First principles electronic and elastic properties of fresnoite Ba2TiSi2O8 (article)

This is the final version of the article. Available from IOP Publishing via the DOI in this record.The research materials supporting this publication can be accessed in ORE at http://hdl.handle.net/10871/30403Electronic, structural and elastic properties of fresnoite, Ba2TiSi2O8 (BTSO), are obtained via first principles calculations. The electronic properties having been comparatively analysed using both the generalised gradient approximation and the hybrid functional method. The indirect band gap of BTSO is found to change significantly through the choice of functional; it shows an increase from 3.79 eV to 5.72 eV. A small indirect gap of 0.33 eV is also present directly above the conduction band edge, which allows for small optical transitions similar to that of defect transitions. The titanium orbitals are dominant near the conduction band edge, with oxygen orbitals being the main contributor to the valence band edge. Dielectric and elastic properties of the material are also obtained, with the bulk modulus being 131.73 GPa and the elastic moduli along the [1 0 0] and [0 0 1] directions being 180.57 GPa and 102.56 GPa, respectively. Theoretical values for Raman frequencies are reported for BTSO. Finally, Bader charge analysis reveals the barium and titanium atoms in BTSO are comparable to their charges in BaTiO3. However, due to the presence of the Si–O bonds, oxygen exhibits a significant charge redistribution. Through the choice of functional, charge can become more localised on the oxygen atoms.Via our membership of the UK's HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202), this work used the ARCHER UK National Supercomputing Service (www.archer.ac.uk). We acknowledge financial support from the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom, via the EPSRC Centre for Doctoral Training in Metamaterials (Grant No. EP/L015331/1)

Effect of charge transfer on band alignment in 2D|3D heterostructures: A study of HfS 2 | HfO 2 interfaces (article)

This is the final version. Available from the American Physical Society via the DOI in this record. The dataset associated with this article is in ORE at https://doi.org/10.24378/exe.4644HfS 2 | HfO 2 interfaces present a uniquely interesting study in band alignment. The band alignment between materials determines the viability of many electronic devices. We have modeled a variety of two-dimensional|three-dimensional (2D|3D) interfaces HfS 2 | HfO 2 interfaces, showing that the band alignment can change substantially depending on the geometric alignment. Our results have shown that there exists almost no electronic reconstruction when layers of HfS 2 are placed on a HfO 2 substrate. Conversely, when the in-plane connection between HfS 2 and HfO 2 is made (lateral), there is a more significant interface reconstruction present. In the latter case, all examples considered yielded a type I alignment, whereas in the case that layers were parallel to the HfO 2 substrate (stacked) we found that the alignment was either type I or type II with a very small difference between the valance band offsets of the two constituents. We show that the range in the barrier heights between these two systems can vary by up to 2.46 eV. This variation is driven by the amount of charge transfer across the interface and indicate that 2D|3D interfaces have considerably more tunability in their band alignment than 2D|2D or 3D|3D interfaces.Leverhulme TrustEngineering and Physical Sciences Research Counci

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Predicting Phase Stability at Interfaces

This is the final version. Available on open access from the American Physical Society via the DOI in this recordData availability: The data that supports this Letter is openly available in ORE at https://doi.org/10.24378/exe.4966We present the RAFFLE methodology for structural prediction of the interface between two materials and demonstrate its effectiveness by applying it to MgO encapsulated by two layers of graphene. To address the challenge of interface structure prediction, our methodology combines physical insights derived from morphological features observed in related systems with an iterative machine learning technique. This employs physical-based methods, including void-filling and n-body distribution functions to predict interface structures. For the carbon-MgO encapsulated system, we have shown the rocksalt and hexagonal phases of MgO to be the two most energetically stable in the few-layer regime. We demonstrate that monolayer rocksalt is heavily stabilized by interfacing with graphene, becoming more energetically favorable than the graphenelike monolayer hexagonal MgO. The RAFFLE methodology provides valuable insights into interface behavior, and a route to finding new materials at interfaces.Engineering and Physical Sciences Research Council (EPSRC)Leverhulme Trus

Implementing measurable goals for diversity, equity, and inclusion in Clinical and Translational Science Awards leadership

Charting a benchmarking strategy is recommended to measure improvements in equal leadership opportunities for minorities and women in the Clinical Translational Science Awards Consortium (CTSAs). Academic institutions that support diversity, equity, and inclusion (DEI) initiatives should demonstrate a willingness to track their progress with established metrics. In the fall of 2020, the CTSAs convened a virtual conference, which started a dialogue on developing measurable objectives to ensure accountability for DEI goals. Using qualitative and quantitative data from breakout sessions, the authors analyze participant responses to the following recommendation, “develop a common metric and dashboard with regular reporting on diversity in CTSA leadership, with an emphasis on increasing female and Black Indigenous, People Of Color (BIPOC) representation to 30% each,” to understand the impact and challenges associated with implementing metrics within CTSAs. Thematic analysis revealed that white supremacist culture and demographic composition are obstacles to establishing metrics. Participants expressed uncertainty about the perception of token roles. Additionally, participants believed that DEI targets can increase diversity in perspectives and approaches to translational science. Implications for CTSAs include establishing CTSA-wide benchmarks for DEI initiatives, which includes a baseline of the existing DEI climate to assess institutional norms and measurable objectives to track progress

Improving the equity landscape at U.S. academic institutions: 10 strategies to lead change

In the United States, disparities with respect to race, ethnicity, and gender are common across academic institutions, particularly those that are large and have health research-oriented missions. Disparity-affected issues include leadership roles, funding, tenure, and salary. This paper presents a review of the current literature describing those disparities, with a focus on health professions serving major universities in the United States, and proposes approaches to create greater diversity, equity, inclusion and belonging (DEIB) within them. While many organizations nationally are working to address DEIB disparities, academic institutions can benefit from implementing structured approaches and training to nurture their cultures, foster DEIB, and promote psychological safety. We present a literature-based 10-component approach institutions can adopt with relative ease and thus positively support advancing their DEIB engagement. These 10 strategies include the following: Clearly stating DEI values; Conducting gap analyses to identify issues; Using incentives to propel change; Removing bias from recruiting processes; Implementing blind applications processes; Diversifying selection committees; Creating inter-institutional partnerships that truly represent shared power; Developing people and the pipeline; Formalizing mentorship and sponsorship programs; and instituting anti-bias training. Easily implementable strategies can both foster change and build the will and confidence to pursue larger DEIB goals in the future

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses

Genomic and phenotypic analyses of recent Acinetobacter baumannii isolates from tertiary care hospitals in Thailand

Antibiotic resistant strains of Acinetobacter baumannii are responsible for a large and increasing burden of nosocomial infections in Thailand and other countries of Southeast Asia. New approaches to their control and treatment are urgently needed and we are actively seeking biological agents that remove the polysaccharide capsules that protect these pathogens from the host’s immune system. To examine phylogenetic relationships, distribution of capsule chemotypes, acquired antibiotic resistance determinants, susceptibility to complement and other traits associated with systemic infection, we sequenced 191 recent isolates from three tertiary referral hospitals in Thailand and used phenotypic assays to characterise key aspects of infectivity. Several distinct lineages were circulating in three hospitals and the majority belonged to global clonal group 2 (GC2). Very high levels of resistance to carbapenems and other front-line antibiotics were found, as were a number of widespread plasmid replicons. A high diversity of capsule genotypes were encountered with only three (KL6, KL10 and KL47) above 10% frequency. Almost 90% of GC2 isolates belonged to the most common capsule genotypes and were fully resistant to the bactericidal action of human serum complement; we attribute this trait to the presence of a substantial protective capsule and for this to represent a key determinant of virulence for systemic infection. We conclude that current Thai nosocomial isolates represent potential targets for therapeutic strategies designed to remove the polysaccharide capsule from extensively drug-resistant A. baumanii during the course of systemic infection