). As a result of the analysis with logistic regression more than 150 gr of herby cheese consumption per day was found to increase the cancer risk (odds ratio 1.017; 95% CI: 1.012–1.022). Conclusion. A high consumption of herby cheese, cooking bread on tandoor, and heavy smoking were seen to be important risk factors for esophageal and gastric cancers.
Effects of Frequency Distribution on Linear Menu Performance

While it is well known that menu usage follows a Zipfian distribution, there has been little interest in the impact of menu item frequency distribution on user's behavior. In this note, we explore the effects of frequency distribution on average menu performance as well as individual item performance. We compare three frequency distributions of menu item usage: Uniform; Zipfian with s=1 and Zipfian with s=2. The results show that (1) user's behavior is sensitive to different frequency distributions at both menu and item level; (2) individual item selection time depends on, not only its frequency, but also the frequency of other items in the menu. Finally, we discuss how these findings might have impacts on menu design, empirical studies and menu modeling.
Iodine Concentration in Breastmilk and Urine among Lactating Women of Bhaktapur, Nepal

Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130, 370) µg/L and 230 (135–377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (β 3.0, 95% CI (0.2, 5.0)) and UIC (β 1.0, 95% CI (0.1, 2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants.
Homocysteine and Carotid Intima-Media Thickness in a German Population: Lack of Clinical Relevance

Background and Purpose— Common carotid artery intima-media thickness (CCA IMT) is a predictor of stroke. This study aimed to analyze whether homocysteine (Hcys) metabolism influences CCA IMT. Methods— We analyzed the association of personal, clinical, and biochemical data (multivariate analysis) and of 9 polymorphisms involved in Hcys metabolism (ANOVA) with CCA IMT in 714 individuals of 187 families. Results— CCA IMT was significantly predicted by age, sex, creatinine levels, lipoprotein(a) levels, pack-years of smoking, the presence of hypertension, and the presence of diabetes mellitus but not by Hcys levels. Homozygosity for the T allele of the polymorphism methylenetetrahydrofolate reductase c.677C>T was significantly associated with higher Hcys levels but not with a higher CCA IMT. Conclusions— These data do not support the thesis that elevated Hcys levels are causally involved in cerebrovascular disease.
Toxicological profile for boron

DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. A Toxicological Profile for Boron Draft for Public Comment was released in October 2007. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at: iv BORON This page is intentionally blank. FOREWORD This toxicological profile is prepared in accordance with guidelines* developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects infonnation for these toxic substances described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The focus of the profiles is on health and toxicologic infonnation; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's relevant toxicological properties. Following the public health statement is infonnation concerning levels of significant human exposure and, where known, significant health effects. The adequacy of infonnation to detennine a substance's health effects is described in a health effects summary. Data needs that are of significance to protection of public health are identified by ATSDR. Each profile includes the following: (A) The examination, summary, and interpretation of available toxicologic infonnation and epidemiologic evaluations on a toxic substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (B) A determination of whether adequate infonnation on the health effects of each substance is available or in the process of development to detennine levels of exposure that present a significant risk to human health of acute, subacute, and chronic health effects; and (C) Where appropriate, identification of toxicologic testing needed to identifY the types or levels of exposure that may present significant risk of adverse health effects in humans. The principal audiences for the toxicological profiles are health professionals …
Has Japan Been Left Out in the Cold by Regional Integration?

Despite the ongoing worldwide trend toward regional integration, Japan has remained outside of all regional trading agreements. Because more than 60 percent of Japan's trade is with countries that are members of a major regional bloc, this reluctance may have had significant effects on its pattern and volume of trade. Indeed, I find that Japan's exports have been reduced by the integration of its trading partners, and that this effect has been fairly uniform across integration regimes. I also find that regional trading agreements have tended to have a much more negative effect on Japanese trade than on the trade of other nonmembers.
SWI/SNF Protein Component BAF250a Regulates Cardiac Progenitor Cell Differentiation by Modulating Chromatin Accessibility during Second Heart Field Development*

Background: Epigenetic mechanisms governing cardiac progenitor cell (CPC) differentiation are not well understood. Results: Chromatin remodeler BAF250a/SWI/SNF regulates CPC differentiation in vivo and in vitro by modeling the chromatin accessibility at a subset of key genes essential for cardiogenesis. Conclusion: BAF250a/SWI/SNF plays a key role in CPC differentiation. Significance: Understanding the SWI/SNF-mediated epigenetic mechanism in CPC differentiation may provide molecular basis for novel heart therapies. ATP-dependent SWI/SNF chromatin remodeling complexes alter the structure of chromatin at specific loci and facilitate tissue-specific gene regulation during development. Several SWI/SNF subunits are required for cardiogenesis. However, the function and mechanisms of SWI/SNF in mediating cardiac progenitor cell (CPC) differentiation during cardiogenesis are not well understood. Our studies of the SWI/SNF chromatin remodeling complex identified that BAF250a, a regulatory subunit of the SWI/SNF, plays a key role in CPC differentiation. BAF250a ablation in mouse second heart field (SHF) led to trabeculation defects in the right ventricle, ventricular septal defect, persistent truncus arteriosus, reduced myocardial proliferation, and embryonic lethality around E13. Using an embryonic stem cell culture system that models the formation and differentiation of SHF CPCs in vivo, we have shown that BAF250a ablation in CPCs specifically inhibits cardiomyocyte formation. Moreover, BAF250a selectively regulates the expression of key cardiac factors Mef2c, Nkx2.5, and Bmp10 in SHF CPCs. Chromatin immunoprecipitation and DNase I digestion assays indicate that BAF250a regulates gene expression by binding selectively to its target gene promoters and recruiting Brg1, the catalytic subunit of SWI/SNF, to modulate chromatin accessibility. Our results thus identify BAF250a-mediated chromatin remodeling as an essential epigenetic mechanism mediating CPC differentiation.
Periodic event-triggered control for nonlinear systems

Resources limitations of embedded systems and networked control systems have motivated the development of novel controller implementation paradigms in order to reduce the potential conservatism of traditional clock-driven setups. In this context periodic event-triggered control has recently been proposed. Based on a periodically evaluated and state-dependent criterion, it is decided, at every sampling instant, whether the control input needs to be updated or not. In this paper we propose a method for the design of periodic event-triggered controllers for nonlinear systems. We follow an emulation-based approach as we start from a known (continuously evaluated) event-triggered controller and we provide a systematic technique to select the sampling period and to redesign the triggering condition to approximately maintain the guarantees ensured by the original controller. The method is illustrated on a physical system and we compare the obtained results with other available event-based implementations.
Low-temperature rheology of bitumen and its relationship with chemical and thermal properties

The thermal cracking performance of asphalt pavements is largely governed by the properties of the bituminous binder, and thus the low-temperature rheological characterization of bitumen is of great importance. Recently, a novel testing technique has been developed for the measurement of the low-temperature rheological properties of bituminous materials. This testing technique, commonly referred to as the 4-mm DSR, uses a 4-mm parallel plate geometry on a dynamic shear rheometer (DSR) with radial instrument compliance corrections. However, very little data produced by using the 4-mm DSR technique is currently available in the literature. The primary objective of this study was to examine the low-temperature rheological characteristics of various unmodified bitumens by using the 4-mm DSR technique. In addition, the correlations of the chemical and thermal properties with the low-temperature rheology of bitumen were investigated. The secondary purpose of this thesis was to study physical aging in bitumen. The 4-mm DSR technique was used to test twenty-seven bitumen samples originating from various crude oil sources and refineries. The chemical properties of the bitumens were described in terms of their molecular weight properties, as measured by gel permeation chromatography (GPC), and aromatic properties, as measured by ultraviolet-visible spectroscopy (UV-vis), infrared spectroscopy (FT-IR) and refractive index (RI) techniques. The thermal properties of the studied bitumens, including the glass transition temperatures (Tg), were determined by differential scanning calorimetry (DSC). Both horizontal and vertical shifts were needed to produce smooth master curves in the vicinity of Tg. The temperature dependence of horizontal shift factors was shown to accurately follow the Kaelble-WLF equation in the temperature range of Tg-30 K to Tg+115 K. The calculated relaxation time spectra H(τ) evidenced a transition from small-scale molecular to large-scale cooperative relaxation processes when bitumen was cooled below its Tg. It was shown that the low-temperature rheological properties of bitumen can be fairly accurately predicted from the molecular weight and aromatic properties. Physical aging in bitumen was successfully analyzed by means of time-aging time superposition, and, based on the limited data available, equilibrium is attained in approximately 2-3 days at Tg. However, additional studies are needed to properly assess the effect of physical aging on the low-temperature rheological properties of various bitumens.