Mutant Study of Sinorhizobium meliloti Proline Utilization A (PutA)

The purpose of this project is to purify and characterize the reaction kinetics of mutant versions the enzyme Proline Utilization A (PutA) in Sinorhizobium meliloti. The enzyme catalyzes the first step in proline metabolism. It has two active sites. The first is proline dehydrogenase (PRODH) which converts proline to pyrroline-5-carboxylate (P5C). The second is P5C dehydrogenase (P5CDH) which converts P5C to glutamate. Although many bacterial organisms have PutA, there are still significant interspecies variations, resulting in an entire family of PutA enzymes. The main difference is the length of the amino acid sequence. This affects the protein’s structure or its shape, and the protein’s kinetics or how it behaves in reactions. In order to have a complete understanding of proline metabolism, all the variations of PutA must be characterized both structurally and kinetically. The version of PutA found in S. meliloti (SmPutA) has been categorized structurally but not kinetically. This project aims to fill this gap in our knowledge of proline metabolism and PutA from S. meliloti

A Review of Discrete Element Method (DEM) Particle Shapes and Size Distributions for Lunar Soil

As part of ongoing efforts to develop models of lunar soil mechanics, this report reviews two topics that are important to discrete element method (DEM) modeling the behavior of soils (such as lunar soils): (1) methods of modeling particle shapes and (2) analytical representations of particle size distribution. The choice of particle shape complexity is driven primarily by opposing tradeoffs with total number of particles, computer memory, and total simulation computer processing time. The choice is also dependent on available DEM software capabilities. For example, PFC2D/PFC3D and EDEM support clustering of spheres; MIMES incorporates superquadric particle shapes; and BLOKS3D provides polyhedra shapes. Most commercial and custom DEM software supports some type of complex particle shape beyond the standard sphere. Convex polyhedra, clusters of spheres and single parametric particle shapes such as the ellipsoid, polyellipsoid, and superquadric, are all motivated by the desire to introduce asymmetry into the particle shape, as well as edges and corners, in order to better simulate actual granular particle shapes and behavior. An empirical particle size distribution (PSD) formula is shown to fit desert sand data from Bagnold. Particle size data of JSC-1a obtained from a fine particle analyzer at the NASA Kennedy Space Center is also fitted to a similar empirical PSD function

Further Evidence for a Merger Origin for the Thick Disk: Galactic Stars Along Lines-of-sight to Dwarf Spheroidal Galaxies

The history of the Milky Way Galaxy is written in the properties of its stellar populations. Here we analyse stars observed as part of surveys of local dwarf spheroidal galaxies, but which from their kinematics are highly probable to be non-members. The selection function -- designed to target metal-poor giants in the dwarf galaxies, at distances of ~100kpc -- includes F-M dwarfs in the Milky Way, at distances of up to several kpc. Thestars whose motions are analysed here lie in the cardinal directions of Galactic longitude l ~ 270 and l ~ 90, where the radial velocity is sensitive to the orbital rotational velocity. We demonstrate that the faint F/G stars contain a significant population with V_phi ~ 100km/s, similar to that found by a targeted, but limited in areal coverage, survey of thick-disk/halo stars by Gilmore, Wyse & Norris (2002). This value of mean orbital rotation does not match either the canonical thick disk or the stellar halo. We argue that this population, detected at both l ~ 270 and l ~ 90, has the expected properties of `satellite debris' in the thick-disk/halo interface, which we interpret as remnants of the merger that heated a pre-existing thin disk to form the thick disk.Comment: Accepted, Astrophysical Journal Letter

The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin

SummaryUbiquitin binding proteins regulate the stability, function, and/or localization of ubiquitinated proteins. Here we report the crystal structures of the zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. Unlike other ubiquitin binding domains, this domain contains a deep binding pocket where the C-terminal diglycine motif of ubiquitin is inserted, thus explaining the specificity of IsoT for an unmodified C terminus on the proximal subunit of polyubiquitin. Mutations in the domain demonstrate that it is required for optimal catalytic activation of IsoT. This domain is present in several other protein families, and the ZnF UBP domain from an E3 ligase also requires the C terminus of ubiquitin for binding. These data suggest that binding the ubiquitin C terminus may be necessary for the function of other proteins

Frictional quantum decoherence

The dynamics associated with a measurement-based master equation for quantum Brownian motion are investigated. A scheme for obtaining time evolution from general initial conditions is derived. This is applied to analyze dissipation and decoherence in the evolution of both a Gaussian and a Schr\"{o}dinger cat initial state. Dependence on the diffusive terms present in the master equation is discussed with reference to both the coordinate and momentum representations.Comment: 18 pages, 7 figure

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers

The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC)

Introduction: The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care. Objectives:We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers. Methods:SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors. Results:From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years. Conclusion:We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research

Neurodevelopment and ages of onset in depressive disorders

How and why do clinical depressive disorders emerge in adolescence? In this Personal View, we present a neurodevelopmental theory to address causes for adolescent onsets of clinical depressive disorders. We argue that theories should account for three perplexing aspects of depressive disorders in adolescence: the episodic nature of depression; differences between sexes in rates of depression across development; and age-differentiated onsets. We consider how theories such as psychosocial acceleration, heterochronic brain development, dual-process models, glucocorticoid vulnerability hypothesis linked to early life stress, and epigenetic and genetic susceptibility might explain some aspects of adolescent depressive disorders. We argue that some synthesis between existing theories might be needed to establish a sufficient neurodevelopmental theoretical framework to explain onsets of depressive disorders in adolescence

Towards an Understanding of Changing-Look Quasars: An Archival Spectroscopic Search in SDSS

The uncertain origin of the recently-discovered `changing-looking' quasar phenomenon -- in which a luminous quasar dims significantly to a quiescent state in repeat spectroscopy over ~10 year timescales -- may present unexpected challenges to our understanding of quasar accretion. To better understand this phenomenon, we take a first step to building a sample of changing-look quasars with a systematic but simple archival search for these objects in the Sloan Digital Sky Survey Data Release 12. By leveraging the >10 year baselines for objects with repeat spectroscopy, we uncover two new changing-look quasars, and a third discovered previously. Decomposition of the multi-epoch spectra and analysis of the broad emission lines suggest that the quasar accretion disk emission dims due to rapidly decreasing accretion rates (by factors of >2.5), while disfavoring changes in intrinsic dust extinction for the two objects where these analyses are possible. Broad emission line energetics also support intrinsic dimming of quasar emission as the origin for this phenomenon rather than transient tidal disruption events or supernovae. Although our search criteria included quasars at all redshifts and transitions from either quasar-like to galaxy-like states or the reverse, all of the clear cases of changing-look quasars discovered were at relatively low-redshift (z ~ 0.2 - 0.3) and only exhibit quasar-like to galaxy-like transitions.Comment: 15 pages, 8 figures. Updated to accepted versio