Molecular Dynamics Study for Tritium Adsorption on Novel Materials

In this study, novel materials will be researched, and their potential uses for tritium control. 12 studies have been collected on various materials that give a solid foundation for future research that will be conducted regarding tritium control. All these studies used molecular dynamics simulation (MDS) to generate results. The first paper found from a university in Crete, Greece discussed pillared graphene to store hydrogen in a novel 3D carbon nanostructure in which pore size and surface area can be adjusted to suit the need. This was the first of several studies that aim to arrange the graphene in such a way that hydrogen isotopes like tritium could be stored. Studies found in Massachusetts, California, Japan, Taiwan, China, Greece, Germany, Spain, and France show some similar methodologies of using MDS to create models of how tritium or deuterium can be safely stored or captured as the molecules move around in a specific environment. A simulation of interest conducted in Sandia National labs shows the diffusion of Hydrogen through aluminum, highlighting the importance of novel solutions to this problem and how difficult it is for these isotopes to be stored using standard methods. We are collating all these methods and techniques made by other institutions and labs to create models that can be used in any scenario within reason. The method of choice for this type of research is to use an MDS software called Large-scale Atomic/Molecular Massively Parallel Simulator or LAMMPS to create functional models of what occurs within a reactor. This is the preferred practice when conducting this research as creating physical models can be expensive and require extensive safety equipment. The future of this research will be to find ways that these and more novel materials can be used to create advanced filtration and extraction methods from existing sources such as active nuclear reactors and be able to store hydrogen isotopes for extended periods of time

SmartTrack: Efficient Predictive Race Detection

Widely used data race detectors, including the state-of-the-art FastTrack algorithm, incur performance costs that are acceptable for regular in-house testing, but miss races detectable from the analyzed execution. Predictive analyses detect more data races in an analyzed execution than FastTrack detects, but at significantly higher performance cost. This paper presents SmartTrack, an algorithm that optimizes predictive race detection analyses, including two analyses from prior work and a new analysis introduced in this paper. SmartTrack's algorithm incorporates two main optimizations: (1) epoch and ownership optimizations from prior work, applied to predictive analysis for the first time; and (2) novel conflicting critical section optimizations introduced by this paper. Our evaluation shows that SmartTrack achieves performance competitive with FastTrack-a qualitative improvement in the state of the art for data race detection.Comment: Extended arXiv version of PLDI 2020 paper (adds Appendices A-E) #228 SmartTrack: Efficient Predictive Race Detectio

The antimicrobial activity of a carbon monoxide releasing molecule (EBOR-CORM-1) is shaped by intraspecific variation within3 Pseudomonas aeruginosa populations

Carbon monoxide releasing molecules (CORMs) have been suggested as a new synthetic class of antimicrobials to treat bacterial infections. Here we utilized a novel EBOR-CORM-1 ([NEt4][MnBr2(CO)4]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinical Pseudomonas aeruginosa strains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of P. aeruginosa strain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between different P. aeruginosa cystic fibrosis (CF) lung isolates. While a reduction in cell growth was observed after 8 h of CORM application, either no effect or even a slight increase in cell densities and the amount of biofilm was observed after 24 h. This variation could be partly explained by differences in bacterial virulence traits: while CF isolates showed attenuated in vivo virulence and growth compared to strain PAO1, they formed much more biofilm, which could have potentially protected them from the CORM. Even though no clear therapeutic benefits against a subset of isolates was observed in an in vivo wax moth acute infection model, EBOR-CORM-1 was more efficient at reducing the growth of CF isolate co-culture populations harboring intraspecific variation, in comparison with efficacy against more uniform single isolate culture populations. Together these results suggest that CORMs could be effective at controlling genetically diverse P. aeruginosa populations typical for natural chronic CF infections and that the potential benefits of some antibiotics might not be observed if tested only against clonal bacterial populations

Dipyrrinato‐Iridium(III) Complexes for Application in Photodynamic Therapy and Antimicrobial Photodynamic Inactivation

The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-eta(5)-cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [Ir-III(dipy)(ppy)(2)] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [Ir-III(Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented

Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4

CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller. Crown Copyright © 2012 Published by Elsevier B.V. on behalf of Federation of European Biochemical society. All rights reserved

Simulations of Mixed Morphology Supernova Remnants With Anisotropic Thermal Conduction

We explore the role of anisotropic thermal conduction on the evolution of supernova remnants through interstellar media with a range of densities via numerical simulations. We find that a remnant expanding in a dense environment can produce centre-bright hard x-ray emission within 20 kyr, and centre-bright soft x-ray emission within 60 kyr of the supernova event. In a more tenuous environment, the appearance of a centre-bright structure in hard x-rays is delayed until about 60 kyr. The soft x-ray emission from such a remnant may not become centre bright during its observable lifetime. This can explain the observations that show that mixed-morphology supernova remnants preferentially occur close to denser, molecular environments. Remnants expanding into denser environments tend to be smaller, making it easier for thermal conduction to make larger changes in the temperatures of their hot gas bubbles. We show that the lower temperatures make it very favorable to use high-stage ions as diagnostics of the hot gas bubbles in SNRs. In particular, the distribution of O VIII transitions from shell-bright at early epochs to centre-bright at later epochs in the evolution of an SNR expanding in a dense ISM when the physics of thermal conduction is included.Comment: 8 pages, 5 figures, submitted to Monthly Notice

Gravitational field and equations of motion of spinning compact binaries to 2.5 post-Newtonian order

We derive spin-orbit coupling effects on the gravitational field and equations of motion of compact binaries in the 2.5 post-Newtonian approximation to general relativity, one PN order beyond where spin effects first appear. Our method is based on that of Blanchet, Faye, and Ponsot, who use a post-Newtonian metric valid for general (continuous) fluids and represent pointlike compact objects with a delta-function stress-energy tensor, regularizing divergent terms by taking the Hadamard finite part. To obtain post-Newtonian spin effects, we use a different delta-function stress-energy tensor introduced by Bailey and Israel. In a future paper we will use the 2.5PN equations of motion for spinning bodies to derive the gravitational-wave luminosity and phase evolution of binary inspirals, which will be useful in constructing matched filters for signal analysis. The gravitational field derived here may help in posing initial data for numerical evolutions of binary black hole mergers.Comment: 18 pages, no figur

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services

Whole blood gene expression profiling of neonates with confirmed bacterial sepsis

peer-reviewedNeonatal infection remains a primary cause of infant morbidity and mortality worldwide and yet our understanding of how human neonates respond to infection remains incomplete. Changes in host gene expression in response to infection may occur in any part of the body, with the continuous interaction between blood and tissues allowing blood cells to act as biosensors for the changes. In this study we have used whole blood transcriptome profiling to systematically identify signatures and the pathway biology underlying the pathogenesis of neonatal infection. Blood samples were collected from neonates at the first clinical signs of suspected sepsis alongside age matched healthy control subjects. Here we report a detailed description of the study design, including clinical data collected, experimental methods used and data analysis workflows and which correspond with data in Gene Expression Omnibus (GEO) data sets (GSE25504). Our data set has allowed identification of a patient invariant 52-gene classifier that predicts bacterial infection with high accuracy and lays the foundation for advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis

A Pharmacogenetic Approach to Identify Mutant Forms of α-Galactosidase A that Respond to a Pharmacological Chaperone for Fabry Disease

Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mutant forms (defined as “responsive”). In this study, we developed a cell-based assay in cultured HEK-293 cells to identify mutant forms of α-Gal A that are responsive to AT1001. Concentration-dependent increases in α-Gal A activity in response to AT1001 were shown for 49 (60%) of 81 mutant forms. The responses of α-Gal A mutant forms were generally consistent with the responses observed in male Fabry patient-derived lymphoblasts. Importantly, the HEK-293 cell responses of 19 α-Gal A mutant forms to a clinically achievable concentration of AT1001 (10 µM) were generally consistent with observed increases in α-Gal A activity in peripheral blood mononuclear cells from male Fabry patients orally administered AT1001 during Phase 2 clinical studies. This indicates that the cell-based responses can identify mutant forms of α-Gal A that are likely to respond to AT1001 in vivo. Thus, the HEK-293 cell-based assay may be a useful aid in the identification of Fabry patients with AT1001-responsive mutant forms. Hum Mutat 32:1–13, 2011. © 2011 Wiley-Liss, Inc