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

Asset Accumulation and Short Term Employment

This paper investigates the search and consumption behavior of workers as they move between readily available low wage employment and uncertain search for a high wage job. Analytic results derived from our model include: (1) voluntary planned quits occur in a cyclical pattern, (2) consumption while searching falls over time until either a good job is found or assets run out and the worker accepts a low wage job, (3) consumption during low wage employment is less than earnings, and (4) the durations of job search and employment as well as the pattern of consumption are related to turnover costs and wages. Empirical evidence from the 1995 Canadian out of Employment Panel (COEP) broadly supports these relationships. In these data, there exists a high incidence of displaced workers taking temporary low wage jobs. Examining the income, consumption and savings patterns of workers in different regimes, we fiind that these accord with the theoretical predictions.unemployment; search; consumption; assets

Enhancing the Quality of Data on Income: Recent Developments in Survey Methodology

In this paper, we evaluate two survey innovations aimed at improving income measurement. These innovations are (1) integrating the question sequences for income and wealth which may elicit more accurate estimates of income from capital than has been true in the past, and (2) changes in the periodicity over which income flows are measured, which may provide a closer match between what the survey respondent knows best and the periodicity contained in survey measurement. These innovations have been introduced into both the Health and Retirement Study (HRS) and the study of Asset and Health Dynamics Among the Oldest Old (AHEAD). Based on the results reported in this paper, the potential return in quality of income measurement from these innovations is substantial.

Developing modern multifunctional agroforestry systems for sustainable intensification

Agroforestry is a land-use system that integrates trees and shrubs with crops and/or livestock production. It has been identified by the International Assessment of Agricultural Knowledge, Science and Technology for Development (IAASTD, 2008) as a ‘win-win’ approach that balances the production of commodities (food, feed, fuel, fibre, etc.) with non-commodity outputs such as environmental protection and cultural and landscape amenities. This paper will review the potential of agroforestry as part of a multifunctional working landscape in temperate regions, and will consider management and policy implications of widespread adoption of this form of land-use

Relationship Between Child Survival and Malaria Transmission: An Analysis of the Malaria Transmission Intensity and Mortality Burden Across Africa (MTIMBA) Project Data in Rufiji Demographic Surveillance System, Tanzania.

The precise nature of the relationship between malaria mortality and levels of transmission is unclear. Due to methodological limitations, earlier efforts to assess the linkage have lead to inconclusive results. The malaria transmission intensity and mortality burden across Africa (MTIMBA) project initiated by the INDEPTH Network collected longitudinally entomological data within a number of sites in sub-Saharan Africa to study this relationship. This work linked the MTIMBA entomology database with the routinely collected vital events within the Rufiji Demographic Surveillance System to analyse the transmission-mortality relation in the region. Bayesian Bernoulli spatio-temporal Cox proportional hazards models with village clustering, adjusted for age and insecticide-treated nets (ITNs), were fitted to assess the relation between mortality and malaria transmission measured by entomology inoculation rate (EIR). EIR was predicted at household locations using transmission models and it was incorporated in the model as a covariate with measure of uncertainty. Effects of covariates estimated by the model are reported as hazard ratios (HR) with 95% Bayesian confidence interval (BCI) and spatial and temporal parameters are presented. Separate analysis was carried out for neonates, infants and children 1-4 years of age. No significant relation between all-cause mortality and intensity of malaria transmission was indicated at any age in childhood. However, a strong age effect was shown. Comparing effects of ITN and EIR on mortality at different age categories, a decrease in protective efficacy of ITN was observed (i.e. neonates: HR = 0.65; 95% BCI: 0.39-1.05; infants: HR = 0.72; 95% BCI:0.48-1.07; children 1-4 years: HR = 0.88; 95% BCI: 0.62-1.23) and reduction on the effect of malaria transmission exposure was detected (i.e. neonates: HR = 1.15; 95% BCI:0.95-1.36; infants: HR = 1.13; 95% BCI:0.98-1.25; children 1-4 years: HR = 1.04; 95% BCI:0.89-1.18). A very strong spatial correlation was also observed. These results imply that assessing the malaria transmission-mortality relation involves more than the knowledge on the performance of interventions and control measures. This relation depends on the levels of malaria endemicity and transmission intensity, which varies significantly between different settings. Thus, sub-regions analyses are necessary to validate and assess reproducibility of findings

CONTINGENT VALUATION FOCUS GROUPS: INSIGHTS FROM ETHNOGRAPHIC INTERVIEW TECHNIQUES

Despite the many important uses (and potential abuses) of focus groups in survey design, the CV literature presents few guidelines to aid moderators in their interaction with focus group participants. This paper draws on the theory and practice of ethnographic interviewing to introduce general guidelines that can improve focus groups as an aid to CV research. The proposed guidelines illustrate types of questions that should reduce speculation and moderator-introduced bias in focus group responses, and improve the correspondence between focus group responses and actual behavior. The paper illustrates these ethnographic guidelines through a CV application concerning watershed resources.Research Methods/ Statistical Methods,

Three dimensional viscous analysis of a hypersonic inlet

The flow fields in supersonic/hypersonic inlets are currently being studied at NASA Lewis Research Center using 2- and 3-D full Navier-Stokes and Parabolized Navier-Stokes solvers. These tools have been used to analyze the flow through the McDonnell Douglas Option 2 inlet which has been tested at Calspan in support of the National Aerospace Plane Program. Comparisons between the computational and experimental results are presented. These comparisons lead to better overall understanding of the complex flows present in this class of inlets. The aspects of the flow field emphasized in this work are the 3-D effects, the transition from laminar to turbulent flow, and the strong nonuniformities generated within the inlet