Survey of Human Mitochondrial Diseases Using New Genomic/Proteomic Tools

BACKGROUND. We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three-dimensional structures that aid in the interpretation of effects of missense mutations. RESULTS. This survey reports such an analysis for 15 missense mutations one insertion and three deletions involved in Leber's hereditary optic neuropathy, Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Mohr-Tranebjaerg syndrome, iron-storage disorders related to Friedreich's ataxia, and hereditary spastic paraplegia. We present structural correlations for seven of the mutations. CONCLUSIONS. Of the 19 mutations analyzed, 14 involved changes in very highly conserved parts of the affected proteins. Five out of seven structural correlations provided reasonable explanations for the malfunctions. As additional genetic and structural data become available, this methodology can be extended. It has the potential for assisting in identifying new disease-related genes. Furthermore, profiles with structural homologs can generate mechanistic hypotheses concerning the underlying biochemical processes - and why they break down as a result of the mutations.United States Department of Energy (DE-FG02-98ER62558); National Science Foundation (DBI-9807993

Growth Econometrics

This paper provides a survey and synthesis of econometric tools that have been employed to study economic growth. While these tools range across a variety of statistical methods, they are united in the common goals of first, identifying interesting contemporaneous patterns in growth data and second, drawing inferences on long-run economic outcomes from cross-section and temporal variation in growth. We describe the main stylized facts that have motivated the development of growth econometrics, the major statistical tools that have been employed to provide structural explanations for these facts, and the primary statistical issues that arise in the study of growth data. An important aspect of the survey is attention to the limits that exist in drawing conclusions from growth data, limits that reflect model uncertainty and the general weakness of available data relative to the sorts of questions for which they are employed.

A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention

Managing the student experience in English higher education: Differing responses to market pressures

This paper reports on recent research aimed at assessing how the management of the undergraduate student experience in English higher education is changing in the light of the new tuition fee regime introduced in 2012, as well as other government policies aimed at creating market-type pressures within the higher education sector. A distinction was observed between the research-intensive universities studied – defined here as institutions where research income comprised 20 per cent or more of total turnover, with correspondingly strong positions in published research-based rankings – and universities largely dependent on income from teaching, with weaker market positions. Broadly speaking, the latter group were responding to market pressures by centralizing services, standardizing procedures, and strengthening management controls over teaching processes. The research-intensive universities tended to work within existing institutional cultures to respond to students’ needs. Organizational change here usually took the form of creating more coherent functional groupings of student services, rather than comprehensive reorganizations. It appears to us that these different responses to a changed environment point to the creation of two distinct English university types, one strongly managerial with ‘student as customer’ orientations, and a smaller group with less centralized, more collegial cultures

Validation of Geant4 upgrade to model response from muons passing through the KLM detector at the Belle II experiment.

The KLM detector or K0L- Muon Detector is equipped on the outermost layer of the Belle II detector structure. The detector is designed to detect the KL mesons and muons above 600 MeV/c with high efficiency. The barrel shaped region around the intersection point covers a polar angular range of 45° to 125° while the forward and backward end caps extend this range to 20° to 155°. With the upgraded Geant4 model we observe the effectiveness of the new PhysicsList.https://ir.library.louisville.edu/uars/1020/thumbnail.jp

Un déterminant de l'innovation technique en agriculture : les coordinations sur le travail dans la production bananière

The growth of the international market of the horticultural products is made possible by the globalization of an intensive mode of production in synthetic products which mobilizes salaried workers. In the Antilles changes in technological trajectories enables the consideration of other modes of production. This article brings to light how the technical innovation allowing a decrease in the necessity to use pesticides is dependent on an adaptation of the coordination in the mobilization of the salaried work. For this purpose we compare two systems of the use of manual labour between Martinique and Guadeloupe by widening on certain aspects in the transnational. The comparison is based on the characterization of these systems in which manual labour is used and the indicators of performance of the sectors of banana as well as on the adaptation of the technical changes. ...French Abstract : La croissance du marché international des produits horticoles se réalise par la globalisation d'un mode de production intensif en produits de synthèses qui mobilise une main d'oeuvre salariée. Dans les Antilles des changements de trajectoires technologiques permettent d'envisager d'autres modes de production. Cet article met en évidence comment l'innovation technique permettant de diminuer le recours aux pesticides est tributaire d'une adaptation des coordinations dans la mobilisation du travail salarié. Pour cela nous caractérisons les systèmes d'emploi de la main d'oeuvre salarié entre différentes origines et leurs impact sur des indicateurs de performance des filières de banane et d'adaptation des changements techniques.BANANA; WORK; INNOVATION; PESTICIDE; ANTILLES

Release of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) from polymer-bonded explosives (PBXN 109) into water by artificial weathering

Polymer-bonded explosives (PBX) fulfil the need for insensitive munitions. However, the environmental impacts of PBX are unclear, even though it is likely that PBX residues from low-order detonations and unexploded ordnance are deposited on military training ranges. The release of high explosives from the polymer matrix into the environment has not been studied in detail, although as polymers degrade slowly in the environment we anticipate high explosives to be released into the environment. In this study, PBXN-109 (nominally 64% RDX) samples were exposed to variable UK climatic conditions reproduced in the laboratory to determine the effects of temperature, UV irradiation and rainfall on the release of RDX from the polymer binder. The most extreme conditions for spring, summer and winter in the UK were artificially reproduced. We found that up to 0.03% of RDX was consistently released from PBXN-109. The rate of RDX release was highest in samples exposed to the summer simulation, which had the lowest rainfall, but the highest temperatures and longest UV exposure. This was confirmed by additional experiments simulating an extreme summer month with consistently high temperatures and long periods of sunlight. These results probably reflect the combination of polymer swelling and degradation when samples are exposed to higher temperatures and prolonged UV irradiation

Lesbian, Gay, Bisexual, and Transgender (LGBT) Issues in Dental School Environments: Dental Student Leaders’ Perceptions

The objectives of the study reported in this article were to assess dental student leaders’ perceptions of educational efforts concerning lesbian, gay, bisexual, and transgender (LGBT) topics and the cultural climate concerning LGBT issues in dental schools in the United States and Canada. In addition, the perceptions of student leaders who self‐identified as belonging to the LGBT community and of students with a heterosexual orientation were compared. Data were collected from 113 dental student leaders from twenty‐seven dental schools in the United States and three in Canada. Fifty student leaders were females, and sixty‐two were males. Only 13.3 percent of the respondents agreed that their dental education prepared them well to treat patients from LGBT backgrounds. The more the student leaders believed that their university has an honest interest in diversity, the better they felt prepared by their dental school program to treat patients from LGBT backgrounds (r=.327; p<.001). The better they felt prepared, the more they perceived the clinic environment as sensitive and affirming for patients with different sexual orientations (r=.464; p<.001). The more they reported that dental schools’ administrations create a positive environment for students with LGBT orientations, the more they agreed that persons can feel comfortable regardless of their sexual orientation (r=.585; p<.001). In conclusion, the findings indicate that dental school administrators play an important role in ensuring that future care providers are well prepared to treat patients from LGBT backgrounds and that staff, faculty, students, and patients from these backgrounds are not discriminated against.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153661/1/jddj002203372009731tb04643x.pd

Imaging characteristics and treatment of a penetrating brain injury caused by an oropharyngeal foreign body in a dog

A 4-year-old Border collie was presented with one episode of collapse, altered mentation, and a suspected pharyngeal stick injury. Magnetic resonance imaging (MRI) and computed tomography showed a linear foreign body penetrating the right oropharynx, through the foramen ovale and the brain parenchyma. The foreign body was surgically removed and medical treatment initiated. Complete resolution of clinical signs was noted at recheck 8 weeks later. Repeat MRI showed chronic secondary changes in the brain parenchyma. To the authors' knowledge, this is the first report of the advanced imaging findings and successful treatment of a penetrating oropharyngeal intracranial foreign body in a dog