Miracle-dz/UniFAR-FTUs huggingface dataset:
The second Ca2+-binding domain of the Na+–Ca2+ exchanger is essential for regulation: Crystal structures and mutational analysis

The Na+–Ca2+ exchanger plays a central role in cardiac contractility by maintaining Ca2+ homeostasis. Two Ca2+-binding domains, CBD1 and CBD2, located in a large intracellular loop, regulate activity of the exchanger. Ca2+ binding to these regulatory domains activates the transport of Ca2+ across the plasma membrane. Previously, we solved the structure of CBD1, revealing four Ca2+ ions arranged in a tight planar cluster. Here, we present structures of CBD2 in the Ca2+-bound (1.7-Å resolution) and -free (1.4-Å resolution) conformations. Like CBD1, CBD2 has a classical Ig fold but coordinates only two Ca2+ ions in primary and secondary Ca2+ sites. In the absence of Ca2+, Lys585 stabilizes the structure by coordinating two acidic residues (Asp552 and Glu648), one from each of the Ca2+-binding sites, and prevents a substantial protein unfolding. We have mutated all of the acidic residues that coordinate the Ca2+ ions and have examined the effects of these mutations on regulation of exchange activity. Three mutations (E516L, D578V, and E648L) at the primary Ca2+ site completely remove Ca2+ regulation, placing the exchanger into a constitutively active state. These are the first data defining the role of CBD2 as a regulatory domain in the Na+–Ca2+ exchanger.
Vitamin D Activation and Function in Human Corneal Epithelial Cells During TLR-Induced Inflammation.

PURPOSE Vitamin D is recognized to be an important modulator of the immune system. In the eye, studies have shown that deficiencies and genetic differences in vitamin D-related genes have a significant impact on the development of various ocular diseases. Our current study examines the ability of human corneal epithelial cells (HCEC) to activate vitamin D and the effect of vitamin D treatment on antimicrobial peptide production and cytokine modulation during inflammation, with the ultimate goal of using vitamin D therapeutically for corneal inflammation. METHODS Human corneal epithelial cells were treated with 10-7M vitamin D3 (D3) or 25-hydroxyvitamin D3 (25D3) for 24 hours and 1,25-dihydroxyvitamin D3 (1,25D3) detected by immunoassay. Human cathelicidin (LL-37) expression was examined by RT-PCR, immunoblot, and immunostaining following 1,25D3 treatment and antimicrobial activity of 1,25D3-treated cells was determined. Cells were stimulated with TLR3 agonist polyinosinic-polycytidylic acid (Poly[I:C]) for 24 hours and cytokine levels measured by RT-PCR, ELISA, and Luminex. Immunostaining determined expression of vitamin D receptor (VDR) and retinoic acid inducible gene-1 receptor (RIG-1) as well as NF-κB nuclear translocation. RESULTS When treated with inactive vitamin D metabolites, HCEC produced active 1,25D3, leading to enhanced expression of the antimicrobial peptide, LL-37, dependent on VDR. 1,25-D3 decreased the expression of proinflammatory cytokines (IL-1β, IL-6, TNFα, and CCL20) and MMP-9 induced by Poly(I:C) as well as pattern recognition receptor expression (TLR3, RIG-1, MDA5). However, early activation of NF-κB was not affected. CONCLUSIONS These studies demonstrate the protective ability of vitamin D to attenuate proinflammatory mediators while increasing antimicrobial peptides and antipseudomonas activity in corneal cells, and further our knowledge on the immunomodulatory functions of the hormone.
Helix‐destabilizing properties of the human single‐stranded DNA‐ and RNA‐binding protein Purα

Purα is a ubiquitous nucleic acid‐binding protein which has been implicated in the control of eukaryotic gene transcription. Further, Purα associates with DNA sequences positioned in close proximity to viral and cellular origins of replication suggesting a role for this protein in DNA replication. As initiation of transcription and replication require alteration in the structure of duplex DNA, we investigated the DNA unwinding activity of this single‐stranded nucleic acid‐binding protein. Here we demonstrate that Purα has the ability to displace an oligonucleotide annealed to single‐stranded M13 DNA. The helix unwinding activity of Purα was dose‐, time‐ and temperature‐dependent and ATP‐independent. Results from mapping studies revealed that the central region of Purα, spanning amino acids 72–274, was important for the helix‐destabilizing activity of this protein. The region of Purα which was involved in the helix‐destabilizing activity mapped to the DNA‐binding domain of this protein. Results from heat inactivation experiments demonstrated that the helix‐destabilizing activity of Purα correlates with its capacity to interact with DNA containing the PUR element. Taken together, these studies demonstrate that Purα possesses helix‐destabilizing activity and that this activity maps to and correlates with its ability to interact with DNA. J. Cell. Biochem. 80:589–595, 2001. © 2001 Wiley‐Liss, Inc.
Thermotherapy for treating rheumatoid arthritis.

BACKGROUND Thermotherapy is often used as adjunct in the treatment of rheumatoid arthritis (RA) by rehabilitation specialists. OBJECTIVES To evaluate the effectiveness of different thermotherapy applications on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY We searched Medline, EMBASE, Pedro, Current Contents, Sports Discus and CINAHL up to and including September 2001. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Hand searching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA Comparative controlled studies, such as randomized controlled trials, controlled clinical trials, cohort studies or case/control studies, of thermotherapy compared to control or active interventions in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS Two independent reviewers identified potential articles from the literature search (VR, LB). These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS Seven studies (n=328 subjects) met the inclusion criteria. The results of this systematic review of thermotherapy for RA found that there was no significant effect of hot and ice packs applications (Ivey 1994), cryotherapy (Rembe 1970) and faradic baths (Hawkes 1986) on objective measures of disease activity including joint swelling, pain, medication intake, range of motion (ROM), grip strength, hand function compared to a control (no treatment) or active therapy. There is no significant difference between wax and therapeutic ultrasound as well as between wax and faradic bath combined to ultrasound for all the outcomes measured after 1, 2 or 3 week(s) of treatment (Hawkes 1986). There was no difference in patient preference for all types of thermotherapy. No harmful effects of thermotherapy were reported. REVIEWER'S CONCLUSIONS Superficial moist heat and cryotherapy can be used as a palliative therapy. Paraffin wax baths combined with exercises can be recommended for beneficial short term effects for arthritic hands. These conclusions are limited by methodological considerations such as the poor quality of trials.
Difficulties in screening for adjustment disorder, Part I: Use of existing screening instruments in cancer patients undergoing bone marrow transplantation

Objective: Although success rates for bone marrow transplantation (BMT) continue to improve, there is still a high level of morbidity and physical and emotional distress associated with BMT. To date, limited research has focused on the assessment of and screening for specific psychiatric disorders of patients facing BMT. This is especially true with regard to identifying adjustment disorder (AD), despite the fact that AD is the most prevalent psychiatric diagnosis in cancer patients. Methods: A sample of 95 BMT patients were interviewed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID) and completed several commonly used self-report instruments to determine if these tools could be used to identify patients with adjustment disorder in need of further assessment and intervention. Results: Of these patients, 34.7% were diagnosed with adjustment disorder, 11.6% with major depression, and 5.3% with generalized anxiety disorder. The instruments were not found to be predictive of AD. However, the results of a regression analysis showed that the Social Subscale of the Functional Assessment of Cancer Therapy–General (R2 Δ = 0.04, F = 4.30, p < 0.05) was a significant predictor of adjustment disorder. Significance of results: We conclude that there is little efficacy in using existing scales for detecting adjustment disorders in cancer patients undergoing bone marrow transplantation, and that other tools for identifying patients with adjustment disorder who might benefit from counseling are needed.
Single-Source Multiple-Coil Homogeneous Induction Heating

This paper proposes and implements an approach to achieve homogeneous heating in a single-source multiple-coil induction heating system. In a traditional induction heating system, one of the key disadvantages is the inhomogeneous heating effect. In particular, the heating power concentrates on a small ring area of the pan, while the outer part receives much lower power. The proposed induction heating system consists of two concentric coils with its compensated capacitors connecting in series, respectively. Currents in the two coils are controlled by newly employing the magnetic resonant coupling mechanism so that the heating power distribution in the inner and outer parts of the pan can be adjusted accordingly. Therefore, the proposed induction heating can achieve homogeneity and simplicity simultaneously by optimizing the operating frequency of only one inverter. Both the simulation and experimental results are given to validate the feasibility of the proposed homogeneous induction heating.
Ben Bernanke in Doha: The Effect of Monetary Policy on Optimal Tariffs

Trade liberalization can imply slow and long adjustment processes. Taking account of these adjustment processes can change the evaluation of trade policy, especially when policy makers care more about the next couple of years than the infinite future. In this paper I analyze the setting of tariffs in a two-country model taking account of adjustment processes with special emphasis on the effects of nominal price rigidity and monetary policy. I show that nominal price rigidity induces policy makers with a short planning horizon to set lower tariffs because it enhances the short run boom following a cut in tariffs. Monetary policy that aggressively fights deviations from its inflation target leads to even lower tariffs.
The Effect of Information on TOU Electricity Use: An Irish Residential Study

ABSTRACT The disconnect between the time of use and the time of payment is sometimes blamed for the little awareness that many consumers appear to have about their usage of electricity. Real time information feedback combined with various pricing schemes has been found to reduce residential energy consumption more than information and pricing policies alone. I examine the effect of information provision with bi-monthly billing, monthly billing, and in-home displays in addition to a time-of-use pricing scheme on consumption over each month of the Irish Consumer Behavior Trial. I find that time-of-use pricing with real time usage information reduces electricity usage up to 8.7 percent during peak times at the start of the trial but the effect becomes indistinguishable from other treatment groups after the first three months. Increasing billing reports to the monthly level or a web application providing real time information may be more cost effective than in-home displays.
Liquidity, momentum and price bubbles : evidence from the UK

The asset pricing anomalies have existed in the UK stock market for a long time. This thesis aims to study different liquidity measures, liquidity commonality, systematic liquidity risk, different momentum trading strategies, asset pricing risks with momentum, investor behaviours with momentum and the causal link between financial crisis and asset pricing anomalies using various methods and tests. The first empirical chapter examines the performance of the standard SharpeLintner CAPM, the Fama-French three factor model, and the four factor model of Carhart (1997) both with, and without, the first component of multiple illiquidity measures. The results show that no individual illiquidity proxy outperforms the others, and further that the illiquidity proxies have a systematic common illiquidity component. The results also reveal that the inclusion of the illiquidity factor in the capital asset pricing model plays a significant role in explaining the crosssectional variation in stock returns. The second empirical chapter analyses the relationship between momentum profits and stock market illiquidity. This study finds negative and significant relationship between aggregate market illiquidity and momentum profits. The model applied in this chapter captures significant bounce in varying beta coefficients changing over time. The analysis also indicates that the stocks associated with high liquidity performs better relative to illiquid stocks under systemic shocks. The final empirical chapter investigated momentum anomaly and the hypothesis that individual investors trade differently from institutional investors and significantly overreact to economic shocks, creating destabilising effect in the stock market. The results reveal that stock
The Efficacy and Safety of Probiotic Lactobacillus rhamnosus GG on Prolonged, Noninfectious Diarrhea in HIV Patients on Antiretroviral Therapy: A Randomized, Placebo-Controlled, Crossover Study

Abstract Purpose: The aim of this placebo-controlled, crossover study was to evaluate the efficacy and safety of probiotic Lactobacillus rhamnosus GG (LGG) in ameliorating gastrointestinal symptoms in HIV-infected patients on antiretroviral therapy. Method: Infectious causes for diarrhea (bacteria, ova, parasites, and viruses including cryptosporidium, microsporidia, and cyclospora) were excluded with fecal samples before the study. HIV-infected patients with diarrhea for more than 1 month received in randomized order probiotic LGG preparation (containing viable LGG 1-5 × 1010 cfu/dose) and placebo twice a day for 2 weeks. Gastrointestinal symptoms were assessed daily and included the daily number of bowel movements, classification of stool consistency (watery, semi-watery, loose, firm, or foaming), and Visual Analog Scale (VAS) of gastrointestinal symptoms (flatulence, stomach pain, bloating disorders, general well-being). Results: Seventeen HIV-infected patients completed the study. There were no significant differences between the treatment groups in the frequency or the consistency of diarrhea. In the VAS assessments of gastrointestinal symptoms, no difference between LGG and placebo could be detected. No adverse events were reported. The number of HIV RNA copies in the blood and CD4 cell counts remained stable during the study. Conclusion: Probiotic LGG preparation was well-tolerated in HIV infected patients. No significant differences in noninfectious diarrhea or gastrointestinal symptoms compared to placebo could be observed in this crossover study.
Validity of 20 meter multi stage shuttle run test for prediction of maximum oxygen uptake in Indian female university students.

BACKGROUND The 20-meter multi stage shuttle run test (20-m MST) has not yet been used by Indian scientists and validity of the test has not been studied for use with any of the Indian population. AIMS The purpose of this study was to validate the applicability of the 20-m MST in Indian adult female. MATERIALS AND METHODS For application of direct method cross over design was followed. For validity of the results repeatability was used. METHODS AND MATERIAL 32 female university students (age range 20.4 approximately 24.8 years) from three different universities of West Bengal, India were recruited for the study. Direct estimation of VO2 max comprised treadmill exercise followed by expired gas analysis by scholander micro-gas analyzer whereas VO2 max was indirectly predicted by the 20-m MST. STATISTICAL ANALYSIS Paired t-test, Pearson's product moment correlation, linear regression statistics and Bland and Altman approach for limit of agreement were adopted for statistical analysis of the data. RESULTS The difference between the mean (SD) VO2 max values of direct measurement (VO2 max = 32.84 +/- 2.92 ml/kg/min) and the 20-m MST (SPVO2 max = 32.60 +/- 3.40 ml/kg/min) was statistically insignificant (p>0.10). Limits of agreement analysis also suggest that the 20-m MST can be applied for use with the studied population. CONCLUSIONS The results suggest that the application of the present form of the 20-m MST be justified in the studied population. For better prediction of VO2 max a new equation has been computed based on present data for use with Indian female university students.
[Influence of air pollution on birth weight].

INTRODUCTION Epidemiological studies point out that exposure to air pollution during pregnancy is a risk for low birth weight. OBJECTIVE The aim of this study was to evaluate the effects of outdoor and indoor air pollution on the occurrence of low birth weight. METHODS The measurement of outdoor air pollutants, sulphur dioxide and black smoke was carried out daily at the Institute for Public Healthcare of Nis at two measuring locations, in Nis and Niska Banja during 2003. Subjects were 367 pregnant women, nonsmokers and who were not profesionally exposed to air pollution. Data on exposure to source of indoor air pollution (passive smoking and mode of heating) was determined on the basis of a questionnaire. Data on the characterisitics of newborns were taken from the register of Obstetrics and Gyanecology Clinic of Nis. RESULTS We determined that exposure of pregnant women to outdoor air pollution and wood heating systems had influence on the occurence of low birth weight. Exposure to passive smoking had no influence on neonatal low birth weight. CONCLUSION Exposure of pregnant women to outdoor and indoor air pollutants can have negative influence on the occurrence of low birth weight.
Back from the brink: Social transformation and developing tourism in post-conflict Medellin, Colombia

Purpose Emerging from 20 years of violence and terrorism, the city of Medellin, Colombia, has used social transformation to improve civic culture, leading to a renaissance. The purpose of this study is to explore how social transformation can lead to urban transformation, forming the basis for sustainable, post-conflict tourism. Design/methodology/approach This case study is based on available descriptive data and direct observation supported by secondary sources. Findings The results of the research help to provide a better understanding of the conditions needed to develop and manage sustainable tourism in post-conflict environments. In so doing, it should be possible to make better policy decisions, with particular reference to social and urban interventions on planning, design and entrepreneurship. Research limitations/implications The transformation of Medellin’s civic culture can be a model for destination with similar histories that present significant destination image and branding challenges – though each will take different paths. Originality/value This paper is one of the first on post-conflict tourism that analyzes the impact on a destination and country of internal turmoil due to narco-terrorism and insurgency over a lengthy period.
Eating disorder prevention initiatives for athletes: A review

Abstract A substantial amount of evidence suggests that collegiate and elite athletes involved in weight-sensitive sports are at greater risk of developing eating disorders (EDs) than the general population. With the limited effectiveness of treatment for EDs, prevention of EDs has been broadly considered in the literature. The present paper reviewed the existing literature on ED prevention programmes for athletes in order to determine the current status of prevention programmes and recommend future directions. The available literature suggests that selective, primary interventions with multiple targets and an interactive multimodal approach appear most effective. Current challenges in the field, including lack of longitudinal research, hesitation by the sport community to be involved in ED research and poor cross-field communication and collaboration, are also explored. The lack of dissemination of evidence-based prevention programmes and the simultaneous promotion of prevention programmes that have not yet been empirically examined are also discussed. Based on these observations future directions are recommended.
A Mutant Form of the Neisseria gonorrhoeae Pilus Secretin Protein PilQ Allows Increased Entry of Heme and Antimicrobial Compounds

ABSTRACT A spontaneous point mutation in pilQ (pilQ1) resulted in phenotypic suppression of a hemoglobin (Hb) receptor mutant (hpuAB mutant), allowing gonococci to grow on Hb as the sole source of iron. PilQ, formerly designated OMP-MC, is a member of the secretin family of proteins located in the outer membrane and is required for pilus biogenesis. The pilQ1 mutant also showed decreased piliation and transformation efficiency. Insertional inactivation of pilQ1 resulted in the loss of the Hb utilization phenotype and decreased entry of free heme. Despite the ability of the pilQ1 mutant to use Hb for iron acquisition and porphyrin, there was no demonstrable binding of Hb to the cell surface. The pilQ1 mutant was more sensitive to the toxic effect of free heme in growth medium and hypersensitive to the detergent Triton X-100 and multiple antibiotics. Double mutation in pilQ1 and tonB had no effect on these phenotypes, but a double pilQ1 pilT mutant showed a reduction in Hb-dependent growth and decreased sensitivity to heme and various antimicrobial agents. Insertional inactivation of wild-type pilQ also resulted in reduced entry of heme, Triton X-100, and some antibiotics. These results show that PilQ forms a channel that allows entry of heme and certain antimicrobial compounds and that a gain-of function point mutation in pilQ results in TonB-independent, PilT-dependent increase of entry.