Miracle-dz/UniFAR-FTUs huggingface dataset:
Granisetron shows no pro-arrhythmic effect in normal subjects during or after exercise in a hot environment.

BACKGROUND 5-HT3 receptor antagonists are being evaluated as possible agents to prevent nausea and vomiting associated with radiation exposure in a non-clinical military setting. Because of concern about potential cardiovascular toxicity and the observation that certain developmental 5-HT3 antagonists produced undesirable effects, all drugs in this class are being carefully scrutinized for possible adverse cardiac effects. METHOD In this study, nine subjects underwent ambulatory ECG monitoring for an average of 21.6 h after a 2-mg oral dose of granisetron or placebo in a double-blind crossover protocol. Monitoring included a 3-h period of submaximal exercise in a 40 degrees C environment. RESULTS Although isolated ventricular and supraventricular ectopic activity, sinus bradycardia, and pauses were found, there were no sustained arrhythmias observed in either the placebo or granisetron conditions. CONCLUSION Although the generalizability of this study is limited by the small number of subjects, these observations add to the body of evidence confirming the lack of cardiovascular toxicity of granisetron.
Proteomic analysis of the proteins regulated by HrpB from the plant pathogenic bacterium Burkholderia glumae

Plant pathogenic bacteria transfer effector proteins into plant cells via the hypersensitive response and pathogenicity (Hrp) type III protein secretion system (T3SS) during infection. The genes encoding the Hrp T3SS are expressed only under plant apoplast‐mimicking conditions in an AraC‐type transcriptional activator HrpB‐dependent manner. To identify the proteins controlled by HrpB in Burkholderia glumae in vitro, we constitutively expressed hrpB and analyzed the proteins showing altered expression using 2‐DE and ESI‐MS/MS. Among 46 proteins exhibiting consistently altered expression, which were encoded by 34 different genes, 34 were secretory proteins and 12 were cytoplasmic. Twenty‐eight of the secreted proteins showed increased accumulation, whereas the other six showed decreased accumulation. None of the HrpB‐dependent proteins had significant homology to known T3SS‐dependent proteins, except for HrpK from Pseudomonas syringae pv. syringae and two T3SS‐associated cytoplasmic proteins from Ralstonia solanacearum. Twenty‐one of the 34 genes had putative HrpB‐binding sequences in their upstream regulatory regions. Secretion of all 34 extracellular proteins was independent of the Hrp T3SS, and 16 were secreted via a type II protein secretion system (T2SS). Mutants lacking the T2SS or Hrp T3SS produced toxoflavin but were less virulent to rice panicles, indicating the importance of these proteins in pathogenicity.
Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project

Background: HIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings. Setting: Demonstration project in 2 sexually transmitted infection clinics and a community health center. Methods: We evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft–Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI). Results: From October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR <70 mL/min/1.73 m2; independent predictors of this outcome were age ≥40 years (OR 3.79, 95% CI: 1.43 to 10.03) and baseline eGFR <90 mL/min/1.73 m2 (OR 9.59, 3.69–24.94). Conclusions: In a demonstration setting, daily tenofovir-disoproxil-fumarate/emtricitabine PrEP leads to reduced CrCl and eGFR; however, these eGFR changes are based on very small changes in serum creatinine and seem to be nonprogressive after the first 12 weeks. Future studies are needed to understand the prognostic significance of these small changes.
Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

Background New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. Methods This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease.
Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates

Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963–2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.
Phonological W orking Memory Deficit s in ADHD Revisited : The Role of Lower Level Informat ion-Processing Deficit s in Impaired W orking Memory Per formance

Abst ract Object ive: The current study dissociates lower level information-processing abilities (visual registration/encoding, visual-to-phonological conversion, and response output) and examines their contribution to ADHD-related phonological working memory (PHWM) deficits. Method: Twenty children with ADHD and 15 typically developing (TD) children completed tasks assessing PHWM, visual registration/encoding, visual-to-phonological conversion, and response output. Result s: Relative to TD children, children with ADHD exhibited deficient visual registration/encoding (d = 0.60), visualto-phonological conversion (d = 0.56), and PHWM (d = 0.72) but faster response output (d = −0.66). Bias-corrected, bootstrapped mediation analyses revealed that visual registration/encoding, but not visual-to-phonological conversion, partially mediated ADHD-related PHWM impairments. In contrast, faster response output in children with ADHD served as a suppressor variable, such that greater PHWM deficits were observed in children with ADHD after controlling for their faster response output (d = 0.72 vs. 0.85). Conclusion: Results implicate both lower level (visual registration/encoding) and higher order (PHWM) impairments in ADHD. Implications for designing educationally relevant cognitive interventions are discussed. (J. of Att. Dis. XXXX; XX(X) XX-XX)
Centrosome replication in hydroxyurea-arrested CHO cells expressing GFP-tagged centrin2

Centrosome duplication is tightly coupled with the cell cycle and neither too many nor too few centrosomes are induced in a normal cell. To study how centrosome assembly is regulated, we analyzed the abnormal process of multiple centrosome replications in Chinese hamster ovary (CHO) cells induced by hydroxyurea (HU), which is known to uncouple the centrosome cycle from the cell cycle. Green fluorescent protein (GFP)-tagged centrin2 expressed in CHO cells labels both centrioles and the pericentriolar material (PCM). Counting fluorescent spots of GFP-centrin in synchronized cells showed that in G1/S-arrested cells, centrioles are initially duplicated in a template manner. Further treatment with HU overrides the suppression of excess centriole/centrosome replication in a cell where the full complement of centrioles/centrosomes already exists. Time-lapse fluorescence microscopy revealed that small centrin-containing foci emerged in the cytoplasm during HU treatment. These foci are surrounded by a PCM cloud and their number continuously increases as cells are exposed to HU for longer periods of time. Both the centrosome and cytoplasmic foci are highly mobile, continuously changing their position in a manner dependent on microtubules/microtubule dynamics. The centrosome number increases as small foci grow in size and resolve into recognizable centrosomes. As this occurs in a random fashion, the cells arrested longer with HU induced highly heterogeneous numbers of centrosomes.
Multi-Modal Sensing Techniques for Interfacing Hand Prostheses: A Review

This paper provides a comprehensive survey of current state of the bio-sensing technologies focusing on hand motion capturing and its application to interfacing hand prostheses. These sensing techniques include electromyography, sonomyography, mechnomyography, electroneurography, electroencephalograhy, electrocorticography, intracortical neural interfaces, near infrared spectroscopy, magnetoencephalography, and functional magnetic resonance imaging. Relevant approaches that interpret bio-signals in the view of prosthetic hand manipulation are discussed as well. Multi-modal sensory fusion provides a new strategy in this area, and the latest multi-modal sensing techniques are surveyed. This paper also outlines the new challenges and directions: 1) exploration of robust sensing technology; 2) multi-modal sensory fusion; 3) online signal processing and learning algorithms; and 4) bio-feedbacks.
Inside Debt

Existing theories advocate the exclusive use of equity-like instruments in executive compensation. However, recent empirical studies document the prevalence of debt-like instruments such as pensions. This paper justifies the use of debt as efficient compensation. Inside debt is a superior solution to the agency costs of debt than the solvency-contingent bonuses and salaries proposed by prior literature, since its payoff depends not only on the incidence of bankruptcy but also firm value in bankruptcy. Contrary to intuition, granting the manager equal proportions of debt and equity is typically inefficient. In most cases, an equity bias is desired to induce effort. However, if effort is productive in increasing liquidation value, or if bankruptcy is likely, a debt bias can improve effort as well as deter risk shifting. The model generates a number of empirical predictions consistent with recent evidence.
Antibiotics in the control of plant diseases.

The use of antibiotics is a comparatively new method of plant disease control, but antibiosis, or antagonistic phenomena among microorganisms, and its relation to plant diseases have been recognized for more than 75 years. Gliotoxin, the first antibiotic to be used for plant disease control, was isolated and purified by a plant pathologist even before the discovery of penicillin. In 1932 Weindling (1) noted the antagonism of Gliocladium fimbria tum to a number of fungi. In 1934 he studied (2) a lethal principle produced by this organism and found that it was responsible for the para­ sitic action of G. fimbriatum on Rhizoctonia solani and other soil fungi. Two years later Weindling & Emerson (3) isolated in crystalline form the sub­ stance known as gliotoxin, thus becoming the first to isolate an antibiotic in a pure state. The next report of the control of a plant disease by an anti­ biotic was by Brown & Boyle (4, 5) in 1944. They observed that a crude culture filtrate of Penicillium notalum was effective against crown gall, caused by Agrobacterium tumefaciens. No in vivo evidence of the antibiotic effect of the filtrate on the pathogen was reported, and later studies showed that the effect was largely on the gall tissue. In 1945 Brian & Hemming (6) showed that gliotoxin reduced infection of covered smut of barley, bunt of wheat, and helminthosporium leaf spot of oats. In 1946 Brown & Heep (7) reported the eradication of Xanthomonas pruni from cankers on plum twigs. It was not until 1952, however, that an antibiotic was used under field condi­ tions for the control of plant disease. Zaumeyer et al. (8) showed that beans were protected from infection by the halo blight organism (Pseudomonas phaseolicola) with a streptomycin spray, and Ark (9) reported good control of pear blight (Erwinia amylovora) with a streptomycin dust. Previously, most of the investigations consisted of screening plant patho­ gens in vitro to determine their sensitivity to antibiotics. Although screening tests in vitro demonstrated the effectiveness of a number of antibiotics against many pathogens, tests in vivo frequently failed to corroborate them. This review deals primarily with the control of diseases of plants, under greenhouse and field conditions, by means of the antibiotics which are com­ monly available. Certain compounds which have been studied only a little and are unavailable to growers are not discussed. It is likely that among the large number of papers published in this field, some important ones were over1 The survey of the literature pertaining to this review was concluded in De­ cember, 1957.
Prediction of partial membrane protein topologies using a consensus approach

We have developed a method to reliably identify partial membrane protein topologies using the consensus of five topology prediction methods. When evaluated on a test set of experimentally characterized proteins, we find that approximately 90% of the partial consensus topologies are correctly predicted in membrane proteins from prokaryotic as well as eukaryotic organisms. Whole‐genome analysis reveals that a reliable partial consensus topology can be predicted for ∼70% of all membrane proteins in a typical bacterial genome and for ∼55% of all membrane proteins in a typical eukaryotic genome. The average fraction of sequence length covered by a partial consensus topology is 44% for the prokaryotic proteins and 17% for the eukaryotic proteins in our test set, and similar numbers are found when the algorithm is applied to whole genomes. Reliably predicted partial topologies may simplify experimental determinations of membrane protein topology.
Reduced Polymorphism in the Kelch Propeller Domain in Plasmodium vivax Isolates from Cambodia

ABSTRACT Polymorphism in the ortholog gene of the Plasmodium falciparum K13 gene was investigated in Plasmodium vivax isolates collected in Cambodia. All of them were Sal-1 wild-type alleles except two (2/284, 0.7%), and P. vivax K12 polymorphism was reduced compared to that of the P. falciparum K13 gene. Both mutant allele isolates had the same nonsynonymous mutation at codon 552 (V552I) and were from Ratanak Kiri province. These preliminary data should encourage additional studies for associating artemisinin or chloroquine resistance and K12 polymorphism.
Early diagnosis of breast cancer by hair diffraction

A correlation between the incidence of breast cancer and an observed change in the X‐ray diffraction pattern of hair from the afflicted individuals was first reported in 1999. Since that time, over 500 hair samples have been analyzed in double‐blinded breast cancer studies with no false negatives being detected. To correlate this observed change with the presence of breast cancer, we examined whiskers removed from nude mice prior to and 8 weeks after subcutaneous implantation of a human breast cancer cell line. Here we show that the change observed in human hair was also evident in whiskers and that it appeared soon after cancer cell implantation. © 2004 Wiley‐Liss, Inc.
N-glycosylation is required for binding of murine pregnancy-specific glycoproteins 17 and 19 to the receptor CD9.

PROBLEM Murine pregnancy-specific glycoproteins (PSGs) are encoded by 17 different genes. Different family members have different expression levels at different stages of embryonic development. It is currently unknown whether all members of this family of placentally secreted proteins have the same function and bind to the same receptor. Furthermore, the requirement of post-translational modifications for the activity of these highly glycosylated proteins remains undetermined. METHOD OF STUDY Recombinant PSG17 and PSG19 were generated and purified by affinity chromatography. An expression library was screened to identify the receptor for mouse PSG19. Binding to the receptor by proteins generated in different expression systems and mapping of the binding domain were analyzed by pull-down assays. Analysis of the carbohydrate composition of the receptor-binding domain was performed with the DIG glycan differentiation kit. RESULTS PSG19 binds to the tetraspanin CD9, specifically to extra cellular loop 2 and can induce secretion of TGFbeta1 by a macrophage cell line. The receptor-binding domain of PSG17 and PSG19 is post-translationally modified by the addition of N-linked carbohydrates and, when expressed in CHO cells, terminal sialic acids are detected. PSGs produced in bacteria do not bind CD9. CONCLUSION PSG19, as previously determined for PSG17, binds to the second extracellular loop 2 of the tetraspanin CD9. The first immunoglobulin variable-like domain of PSG19 is sufficient for receptor binding and function. Analysis of receptor usage by the remaining 15 murine PSGs will most likely require that the proteins be generated in eukaryotic expression systems, as we have demonstrated that the addition of carbohydrates is essential for PSG-receptor interaction.
A virtual headphone based on wave field synthesis

The term "virtual headphone" refers to specially designed loudspeaker systems aiming for transmission characteristics equal to real headphones. Particularly of interest is the exact pre‐filtering of the speaker signals to compensate the effect of head related transfer functions (HRTFs) between loudspeakers and ear canal. These so‐called "HRTF inverse filters" are dependent on geometrical conditions and so they have to be updated with every head movement. In order to avoid problematic adaptive HRTF inverse filtering, the real loudspeakers are replaced by focussed sources generated according to the principles of Wave Field Synthesis (WFS). Head tracking controlled adjustment of driving functions allows easy source movement and thus fixed source positions in relation to the listener's ears, providing stable virtual headphone reproduction. A single static HRTF inverse filter network can be used. It is designed to ensure precise headphone equalization according to ITU‐R BS.708 and offers accurate reproduction .
Whole-transcriptome analysis of flow-sorted cervical cancer samples reveals that B cell expressed TCL1A is correlated with improved survival

Cervical cancer is typically well infiltrated by immune cells. Because of the intricate relationship between cancer cells and immune cells, we aimed to identify both cancer cell and immune cell expressed biomarkers. Using a novel approach, we isolated RNA from flow-sorted viable EpCAM+ tumor epithelial cells and CD45+ tumor-infiltrating immune cells obtained from squamous cell cervical cancer samples (n = 24). Total RNA was sequenced and differential gene expression analysis of the CD45+ immune cell fractions identified TCL1A as a novel marker for predicting improved survival (p = 0.007). This finding was validated using qRT-PCR (p = 0.005) and partially validated using immunohistochemistry (p = 0.083). Importantly, TCL1A was found to be expressed in a subpopulation of B cells (CD3−/CD19+/CD10+/CD34−) using multicolor immunofluorescence. A high TCL1A/CD20 (B cell) ratio, determined in total tumor samples from a separate patient cohort using qRT-PCR (n = 52), was also correlated with improved survival (p = 0.027). This is the first study demonstrating the prognostic value of separating tumor epithelial cells from tumor-infiltrating immune cells and determining their RNA expression profile for identifying putative cancer biomarkers. Our results suggest that intratumoral TCL1A+ B cells are important for controlling cervical cancer development.
Ear protection against water-borne infection: an objective evaluation

Abstract Eight different ear plug materials were tested, in 5 ears each, in artificial shallow underwater conditions for 30 minutes, in order to determine their efficacy in sealing the ear canals to avoid water-borne infections in ear canals and open middle ears. Most of the plugs tested would meet everyday requirements for protection, but the polymeric foam plugs, treated with petroleum jelly, and moldable plastic materials were most effective in protecting both the middle ear and the ear canal skin.