Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.     

The emittance of yttrium-beryllium oxide thermocouple coating

The emittance of a yttrium-beryllium oxide thermocouple coating was determined by an electrical heating method and by sodium line reversal measurements in the overall temperature range 1465–1830K. The emittance determined by both methods was 0.60. Comparison of emittances measured with different sized thermocouples in one-dimensional flames implied that the appropriate thermocouple heat transfer model was a cylinder in cross flow. Good agreement was obtained between radiation-corrected temperatures measured with silica coated (emittance of 0.22) and yttrium-beryllium oxide coated thermocouples.     

Global Optimization of Adsorbate–Surface Structures While Preserving Molecular Identity

As the complexity of atomistic simulations in catalysis and surface science increases, the challenge of manually finding the lowest-energy adsorbate–surface geometries grows significantly. In the current work, a global optimization approach that preserves adsorbate identity is applied to enable the automated search for optimized binding geometries. This technique is based on the minima hopping method developed by Goedecker, but is modified to preserve the molecular identity of adsorbates by the application of a new class of Hookean constraints. These constraints are completely inactive when the adsorbate identity is preserved, but act to restore the adsorbate structure via a Hookean force when the bond length exceeds a threshold distance. Additionally, a related Hookean constraint has been developed to prevent adsorbates (particularly such adsorbates as CO and CH₂O that have stable gas-phase forms) from volatilizing during the molecular dynamics portion of the minima hopping technique. This combination, referred to herein as the constrained minima hopping method, was tested for its suitability in finding the minimum-energy binding configuration for a set of 17 C _x H _y O _z adsorbates on a stepped Cu fcc(211) surface and in all cases found the global minima in comparable or fewer steps than the previous brute force methodologies. It is expected that methods such as this will be crucial to finding low-energy states in more complex systems, such as those with high coverages of adsorbed species or in the presence of explicit solvent molecules.     

Cyp1 Inhibition Prevents Doxorubicin-Induced Cardiomyopathy in a Zebrafish Heart-Failure Model

Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection.     

Ion Exchange of Selected Group II Metals and Lead by Crystalline Silicotitanate and Competition for Cs Exchange Sites

ABSTRACT

A series of batch contact tests were conducted to evaluate the exchange behavior of Ba, Ca, Pb, and Sr onto crystalline silicotitanate (CST) in support of an expedited Cs removal and pretreatment system at the Hanford site. Binary Na/M²⁺ and ternary Na/Cs/M²⁺ isotherms were generated to understand selectivity, capacity, and competitive impact of each analyte on Cs uptake from a simple 1 M NaOH/4.6 M NaNO₃ simulant. Analyte loading from a 0.1 M NaOH/5.5 M NaNO₃ simulant was assessed to determine the effect of hydroxide concentration on binary Na/M²⁺ isotherms. Results from binary and ternary isotherms indicated that Group II metals Ca, Sr, and Ba (and Pb) do not impact CST performance toward Cs removal at concentrations expected in Hanford tank-waste supernate.     

Effectiveness of cationically modified cellulose polymers for dewatering algae

A method to flocculate algal cultures of Chlamydomonas reinhardtii using four different industrially produced polymers is presented. Starting with a 1 wt% stock polymer solution, flocculation times less than 60 min were observed for 0.1 to 0.6 g polymer per L of algae culture, while control samples took greater than 1400 min to flocculate. Cell counts showed that 99% of the cells were flocculated using the polymers compared to 73% for the control. Finally, the flocculation process was successful at both 5 and 40 mL batch sizes for one polymer; therefore, the method is efficient, effective and may be scalable.     

To what does perceived criticism refer? Constructive, destructive, and general criticism.

General spousal perceived criticism (PC) robustly predicts psychological symptoms and is associated with marital discord (e.g., Hooley & Teasdale, 1989); however, it is unclear what types of criticism PC encompasses (Renshaw, 2008). One hundred eighteen couples rated general PC and both constructive and destructive criticism from their own videotaped spousal discussions. Independent judges also coded criticism from the discussions. Results suggest that destructive rather than constructive criticism is related to PC. That PC primarily reflects destructive criticism may explain its utility in predicting relapse. Future studies will benefit from separate application of constructive and destructive criticism measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does it matter where we live?: The urban psychology of character strengths.

Psychology has neglected the study of variation across cities. An urban psychology is needed that takes seriously such variation and focuses on strengths and assets contributing to the good life as much as on problems of urbanization. To illustrate the value of an urban psychology, we describe studies of character strengths among residents in the 50 largest U.S. cities (N = 47,369). Differences in character strengths were found to exist across cities, were robustly related to important city-level outcomes such as entrepreneurship and 2008 presidential election voting, and were associated in theoretically predicted ways with city-level features. We propose a framework that distinguishes between strengths of the “head,” which are intellectual and self-oriented, and strengths of the “heart,” which are emotional and interpersonal. Cities whose residents had higher levels of head strengths were those rated as creative and innovative. Head strengths predicted the likelihood of a city voting for Barack Obama, whereas heart strengths predicted voting for John McCain. More than half of the world's population now resides in cities, and urban psychology deserves greater attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The experimental research of a digital sampling signal converter

The sensitivity and rise time of a transient characteristic of a digital sampling signal converter are experimentally researched. The sampling converter is built at a clocked tunnel-diode comparator.