Miracle-dz/UniFAR-FTUs huggingface dataset:
Desensitization of Chemical Activation by Auxiliary Subunits

Chemical openers for KCNQ potassium channels are useful probes both for understanding channel gating and for developing therapeutics. The five KCNQ isoforms (KCNQ1 to KCNQ5, or Kv7.1 to Kv7.5) are differentially localized. Therefore, the molecular specificity of chemical openers is an important subject of investigation. Native KCNQ1 normally exists in complex with auxiliary subunits known as KCNE. In cardiac myocytes, the KCNQ1-KCNE1 (IsK or minK) channel is thought to underlie the IKs current, a component critical for membrane repolarization during cardiac action potential. Hence, the molecular and pharmacological differences between KCNQ1 and KCNQ1-KCNE1 channels have been important topics. Zinc pyrithione (ZnPy) is a newly identified KCNQ channel opener, which potently activates KCNQ2, KCNQ4, and KCNQ5. However, the ZnPy effects on cardiac KCNQ1 potassium channels remain largely unknown. Here we show that ZnPy effectively augments the KCNQ1 current, exhibiting an increase in current amplitude, reduction of inactivation, and slowing of both activation and deactivation. Some of these are reminiscent of effects by KCNE1. In addition, neither the heteromultimeric KCNQ1-KCNE1 channels nor native IKs current displayed any sensitivity to ZnPy, indicating that the static occupancy by a KCNE subunit desensitizes the reversible effects by a chemical opener. Site-directed mutagenesis of KCNQ1 reveals that residues critical for the potentiation effects by either ZnPy or KCNE are clustered together in the S6 region overlapping with the critical gating determinants. Thus, the convergence of potentiation effects and molecular determinants critical for both an auxiliary subunit and a chemical opener argue for a mechanistic overlap in causing potentiation.
Speaker recognition system using mel-frequency cepstrum coefficients, linear prediction coding and vector quantization

Identity verification is very important issue in current era of information technology. Conventional means of identity verification using keys or personal identification numbers and passwords can be stolen and are not well suited for such critical purposes. To overcome this problem new bio metric verification method have been e m e r g e d. Now, the i n c r e a s ed computing power and decreased microchip size has given thrust for implementing realistic biometric authentication systems such as speech recognition system. In this paper, authors implemented a speaker recognition system (SRS) using Mel-Frequency Cepstrum Coefficients (MFCC), Linear Prediction Coding (LPC) as feature extraction techniques and Vector Quantization (VQ) as speaker classification technique.
Examining Child Welfare Decisions and Services for Asian-Canadian Versus White-Canadian Children and Families in the Child Welfare System

Using administrative child welfare data from the Ontario Child Abuse and Neglect Data System (OCANDS), this study compared the profiles of Asian-Canadian and White-Canadian children and families that experienced a case closure after an investigation instead of being transferred to ongoing child protection services (CPS). Child protection investigations involving Asian-Canadian and White-Canadian children and families that were transferred to ongoing CPS presented a different profile of case characteristics and caregiver and child clinical needs. Asian-Canadian children and families received ongoing CPS for over a month longer than White-Canadian children and families and were less likely (odds ratio [OR] = 0.39) to be reinvestigated for any form of maltreatment-related concerns within 1 year after case closure. It appears that child protection investigations involving Asian-Canadian children and families are less likely to be closed prematurely than White-Canadian children and families, and the child protection system may be meeting the needs of Asian-Canadian communities. Alternatively, it is possible there is unaccounted biases that may be reflective of systemic problem of discriminative practices in the child protection system. Further research is needed to explore this phenomenon.
Work-Life Balance: The Good and the Bad of Boundary Management

Work-life balance is an important issue in today’s world and the different strategies used by people to manage their work and their personal life can have a great impact. Two studies were conducted (study 1: n = 117; study 2: n = 293) to examine how boundary segmentation preferences (studies 1 & 2) and boundary integration strategies (study 2) affect work-family conflict and enrichment. Results from structural equation modeling partly confirmed the hypothetical model in both studies. Study 1 showed that work-home segmentation preference negatively predicted work-family enrichment, while home-work segmentation preference negatively predicted family-work enrichment. Study 2 provided similar results, as it showed that work-home segmentation preference negatively predicted work-family enrichment. It also showed that work-home segmentation preference positively predicted work-family conflict and home-work segmentation preference positively predicted work-family enrichment, while work-life integration strategy positively predicted work-family conflict, family-work conflict, work-family enrichment and family-work enrichment. No significant relationship was found between life-work integration strategy and any of the dependent variables. Findings from these studies highlight the importance of using appropriate boundary management strategies in order to promote a better work-life balance. They also enhance current knowledge related to boundary management and work-life balance by examining relationships with work-family enrichment.
Econometrics of auctions by least squares

I investigate using the method of ordinary least squares (OLS) on auction data. I find that for parameterizations of the valuation distribution that are common in empirical practice, an adaptation of OLS provides unbiased estimators of structural parameters. Under symmetric independent private values, adapted OLS is a specialization of the method of moments strategy of Laffont, Ossard and Vuong (1995). In contrast to their estimator, here simulation is not required, leading to a computationally simpler procedure. The paper also discusses using estimation results for inference on the shape of the valuation distribution, and applicability outside the symmetric independent private values framework. Copyright © 2008 John Wiley & Sons, Ltd.
Lysis and Lysis Inhibition in Bacteriophage T4:rV Mutations Reside in the Holin t Gene

ABSTRACT Upon infecting populations of susceptible host cells, T-even bacteriophages maximize their yield by switching from lysis at about 25 to 35 min at 37°C after infection by a single phage particle to long-delayed lysis (lysis inhibition) under conditions of sequential infection occurring when free phages outnumber host cells. The timing of lysis depends upon gene t and upon one or more rapid-lysis (r) genes whose inactivation prevents lysis inhibition. t encodes a holin that mediates the movement of the T4 endolysin though the inner cell membrane to its target, the cell wall. The rI protein has been proposed to sense superinfection. Of the five reasonably well characterized r genes, only two,rI and rV, are clearly obligatory for lysis inhibition. We show here that rV mutations are alleles oft that probably render the t protein unable to respond to the lysis inhibition signal. The tr alleles cluster in the 5′ third of t and produce a strong r phenotype, whereas conditional-lethal t alleles produce the classical t phenotype (inability to lyse) and other t alleles produce additional, still poorly understood phenotypes. trmutations are dominant to t+, a result that suggests specific ways to probe T4 holin function.
Utility of Transthoracic Fine Needle Aspiration Cytology in Diagnosis of Pulmonary Lesions

The combination of Fine Needle Aspiration Cytology (FNAC) with radioimaging has revolutionized diagnosis of lung masses.The present study was carried out to assess diagnostic utility of Transthoracic FNAC in lung lesions. The present study comprises 73 patients undergoing the procedure under Computed Tomography (CT) guidancein 57 cases and under Ultrasonography (USG) in 16 cases. With a high sensitivity (95.65%), high specificity (100%) high NPV (83.33%) and high PPV (100%), Transthoracic FNAC is advocated as being highly accurate diagnostic modality.
Myocardial revascularization using the arterial T graft: which conduit should be chosen for the free graft?

BACKGROUND The T graft is achieved by the end-to-side implantation of a free arterial graft into the left internal thoracic artery, which remains in situ. Which conduit is best suited as the free graft is still being discussed. METHODS Two groups of patients are compared. The right internal thoracic artery (RITA) was used as a free graft in group I (n = 129), and the radial artery was used in group II (n = 84). RESULTS The RITA was used more often with male patients (P < .02) and with patients presenting a reduced left ventricular ejection fraction (P < .03). The average number of coronary anastomoses per patient was higher in group II than in group I (P < .002). There were no significant differences between the groups in early mortality (0.8% in group I and 1.2% in group II) and morbidity. Postoperative chest tube output was significantly higher in group I than in group II (P < .05). The mean follow-up time was 35.2 +/-28.3 months. There were no significant differences regarding late mortality (6.9% in group I and 5.3% in group II) and the recurrence of angina (group I, 6 cases or 5.5%; group II, 3 cases or 4.2%). Because of the recurrence of angina or questionable chest pain in 22 patients, angiography was performed, and results showed a patency rate of 90.9% in group I and 93.1% in group II. CONCLUSIONS Based on our experience, we advise using the RITA as a free graft with tall men and also in patients with a reduced left ventricular ejection fraction, diabetes, and obesity. The radial artery should be used with small women if there is a high risk of bleeding and if several coronary anastomoses are necessary.
Synthesis and antimalarial activities of optically active labdane-type diterpenes

An efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). Compounds 5, 6, 7 and 9 were evaluated as inhibitors of the β-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. Compound 9 was the most promising compound, showing a positive correlation between in vitro and in vivo activities.
Metabolic Effects of a Medium-Chain Triglyceride Emulsion Injected Intravenously in Man

By virtue of their metabolie properties the medium chain triglycerides are potentially valuable in parenteral nutrition. Hav ing fllst investigated their metabolie efTects in the dog (Guisard, Bach, Debry and Metais 1972), we have again taken up the initial trials of Werk, Mc Pherron, Hamrick, Mayers and Engel (1955).
Longitudinal cohort study on medical student retention of anatomical knowledge in an integrated problem-based learning curriculum

Abstract Background: When modifying a curriculum to accommodate changes in the methods of subject matter presentation or fit within a shortened time frame, student retention of knowledge remains an important issue. Aim: This study evaluates medical student retention of anatomical knowledge as they matriculate through an anatomy curriculum where the instruction hours are less than half of the current national average. Method: Medical students completed an assessment tool developed to evaluate their baseline level of anatomical knowledge at the beginning of the first year. They then completed the instrument at the end of their 1st, 2nd, 3rd, and 4th years to assess their retention of anatomical knowledge during medical school. Data collection began in September 2010 and concluded in June 2015. Results: Results demonstrate that students began medical school with a low level of anatomical knowledge (baseline), that knowledge increased during their first year (p < 0.001), continued to increase during their second year (p < 0.001), but was over 90% maintained through years 3 and 4. Conclusion: In conclusion, an anatomy course with reduced hours (∼60), using active learning methods, contextual learning, cadaver demonstrations, increased exposure to imaging, and longitudinal reinforcement can help students build a strong foundation of anatomical knowledge.
Inspiratory flow rate through a dry powder inhaler (Clickhaler®) in children with asthma

Dry powder inhalers (DPIs) are increasingly being used to deliver drugs for the treatment of asthma. Both the aerosolization and delivery of the drug from a DPI to the lung are dependent on an adequate inspiratory effort from the patient, and it is well‐known that the air flow achieved early in the inspiratory profile is important in determining particle size distribution from the inhaler. The present study assessed the peak inspiratory flow (PIF) generated through the Clickhaler® DPI, and the early inspiratory flow at 150 mL of inspired volume (IF150), in asthmatic children. These measurements were made in a well‐controlled setting, and two attempts were recorded to establish maximum achievement. Results were obtained from 57 children aged 6–17 years, showing a (mean ± SD) best PIF of 60.5 ± 18.7 L/min (range, 26.8–97.0). The mean PIF overall was 54.2 ± 20.8 L/min (7.9–97.0). For children aged 6–8 years, the mean best PIF was 46.5 ± 14.6 L/min (26.8–71.1); for those aged 9 years or more, it was >65 L/min (30.3–97.0). PIF values were unrelated to % predicted FEV1 measurements. Best IF150 (mean ± SD) was 42.9 ± 13.6 L/min (23.1–66.6) in children aged 6–8 years, and >55 L/min (28.0–86.4) for the older children, showing that high flow rates were achieved early in the inspiratory profile. These data indicate that children with stable asthma can generate adequate inspiratory flow rates to operate the Clickhaler® effectively. Pediatr Pulmonol. 2003; 35:220–226. © 2003 Wiley‐Liss, Inc.
Peripheral input and its importance for central sensitization

Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long‐term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus‐independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non‐nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. Ann Neurol 2013;74:630–636
Wingless Signaling Induces Widespread Chromatin Remodeling of Target Loci

ABSTRACT How signaling cascades influence gene regulation at the level of chromatin modification is not well understood. We studied this process using the Wingless/Wnt pathway in Drosophila. When cells sense Wingless ligand, Armadillo (the fly β-catenin) becomes stabilized and translocates to the nucleus, where it binds to the sequence-specific DNA binding protein TCF to activate transcription of target genes. Here, we show that Wingless signaling induces TCF and Armadillo recruitment to a select subset of TCF binding site clusters that act as Wingless response elements. Despite this localized TCF/Armadillo recruitment, histones are acetylated over a wide region (up to 30 kb) surrounding the Wingless response elements in response to pathway activation. This widespread histone acetylation occurs independently of transcription. In contrast to Wingless targets, other active genes not regulated by the pathway display sharp acetylation peaks centered on their core promoters. Widespread acetylation of Wingless targets is dependent upon CBP, a histone acetyltransferase known to bind to Armadillo and is correlated with activation of target gene expression. These data suggest that pathway activation induces localized recruitment of TCF/Armadillo/CBP to Wingless response elements, leading to widespread histone acetylation of target loci prior to transcriptional activation.
Chemotherapy of thyroid cancer with adriamycin. Experience with 30 patients.

Abstract Thirty patients with advanced refractory metastatic thyroid carcinoma received chemotherapy with adriamycin at a starting dose of 45 to 75 mg per square meter intravenously every three weeks. Eleven patients demonstrated a greater than 50 per cent decrease in the size of their metastases. Subjective improvement, particularly relief of pain from bony metastases, was also observed. Histologic cell types responding included medullary (solid) (three of five), papillary-follicular (three of 10), Hurthle cell (two of five), spindle and giant cell (two of nine) and unclassified thyroid carcinoma (one of one). Although the rate of disease progression in the responding and nonresponding patients was similar before the start of adriamycin, the median survival from this point on was significantly superior (p<0.005) in the responders (median 11 + and range of over five to 40 + months, six of 11 living) to that of the nonresponders (median four and range of 0.1 to 23 + months, five of 19 living). Before the n.
Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease.

BACKGROUND Glutamine is a major fuel and an important nitrogen source for the small intestinal cell. It plays a key role in maintaining mucosal cell integrity and gut barrier function. Increased permeability may be a factor in the pathogenesis of Crohn's disease and may be an interesting parameter in the follow-up of the disease. Therefore, the aim of this study was to examine whether oral glutamine supplements are able to restore an increased intestinal permeability in patients with Crohn's disease. METHODS The inclusion criteria for the study were Crohn's disease and a disturbed small intestinal permeability for 51Cr-EDTA. Of 38 patients screened, 18 had an increased permeability (6 hours urinary excretion >1.1% of label recovered in urine). Fourteen patients were included in the study and were randomized to receive either oral glutamine (7 g three times per day; n = 7) or placebo (7 g glycine three times per day; n = 7) in addition to their normal treatment during a 4-week period. The study was performed in a double-blind manner. RESULTS Baseline permeability (mean +/- SD) was 2.32%+/-0.77% dose in the glutamine group and 2.29%+/-0.67% dose in the placebo group. Permeability did not change significantly after glutamine (3.26%+/-2.15% dose) or after placebo (2.27%+/-1.32% dose). There was no significant effect on plasma glutamine, plasma glutamate, plasma ammonium, Crohn's disease activity index, C-reactive protein, or nutritional status. CONCLUSIONS Oral glutamine supplements, in the dose administered, do not seem to restore impaired permeability in patients with Crohn's disease.
Influence of monovalent cations on yeast cytoplasmic and vacuolar pH

The effects of monovalent cations on the internal pH of yeast were studied. Our former procedure was modified, inducing maximal alkalinization of the cells with 100 mM‐NH4OH instead of Tris base. The pH values were lower than reported before (Peña et al., J. Bacteriol. 1995 177, 1017–1022). With glucose as substrate, the internal cytoplasmic pH reached higher values when incubating at an external pH of 6·0, as compared to pH 4·0. Monovalent cations added approximately 5 min after glucose produced a further increase in the internal pH, which was higher at a previous incubation pH of 4·0 than that observed at pH 6·0. The selectivity of the changes followed a similar order to that of the transport system for monovalent cations.
Association between recent herpes zoster but not herpes simplex infection and subsequent risk of malignancy in women: a retrospective cohort study

SUMMARY The association between herpes zoster and subsequent cancer risk is still unclear. Consequently, doubts remain regarding the need for investigation of herpes patients for co-existing or subsequent malignancy. This is a retrospective cohort study comparing cancer risk in patients after herpes zoster and age-/sex-matched non-herpes zoster patients, in a primary care-based continuous morbidity database. We tested for interaction by gender, age, diabetes, HRT use or antiviral therapy. Analyses were repeated for patients with and without herpes simplex. The hazard ratio (HR) comparing cancer risk in herpes zoster vs. control patients was significant in all women, women aged > 65 years and subgroups of breast and colorectal cancer (HRs 1·60, 1·82, 2·14, 2·19, respectively). For men, a significant association was found for haematological cancers (HR 2·92). No associations were found with herpes simplex. No interaction was identified with antiviral therapy, diabetes or HRT treatment. We concluded that there was a moderate significant association between herpes zoster and subsequent cancer risk in women aged > 65 years, without any influence of antiviral therapy. No association was found with herpes simplex. There is insufficient reason for extensively testing older patients with herpes zoster or herpes simplex for the presence of occult cancer.