Miracle-dz/UniFAR-FTUs huggingface dataset:
Patients with sickle cell disease have increased sensitivity to cold and heat

Sickle cell disease (SCD) pain is associated with colder temperatures and touch and described as “cold,” “hot,” and “shooting” suggesting hypersensitivity to tactile stimuli. Sickle mice exhibit hypersensitivity to thermal (cold, heat) and mechanical stimuli compared to controls. It is unknown whether humans experience this same hypersensitivity. Thus, we quantified thermal and mechanical sensitivity differences between patients with SCD and controls. Our primary hypothesis was that patients with SCD will exhibit hypersensitivity to thermal and mechanical stimuli compared to race‐matched controls. Our secondary hypothesis was this hypersensitivity will be associated with older and female subjects, and with frequent pain and hemolysis in patients with SCD. A total of 55 patients and 57 controls ≥7 years completed quantitative sensory testing. Patients with SCD detected the sensation of cold and warm temperatures sooner as seen in their significantly lower median cold and heat detection thresholds [29.5°C vs. 28.6°C, P = 0.012 and 34.5°C vs. 35.3°C, P = 0.02] and experienced cold and heat pain sooner as seen in their significantly lower median cold and heat pain thresholds [21.1°C vs. 14.8°C, P = 0.01 and 42.7°C vs. 45.2°C, P = 0.04]. We found no mechanical threshold differences. Older age was associated with lower cold, heat, and mechanical pain thresholds in both groups. No association with pain, gender, or hemolysis was found. Patients with SCD exhibit hypersensitivity to thermal stimuli suggesting peripheral or central sensitization may exist and could contribute to SCD pain. Am. J. Hematol. 2013. © 2012 Wiley Periodicals, Inc.
Inhibition of Kv 4 . 3 / KChIP 2 . 2 Channels by Bupivacaine and Its Modulation by the Pore Mutation Kv 4 . 3 V 401 I

Background: The transient outward current Ito is an important repolarizing K current in human ventricular myocardium mediated by Kv4.3 and KChIP2.2 subunits. Inhibition of Ito by amino-amide local anesthetics may be involved in severe cardiotoxic side effects. This study elucidates the molecular mechanisms of bupivacaine interaction with complexes formed by Kv4.3 and KChIP2.2 as well as the modulatory effect of KChIP2.2. For this purpose, the pharmacologic effects of bupivacaine on Kv4.3wt/KChIP2.2 channels and on the pore mutant Kv4.3V401I were investigated. Methods: Kv4.3/KChIP2.2 cDNA was transiently expressed in Chinese hamster ovary cells. Site-directed mutagenesis and patch clamp experiments were performed to analyze the effects of bupivacaine on wild-type and mutant channels. Results: Inhibition of Kv4.3wt/KChIP2.2 channels by bupivacaine was concentration-dependent and reversible. The IC50s for inhibition of the charge conducted by Kv4.3wt/KChIP2.2 channels by bupivacaine and levobupivacaine were 55 8 and 50 5 M, respectively. The local anesthetic accelerated macroscopic current decline of Kv4.3wt/KChIP2.2 and slowed recovery from inactivation without altering steady state inactivation. KChIP2.2 altered the response of Kv4.3wt channels to bupivacaine and bupivacaine modulated KChIP2.2 effects on Kv4.3wt channels. The pore mutation V401I slowed macroscopic current decline of Kv4.3 channels and recovery from inactivation, and it diminished modulation of gating by KChIP2.2. Bupivacaine inhibition of Kv4.3V401I resembled Kv4.3wt and was not changed by coexpression of KChIP2.2. Conclusions: These results indicate that bupivacaine blocks Kv4.3/KChIP2.2 channels from the open state. They furthermore give structural evidence that amino-amide local anesthetics interfere with the effects of KChIP2.2 on Kv4.3 by an indirect mechanism.
Gate Fringe-Induced Barrier Lowering in Underlap FinFET Structures and Its Optimization

The difficulty to fabricate and control precisely defined doping profiles in the source/drain underlap regions of FinFETs necessitates the use of undoped gate underlap regions as the technology scales down. We present a phenomenon called the gate fringe-induced barrier lowering (GFIBL) in FinFETs with undoped underlap regions. In these FinFETs, we show that the GFIBL can be effectively used to improve Ion. We propose the use of high-kappa spacers in such FinFETs to enhance the effect of GFIBL and thereby achieve better device and circuit performance. When compared with the underlap FinFETs with Si3N4 spacers, with kappa=20 spacers, we show that it is possible to achieve an 80% increase in Ion at iso-Ioff conditions and a 15% decrease in the inverter delay for a fan-out of four.
STANDING GENETIC VARIANCE FOR FEMALE RESISTANCE TO HARM FROM MALES AND ITS RELATIONSHIP TO INTRALOCUS SEXUAL CONFLICT

Abstract Interlocus sexual conflict theory predicts that some male adaptations are harmful to their mates. Females are therefore expected to evolve resistance to this harm. Using cytogenetic cloning techniques, we tested for heritable genetic variation among females for resistance to harm from males and determined whether propensity to remate, female body size, and intralocus conflict contributes to this variation. We found low but significant heritability for female resistance, but this variation accounted for more than half of the standing genetic variation for net fitness among females. We found no association between female resistance and female body size or level of intralocus sexual conflict. Reluctance to remate was found to be an important factor contributing to the female resistance phenotype, and we found a positive selection gradient on this trait. However, we observed only a nonsignificant positive correlation between a female's resistance and her net fitness. One factor contributing to the observed nominal level of selection on female resistance was that males cause the greatest amount of harm to females with the highest intrinsic fecundity.
ICP27 Recruits Aly/REF but Not TAP/NXF1 to Herpes Simplex Virus Type 1 Transcription Sites although TAP/NXF1 Is Required for ICP27 Export

ABSTRACT Herpes simplex virus type 1 (HSV-1) protein ICP27 interacts with the cellular export adaptor protein Aly/REF, which is part of the exon junction complex implicated in cellular mRNA export. We previously reported that Aly/REF was no longer associated with splicing factor SC35 sites during infection but instead colocalized with ICP27 in distinct structures. Here we show that these structures colocalize with ICP4 and are sites of HSV-1 transcription. ICP27 mutants with lesions in the region required for the interaction with Aly/REF failed to recruit Aly/REF to viral transcription sites; however, ICP27 export to the cytoplasm was unimpaired, indicating that the interaction of ICP27 with Aly/REF is not required for ICP27 shuttling. ICP27 has also been shown to interact with the cellular mRNA export receptor TAP/NXF1. We report that ICP27 interacts directly with TAP/NXF1 and does not require Aly/REF to bridge the interaction. The C terminus of ICP27 is required; however, the N-terminal leucine-rich region also contributes to the interaction of ICP27 with TAP/NXF1. In contrast to the results found for Aly/REF, mutants that failed to interact with TAP/NXF1 were not exported to the cytoplasm, and TAP/NXF1 was not recruited to sites of HSV-1 transcription. Therefore, the interaction of ICP27 with TAP/NXF1 occurs after ICP27 leaves viral transcription sites. We conclude that ICP27 and the viral RNAs to which it binds are exported via the TAP/NXF1 export receptor.
Continuity Theory of Ageing and Leisure Participation among Elderly Attending Selected Health Clinics in Selangor

Introduction: Leisure participation in old age is often a continuation of their participation at younger age. This study aims to explore the association between current and former leisure participation of the elderly. Methods: A cross-sectional survey was conducted among 268 persons aged 60 years and above, purposively selected from eight health clinics in Selangor. Current leisure participation was measured using a validated Leisure Participation Questionnaire (LPQ), specific for Malaysian elderly. The LPQ consists of 25 activities, categorized into recreational (physical), cognitive, social and productive activity. Frequency of participation in each activity was measured on a 6-point scale. Leisure participation at younger age only involved their general participation in leisure. The most common daily leisure activities were having conversations while relaxing (78.7%) and watching television (74.6%), while the least were from playing golf (0.01±0.12) and performing musical instruments (0.04±0.36). More than half (64.9%) reported being actively involved in any leisure activity at younger age. Results: The study found there was a significant association between former and current leisure participation, especially for cognitive (t=-2.45, p=0.015), social (t=-2.68, p=0.008) and productive (t=-2.89, p=0.004) activities. However, only productive activity involvement was predicted by their leisure participation while younger (B=1.304, p=0.027). Conclusion: The findings suggest the importance of considering active intervention programmes at younger age to ensure better leisure participation of the elderly, especially in recreational physical activity.
Chemical Properties and Antioxidant and Antimicrobial Activities of Slovenian Propolis

The chemical composition as well as the antioxidant and antimicrobial activities of two EtOH extracts of propolis (PEEs) from Slovenia were determined. EtOH was used as extracting solvent at 70 and 96%, providing the extracts PEE70 and PEE96, respectively. The extraction with 70% EtOH was more efficient than that with 96% EtOH, as the PEE70 was richer in total phenolic compounds than the PEE96. The Slovenian propolis was characterized by different phenolic acids and flavonoids. The PEE96 was slightly richer in three specific compounds, i.e., caffeic acid, ferulic acid, and luteolin, while all other substances detected showed higher contents in the PEE70. The PEE70 showed a stronger reducing power and ability to scavenge free radicals and metal ions than the PEE96. Both PEEs were in the main more effective against Gram‐positive bacteria than against fungi and Gram‐negative bacteria like Salmonella and Escherichia coli, with the exception of Campylobacter. The PEE96 decreased the intracellular oxidation in Saccharomyces cerevisiae in a dose‐dependent manner. The antimicrobial activities and antioxidant properties were related to the total phenolic contents. The two PEEs have the potential for use as natural antimicrobial and antioxidant additives in foods.
Effects of Ingestion of Grapefruit Juice or Grapefruit on the Hypotensive Effect and Plasma Concentrations of Dihydropyridine Calcium Antagonists (Amlodipine and Nifedipine): A Case Study

The purpose of this study was to examine the effects of ingestion of grapefruit juice or grapefruit on the hypotensive effect and plasma concentration of dihydropyridine calcium antagonists, i.e., amlodipine and nifedipine. A 50-year-old man with essential hypertension was studied. Grapefruit juice (500 ml) was taken together with the antihypertensive drug, while one grapefruit was taken before drug ingestion. Blood pressures were measured using a digital automatic blood pressure monitor over a certain period. A single ingestion of grapefruit juice had no effect on plasma amlodipine concentration, but rapidly increased plasma nifedipine concentration and decreased blood pressure, while the effect on blood pressure was short-lasting. Grapefruit had no effect on either drug. It should be of concern that ingestion of a relatively large volume of grapefruit juice causes rapid decrease in blood pressure when the subject is treated by nifedipine.
Interferon-γ Rapidly Increases Peptide Transporter (TAP) Subunit Expression and Peptide Transport Capacity in Endothelial Cells*

Human cytotoxic T lymphocytes (CTL) recognize specific complexes of HLA class I molecules and peptides, which assemble when nascent class I molecules bind peptides transported from the cytoplasm into the endoplasmic reticulum by the heterodimeric transporter associated with antigen processing (TAP). Increased class I molecule expression on the cell surface increases the efficiency of CTL lysis. The kinetics of interferon (IFN)-γ induction of TAP, peptide transport capacity, and HLA class I molecule expression was determined in endothelial cells, which are targets of CTL following transplantation or viral infection. TAP mRNAs are induced rapidly, increasing 20-fold (TAP1) or 10-fold (TAP2) by 12 h, whereas HLA class I mRNA is induced more slowly, increasing 10-fold in 24 h. TAP1 and TAP2 proteins are also induced rapidly, increasing 10-fold in 24 h, whereas HLA class I heavy chain proteins and surface expression increase more slowly. Peptide transport capacity in endothelial and HeLa cells increases within 6 h of IFN-γ treatment, suggesting that the IFN-γ-induced TAP heterodimers are functional. Therefore, the IFN-γ-induced increase in TAP proteins is accompanied by an increased peptide transport capacity, which may be important in supporting the subsequent rise in HLA class I protein expression.
The impact of ubiquitous decision support systems on decision quality through individual absorptive capacity and perceived usefulness

Purpose – The purpose of this study is to examine a mobile delivery system as a working ubiquitous decision support system (UDSS) and determine whether it would improve decision quality.Design/methodology/approach – Ubiquitous mobility and context awareness are the two core functions of the UDSS. Hence the authors examined how they might influence individual absorptive capacity and perceived usefulness. Moreover the authors investigated how individual absorptive capacity and perceived usefulness might be related to decision quality. A total of 174 completed questionnaires were collected from delivery workers, and a financial incentive was provided to participants. To test the hypotheses the research model was analysed with the partial least square method.Findings – The results reveal that all paths are statistically valid. Individual absorptive capacity and perceived usefulness were positively influenced by ubiquitous mobility and context awareness. In addition individual absorptive capacity and perceived.
Impact of 2.45 GHz microwave radiation on the testicular inflammatory pathway biomarkers in young rats: The role of gallic acid

The aim of this study was to investigate electromagnetic radiation (EMR) transmitted by wireless devices (2.45 GHz), which may cause physiopathological or ultrastructural changes, in the testes of rats. We addressed if the supplemental gallic acid (GA) may reduce these adverse effects. Six‐week‐old male Sprague Dawley rats were used in this study. Forty eight rats were equally divided into four groups, which were named: Sham, EMR only (EMR, 3 h day−1 for 30 days), EMR + GA (30 mg/kg/daily), and GA (30 mg/kg/daily) groups. Malondialdehyde (MDA) and total oxidant status (TOS) levels increased (p = 0.001 for both) in EMR only group. TOS and oxidative stress index (OSI) levels decreased in GA treated group significantly (p = 0.001 and p = 0.045, respectively). Total antioxidant status (TAS) activities decreased in EMR only group and increased in GA treatment group (p = 0.001 and p = 0.029, respectively). Testosterone and vascular endothelial growth factor (VEGF) levels decreased in EMR only group, but this was not statistically significant. Testosterone and VEGF levels increased in EMR+GA group, compared with EMR only group (p = 0.002), and also increased in GA group compared with the control and EMR only group (p = 0.044 and p = 0.032, respectively). Prostaglandin E2 (PGE2) and calcitonin gene releated peptide (CGRP) staining increased in tubules of the testes in EMR only group (p < 0.001 for both) and decreased in tubules of the testes in EMR+GA group (p < 0.001 for all parameters). In EMR only group, most of the tubules contained less spermatozoa, and the spermatozoon counts decreased in tubules of the testes. All these findings and the regenerative reaction, characterized by mitotic activity, increased in seminiferous tubules cells of the testes in EMR+GA group (p < 0.001). Long term EMR exposure resulted in testicular physiopathology via oxidative damage and inflammation. GA may have ameliorative effects on the prepubertal rat testes physiopathology. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1771–1784, 2016.
Illness-specific catastrophic thinking and overperception in asthma.

OBJECTIVE This study investigated the role of illness-specific catastrophic thinking in symptom perception in asthma. DESIGN AND MAIN OUTCOME MEASURES A total sample of 72 patients with intermittent to moderate persistent asthma completed the Catastrophizing about Asthma Scale and completed the Asthma Symptom Checklist to measure retrospective symptom reporting. In addition, symptoms were concurrently assessed during different respiratory challenges eliciting mild and ambiguous versus salient and pronounced symptoms. RESULTS Catastrophic thinking in general, when patients are not having an exacerbation, is related to an increase in emotional symptoms, especially in ambiguous situations where respiratory difficulties could occur. Catastrophic thinking during exacerbations is related to an increase in emotional symptoms as well as in respiratory symptoms during respiratory challenges. CONCLUSION These strong relationships between catastrophic thinking and increased perception of asthma symptoms suggest a link between illness-specific catastrophic thinking and overperception. Consequently, catastrophic thoughts are an important target for psychological interventions in support of drug treatment.
Simple design rules for optimal design of dielectric temperature-compensated sapphire resonators

It has been shown that the use of two dielectric crystals with opposite temperature coefficient of permittivity allows the realization of a resonator with a zero temperature coefficient of frequency. By using sapphire and rutile materials, which have low-loss tangents, some compensated resonators with very high Q-factors have been realized. In this work we develop rules that greatly simplify the design of a dielectric-compensated resonator. We show that the optimum design for compensation at a specific temperature may be determined by simply selecting the aspect ratio of the sapphire resonator.
Optimization Strategies for Interactive Classification of Interstitial Lung Disease Textures

For computerized analysis of textures in interstitial lung disease, manual annotations of lung tissue are necessary. Since making these annotations is labor-intensive, we previously proposed an interactive annotation framework. In this framework, observers iteratively trained a classifier to distinguish the different texture types by correcting its classification errors. In this work, we investigated three ways to extend this approach, in order to decrease the amount of user interaction required to annotate all lung tissue in a CT scan. First, we conducted automatic classification experiments to test how data from previously annotated scans can be used for classification of the scan under consideration. We compared the performance of a classifier trained on data from one observer, a classifier trained on data from multiple observers, a classifier trained on consensus training data, and an ensemble of classifiers, each trained on data from different sources. Experiments were conducted without and with texture selection. In the former case, training data from all 8 textures was used. In the latter, only training data from the texture types present in the scan were used, and the observer would have to indicate textures contained in the scan to be analyzed. Second, we simulated interactive annotation to test the effects of (1) asking observers to perform texture selection before the start of annotation, (2) the use of a classifier trained on data from previously annotated scans at the start of annotation, when the interactive classifier is untrained, and (3) allowing observers to choose which interactive or automatic classification results they wanted to correct. Finally, various strategies for selecting the classification results that were presented to the observer were considered. Classification accuracies for all possible interactive annotation scenarios were compared. Using the best performing protocol, in which observers select the textures that should be distinguished in the scan and in which they can choose which classification results to use for correction, a median accuracy of 88% was reached. The results obtained using this protocol were significantly better than results obtained with other interactive or automatic classification protocols.
Engagement of the T lymphocyte antigen receptor regulates association of son‐of‐sevenless homologues with the SH3 domain of phospholipase Cγ1

One mechanism for transducing signals downstream of lymphocyte receptor activation involves the stable association between signaling proteins. To identify protein ligands of the signal activator phospholipase Cγ1 (PLCγ1), we screened T cell cDNA libraries with the PLCγ1‐SH3 domain by the yeast two‐hybrid assay. We observed association between the PLCγ1‐SH3 domain and the human Ras guanine nucleotide exchange factor son‐of‐sevenless‐2 (hSos2) through a proline‐rich domain interaction. Stable and abundant hSos2 / PLCγ1 and hSos1 / PLCγ1 complexes were observed in unstimulated T cells. The interaction between these enzymes was augmented following engagement of the T cell antigen receptor (TCR / CD3). The kinetics of protein complex enhancement correlated with TCR / CD3‐induced tyrosine phosphorylation of PLCγ1; however, those PLCγ1 molecules in complex with hSos2 were non‐phosphorylated after TCR / CD3 stimulation, in contrast to the phosphorylated PLCγ1 associated with the linker for activation of T cells, LAT. The Grb2 adapter protein was detected in complex with hSos / PLCγ1, suggesting a regulatory role for Grb2. SH3 domains from both Grb2 and PLCγ1, but not RasGAP, bound directly to hSos homologues. The SH2 domain from Grb2 formed an association with the hSos / PLCγ1 complex, which was enhanced following TCR / CD3 ligation. Together, the data suggest a mechanism for the son‐of‐sevenless and PLCγ1 signal transducing enzymes in recruitment to protein complexes with potentially differential signaling consequences in T lymphocytes.
Sensitivity analysis for missing outcomes in time-to-event data with covariate adjustment

ABSTRACT Covariate-adjusted sensitivity analyses is proposed for missing time-to-event outcomes. The method invokes multiple imputation (MI) for the missing failure times under a variety of specifications regarding the post-withdrawal tendency for having the event of interest. With a clinical trial example, we compared methods of covariance analyses for time-to-event data, i.e., the multivariable Cox proportional hazards (PH) model and nonparametric analysis of covariance, and then illustrated how to incorporate these methods into the proposed sensitivity analysis for covariate adjustment. The MI methods considered are Kaplan–Meier multiple imputation and covariate-adjusted and unadjusted PH multiple imputation. The assumptions, statistical issues, and features for these methods are discussed.