SULISO: The Bath suite of vibrational characterization and isotope effect calculation software

This is an Open Access article.Isotope effects are subtle but powerful probes of chemical reaction mechanisms and environmental conditions, with applications across chemical, biological and earth sciences. Their meaningful interpretation often relies on calculations based upon fundamental theories for their origin. The SULISO suite consists of four programs for the calculation of vibrational frequencies and isotope effects. CAMVIB is a broad vibrational characterization code developed for analysis of calculated harmonic frequencies and of normal modes in terms of internal coordinates. LIPFR calculates isotopic partition function ratios for pairs of isotopically substituted whole molecules, corresponding to conventional methodology, whereas UJISO is designed to perform similar calculations on subsets of atoms from very large systems. CUTOFF is a utility which truncates a force-constant matrix for a large system to obtain a smaller matrix appropriate for a specified subset of atoms

First Order Transition in the Ginzburg-Landau Model

The d-dimensional complex Ginzburg-Landau (GL) model is solved according to a variational method by separating phase and amplitude. The GL transition becomes first order for high superfluid density because of effects of phase fluctuations. We discuss its origin with various arguments showing that, in particular for d = 3, the validity of our approach lies precisely in the first order domain.Comment: 4 pages including 2 figure

Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits

Background: The trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically. Results: We used surface plasmon resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the proteolytically cleaved SOSIP.664 trimers, cleaved gp120-gp41ECTO protomers, and gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the trimers but equally well to gp120-gp41ECTO protomers and gp120 monomers, whereas the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast, bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or exclusively (PGT145) to trimers. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41ECTO, and proteolytic cleavage at the gp120-gp41ECTO junction. Each of these three features incrementally promoted native-like trimer antigenicity. We compared Fab and IgG versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed widely divergent binding kinetics and degrees of binding to native-like BG505 SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb binding were associated with large amounts of residual infectivity after NAb neutralization of the corresponding BG505.T332N pseudovirus. Conclusions: The antigenicity and structural integrity of cleaved BG505 SOSIP.664 trimers render these proteins good mimics of functional Env spikes on virions. In contrast, uncleaved gp140s antigenically resemble individual gp120-gp41ECTO protomers and gp120 monomers, but not native trimers. Although NAb binding to functional trimers may thus be both necessary and sufficient for neutralization, the kinetics and stoichiometry of the interaction influence the neutralizing efficacy of individual NAbs

Delivery of Dark Material to Vesta via Carbonaceous Chondritic Impacts

NASA's Dawn spacecraft observations of asteroid (4) Vesta reveal a surface with the highest albedo and color variation of any asteroid we have observed so far. Terrains rich in low albedo dark material (DM) have been identified using Dawn Framing Camera (FC) 0.75 {\mu}m filter images in several geologic settings: associated with impact craters (in the ejecta blanket material and/or on the crater walls and rims); as flow-like deposits or rays commonly associated with topographic highs; and as dark spots (likely secondary impacts) nearby impact craters. This DM could be a relic of ancient volcanic activity or exogenic in origin. We report that the majority of the spectra of DM are similar to carbonaceous chondrite meteorites mixed with materials indigenous to Vesta. Using high-resolution seven color images we compared DM color properties (albedo, band depth) with laboratory measurements of possible analog materials. Band depth and albedo of DM are identical to those of carbonaceous chondrite xenolith-rich howardite Mt. Pratt (PRA) 04401. Laboratory mixtures of Murchison CM2 carbonaceous chondrite and basaltic eucrite Millbillillie also show band depth and albedo affinity to DM. Modeling of carbonaceous chondrite abundance in DM (1-6 vol%) is consistent with howardite meteorites. We find no evidence for large-scale volcanism (exposed dikes/pyroclastic falls) as the source of DM. Our modeling efforts using impact crater scaling laws and numerical models of ejecta reaccretion suggest the delivery and emplacement of this DM on Vesta during the formation of the ~400 km Veneneia basin by a low-velocity (<2 km/sec) carbonaceous impactor. This discovery is important because it strengthens the long-held idea that primitive bodies are the source of carbon and probably volatiles in the early Solar System.Comment: Icarus (Accepted) Pages: 58 Figures: 15 Tables:

Quasiequilibrium sequences of synchronized and irrotational binary neutron stars in general relativity. I. Method and tests

We present a numerical method to compute quasiequilibrium configurations of close binary neutron stars in the pre-coalescing stage. A hydrodynamical treatment is performed under the assumption that the flow is either rigidly rotating or irrotational. The latter state is technically more complicated to treat than the former one (synchronized binary), but is expected to represent fairly well the late evolutionary stages of a binary neutron star system. As regards the gravitational field, an approximation of general relativity is used, which amounts to solving five of the ten Einstein equations (conformally flat spatial metric). The obtained system of partial differential equations is solved by means of a multi-domain spectral method. Two spherical coordinate systems are introduced, one centered on each star; this results in a precise description of the stellar interiors. Thanks to the multi-domain approach, this high precision is extended to the strong field regions. The computational domain covers the whole space so that exact boundary conditions are set to infinity. Extensive tests of the numerical code are performed, including comparisons with recent analytical solutions. Finally a constant baryon number sequence (evolutionary sequence) is presented in details for a polytropic equation of state with gamma=2.Comment: Minor corrections, references updated, 42 pages, 25 PostScript figures, accepted for publication in Phys. Rev.

Progress in low-field benchtop NMR spectroscopy in chemical and biochemical analysis

The employment of spectroscopically-resolved NMR techniques as analytical probes have previously been both prohibitively expensive and logistically challenging in view of the large sizes of high-field facilities. However, with recent advances in the miniaturisation of magnetic resonance technology, low-field, cryogen-free “benchtop” NMR instruments are seeing wider use. Indeed, these miniaturised spectrometers are utilised in areas ranging from food and agricultural analyses, through to human biofluid assays and disease monitoring. Therefore, it is both intrinsically timely and important to highlight current applications of this analytical strategy, and also provide an outlook for the future, where this approach may be applied to a wider range of analytical problems, both qualitatively and quantitatively

The Leicester, Leicestershire and Rutland quality improvement project and integrated chronic kidney disease system: implementation within a primary care network

Background: The optimisation of patients in primary care is a prime opportunity to manage patient care within the community and reduce the burden of referrals on secondary care. This paper presents a quality improvement clinical programme taking place within an NHS Primary Care Network as part of the wider Leicester Leicestershire Rutland integrated chronic kidney disease programme. Method: Patients are optimised to guidelines from the National Institute for Health and Care Excellence, by a primary care clinical team who are supported by nephrology consultants and nephrology pharmacists. Multidisciplinary team meetings take place with secondary care specialists and primary care staff. Learning is passed to the community clinicians for better patient treatment locally. Results: A total of 526 patients were reviewed under this project.The total number of referrals to secondary care which were discharged following first outpatient appointment, reduced from 42.9% to 10%. This reduction of 32.9% represents the optimisation of patient cases through this quality improvement project. Patients can be optimised and managed within the community, reducing the number of unnecessary referrals to secondary care. Conclusion: This programme has the potential to offer significant improvement in patient outcomes when expanded to a larger patient base. Medicine management and the use of clinical staff are optimised in both primary and secondary care

A computational study of the influence of methyl substituents on competitive ring closure to α- and β-lactones

Ring-closure of substituted 2-chlorosuccinates to α- or β-lactones has been studied by means of MP2/6-311+G(d,p)//MP2/6-31+G(d) calculations in water treated as a polarised continuum (PCM) and in vacuum. Optimised geometries have been obtained for 2-chlorosuccinate and its 2-methyl, 3,3-dimethyl, and 2,3,3-trimethyl derivatives, along with the transition structures and products for intramolecular nucleophilic displacement leading to the 3- or 4-membered rings. Relative enthalpies and Gibbs free energies of activation and reaction are presented, along with key geometrical parameters, and changes in electrostatic-potential-derived atomic charges. The difference in free-energy barriers for α- and β-lactone formation from the 2-methyl substrate at 298 K is less than 1 kJ mol−1. Primary 14C kinetic isotope effects calculated for substitution at C2 are significantly smaller for α-lactone formation than for β, suggesting a possible way to distinguish between the competing pathways of reaction. The B3LYP method without dispersion corrections predicts the wrong relative stability order for methyl-substituted succinate dianions in PCM water