Characterization of the Arabidopsis thaliana Auxin F-Box Family Members AFB4 and AFB5

Thesis (PhD) - Indiana University, Molecular, Cellular, and Developmental Biology, 2007Ubiquitination is a three-step pathway that links a chain of small molecules, UBQ, onto a substrate protein. UBQ serves as a signal that the tagged protein is to be targeted for degradation by the 26S proteasome. This ubiquitin-mediated protein degradation system is highly conserved throughout eukaryotic cells, including the model plant Arabidopsis thaliana. In Arabidopsis many growth and developmental process are influenced by the plant hormone auxin. Transcription factors involved in auxin response have been shown to be targets for ubiquitination and subsequent degradation. Recent work has identified a family of auxin receptors, TIR1, AFB1, AFB2 and AFB3, are key components of this process. This work is focused on the characterization of two additional members of this family AFB4 and AFB5. Using a combination of molecular biology, genetics and biochemistry I have begun the characterization of these two proteins plant development and their possible function as auxin receptors. While both proteins are clearly involved in auxin response, AFB4 has a more pleiotropic role in all aspects of the plant life cycle. This work also shows that AFB5, and AFB4 to a lesser extent, can mediate a receptor-like interaction in the presence of the synthetic auxin picloram, leaving open the question of whether or not they participate as auxin receptors in the plant to the same level as the other four family members

Health-state utilities in a prisoner population : a cross-sectional survey

Background: Health-state utilities for prisoners have not been described. Methods: We used data from a 1996 cross-sectional survey of Australian prisoners (n = 734). Respondent-level SF-36 data was transformed into utility scores by both the SF-6D and Nichol's method. Socio-demographic and clinical predictors of SF-6D utility were assessed in univariate analyses and a multivariate general linear model. Results: The overall mean SF-6D utility was 0.725 (SD 0.119). When subdivided by various medical conditions, prisoner SF-6D utilities ranged from 0.620 for angina to 0.764 for those with none/mild depressive symptoms. Utilities derived by the Nichol's method were higher than SF-6D scores, often by more than 0.1. In multivariate analysis, significant independent predictors of worse utility included female gender, increasing age, increasing number of comorbidities and more severe depressive symptoms. Conclusion: The utilities presented may prove useful for future economic and decision models evaluating prison-based health programs

Genotype-Specific Changes in Vitamin B 6

Vitamin B(6) is one of the most versatile cofactors in plants and an essential phytonutrient in the human diet that benefits a variety of human health aspects. Although biosynthesis of the vitamin has been well resolved in recent years, the main research is currently based on Arabidopsis thaliana with very little work done on major crop plants. Here we provide the first report on interactions and expression profiles of PDX genes for vitamin B(6) biosynthesis in potato and how vitamin B(6) content varies in tubers of different genotypes. The results demonstrate that potato is an excellent resource for this vitamin and that strong natural variation in vitamin B(6) content among the tested cultivars indicates high potential to fortify vitamin B(6) nutrition in potato-based foods

Reducing avoidable inequalities in health: a new criterion for setting health care capitation payments

Traditionally, most health care systems which pretend to any sort of rationality and cost control have sought to allocate their limited funds in order to secure equal opportunity of access for equal need. The UK government is implementing a fundamental change of resource allocation philosophy towards contributing to the reduction of avoidable health inequalities. The purpose of this essay is to explore some of the economic issues that arise when seeking to allocate health care resources according to the new criterion. It indicates that health inequalities might arise because of variations in the quality of health services, variations in access to those services, or variations in the way people produce health, and that the resource allocation consequences differ depending on which source is being addressed. The paper shows that an objective of reducing health inequalities is not necessarily compatible with an objective of equity of access, nor with the objective of maximising health gain. The results have profound consequences for approaches towards economic evaluation, the role of clinical guidelines and performance management, as well as for resource allocation methods

Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England:the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial

BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only.METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216).FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p&lt;0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention.INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms.FUNDING: UK National Institute for Health and Care Research.</p

Outside Caste? The Enclosure of Caste and Claims to Castelessness in India and the United Kingdom

Caste has always generated political and scholarly controversy but the forms that this takes today newly combine anti-caste activism with counter-claims about the irrelevance or non-existence of caste, or claims to castelessness. Such claims to castelessness are in turn viewed as a new disguise for caste power and privilege, as well as being an aspiration for people subject to caste-based discrimination. This article looks at elite claims to ‘enclose’ caste within religion (specifically Hinduism) and the (Indian) nation so as to restrict the field of social policy with regard to caste, to exempt caste (as a basis of discrimination) from the law, and limit the social politics of caste. It does so taking the comparative cases of caste and caste-based discrimination among non-Hindus, and outside India — the exclusion of Christian and Muslim Dalits (members of castes subordinated as ‘untouchable’) from provisions and protections as Scheduled Castes in India, and responses to the introduction of caste into anti-discrimination law in the UK. While Hindu organisations in the UK reject ‘caste’ as a colonial and racist term, deploying postcolonial scholarship to deny caste discrimination, Dalit organisations (representing its potential victims) turn to scholarly discourse on caste, race or human rights. These are epistemological disputes about categories of description and how ‘the social’ is made available for public debate, and especially for law. Such disputes engage with anthropology whose analytical terms animate and change the social world that is their subject

Animated molecular dynamics simulations of hydrated caesium-smectite interlayers

Computer animation of center of mass coordinates obtained from 800 ps molecular dynamics simulations of Cs-smectite hydrates (1/3 and 2/3 water monolayers) provided information concerning the structure and dynamics of the interlayer region that could not be obtained through traditional simulation analysis methods. Cs(+ )formed inner sphere complexes with the mineral surface, and could be seen to jump from one attracting location near a layer charge site to the next, while water molecules were observed to migrate from the hydration shell of one ion to that of another. Neighboring ions maintained a partial hydration shell by sharing water molecules, such that a single water molecule hydrated two ions simultaneously for hundreds of picoseconds. Cs-montmorillonite hydrates featured the largest extent of this sharing interaction, because interlayer ions were able to inhabit positions near surface cavities as well as at their edges, close to oxygen triads. The greater positional freedom of Cs(+ )within the montmorillonite interlayer, a result of structural hydroxyl orientation and low tetrahedral charge, promoted the optimization of distances between cations and water molecules required for water sharing. Preference of Cs(+ )for locations near oxygen triads was observed within interlayer beidellite and hectorite. Water molecules also could be seen to interact directly with the mineral surface, entering its surface cavities to approach attracting charge sites and structural hydroxyls. With increasing water content, water molecules exhibited increased frequency and duration of both cavity habitation and water sharing interactions. Competition between Cs(+ )and water molecules for surface sites was evident. These important cooperative and competitive features of interlayer molecular behavior were uniquely revealed by animation of an otherwise highly complex simulation output

Generalisation in named entity recognition: A quantitative analysis

Named Entity Recognition (NER) is a key NLP task, which is all the more challenging on Web and user-generated content with their diverse and continuously changing language. This paper aims to quantify how this diversity impacts state-of-the-art NER methods, by measuring named entity (NE) and context variability, feature sparsity, and their effects on precision and recall. In particular, our findings indicate that NER approaches struggle to generalise in diverse genres with limited training data. Unseen NEs, in particular, play an important role, which have a higher incidence in diverse genres such as social media than in more regular genres such as newswire. Coupled with a higher incidence of unseen features more generally and the lack of large training corpora, this leads to significantly lower F1 scores for diverse genres as compared to more regular ones. We also find that leading systems rely heavily on surface forms found in training data, having problems generalising beyond these, and offer explanations for this observation

Design and construction of the MicroBooNE Cosmic Ray Tagger system

The MicroBooNE detector utilizes a liquid argon time projection chamber (LArTPC) with an 85 t active mass to study neutrino interactions along the Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground level, the detector records many cosmic muon tracks in each beam-related detector trigger that can be misidentified as signals of interest. To reduce these cosmogenic backgrounds, we have designed and constructed a TPC-external Cosmic Ray Tagger (CRT). This sub-system was developed by the Laboratory for High Energy Physics (LHEP), Albert Einstein center for fundamental physics, University of Bern. The system utilizes plastic scintillation modules to provide precise time and position information for TPC-traversing particles. Successful matching of TPC tracks and CRT data will allow us to reduce cosmogenic background and better characterize the light collection system and LArTPC data using cosmic muons. In this paper we describe the design and installation of the MicroBooNE CRT system and provide an overview of a series of tests done to verify the proper operation of the system and its components during installation, commissioning, and physics data-taking