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

Negotiating the Korea-United States Free Trade Agreement

Difficult and sensitive issues will command the attention of US and Korean officials as they negotiate a bilateral free trade agreement (FTA). The United States will have to put long-standing US barriers to Korean exports of textiles, apparel, and steel on the table and resolve problems with South Korean access to the US visa waiver program. In turn, South Korea will have to open new opportunities for US goods and services, including autos, beef, and rice. Such a deal will pose a stiff political challenge for Korean officials. However, they will be under pressure in any event to reform their farm programs--either in the context of a final deal in the WTO talks or in response to Chinese initiatives in the region, which Korea will need to match. Both Korea and the United States also have important foreign policy interests in the FTA, particularly enhanced security on the Korean peninsula. South Korea would like the FTA to promote the policy of constructive engagement with North Korea, which the former has been pursuing by extending trade preferences to goods produced in the Kaesong industrial complex in North Korea. However, such a request would put the entire negotiation in jeopardy since the US Congress would reject preferences for the North Korean regime.

A STRUCTURAL-EQUATION GME ESTIMATOR

A generalized maximum entropy estimator is developed for the linear simultaneous equations systems model. We provide results on large and small sample properties of the estimator. Empirical results illustrate efficiency advantages of the generalized maximum entropy estimator proposed in this study over traditional estimators (e.g., 2SLS and 3SLS).Research Methods/ Statistical Methods,

Bounce-free spherical hydrodynamic implosion

In a bounce-free spherical hydrodynamic implosion, the post-stagnation hot core plasma does not expand against the imploding flow. Such an implosion scheme has the advantage of improving the dwell time of the burning fuel, resulting in a higher fusion burn-up fraction. The existence of bounce-free spherical implosions is demonstrated by explicitly constructing a family of self-similar solutions to the spherically symmetric ideal hydrodynamic equations. When applied to a specific example of plasma liner driven magneto-inertial fusion, the bounce-free solution is found to produce at least a factor of four improvement in dwell time and fusion energy gain.Comment: accepted by Phys. Plasmas (Nov. 7, 2011); for Ref. 11, please see ftp://ftp.lanl.gov/public/kagan/liner_evolution.gi

Comparison of Student Versus Employee Test Populations for Warning Sign Research Based on Severity Ratings for Signal Words

Most studies of warning signs involve undergraduate students as subjects. This paper reports a direct comparison of findings from an undergraduate population and an employed population. The 48 employed subjects from this study were compared with 59 undergraduate subjects from a companion study. Subjects from both populations were shown the same signs and asked to rate the severity level connoted by each sign. The signs differed only in signal word. Results for each population indicated that signal word had a highly significant effect on severity ratings. When the two populations were compared for ratings of each signal word, the only significant difference was for Caution. Median ratings of each population were the same: Deadly (4), Danger (3), Warning (2), Caution (1), and Notice (0)

Shipboard acoustic observations of flow rate from a seafloor-sourced oil spill

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Loranger, S., & Weber, T. C. . Shipboard acoustic observations of flow rate from a seafloor-sourced oil spill. Journal of Geophysical Research: Oceans, 125(10), (2020): e2020JC016274, https://doi.org/10.1029/2020JC016274.In 2004 a debris flow generated by Hurricane Ivan toppled an oil production platform in Mississippi Canyon lease block 20 (MC20). Between 2004 and the installation of a containment system in 2019 MC20 became an in situ laboratory for a wide range of hydrocarbon in the sea‐related research, including different methods of assessing the volumetric flow rate of hydrocarbons spanning different temporal scales. In 2017 a shipboard acoustic Doppler current profiler (ADCP) and high‐frequency (90 to 154 kHz) broadband echosounder were deployed to assess the flow rate of liquid and gas phase hydrocarbons. Measurements of horizontal currents were combined with acoustic mapping to determine the rise velocity of the seep as it moved downstream. Models of the rise velocity for fluid particles were used to predict the size of oil droplets and gas bubbles in the seep. The amplitude and shape of the broadband acoustic backscatter were then used to differentiate between, and determine the flow rate of, hydrocarbons. Oil flow rate in the seep was estimated to be 56 to 86 barrels/day (mean urn:x-wiley:jgrc:media:jgrc24228:jgrc24228-math-0001 barrels/day) while the flow rate of gaseous hydrocarbons was estimated to be 98 to 359 m3/day (mean urn:x-wiley:jgrc:media:jgrc24228:jgrc24228-math-0002 m3/day).The work was supported by the National Oceanic and Atmospheric Administration (Grant NA15NOS4000200)