A semiglobal potential energy surface (PES) and quartic force field (QFF) based on fitting high-level electronic structure energies are presented to describe the structures and spectroscopic ...properties of NNHNN+. The equilibrium structure of NNHNN+ is linear with the proton equidistant between the two nitrogen groups and thus of D ∞h symmetry. Vibrational second-order perturbation theory (VPT2) calculations based on the QFF fails to describe the proton “rattle” motion, i.e., the antisymmetric proton stretch, due to the very flat nature of PES around the global minimum but performs properly for other modes with sharper potential wells. Vibrational self-consistent field/virtual state configuration interaction (VSCF/VCI) calculations using a version of MULTIMODE without angular momentum terms successfully describe this motion and predict the fundamental to be at 759 cm–1. This is in good agreement with the value of 746 cm–1 from a fixed-node diffusion Monte Carlo calculation and the experimental Ar-tagged result of 743 cm–1. Other VSCF/VCI energies are in good agreement with other experimentally reported ones. Both double-harmonic intensity and rigorous MULTIMODE intensity calculations show the proton-transfer fundamental has strong intensity.
Protonated acetylene, C2H3 +, is among the simplest carbocations. Comprehensive experimental or highly accurate computational spectroscopic data is lacking for this system due to its inherent ...complexities. Utilizing state-of-the-art quartic force fields (QFFs), the spectroscopic constants and fundamental vibrational frequencies are provided in this work for the nonclassical, bridged, cyclic global minimum. The rotational constants match experiment to better than 0.1%, and the computed ν2 antisymmetric HCCH stretch is less than 3.0 cm–1 different from experiment. Hence, the rovibrational spectroscopic data provided herein for c-C2H3 + and its deuterated isotopologues enrich the chemical understanding of this system. Unfortunately, the same rovibrational spectroscopic data is not as trustworthy for the classical, linear form of protonated acetylene due to the shallow well in which it resides on the potential energy surface. However, spectroscopic data are provided for this isomer in the Supporting Information to enhance future studies.
Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to ...transition to infection. The initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus: SasG-I and SasG-II. Structural analyses of SasG-II identify a nonaromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicate that SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment results in different binding profiles between SasG-I and SasG-II on skin cells. In addition, SasG-mediated adhesion is recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization.
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•There are two major divergent SasG alleles in S. aureus, SasG-I and SasG-II•SasG-II contains a nonaromatic arginine residue in the lectin-binding pocket•SasG-II has a different adhesion profile than SasG-I and binds a broader variety of ligands
Mills et al. show that Staphylococcus aureus surface protein G (SasG) has two major divergent alleles, SasG-I and SasG-II. SasG-II has a broader binding profile than SasG-I, which confers an advantage to these S. aureus SasG-II-expressing strains in colonizing human skin.
Multispectrum analysis of the oxygen A-band Drouin, Brian J.; Benner, D. Chris; Brown, Linda R. ...
Journal of Quantitative Spectroscopy & Radiative Transfer/Journal of quantitative spectroscopy & radiative transfer,
01/2017, Letnik:
186
Journal Article
Recenzirano
Odprti dostop
Retrievals of atmospheric composition from near-infrared measurements require measurements of airmass to better than the desired precision of the composition. The oxygen bands are obvious choices to ...quantify airmass since the mixing ratio of oxygen is fixed over the full range of atmospheric conditions. The OCO-2 mission is currently retrieving carbon dioxide concentration using the oxygen A-band for airmass normalization. The 0.25% accuracy desired for the carbon dioxide concentration has pushed the required state-of-the-art for oxygen spectroscopy. To measure O2 A-band cross-sections with such accuracy through the full range of atmospheric pressure requires a sophisticated line-shape model (Rautian or Speed-Dependent Voigt) with line mixing (LM) and collision induced absorption (CIA). Models of each of these phenomena exist, however, this work presents an integrated self-consistent model developed to ensure the best accuracy.
It is also important to consider multiple sources of spectroscopic data for such a study in order to improve the dynamic range of the model and to minimize effects of instrumentation and associated systematic errors. The techniques of Fourier Transform Spectroscopy (FTS) and Cavity Ring-Down Spectroscopy (CRDS) allow complimentary information for such an analysis. We utilize multispectrum fitting software to generate a comprehensive new database with improved accuracy based on these datasets. The extensive information will be made available as a multi-dimensional cross-section (ABSCO) table and the parameterization will be offered for inclusion in the HITRANonline database.
•Comprehensive study of resonant and non-resonant oxygen absorption in the NIR.•Multispectrum analysis combining Fourier Transform and Cavity Ringdown Spectra.•Speed dependence of lineshape determined.•Temperature dependences of lineshape parameters obtained.•Modified models for collision induced absorption and collisional relaxation.
IMPORTANCE: The National Action Plan for Adverse Drug Event (ADE) Prevention identified 3 high-priority, high-risk drug classes as targets for reducing the risk of drug-related injuries: ...anticoagulants, diabetes agents, and opioids. OBJECTIVE: To determine whether a multifaceted clinical pharmacist intervention improves medication safety for patients who are discharged from the hospital and prescribed medications within 1 or more of these high-risk drug classes. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted at a large multidisciplinary group practice in Massachusetts and included patients 50 years or older who were discharged from the hospital and prescribed at least 1 high-risk medication. Participants were enrolled into the trial from June 2016 through September 2018. INTERVENTIONS: The pharmacist-directed intervention included an in-home assessment by a clinical pharmacist, evidence-based educational resources, communication with the primary care team, and telephone follow-up. Participants in the control group were provided educational materials via mail. MAIN OUTCOMES AND MEASURES: The study assessed 2 outcomes over a 45-day posthospital discharge period: (1) adverse drug-related incidents and (2) a subset defined as clinically important medication errors, which included preventable or ameliorable ADEs and potential ADEs (ie, medication-related errors that may not yet have caused injury to a patient, but have the potential to cause future harm if not addressed). Clinically important medication errors were the primary study outcome. RESULTS: There were 361 participants (mean SD age, 68.7 9.3 years; 177 women 49.0%; 319 White 88.4% and 8 Black individuals 2.2%). Of these, 180 (49.9%) were randomly assigned to the intervention group and 181 (50.1%) to the control group. Among all participants, 100 (27.7%) experienced 1 or more adverse drug-related incidents, and 65 (18%) experienced 1 or more clinically important medication errors. There were 81 adverse drug-related incidents identified in the intervention group and 72 in the control group. There were 44 clinically important medication errors in the intervention group and 45 in the control group. The intervention did not significantly alter the per-patient rate of adverse drug-related incidents (unadjusted incidence rate ratio, 1.13; 95% CI, 0.83-1.56) or clinically important medication errors (unadjusted incidence rate ratio, 0.99; 95% CI, 0.65-1.49). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, there was not an observed lower rate of adverse drug-related incidents or clinically important medication errors during the posthospitalization period that was associated with a clinical pharmacist intervention. However, there were study recruitment challenges and lower than expected numbers of events among the study population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02781662
The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side ...effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine ...biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2–4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism.
•Ketamine increased the locomotion of female rats across ontogeny, but only minimally enhanced the locomotion of male adolescent and adult rats.•Ketamine’s locomotor stimulating effects are mediated ...through a monoaminergic mechanism.•It appears that ketamine enhances locomotor activity through indirect actions rather than having direct effects at the presynaptic terminal.
Ketamine significantly increases the locomotor activity of rodents, however this effect varies according to the sex and age of the animal being tested. To determine the role monoamine systems play in ketamine’s locomotor activating effects: (a) male and female preweanling, adolescent, and adult rats were pretreated with vehicle or the monoamine depleting agent reserpine (1 or 5 mg/kg), and (b) the behavioral actions of ketamine (20 or 40 mg/kg) were then compared to d-amphetamine (2 mg/kg) and cocaine (10 or 15 mg/kg). The ability of reserpine to deplete dorsal striatal dopamine (DA) and serotonin (5-HT) in male and female rats was determined using HPLC. Ketamine caused substantial increases in the locomotion of preweanling rats and older female rats (adolescents and adults), but had only small stimulatory effects on adolescent and adult male rats. When compared to cocaine and d-amphetamine, ketamine was especially sensitive to the locomotor-inhibiting effects of monoamine depletion. Ketamine-induced locomotion is at least partially mediated by monoamine systems, since depleting DA and 5-HT levels by 87–96% significantly attenuated the locomotor activating effects of ketamine in male and female rats from all three age groups. When administered to reserpine-pretreated rats, ketamine produced a different pattern of behavioral effects than either psychostimulant, suggesting that ketamine does not stimulate locomotor activity via actions at the presynaptic terminal. Instead, our results are consistent with the hypothesis that ketamine increases locomotor activity through a down-stream mechanism, possibly involving ascending DA and/or 5-HT projection neurons.
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