A semi-classical model of proton tunnelling in hydrogen-bonded compounds

Bibliography: pages 233-238.Two back-to-back Morse potentials are used to model the protonic potential in a hydrogen bond. A mathematical method is developed to obtain semi-classical solutions for the eigenvalues and eigenfunctions of the potential. Particular care is taken over the form of approximation used in the vicinity of the barrier top. The double Morse potential is then used as the fundamental element in the analysis of the proton dynamics in a number of hydrogen-bonded species: a) Chromous acid. A consistent, quantitative explanation is found for the νs(OH)/vs(OD) bands in the mid-infrared spectra of CrOOH/CrOOD. The 226 cm⁻¹ band in the far infrared and neutron scattering spectra of CrOOH is shown to be caused by the protonic tunnelling mode. b) Carboxylic and Dicarboxylic acids. The 140 cm⁻¹ protonic upper state splitting in dimeric formic acid proposed by Excoffon and Marechal (1972) is shown to be supported by the double Morse potential analysis. The analysis suggest's however that the two hydrogen-bonded protons in (HCOOH)₂ tunnel independently. The anomalous vs(OH)/vs(OD) intensity ratios observed in the infrared spectra of both adipic acid and dimeric formic acid could not be explained in terms of mechanical anharmonicity alone. The protonic tunnelling frequency in crystalline formic acid is shown to be about 23 cm⁻¹ , which supports the order-disorder interpretation of the observed phase transition in this crystal. c) Potassium Dihydrogen Phosphate (KDP). The crystallographic and infrared spectroscopic data for KDP and DKDP are interpreted consistently using the double Norse potential. The bare single-particle tunnelling frequency Ω is estimated to be 320 ± 10 cm⁻¹ and the overtone band at 4600 cm⁻¹ in the infrared spectrum of KDP is shown to be a :0 →:3> single particle transition. The model is capable of predicting the temperature and pressure dependence of both the protonic tunnelling frequency and the protonic inter-site separation δ. The soft-mode Raman data of Peercy (1975) is re-analysed allowing for the temperature dependence of Ω

Landmarks in Insulin Research

Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor

Structural Congruency of Ligand Binding to the Insulin and Insulin/Type 1 Insulin-like Growth Factor Hybrid Receptors

SummaryThe homodimeric insulin and type 1 insulin-like growth factor receptors (IR and IGF-1R) share a common architecture and each can bind all three ligands within the family: insulin and insulin-like growth factors I and II (IGF-I and IFG-II). The receptor monomers also assemble as heterodimers, the primary ligand-binding sites of which each comprise the first leucine-rich repeat domain (L1) of one receptor type and an α-chain C-terminal segment (αCT) of the second receptor type. We present here crystal structures of IGF-I bound to such a hybrid primary binding site and of a ligand-free version of an IR αCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures, refined at 3.0-Å resolution, prove congruent to respective existing structures of insulin-complexed IR310.T and the intact apo-IR ectodomain. As such, they provide key missing links in the emerging, but sparse, repertoire of structures defining the receptor family

Radiation modeling in the Earth and Mars atmospheres using LRO/CRaTER with the EMMREM Module

Abstract We expand upon the efforts of Joyce et al. (2013), who computed the modulation potential at the Moon using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument on the Lunar Reconnaissance Orbiter (LRO) spacecraft along with data products from the Earth-Moon-Mars Radiation Environment Module (EMMREM). Using the computed modulation potential, we calculate galactic cosmic ray (GCR) dose and dose equivalent rates in the Earth and Mars atmospheres for various altitudes over the course of the LRO mission. While we cannot validate these predictions by directly comparable measurement, we find that our results conform to expectations and are in good agreement with the nearest available measurements and therefore may be used as reasonable estimates for use in efforts in risk assessment in the planning of future space missions as well as in the study of GCRs. PREDICCS (Predictions of radiation from REleASE, EMMREM, and Data Incorporating the CRaTER, COSTEP, and other solar energetic particles measurements) is an online system designed to provide the scientific community with a comprehensive resource on the radiation environments of the inner heliosphere. The data products shown here will be incorporated into PREDICCS in order to further this effort and daily updates will be made available on the PREDICCS website (http://prediccs.sr.unh.edu). Key Points We model GCR dose and dose equivalent rates in Earth and Mars atmospheres Dose rates are in reasonable agreement with nearby measurements Data products will soon be made available on PREDICCS website

Multiple generation distinct toxicant exposures induce epigenetic transgenerational inheritance of enhanced pathology and obesity

Three successive multiple generations of rats were exposed to different toxicants and then bred to the transgenerational F5 generation to assess the impacts of multiple generation different exposures. The current study examines the actions of the agricultural fungicide vinclozolin on the F0 generation, followed by jet fuel hydrocarbon mixture exposure of the F1 generation, and then pesticide dichlorodiphenyltrichloroethane on the F2 generation gestating females. The subsequent F3 and F4 generations and F5 transgenerational generation were obtained and F1-F5 generations examined for male sperm epigenetic alterations and pathology in males and females. Significant impacts on the male sperm differential DNA methylation regions were observed. The F3-F5 generations were similar in ∼50% of the DNA methylation regions. The pathology of each generation was assessed in the testis, ovary, kidney, and prostate, as well as the presence of obesity and tumors. The pathology used a newly developed Deep Learning, artificial intelligence-based histopathology analysis. Observations demonstrated compounded disease impacts in obesity and metabolic parameters, but other pathologies plateaued with smaller increases at the F5 transgenerational generation. Observations demonstrate that multiple generational exposures, which occur in human populations, appear to increase epigenetic impacts and disease susceptibility

Evidence for He I 10830 \AA~ absorption during the transit of a warm Neptune around the M-dwarf GJ 3470 with the Habitable-zone Planet Finder

Understanding the dynamics and kinematics of out-flowing atmospheres of hot and warm exoplanets is crucial to understanding the origins and evolutionary history of the exoplanets near the evaporation desert. Recently, ground based measurements of the meta-stable Helium atom's resonant absorption at 10830 \AA~has become a powerful probe of the base environment which is driving the outflow of exoplanet atmospheres. We report evidence for the He I 10830 \AA~in absorption (equivalent width $\sim$ $0.012 \pm 0.002$ \AA) in the exosphere of a warm Neptune orbiting the M-dwarf GJ 3470, during three transits using the Habitable Zone Planet Finder (HPF) near infrared spectrograph. This marks the first reported evidence for He I 10830 \AA\, atmospheric absorption for a planet orbiting an M-dwarf. Our detected absorption is broad and its blueshifted wing extends to -36 km/sec, the largest reported in the literature to date. We modelled the state of Helium atoms in the exosphere of GJ3470b based on assumptions on the UV and X-ray flux of GJ 3470, and found our measurement of flux-weighted column density of meta-stable state Helium $(N_{He^2_3S} = 2.4 \times 10^{10} \mathrm{cm^{-2}})$, derived from our transit observations, to be consistent with model, within its uncertainties. The methodology developed here will be useful to study and constrain the atmospheric outflow models of other exoplanets like GJ 3470b which are near the edge of the evaporation desert.Comment: Accepted in Ap

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

Objective: To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results? Methods: A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus. Results: Testing of VKORC1 (-1639G\u3eA), CYP2C92, and CYP2C93 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C95, 6, 8, or 11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose. Significance: This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotype-guided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

Exploring the dynamics of compliance with community penalties

In this paper, we examine how compliance with community penalties has been theorized hitherto and seek to develop a new dynamic model of compliance with community penalties. This new model is developed by exploring some of the interfaces between existing criminological and socio-legal work on compliance. The first part of the paper examines the possible definitions and dimensions of compliance with community supervision. Secondly, we examine existing work on explanations of compliance with community penalties, supplementing this by drawing on recent socio-legal scholarship on private individuals’ compliance with tax regimes. In the third part of the paper, we propose a dynamic model of compliance, based on the integration of these two related analyses. Finally, we consider some of the implications of our model for policy and practice concerning community penalties, suggesting the need to move beyond approaches which, we argue, suffer from compliance myopia; that is, a short-sighted and narrowly focused view of the issues

Ghosts of NEID's Past

The NEID spectrograph is a R $\sim$ 120,000 resolution fiber-fed and highly stabilized spectrograph for extreme radial velocity (RV) precision. It is being commissioned at the 3.5 m WIYN telescope in Kitt Peak National Observatory with a desired instrumental precision of better than 30 \cms{}. NEID's bandpass of 380 -- 930 nm enables the simultaneous wavelength coverage of activity indicators from the Ca HK lines in the blue to the Ca IR triplet in the IR. In this paper we will present our efforts to characterize and mitigate optical ghosts in the NEID spectrograph during assembly, integration and testing, and highlight several of the dominant optical element contributors such as the cross dispersion prism and input optics. We shall present simulations of the 2-D spectrum and discuss the predicted ghost features on the focal plane, and how they may impact the RV performance for NEID. We also present the mitigation strategy adopted for each ghost which may be applied to future instrument designs. This work will enable other instrument builders to potentially avoid some of these issues, as well as outline mitigation strategies.Comment: Conference Proceeding from SPIE Astronomical Telescopes + Instrumentation (2020): 12 page