Computed terahertz near-field mapping of molecular resonances of lactose stereo-isomer impurities with sub-attomole sensitivity

Terahertz near-field microscopy (THz-NFM) could locally probe low-energy molecular vibration dynamics below diffraction limits, showing promise to decipher intermolecular interactions of biomolecules and quantum matters with unique THz vibrational fingerprints. However, its realization has been impeded by low spatial and spectral resolutions and lack of theoretical models to quantitatively analyze near-field imaging. Here, we show that THz scattering-type scanning near-field optical microscopy (THz s-SNOM) with a theoretical model can quantitatively measure and image such low-energy molecular interactions, permitting computed spectroscopic near-field mapping of THz molecular resonance spectra. Using crystalline-lactose stereo-isomer (anomer) mixtures (i.e., alpha-lactose (>= 95%, w/w) and beta-lactose (<= 4%, w/w)), THz s-SNOM resolved local intermolecular vibrations of both anomers with enhanced spatial and spectral resolutions, yielding strong resonances to decipher conformational fingerprint of the trace beta-anomer impurity. Its estimated sensitivity was similar to 0.147 attomoles in similar to 8 x 10(-4) mu m(3) interaction volume. Our THz s-SNOM platform offers a new path for ultrasensitive molecular fingerprinting of complex mixtures of biomolecules or organic crystals with markedly enhanced spatio-spectral resolutions. This could open up significant possibilities of THz technology in many fields, including biology, chemistry and condensed matter physics as well as semiconductor industries where accurate quantitative mappings of trace isomer impurities are critical but still challenging.11Ysciescopu

High-precision THz Dielectric Spectroscopy of Tris-HCl Buffer

Tris-HCl buffer solution is extensively used in biochemistry and molecular biology to maintain a stablepH for biomolecules such as nucleic acids and proteins. Here we report on the high-precision THz dielectricspectroscopy of a 10 mM Tris-HCl buffer. Using a double Debye model, including conductivity of ionicspecies, we measured the complex dielectric functions of Tris-HCl buffer. The fast relaxation time of watermolecules in Tris-HCl buffer is ~20% longer than that in pure water while the slow relaxation time changeslittle. This means that the reorientation dynamics of Tris-HCl buffer with such a low Tris concentrationis quite different from that of pure water.1111Ysciescopuskc

Arabidopsis ABCG14 is essential for the root-to-shoot translocation of cytokinin.

Cytokinins are phytohormones that induce cytokinesis and are essential for diverse developmental and physiological processes in plants. Cytokinins of the trans-zeatin type are mainly synthesized in root vasculature and transported to the shoot, where they regulate shoot growth. However, the mechanism of long-distance transport of cytokinin was hitherto unknown. Here, we report that the Arabidopsis ATP-binding cassette (ABC) transporter subfamily G14 (AtABCG14) is mainly expressed in roots and plays a major role in delivering cytokinins to the shoot. Loss of AtABCG14 expression resulted in severe shoot growth retardation, which was rescued by exogenous trans-zeatin application. Cytokinin content was decreased in the shoots of atabcg14 plants and increased in the roots, with consistent changes in the expression of cytokinin-responsive genes. Grafting of atabcg14 scions onto wild-type rootstocks restored shoot growth, whereas wild-type scions grafted onto atabcg14 rootstocks exhibited shoot growth retardation similar to that of atabcg14. Cytokinin concentrations in the xylem are reduced by similar to 90% in the atabcg14 mutant. These results indicate that AtABCG14 is crucial for the translocation of cytokinin to the shoot. Our results provide molecular evidence for the long-distance transport of cytokinin and show that this transport is necessary for normal shoot development.open118380Ysciescopu

Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank

PURPOSE. The purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits. METHODS. In a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes. RESULTS. Statin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = −0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = −0.15 microns, 95% CI = −0.28 to −0.01, P = 0.03) but not with mGCIPL thickness (difference = −0.12 microns, 95% CI = −0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (Pinteraction ≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14). CONCLUSIONS. We found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders

Intraocular pressure, glaucoma and dietary caffeine consumption: a gene-diet interaction study from the UK Biobank

Objective: We examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether these associations were modified by genetic predisposition to higher IOP. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP. Design: A cross-sectional study in the UK Biobank. Participants: We included 121,374 participants (baseline ages 39-73 years) with data on coffee and tea intake (collected 2006-2010) and corneal-compensated IOP measurements in 2009. In a subset of 77,906 participants with up to five web-based 24-hour-recall food frequency questionnaires (2009-2012) we evaluated total caffeine intake. We also assessed the same relations with any glaucoma (9,286 cases and 189,763 controls). Method: We evaluated multivariable-adjusted associations with IOP using linear regression, and with glaucoma using logistic regression. For both outcomes, we examined gene-diet interactions, using a polygenic risk score (PRS), which combined the effects of 111 genetic variants associated with IOP. We also performed two-sample Mendelian Randomization (MR) using 8 genetic variants associated with coffee intake, to assess potential causal effects of coffee consumption on IOP. Main Outcome and Measures: IOP; glaucoma. Results: Mean IOP was 16.0 mmHg (Standard Deviation=3.8). MR analysis did not support a causal effect of coffee drinking on IOP (P>0.1). Greater caffeine intake was weakly associated with lower IOP: the highest (≥232mg/day) vs. lowest (480mg/day versus <80 mg/day was associated with a 0.35 mmHg higher IOP (Pinteraction=0.01). The relation between caffeine intake and glaucoma was null (P≥0.1). However, this relation was also significantly modified by IOP PRS: compared to those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming ≥321mg/day had a 3.90-fold higher glaucoma prevalence (Pinteraction=0.0003). Conclusions: Habitual caffeine consumption was weakly associated with lower IOP and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

Robust topology optimization of structures under uncertain propagation of imprecise stochastic-based uncertain field

This study introduces a novel computational framework for Robust Topology Optimization (RTO) considering imprecise random field parameters. Unlike the worst-case approach, the present method provides upper and lower bounds for the mean and standard deviation of compliance as well as the optimized topological layouts of a structure for various scenarios. In the proposed approach, the imprecise random field variables are determined utilizing parameterized p-boxes with different confidence intervals. The Karhunen–Loève (K–L) expansion is extended to provide a spectral description of the imprecise random field. The linear superposition method in conjunction with a linear combination of orthogonal functions is employed to obtain explicit mathematical expressions for the first and second order statistical moments of the structural compliance. Then, an interval sensitivity analysis is carried out, applying the Orthogonal Similarity Transformation (OST) method with the boundaries of each of the intermediate variable searched efficiently at every iteration using a Combinatorial Approach (CA). Finally, the validity, accuracy, and applicability of the work are rigorously checked by comparing the outputs of the proposed approach with those obtained using the particle swarm optimization (PSO) and Quasi-Monte-Carlo Simulation (QMCS) methods. Three different numerical examples with imprecise random field loads are presented to show the effectiveness and feasibility of the study

Longitudinal Patterns in Antithrombotic Therapy in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention in the Non-Vitamin K Oral Anticoagulant Era:A Nationwide Population-Based Study

We investigated whether longitudinal patterns in antithrombotic therapy have changed after the introduction of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI). Using a claims database of the Korean AF population who underwent PCI between 2012 and 2016 (n = 18,691), we analyzed prescription records of oral anticoagulants (OACs) and antiplatelets at 3-month intervals over 2 years after PCI. The study population was stratified (pre-NOAC, transition, and NOAC era) using time-periods of NOAC introduction in Korea and an expansion of reimbursement for NOAC in AF as indicators. The overall rates of OAC were low at baseline (24.9%, 26.9%, and 35.2% in pre-NOAC, transition, and NOAC era, respectively), contrary to high rates of dual antiplatelet therapy (DAPT) (73.3%, 71.4%, and 63.6%). However, OAC prescription rates were increased at 1-year (18.5%, 22.5%, and 31.6%), and 2-year follow-up (17.8%, 24.2%, and 31.8%) from pre-NOAC to NOAC era. In NOAC era, 63.5% of baseline OAC prescriptions comprised NOAC, of which 96.4% included triple therapy with DAPT. Over 2 years, we observed increasing rates of double therapy with a single antiplatelet (18.3% and 20.0% at 1- and 2-year follow-up) and OAC monotherapy (2.7% and 8.9% at 1- and 2-year follow-up)

Net clinical benefit of antithrombotic therapy for atrial fibrillation patients with stable coronary artery disease

OBJECTIVES: To compare the net clinical benefit of oral anticoagulant (OAC) monotherapy to OAC plus single antiplatelet therapy (SAPT) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) at 1- and 3-year after percutaneous coronary intervention (PCI). BACKGROUND: It has not been studied whether the net clinical benefit of the antithrombotic treatment options differs depending on the elapsed time from the index PCI. METHODS: Using the Korean nationwide claims database, we included AF patients who underwent PCI from 2009 to 2019 and constructed two cohorts: 1- and 3-year after PCI. In each cohort, the baseline characteristics of two groups were balanced using propensity score weighting. Ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes were analyzed. RESULTS: Among patients with 1-year after PCI, OAC monotherapy (n = 678), and OAC plus SAPT (n = 3,159) showed comparable results for all clinical outcomes. In patients with 3-year after PCI, OAC monotherapy (n = 1,038) and OAC plus SAPT (n = 2,128) showed comparable results for ischemic stroke and myocardial infarction, but OAC monotherapy was associated with a lower risk of composite clinical outcomes (HR 0.762, 95% CI 0.607–0.950), mainly driven by the reduction of major bleeding risk (HR 0.498, 95% CI 0.345–0.701). CONCLUSION: Oral anticoagulant monotherapy may be a comparable choice for patients with AF and stable CAD compared to OAC plus SAPT. In patients with stable CAD more than 3-year after index PCI, OAC monotherapy would be a better choice, being associated with less major bleeding and a positive net clinical benefit