Response and Discrimination Performance of Arrays of Organothiol-Capped Au Nanoparticle Chemiresistive Vapor Sensors

The response and discrimination performance of an array that consisted of 20 different organothiol-capped Au nanoparticle chemiresistive vapor sensors was evaluated during exposure to 13 different organic vapors. The passivating organothiol ligand library consisted of collections of straight-chain alkanethiols, branched alkanethiols, and aromatic thiols. A fourth collection of sensors was formed from composites of 2-phenylethanethiol-capped Au nanoparticles and nonpolymeric aromatic materials that were coembedded in a sensor film. The organic vapors consisted of six hydrocarbons (n-hexane, n-heptane, n-octane, isooctane, cyclohexane, and toluene), three polar aprotic vapors (chloroform, tetrahydrofuran, and ethyl acetate), and four alcohols (methanol, ethanol, isopropanol, and 1-butanol). Trends in the resistance response of the sensors were consistent with expected trends in sorption due to the properties of the test vapor and the molecular structure of the passivating ligands in the sensor films. Classification algorithms including principal components analysis and Fisher’s linear discriminant were used to evaluate the discrimination performance of an array of such sensors. Each collection of sensors produced accurate classification of most vapors, with misclassification occurring primarily for vapors that had mutually similar polarity. The classification performance for an array that contained all of the sensor collections produced nearly perfect discrimination for all vapors studied. The dependence of the array size (i.e., the number of sensors) and the array chemical diversity on the discrimination performance indicated that, for an array of 20 sensors, an array size of 13 sensors or more produced the maximum discrimination performance

Response versus Chain Length of Alkanethiol-Capped Au Nanoparticle Chemiresistive Chemical Vapor Sensors

Au nanoparticles capped with a homologous series of straight chain alkanethiols (containing 4−11 carbons in length) have been investigated as chemiresistive organic vapor sensors. The series of alkanethiols was used to elucidate the mechanisms of vapor detection by such capped nanoparticle chemiresistive films and to highlight the molecular design principles that govern enhanced detection. The thiolated Au nanoparticle chemiresistors demonstrated rapid and reversible responses to a set of test vapors (n-hexane, n-heptane, n-octane, iso-octane, cyclohexane, toluene, ethyl acetate, methanol, ethanol, isopropanol, and 1-butanol) that possessed a variety of analyte physicochemical properties. The resistance sensitivity to nonpolar and aprotic polar vapors systematically increased as the chain length of the capping reagent increased. Decreases in the nanoparticle film resistances, which produced negative values of the differential resistance response, were observed upon exposure of the sensor films to alcohol vapors. The response signals became more negative with higher alcohol vapor concentrations, producing negative values of the sensor sensitivity. Sorption data measured on Au nanoparticle chemiresistor films using a quartz crystal microbalance allowed for the measurement of the partition coefficients of test vapors in the Au nanoparticle films. This measurement assumed that analyte sorption only occurred at the organic interface and not the surface of the Au core. Such an assumption produced partition coefficient values that were independent of the length of the ligand. Furthermore, the value of the partition coefficient was used to obtain the particle-to-particle interfacial effective dielectric constant of films upon exposure to analyte vapors. The values of the dielectric constant upon exposure to alcohol vapors suggested that the observed resistance response changes observed were not significantly influenced by this dielectric change, but rather were primarily influenced by morphological changes and by changes in the interparticle spacing

Neurophysiological Correlates of Emotion Regulation in Children and Adolescents

& Psychologists consider emotion regulation a critical devel-opmental acquisition. Yet, there has been very little research on the neural underpinnings of emotion regulation across childhood and adolescence. We selected two ERP compo-nents associated with inhibitory control—the frontal N2 and frontal P3. We recorded these components before, during, and after a negative emotion induction, and compared their am-plitude, latency, and source localization over age. Fifty-eight children 5–16 years of age engaged in a simple go/no-go pro-cedure in which points for successful performance earned a valued prize. The temporary loss of all points triggered negative emotions, as confirmed by self-report scales. Both the frontal N2 and frontal P3 decreased in amplitude and la-tency with age, consistent with the hypothesis of increasing cortical efficiency. Amplitudes were also greater following the emotion induction, only for adolescents for the N2 but across the age span for the frontal P3, suggesting different but overlapping profiles of emotion-related control mechanisms. No-go N2 amplitudes were greater than go N2 amplitudes following the emotion induction at all ages, suggesting a consistent effect of negative emotion on mechanisms of re-sponse inhibition. No-go P3 amplitudes were also greater than go P3 amplitudes and they decreased with age, whereas go P3 amplitudes remained low. Finally, source modeling in-dicated a developmental decline in central-posterior midline activity paralleled by increasing activity in frontal midline re-gions suggestive of the anterior cingulate cortex. Negative emotion induction corresponded with an additional right ven-tral prefrontal or temporal generator beginning in middle childhood. &amp

Reactome - a knowledgebase of human biological pathways

Pathway curation is a powerful tool for systematically associating gene products with functions. Reactome (www.reactome.org) is a manually curated human pathway knowledgebase describing a wide range of biological processes in a computationally accessible manner. The core unit of the Reactome data model is the Reaction, whose instances form a network of biological interactions through entities that are consumed, produced, or act as catalysts. Entities are distinguished by their molecular identities and cellular locations. Set objects allow grouping of related entities. Curation is based on communication between expert authors and staff curators, facilitated by freely available data entry tools. Manually curated data are subjected to quality control and peer review by a second expert. Reactome data are released quarterly. At release time, electronic orthology inference performed on human data produces reaction predictions in 22 species ranging from mouse to bacteria. Cross-references to a large number of publicly available databases are attached, providing multiple entry points into the database. The Reactome Mart allows query submission and data retrieval from Reactome and across other databases. The SkyPainter tool provides visualization and statistical analysis of user supplied data, e.g. from microarray experiments. Reactome data are freely available in a number of data formats (e.g. BioPax, SBML)

Boundary states for a free boson defined on finite geometries

Langlands recently constructed a map that factorizes the partition function of a free boson on a cylinder with boundary condition given by two arbitrary functions in the form of a scalar product of boundary states. We rewrite these boundary states in a compact form, getting rid of technical assumptions necessary in his construction. This simpler form allows us to show explicitly that the map between boundary conditions and states commutes with conformal transformations preserving the boundary and the reality condition on the scalar field.Comment: 16 pages, LaTeX (uses AMS components). Revised version; an analogy with string theory computations is discussed and references adde

Topical tetracaine prior to arterial puncture: a randomized, placebo-controlled clinical trial

AbstractThe objective of this randomized, double-blind, placebo-controlled clinical trial was to determine whether a topical anesthetic agent (tetracaine) provides effective local analgesia prior to radial arterial puncture. Tetracaine or placebo gel was applied 45min prior to arterial puncture to patients who were referred for elective arterial blood gas. The primary outcome was the patient's perception of pain associated with the procedure as measured by a visual analog scale. Fifty patients were randomized into the study, 24 received tetracaine and 26 placebo. Mean pain score on the visual analog scale was 26.2±32.6 for the tetracaine-treated patients and 23.8±27.4 for the placebo-treated patients (P=0.78). Mean time from the first skin puncture to successful procurement of 1ml of arterial blood was 70±103s in the tetracaine group and 49±48s in the placebo group (P=0.40). Difficulty of arterial puncture as assessed by the respiratory therapist performing the test was identical for the two groups (P=0.86). We conclude that tetracaine gel did not decrease patient's perception of pain associated with arterial puncture, nor did its use facilitate the ABG procedure

Extraction of spatiotemporal response information from sorption-based cross-reactive sensor arrays for the identification and quantification of analyte mixtures

Linear sensor arrays made from small molecule/carbon black composite chemiresistors placed in a low headspace volume chamber, with vapor delivered at low flow rates, allowed for the extraction of chemical information that significantly increased the ability of the sensor arrays to identify vapor mixture components and to quantify their concentrations. Each sensor sorbed vapors from the gas stream to various degrees. Similar to gas chromatography, species having high vapor pressures were separated from species having low vapor pressures. Instead of producing typical sensor responses representative of thermodynamic equilibrium between each sensor and an unchanging vapor phase, sensor responses varied depending on the position of the sensor in the chamber and the time from the beginning of the analyte exposure. This spatiotemporal (ST) array response provided information that was a function of time as well as of the position of the sensor in the chamber. The responses to pure analytes and to multi-component analyte mixtures comprised of hexane, decane, ethyl acetate, chlorobenzene, ethanol, and/or butanol, were recorded along each of the sensor arrays. Use of a non-negative least squares (NNLS) method for analysis of the ST data enabled the correct identification and quantification of the composition of 2-, 3-, 4- and 5-component mixtures from arrays using only 4 chemically different sorbent films and sensor training on pure vapors only. In contrast, when traditional time- and position-independent sensor response information was used, significant errors in mixture identification were observed. The ability to correctly identify and quantify constituent components of vapor mixtures through the use of such ST information significantly expands the capabilities of such broadly cross-reactive arrays of sensors

Origin and Control of Chemoselectivity in Cytochrome c Catalyzed Carbene Transfer into Si–H and N–H bonds

A cytochrome c heme protein was recently engineered to catalyze the formation of carbon–silicon bonds via carbene insertion into Si–H bonds, a reaction that was not previously known to be catalyzed by a protein. High chemoselectivity toward C–Si bond formation over competing C–N bond formation was achieved, although this trait was not screened for during directed evolution. Using computational and experimental tools, we now establish that activity and chemoselectivity are modulated by conformational dynamics of a protein loop that covers the substrate access to the iron–carbene active species. Mutagenesis of residues computationally predicted to control the loop conformation altered the protein’s chemoselectivity from preferred silylation to preferred amination of a substrate containing both N–H and Si–H functionalities. We demonstrate that information on protein structure and conformational dynamics, combined with knowledge of mechanism, leads to understanding of how non-natural and selective chemical transformations can be introduced into the biological world

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF ( Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P \u3e .05. Conclusions and Relevance: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier: NCT02188784

The LKB1-AMPK-α1 signaling pathway triggers hypoxic pulmonary vasoconstriction downstream of mitochondria

International audienceHypoxic pulmonary vasoconstriction (HPV), which aids ventilation-perfusion matching in the lungs, is triggered by mechanisms intrinsic to pulmonary arterial smooth muscles. The unique sensitivity of these muscles to hypoxia is conferred by mitochondrial cytochrome c oxidase subunit 4 isoform 2, the inhibition of which has been proposed to trigger HPV through increased generation of mitochondrial reactive oxygen species. Contrary to this model, we have shown that the LKB1-AMPK-α1 signaling pathway is critical to HPV. Spectral Doppler ultrasound revealed that deletion of the AMPK-α1 catalytic subunit blocked HPV in mice during mild (8% O2) and severe (5% O2) hypoxia, whereas AMPK-α2 deletion attenuated HPV only during severe hypoxia. By contrast, neither of these genetic manipulations affected serotonin-induced reductions in pulmonary vascular flow. HPV was also attenuated by reduced expression of LKB1, a kinase that activates AMPK during energy stress, but not after deletion of CaMKK2, a kinase that activates AMPK in response to increases in cytoplasmic Ca2+ Fluorescence imaging of acutely isolated pulmonary arterial myocytes revealed that AMPK-α1 or AMPK-α2 deletion did not affect mitochondrial membrane potential during normoxia or hypoxia. However, deletion of AMPK-α1, but not of AMPK-α2, blocked hypoxia from inhibiting KV1.5, the classical "oxygen-sensing" K+ channel in pulmonary arterial myocytes. We conclude that LKB1-AMPK-α1 signaling pathways downstream of mitochondria are critical for the induction of HPV, in a manner also supported by AMPK-α2 during severe hypoxia