Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of FGF23-Dependent Egr-1 Cistrome in the Mouse Renal Proximal Tubule

Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphate (Pi) and vitamin D homeostasis. The transcription factor, early growth response 1 (egr-1), is a biomarker for FGF23-induced activation of the ERK1/2 signaling pathway. We have shown that ERK1/2 signaling blockade suppresses renal egr-1 gene expression and prevents FGF23-induced hypophosphatemia and 1,25-dihydroxyvitamin D (1,25(OH)2D) suppression in mice. To test whether egr-1 itself mediates these renal actions of FGF23, we administered FGF23 to egr-1 -/- and wild-type (WT) mice. In WT mice, FGF23 induced hypophosphatemia and suppressed expression of the renal Na/Pi cotransporters, Npt2a and Npt2c. In FGF23-treated egr-1 -/- mice, hypophosphatemic response was greatly blunted and Na/Pi cotransporter expression was not suppressed. In contrast, FGF23 induced equivalent suppression of serum 1,25(OH)2D concentrations by suppressing renal cyp27b1 and stimulating cyp24a1 mRNA expression in both groups of mice. Thus, downstream of receptor binding and ERK1/2 signaling, we can distinguish the effector pathway that mediates FGF23-dependent inhibition of Pi transport from the pathway that mediates inhibition of 1,25(OH)2D synthesis in the kidney. Furthermore, we demonstrate that the hypophosphatemic effect of FGF23 is significantly blunted in Hyp/egr-1 -/- mice; specifically, serum Pi concentrations and renal Npt2a and Npt2c mRNA expression are significantly higher in Hyp/egr-1 -/- mice than in Hyp mice. We then characterized the egr-1 cistrome in the kidney using ChIP-sequencing and demonstrate recruitment of egr-1 to regulatory DNA elements in proximity to several genes involved in Pi transport. Thus, our data demonstrate that the effect of FGF23 on Pi homeostasis is mediated, at least in part, by activation of egr-1.
The effect of inferior turbinate outfracture on nasal resistance to airflow in vasomotor rhinitis assessed by rhinomanometry

Twenty-eight patients with nasal obstruction due to vasomotor rhinitis were assessed using anterior rhinomanometry before and six weeks after the operation of out-fracture and amputation of the posterior ends of the inferior turbinates. It was found that the operation did not significantly improve the nasal airway. Though just over half the patients had an objective improvement in nasal airflow, only half of this group reported a subjective improvement in their symptoms.
The Effect of Three-Monthly Albendazole Treatment on Malarial Parasitemia and Allergy: A Household-Based Cluster-Randomized, Double-Blind, Placebo-Controlled Trial

Background Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. Methods and Findings A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5–15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35–12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74–1.86) at 9 months or 1.37 (0.93–2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. Conclusions The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. Trial Registration Controlled-Trials.com ISRCTN83830814
'Basque for all?' : ideology and identity in migrants' perceptions of Basque

This PhD thesis explores language attitudes and ideologies among migrant students of Basque in the Basque Autonomous Community of Spain. I aim to explore the contexts of language attitude formation in interaction, and how these attitudes in turn, reflect the underlying ideological indexicalities that contribute to the creation of social categories. The processes of attitude construction and ideologies that guide them are then influential and consequential for group identity formation, for instance, when migrant learners position themselves on the scale of belonging to ‘Basqueness’ understood as a group identity. In this project I analyse three areas in which this influence of ideologies on attitudes and identity construction was found particularly significant and consequential for migrant learners of Basque: the construction of space in which Basque group identity is embedded and based on Basque resources subjected to processes of scalar evaluation; the construction of authenticity in relation to speakers, language and spaces; as well as in the construction of Basque language as resources convertible into economic capital. All these three areas show that essentialist and constructionist discourses on minoritised languages and group identity intertwine in the representations of social categories, such as migrants, language, language speaker. This has consequences on the extent to which migrant learners position and identify themselves as belonging to ‘Basqueness’. This project is ethnographically oriented and the data comes from observations and participation in Basque classes for adult migrants, interviews with class participants and interviews with other Basque learners at various language centres throughout the Basque Autonomous Community, as well as from Basque public institutions’ publications with language course descriptions and campaigns directed at migrant Basque learners.
A Meta-Analysis of the Association between TNF-α −308G>A Polymorphism and Type 2 Diabetes Mellitus in Han Chinese Population

Objective A meta-analysis was applied to evaluate the associations between tumor necrosis factor-α (TNF-α) −308G>A (rs1800629) polymorphism and type 2 diabetes mellitus (T2DM). Methods Hardy-Weinberg equilibrium (HWE) was employed to test genetic equilibrium among the genotypes of the selected literature. Power analysis was performed with the Power and Sample Size Calculation (PS) program. A fixed or random effect model was used on the basis of heterogeneity. Publication bias was quantified and examined with the Begg's funnel plot test and Egger's linear regression test. The meta-analysis was performed with Review Manager 5.1 and Stata 11.0. Results There were 10 studies including 1425 T2DM patients and 1116 healthy control subjects involved in this meta-analysis. No significant publication bias was found in the studies. The pooled ORs (95% CIs) for TNF-α −308G>A of A vs. G allele and GA+AA vs. GG genotype were 1.63 (1.17–2.25) and 1.47 (1.17–1.85), respectively. Conclusion This meta-analysis result suggested that TNF-α −308G>A polymorphism was strongly associated with T2DM risk, and A allele at this locus might be a susceptibility allele for the development of T2DM in Han Chinese population.
Thermodynamic calculations using a simulated annealing optimization algorithm

In Chemical Engineering, several thermodynamic calculations can be formulated as optimization problems with or without restrictions. As indicated by Henderson et al. [1] the formulation of thermodynamic calculations for optimization problems offers some advantages: a) the use of a robust optimization method, b) the possibility of using a direct optimization method which requires only calculations of the objective function and c) the use of an iterative procedure whose convergence is almost independent on the initial guesses. Some examples of these calculations are phase stability analysis, phase equilibrium problems, parameter estimation in thermodynamic models, calculation of critical points, among others. These problems are non-linear, multivariable and the objective function used as optimization criterion is non-convex with several local optimums. By consequence, its solving with local optimization methods is not reliable because they generally converge to local optimums. During the last years, the development and application of global optimization strategies have increased in many areas of Chemical Engineering. Global optimization methods can be classified as deterministic and stochastic [2]. The first class offers a guarantee to find the global optimum of the objective function [21, 32, 24]. However, these strategies often require high computational time (generally more time than stochastic methods) and in some cases the problem reformulation is needed. In the other hand, stochastic optimization methods are robust numerical tools that present a reasonable computational effort in the optimization of multivariable functions; they are applicable to ill-structure or unknown structure problems and can be used with all thermodynamic models [3]. Thermodynamic Calculations Using a Simulated Annealing Optimization Algorithm
Antimicrobial, Antioxidant, and Cytotoxic Properties of Vasicine Acetate Synthesized from Vasicine Isolated from Adhatoda vasica L.

Adhatoda vasica (L.) (Acanthaceae) is used in the indigenous system of medicine in India. The alkaloid Vasicine was isolated from ethanolic extract of the leaves of A. vasica using column chromatography. Vasicine acetate was obtained by acetylation of Vasicine. Vasicine acetate exhibited good zone of inhibition against bacteria: 10 mm against E. aerogenes, 10 mm against S. epidermidis, and 10 mm against P. aeruginosa. Vasicine acetate showed minimum inhibitory concentration values against bacteria: M. luteus (125 μg/mL), E. aerogenes (125 μg/mL), S. epidermidis (125 μg/mL), and P. aeruginosa (125 μg/mL). The radical scavenging activity of Vasicine acetate was the maximum at 1000 μg/mL (66.15%). The compound showed prominent cytotoxic activity in vitro against A549 lung adenocarcinoma cancer cell line. Quantification of Vasicine and Vasicine acetate by HPLC-DAD analysis showed their contents to be 0.2293% and 0.0156%, respectively, on dry weight basis of the leaves. Vasicine acetate could be probed further in drug discovery programme.
Self-Management of Oral Anticoagulants with a Whole Blood Prothrombin-Time Monitor in Elderly Patients with Atrial Fibrillation

The efficacy of oral anticoagulants (OAC) in reducing the incidence of stroke in elderly patients with atrial fibrillation (AF) has been well documented. The intensity of OAC therapy and deviations in the prothrombin time (PT) are the strongest risk factor for bleeding complications in elderly patients. The aim of this study was to evaluate a more rigorous regulation of OAC by the use of a portable whole blood PT-monitor (CoaguChek) in elderly patients with AF (age 65–80 years). The study group consisted of 20 patients, of whom 17 were evaluable , which were trained to use to CoaguChek monitor and adjust their anticoagulant dose for 12 months. The control group, 20 patients matched for age, gender and the duration of OAC treatment, were tested in an anticoagulant clinic and their OAC dose was adjusted by a physician. To validate the PT-monitor results, the patients performed a total of 129 simultaneous venous blood PT tests at various time points. The correlation coefficient R2 was 0.707 indicating the accuracy of the CoaguChek results. The self-managed patients perform more frequent measurements 46 ± 8.9 vs. 15.7 ± 3.1 PT tests per patient. They demonstrated a within the therapeutic range INR in 80.5% of the tests (95% confidence interval, 76.5–84.1%) as compared to 72.4% (95% confidence interval, 68.5–76.5%) in the control group (p = 0.057). The median value for all CoaguChek International Normalized Ratio (INR) recordings was within therapeutic range in the self-management group as well as in the control group. There were fewer INR results below or above the therapeutic range in the study group. None of the patients had hemorrhagic or thrombotic events during the study. Overall, the study group expressed high satisfaction from using the home monitor. We conclude that home PT monitoring and self-management of OAC are feasible in a motivated population of elderly patients with atrial fibrillation and are probably cost effective.
Rapid Degradation of Auxin/Indoleacetic Acid Proteins Requires Conserved Amino Acids of Domain II and Is Proteasome Dependent

Auxin rapidly induces auxin/indoleacetic acid (Aux/IAA) transcription. The proteins encoded are short-lived nucleus-localized transcriptional regulators that share four conserved domains. In a transient assay measuring protein accumulation, an Aux/IAA 13–amino acid domain II consensus sequence was sufficient to target firefly luciferase (LUC) for low protein accumulation equivalent to that observed previously for full-length PSIAA6. Single amino acid substitutions in these 13 amino acids, corresponding to known auxin response mutants, resulted in a sixfold to 20-fold increase in protein accumulation. Naturally occurring variant amino acids had no effect. Residues identified as essential by single alanine substitutions were not sufficient when all flanking amino acids were alanine, indicating the importance of flanking regions. Using direct protein degradation measurements in transgenic Arabidopsis seedlings, full-length IAA1, PSIAA6, and the N-terminal 73 PSIAA6 amino acids targeted LUC for rapid degradation with 8-min half-lives. The C-terminal 109 amino acids did not affect LUC half-life. Smaller regions containing domain II also targeted LUC for rapid degradation, but the rates were not equivalent to those of the full-length protein. A single domain II substitution in the context of full-length PSIAA6 increased half-life 30-fold. Proteasome inhibitors affected Aux/IAA::LUC fusion protein accumulation, demonstrating the involvement of the proteasome.
Coupled GCM Simulation of Atmosphere-Ocean Variability Associated with Zonally Asymmetric SST Changes in the Tropical Indian Ocean

Abstract The nature of a recurrent pattern of variability in the tropical Indian Ocean (IO) during the boreal autumn has been investigated using a 900-yr experiment with a coupled atmosphere–ocean general circulation model. This Indian Ocean Pattern (IOP) is characterized by zonal surface wind perturbations along the equator, as well as east–west contrasts in the anomalous sea surface temperature (SST), surface pressure, and precipitation fields. The IOP is seen to be linked to the El Nino–Southern Oscillation (ENSO) phenomenon in the tropical Pacific. By constructing composite charts and analyzing the heat budget for the top ocean layer, it is illustrated that the ENSO-related changes in the surface wind modify the intensity of oceanic upwelling, horizontal temperature advection, and surface heat fluxes in various parts of the IO basin. These processes lead to SST perturbations with opposite signs in the eastern and western equatorial IO. Further diagnosis of the model output reveals that some strong IOP.
Germinal centers in human lymph nodes contain reactivated memory B cells

To reveal migration trails of antigen-responsive B cells in lymphoid tissue, we analyzed immunoglobulin (Ig)M-VH and IgG-VH transcripts of germinal center (GC) samples microdissected from three reactive human lymph nodes. Single B cell clones were found in multiple GCs, one clone even in as many as 19 GCs. In several GCs, IgM and IgG variants of the same clonal origin were identified. The offspring of individual hypermutated IgG memory clones were traced in multiple GCs, indicating repeated engagement of memory B cells in GC reactions. These findings imply that recurring somatic hypermutation progressively drives the Ig repertoire of memory B cells to higher affinities and infer that transforming genetic hits in non-Ig genes during lymphomagenesis do not have to arise during a single GC passage, but can be collected during successive recall responses.
Quantification of intrahepatic total hepatitis B virus DNA in chronic hepatitis B patients and its relationship with liver histology

Aims: This study was conducted to evaluate the relationship between total intrahepatic hepatitis B virus (HBV) DNA levels and liver histology in terms of the degree of histological activity index (HAI) that yields necroinflammation (HAI-NI) and fibrosis (HAI-F) of the liver. Methods: Prospectively, Tru-cut needle biopsy samples were obtained from the livers of 42 patients with chronic hepatitis B. Levels of serum and liver HBV DNA were determined by quantitative real-time PCR. Demographic data of patients, together with hepatitis B serology, alanine aminotransferase levels, and HAI-NI and HAI-F scores, were recorded. Results: Twenty of the patients were hepatitis B e antigen (HBeAg) positive, while 22 patients were positive for antibody to HBeAg (anti-HBe). Serum and liver total HBV DNA levels were found to correlate directly with each other in the two groups (r = 0.669, p = 0.001; and r = 0.880, p<0.001; respectively) and the correlation was more marked in anti-HBe-positive patients. Although serum HBV DNA levels correlated positively with HAI-NI and HAI-F scores in HBeAg-positive and HBeAg-negative patients, total liver HBV DNA levels correlated with HAI-NI and HAI-F scores in anti-HBe-positive patients only. Conclusions: Quantitative measurement of intrahepatic HBV DNA is a valuable marker of the histological status of the liver in anti-HBe-positive patients with chronic hepatitis B, and it may give an insight into the prognosis and the ideal time for the cessation of antiviral treatment.
Mild gestational diabetes as a risk factor for congenital cryptorchidism.

CONTEXT Cryptorchidism is the most common malformation in newborn boys. Maternal diabetes has previously been suggested to be a risk factor for this disorder in one epidemiological study. OBJECTIVE Evaluation of the prevalence of maternal glucose metabolism disorders during pregnancy in newborn boys having normal testicular descent or congenital cryptorchidism. DESIGN Postnatal analysis of maternal history concerning glucose metabolism abnormalities during pregnancy among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS The material of this case-control study comprises 1163 boys with normal testicular descent at birth and 125 boys with congenital cryptorchidism. All these singleton Finnish boys were born in Turku University Central Hospital (1997-2001) and were examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES Information about maternal diabetes diagnosis and abnormality of the result of a 2-h 75-g oral glucose tolerance test during pregnancy were obtained from the hospital records after delivery. RESULTS After adjustment for possible confounding factors, i.e. maternal smoking during pregnancy, maternal age at delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for gestational age, abnormal maternal glucose metabolism was significantly more common in the group of cryptorchid boys [diet-treated gestational diabetes, P = 0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated gestational diabetes or only an abnormal result in oral glucose tolerance test, P = 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared with boys with normal testicular descent. CONCLUSIONS Mildly abnormal glucose metabolism during pregnancy was associated with an increased risk for congenital cryptorchidism. The mechanism remains to be elucidated.
The reconfigurable streaming vector processor (RSVP/spl trade/)

The need to process multimedia data places large computational demands on portable/embedded devices. These multimedia functions share common characteristics: they are computationally intensive and data-streaming, performing the same operation(s) on many data elements. The reconfigurable streaming vector processor (RSVP) is a vector coprocessor architecture that accelerated streaming data operations. Programming the RSVP architecture involves describing the shape and location of vector steams in memory and describing computations as data-flow graphs. These descriptions are intuitive and independent of each other, making the RSVP architecture easy to program. They are also machine independent, allowing binary-compatible implementations with varying cost-performance tradeoffs. This paper presents the RSVP architecture and programming model, a programming case study, and our first implementation. Our results show significant speedups on streaming data functions. Speedups for kernels and applications range from 2 to over 20 times that of an ARM9 host processor alone.
Congestive Heart Failure in Copper-Deficient Mice

Copper Deficiency (CuD) leads to hypertrophic cardiomyopathy in various experimental models. The morphological, electrophysiological, and molecular aspects of this hypertrophy have been under investigation for a long time. However the transition from compensated hypertrophy to decompensated heart failure has not been investigated in the study of CuD. We set out to investigate the contractile and hemodynamic parameters of the CuD mouse heart and to determine whether heart failure follows hypertrophy in the CuD heart. Dams of FVB mice were fed CuD or copper-adequate (CuA) diet starting from the third day post delivery and the weanling pups were fed the same diet for a total period of 5 weeks (pre- and postweanling). At week 4, the functional parameters of the heart were analyzed using a surgical technique for catheterizing the left ventricle. A significant decrease in left ventricle systolic pressure was observed with no significant change in heart rate, and more importantly contractility as measured by the maximal rate of left ventricular pressure rise (+dP/dt) and decline (−dP/dt) were significantly depressed in the CuD mice. However, left ventricle end diastolic pressure was elevated, and relaxation was impaired in the CuD animals; the duration of relaxation was prolonged. In addition to significant changes in the basal level of cardiac function, CuD hearts had a blunted response to the stimulation of the β-adrenergic agonist isoproterenol. Furthermore, morphological analysis revealed increased collagen accumulation in the CuD hearts along with lipid deposition. This study shows that CuD leads to systolic and diastolic dysfunction in association with histopathological changes, which are indices commonly used to diagnose congestive heart failure.