Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in M2 alter the selectivity of the mouse nicotinic acetylcholine receptor for organic and alkali metal cations

We measured the permeability ratios (PX/PNa) of 3 wild-type, 1 hybrid, 2 subunit-deficient, and 22 mutant nicotinic receptors expressed in Xenopus oocytes for alkali metal and organic cations using shifts in the bi-ionic reversal potential of the macroscopic current. Mutations at three positions (2', 6', 10') in M2 affected ion selectivity. Mutations at position 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) near the intracellular end of M2 changed the organic cation permeability ratios as much as twofold and reduced PCs/PNa and PK/PNa by 16-18%. Mutations at positions 6' and 10' increased the glycine ethyl ester/Na+ and glycine methyl ester/Na+ permeability ratios. Two subunit alterations also affected selectivity: omission of the delta subunit reduced PCs/PNa by 16%, and substitution of Xenopus delta for mouse delta increased Pguanidinium/PNa more than twofold and reduced PCs/PNa by 34% and PLi/PNa by 20%. The wild-type mouse receptor displayed a surprising interaction with the primary ammonium cations; relative permeability peaked at a chain length equal to four carbons. Analysis of the organic permeability ratios for the wild-type mouse receptor shows that (a) the diameter of the narrowest part of the pore is 8.4 A; (b) the mouse receptor departs significantly from size selectivity for monovalent organic cations; and (c) lowering the temperature reduces Pguanidinium/PNa by 38% and Pbutylammonium/PNa more than twofold. The results reinforce present views that positions -1' and 2' are the narrowest part of the pore and suggest that positions 6' and 10' align some permeant organic cations in the pore in an interaction similar to that with channel blocker, QX-222.
Evaluation of Interventions to Improve Solar Protection in Primary Schools

Childhood and adolescence are critical periods in the etiology of subsequent melanoma and nonmelanocytic skin cancers. The aims of the study were (a) to develop a valid measure of solar protection in 9 to 11-year-old school students, (b) to evaluate the differential effectiveness of two interventions aimed at changing solar protection in this age group, and (c) to identify the predictors of use of a high level of solar protection. A Solar Protection Behavior Diary was developed and validated during a pilot, after which 11 schools were randomly allocated to one of three groups: intensive intervention (247 students), standard intervention (180 students), or control (185 students), with students in years 5 and 6 participating in the study. Students completed the validated diary (for 5 days) and a knowledge and attitudes questionnaire at pretest and at two posttest periods (4 weeks and 8 months after pretest). Results indicated that students in the intensive intervention group were significantly more likely to have used a high level of protection at both posttest periods compared to the control and standard intervention groups. There was no difference in the protection level of the control and standard intervention groups at either posttest, indicating that this minimal intervention was not effective in changing the solar protection behavior of the students. Students with a high level of solar protection at pretest were also significantly more likely to have a high level of protection at both posttest periods, and those with a greater number of opportunities to protect were less likely to protect at the second posttest.
Combined tadalafil and α-blocker therapy for benign prostatic hyperplasia in patients with erectile dysfunction: a multicenter, prospective study.

This prospective study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms (LUTS) and restores sexual function in patients with erectile dysfunction who are receiving concomitant α-blocker (AB) therapy for benign prostatic hyperplasia (BPH). A total of 158 LUTS/BPH patients receiving AB therapy for ≥3 months were given tadalafil 5 mg once a day. Before treatment with tadalafil (V1), and 4 weeks (V2) and 12 weeks (V3) after starting tadalafil, blood pressure, heart rate, International Prostate Symptom Score (IPSS), maximal urine flow rate (Qmax), postvoiding residual urine volume, and International Index of Erectile Function (IIEF-5) score were measured. Of the 158 LUTS/BPH patients, a total of 119 completed the trial. Blood pressure (systolic and diastolic) and heart rate did not change. IPSS and IIEF-5 scores improved significantly, but Qmax and postvoiding residual urine volume did not; however, in the 39 men with a low baseline Qmax (≤10 mL/s), Qmax rose significantly from 7.97 ± 1.44 mL/s (baseline) to 8.91 ± 1.60 mL/s (V3; P = .012). The remaining patients (baseline Qmax >10 mL/s) did not change. At V2 and V3, adverse side effects were observed in 10 men (7.30%) and 6 men (5.04%), respectively. Facial flushing was the most common adverse side effect (6 men at V2 and 4 men at V3), followed by headache (2 men each at V2 and V3) and dizziness (2 men at V2). Two patients dropped out of the study because of adverse side effects. In conclusion, tadalafil 5 mg once a day in combination with AB appeared to have few adverse effects on hypotensive events and can improve LUTS and restore sexual function.
GIP: An Inconsequential Incretin or Not?

The “incretin effect” refers to the enhancement of insulin secretion in response to an oral glucose load relative to that of an isoglycemic intravenous glucose challenge (1). In humans, the incretin effect is mediated by two peptide hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are secreted from enteroendocrine cells in response to nutrients entering the gut. GLP-1 secretion from L-cells, found in highest density in the distal ileum but also throughout the small and large intestine, is stimulated by glucose, amino acids, and fat. GIP, in contrast, is produced by the K-cells in the proximal duodenum; its secretion is also stimulated by glucose, but is particularly enhanced by fat (2). Both GLP-1 and GIP are derived from prohormones (proglucagon and pro-GIP, respectively) and secreted as active hormones. The effects of both GLP-1 and GIP are mediated by specific G protein–coupled receptors present on the plasma membrane of β-cells and other target tissues. GLP-1 and GIP increase insulin secretion from β-cells in a glucose-dependent manner. In rodents, GLP-1 and GIP also enhance β-cell mass by increasing rates of proliferation and decreasing rates of apoptosis. Many physiological effects of GLP-1 and GIP do not overlap, however. GLP-1 suppresses glucagon secretion, slows gastric emptying, and has central nervous system effects to regulate appetite, whereas GIP does not. GIP, on the other hand, has direct effects on adipocytes to promote triglyceride storage (1). The incretin system, therefore, facilitates integrated physiological responses to meals of different size and composition allowing ingested nutrients to be optimally metabolized. The incretin effect is an important determinant of glucose tolerance. In patients with type 2 diabetes, the incretin effect …
Fucoxanthin prevents H2O2-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway

ABSTRACT Background: As a natural carotenoid abundant in chloroplasts of edible brown algae, fucoxanthin possesses various health benefits, including anti-oxidative activity in particular. Objective: In the present study, we studied whether fucoxanthin protected against hydrogen peroxide (H2O2)-induced neuronal apoptosis. Design: The neuroprotective effects of fucoxanthin on H2O2-induced toxicity were studied in both SH-SY5Y cells and primary cerebellar granule neurons. Results: Fucoxanthin significantly protected against H2O2-induced neuronal apoptosis and intracellular reactive oxygen species. H2O2 treatment led to the reduced activity of phosphoinositide 3-kinase (PI3-K)/Akt cascade and the increased activity of extracellular signal-regulated kinase (ERK) pathway in SH-SY5Y cells. Moreover, fucoxanthin significantly restored the altered activities of PI3-K/Akt and ERK pathways induced by H2O2. Both specific inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK) significantly protected against H2O2-induced neuronal death. Furthermore, the neuroprotective effects of fucoxanthin against H2O2-induced neuronal death were abolished by specific PI3-K inhibitors. Conclusions: Our data strongly revealed that fucoxanthin protected against H2O2-induced neurotoxicity via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway, providing support for the use of fucoxanthin to treat neurodegenerative disorders induced by oxidative stress.
Dimension reduction in EEG data using Particle Swarm Optimization

EEG data contains high-dimensional data that requires considerable computational power for distinguishing different classes. Dimension reduction is commonly used to reduces the necessary training time of the classifiers with some degree of accuracy lost. The dimension reduction is usually performed on either feature or electrode space. In this study, a new dimension reduction method that reduce the number of electrodes and features using variations of Particle Swarm Optimization (PSO) is used. The variation is in terms of parameter adjustment and adding a mutation operator to the PSO. The results are assessed based on the dimension reduction percentage, the potential of selected electrodes and the degree of performance lost. An Extreme Learning Machine (ELM) is used as the primary classifier to evaluate the sets of electrodes and features selected by PSO. Two alternative classifiers such as Polynomial SVM and Perceptron are used for further evaluation of the reduced dimension data. The results indicate the potential of variations of PSO for reducing up to 99% of the data with minimal performance lost.
Inhibition and Retrieval of Facts in Young and Older Adults

Inhibition is considered to have an important role in memory retrieval. However, many experimental results suggest that its efficiency declines with aging. In this study, the authors tested this hypothesis by using the retrieval-practice task. The retrieval-induced forgetting (RIF) observed with this paradigm is normally explained in terms of inhibition. Young (mean age 21.5 years) and older (mean age 71.6 years) adults studied sets of four shared-subject sentences. A retrieval-practice phase required participants to repeatedly recall a subset of the studied sentences. In the final test, participants were provided item-specific cues and told to recall all the studied sentences. RIF was similar for both age groups, suggesting comparable inhibitory efficiency in young and older adults.
Family poverty is associated with cytomegalovirus antibody titers in U.S. children.

OBJECTIVE Early life environmental and psychological influences are thought to play an important role in the development of the immune system. Antibody response to latent herpesviruses has been used as an indirect measure of cell-mediated immune function but has seldom been applied to younger age groups. METHODS We used data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) to test for an association between family poverty and continuous antibody response to cytomegalovirus in U.S. children aged 6-16 (N = 2,226) using ordinary least squares regression. RESULTS Poverty was significantly associated with increased antibody levels among seropositive individuals. The association between income and antibody levels exhibited a threshold effect, with additional income beyond the poverty line not associated with increased antibody titers. This relationship was more robust among older compared with younger children. CONCLUSIONS Early life social factors such as family poverty could have detrimental impacts on the developing immune system, with potentially important consequences for later life health outcomes. Exposure to socioeconomic stressors for longer periods during childhood may further enhance alterations in immune response to cytomegalovirus.
SEASON OF BIRTH AND REPRODUCTIVE PERFORMANCE: AN ANALYSIS OF FAMILY RECONSTITUTIONS OF 800 WOMEN BORN IN THE NETHERLANDS AT THE END OF THE 19TH CENTURY

Background: Several studies have reported associations between season of birth and reproductive characteristics such as menarcheal age, fecundability, and twinning, but the results are inconsistent with respect to the location of high- and low-risk seasons. To assess whether this disagreement could be due to the use of populations from different geographic areas and time frames instead of different etiologic pathways, we investigated the season-of-birth dependency of a variety of reproductive outcomes within one time- and arealimited population. Methods: In a historic follow-up study, the reconstituted families of 800 women born between 1873 and 1887 in or near Rotterdam, The Netherlands, were used to determine eight types of reproductive outcome: childlessness, interval to first pregnancy, pregnancy interval, stillbirth, neonatal death, postneonatal death, multiple birth, and gender of offspring. The relation of these outcomes with season of birth was modeled using cosinor functions with periods of 1 year or a half year. Data were analyzed by use of logistic regression or general estimation equations (GEE), dependent on whether outcomes could occur more than once per woman. Results: Peaks in the model-based risks of reproductive failure were found within two small temporal ranges, January 1 to February 11 and July 1 to August 11 for all outcomes except gender. The picture did not change after controlling for known and possible risk factors, including age, offspring's birth cohort, and some social variables. Conclusions: This study reconfirms the idea that seasonal factors around conception or birth influence later reproductive characteristics. Observing the consistency of the location of high-risk seasons across a variety of outcomes, the explanation of season-of-birth dependency of different reproductive outcomes need not involve multiple etiological pathways. (Chronobiology International, 18(3), 525–539, 2001)
Treatment Evolution after COPD Diagnosis in the UK Primary Care Setting

Rationale To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting. Methods A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009. Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed. Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations. At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up. Results A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis. At diagnosis (0–3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%). Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months. Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months. Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months. Conclusion Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline. The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state.
Two-year impacts on employment and income among adults receiving antiretroviral therapy in Tamil Nadu, India: a cohort study

Objectives:To estimate the economic impact of antiretroviral therapy (ART) on employment and income of treated patients as well as a comparison group of pre-ART patients who receive care and support in Tamil Nadu, India. Methods:A cohort of 1238 HIV-infected patients was followed between 2005 and 2007. Socioeconomic data were collected at 6-month intervals. A total of 515 patients initiated ART during the study period, whereas a comparison group of 723 patients were pre-ART. The impact of ART on four employment outcomes was analyzed: participation in economic activities in the past week, number of hours worked in the past week, individual income earned in the past 30 days and 6 months. Regression models including patient fixed effects were estimated. Data from the comparison group of patients were used to adjust for time trends in employment outcomes. Results:At 6 months after initiation of ART, patients were 10 percentage points more likely to be economically active (P < 0.01) and worked 5.5 additional hours per week (P < 0.01). These increases were over and above those experienced by the comparison group. The estimated 24-month impacts represent a doubling of patients' employment levels at baseline. At 24 months after ART initiation, employment increases remained large and significant. Effects were almost twice as large for men compared with women. Income earned in the past 30 days and 6 months also rose significantly. Conclusion:ART resulted in a rapid and sustained increase in employment and income for patients. The results demonstrate that ART can improve the economic outcomes of HIV-infected patients.
High thermoelectric power factor in two-dimensional crystals of Mo S 2

The quest for high-efficiency heat-to-electricity conversion has been one of the major driving forces toward renewable energy production for the future. Efficient thermoelectric devices require high voltage generation from a temperature gradient and a large electrical conductivity while maintaining a low thermal conductivity. For a given thermal conductivity and temperature, the thermoelectric power factor is determined by the electronic structure of the material. Low dimensionality (1D and 2D) opens new routes to a high power factor due to the unique density of states (DOS) of confined electrons and holes. The 2D transition metal dichalcogenide (TMDC) semiconductors represent a new class of thermoelectric materials not only due to such confinement effects but especially due to their large effective masses and valley degeneracies. Here, we report a power factor of $\mathrm{Mo}{\mathrm{S}}_{2}$ as large as $8.5\phantom{\rule{0.28em}{0ex}}\mathrm{mW}\phantom{\rule{0.28em}{0ex}}{\mathrm{m}}^{\ensuremath{-}1}\phantom{\rule{0.28em}{0ex}}{\mathrm{K}}^{\ensuremath{-}2}$ at room temperature, which is among the highest measured in traditional, gapped thermoelectric materials. To obtain these high power factors, we perform thermoelectric measurements on few-layer $\mathrm{Mo}{\mathrm{S}}_{2}$ in the metallic regime, which allows us to access the 2D DOS near the conduction band edge and exploit the effect of 2D confinement on electron scattering rates, resulting in a large Seebeck coefficient. The demonstrated high, electronically modulated power factor in 2D TMDCs holds promise for efficient thermoelectric energy conversion.
ZEB1 Promotes Invasiveness of Colorectal Carcinoma Cells through the Opposing Regulation of uPA and PAI-1

Purpose: Carcinoma cells enhance their invasive capacity through dedifferentiation and dissolution of intercellular adhesions. A key activator of this process is the ZEB1 transcription factor, which is induced in invading cancer cells by canonical Wnt signaling (β-catenin/TCF4). Tumor invasiveness also entails proteolytic remodeling of the peritumoral stroma. This study aimed to investigate the potential regulation by ZEB1 of the plasminogen proteolytic system constituted by the urokinase plasminogen activator (uPA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Experimental Design: Through multiple experimental approaches, colorectal carcinoma (CRC) cell lines and samples from human primary CRC and ZEB1 (−/−) mice were used to examine ZEB1-mediated regulation of uPA and PAI-1 at the protein, mRNA, and transcriptional level. Results: ZEB1 regulates uPA and PAI-1 in opposite directions: induces uPA and inhibits PAI-1. In vivo expression of uPA depends on ZEB1 as it is severely reduced in the developing intestine of ZEB1 null (−/−) mice. Optimal induction of uPA by Wnt signaling requires ZEB1 expression. ZEB1 binds to the uPA promoter and activates its transcription through a mechanism implicating the histone acetyltransferase p300. In contrast, inhibition of PAI-1 by ZEB1 does not involve transcriptional repression but rather downregulation of mRNA stability. ZEB1-mediated tumor cell migration and invasion depend on its induction of uPA. ZEB1 coexpresses with uPA in cancer cells at the invasive front of CRCs. Conclusions: ZEB1 promotes tumor invasiveness not only via induction in cancer cells of a motile dedifferentiated phenotype but also by differential regulation of genes involved in stroma remodeling. Clin Cancer Res; 19(5); 1071–82. ©2013 AACR.
Co-Occurrence of Regulated, Masked and Emerging Mycotoxins and Secondary Metabolites in Finished Feed and Maize—An Extensive Survey

Global trade of agricultural commodities (e.g., animal feed) requires monitoring for fungal toxins. Also, little is known about masked and emerging toxins and metabolites. 1926 samples from 52 countries were analysed for toxins and metabolites. Of 162 compounds detected, up to 68 metabolites were found in a single sample. A subset of 1113 finished feed, maize and maize silage samples containing 57 compounds from 2012 to 2015 from 44 countries was investigated using liquid chromatography and mass spectrometry. Deoxynivalenol (DON), zearalenone (ZEN) and fumonisins showed large increases of annual medians in Europe. Within a region, distinct trends were observed, suggesting importance of local meteorology and cultivars. In 2015, median DON concentrations increased to 1400 μg·kg−1 in Austria, but were stable in Germany at 350 μg·kg−1. In 2014, enniatins occurred at median concentrations of 250 μg·kg−1 in Europe, at levels similar to DON and ZEN. The latter were frequently correlated with DON-3-glucoside and ZEN-14-sulfate. Co-occurrence of regulated toxins was frequent with e.g., enniatins, and moniliformin. Correlation was observed between DON and DON-3-glucoside and with beauvericin. Results indicate that considerably more than 25% of agricultural commodities could be contaminated with mycotoxins as suggested by FAO, although this is at least partly due to the lower limits of detection in the current survey. Observed contamination percentages ranged from 7.1 to 79% for B trichothecenes and 88% for ZEN.
The phone lock: audio and haptic shoulder-surfing resistant PIN entry methods for mobile devices

Tangible user interfaces are portals to digital information. In the future, securing access to such material will be an important concern. This paper describes the design, implementation and evaluation of a PIN entry system based on audio or haptic cues that is suitable for integration into such physical systems. The current implementation links movements on a mobile phone touch screen with the display of non-visual cues; selection of a sequence of these cues composes a password. Studies reveal the validity of this approach in terms of task times and error rates that improve over prior art. In sum, this paper demonstrates the potential of non-visual PINs as a mechanism for securing access to a range of systems, ultimately incorporating mobile, ubiquitous or tangible interfaces.