Local three-nucleon interaction from chiral effective field theory

The three-nucleon (NNN) interaction derived within the chiral effective field theory at the next-to-next-to-leading order (N2LO) is regulated with a function depending on the magnitude of the momentum transfer. The regulated NNN interaction is then local in the coordinate space, which is advantages for some many-body techniques. Matrix elements of the local chiral NNN interaction are evaluated in a three-nucleon basis. Using the ab initio no-core shell model (NCSM) the NNN matrix elements are employed in 3H and 4He bound-state calculations.Comment: 17 pages, 9 figure

Impact of a 6-wk olive oil supplementation in healthy adults on urinary proteomic biomarkers of coronary artery disease, chronic kidney disease, and diabetes (types 1 and 2): a randomized, parallel, controlled, double-blind study

Background: Olive oil (OO) consumption is associated with cardiovascular disease prevention because of both its oleic acid and phenolic contents. The capacity of OO phenolics to protect against low-density lipoprotein (LDL) oxidation is the basis for a health claim by the European Food Safety Authority. Proteomic biomarkers enable an early, presymptomatic diagnosis of disease, which makes them important and effective, but understudied, tools for primary prevention. Objective: We evaluated the impact of supplementation with OO, either low or high in phenolics, on urinary proteomic biomarkers of coronary artery disease (CAD), chronic kidney disease (CKD), and diabetes. Design: Self-reported healthy participants (n = 69) were randomly allocated (stratified block random assignment) according to age and body mass index to supplementation with a daily 20-mL dose of OO either low or high in phenolics (18 compared with 286 mg caffeic acid equivalents per kg, respectively) for 6 wk. Urinary proteomic biomarkers were measured at baseline and 3 and 6 wk alongside blood lipids, the antioxidant capacity, and glycation markers. Results: The consumption of both OOs improved the proteomic CAD score at endpoint compared with baseline (mean improvement: –0.3 for low-phenolic OO and −0.2 for high-phenolic OO; P < 0.01) but not CKD or diabetes proteomic biomarkers. However, there was no difference between groups for changes in proteomic biomarkers or any secondary outcomes including plasma triacylglycerols, oxidized LDL, and LDL cholesterol. Conclusion: In comparison with low-phenolic OO, supplementation for 6 wk with high-phenolic OO does not lead to an improvement in cardiovascular health markers in a healthy cohort. This trial was registered at www.controlled-trials.com as ISRCTN93136746

Three-Nucleon Electroweak Capture Reactions

Recent advances in the study of the p-d radiative and mu-3he weak capture processes are presented and discussed. The three-nucleon bound and scattering states are obtained using the correlated-hyperspherical-harmonics method, with realistic Hamiltonians consisting of the Argonne v14 or Argonne v18 two-nucleon and Tucson-Melbourne or Urbana IX three-nucleon interactions. The electromagnetic and weak transition operators include one- and two-body contributions. The theoretical accuracy achieved in these calculations allows for interesting comparisons with experimental data.Comment: 12 pages, 4 figures, invited talk at the CFIF Fall Workshop: Nuclear Dynamics, from Quarks to Nuclei, Lisbon, 31st of October - 1st of November 200

The self-reported Montgomery-Åsberg depression rating scale is a useful evaluative tool in major depressive disorder

Abstract Background The use of Patient-reported Outcomes (PROs) as secondary endpoints in the development of new antidepressants has grown in recent years. The objective of this study was to assess the psychometric properties of the 9-item, patient-administered version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S). Methods Data from a multicentre, double-blind, 8-week, randomised controlled trial of 278 outpatients diagnosed with Major Depressive Disorder were used to evaluate the validity, reliability and sensitivity to change of the MADRS-S using psychometric methods. A Receiver Operating Characteristic (ROC) curve was plotted to identify the most appropriate threshold to define perceived remission. Results No missing values were found at the item level, indicating good acceptability of the scale. The construct validity was satisfactory: all items contributed to a common underlying concept, as expected. The correlation between MADRS-S and physicians' MADRS was moderate (r = 0.54, p Conclusion Taking account of patient's perceptions of the severity of their own symptoms along with the psychometric properties of the MADRS-S enable its use for evaluative purposes in the development of new antidepressant drugs.</p

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

Ethanol Oxidation and Toxicity: Role of Alcohol P-450 Oxygenase

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66172/1/j.1530-0277.1986.tb05179.x.pd

c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

INTRODUCTION: c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. METHODS: In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. RESULTS: Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. CONCLUSION: The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

Genome-Wide Linkage Scan to Identify Loci Associated with Type 2 Diabetes and Blood Lipid Phenotypes in the Sikh Diabetes Study

In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D) and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS). A total of 870 individuals (526 male/344 female) from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using Sall statistics (implemented in Merlin) did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011) occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016) and 5p15.33 (p = 0.0031) and for LDL cholesterol at 10p11.23 (p = 0.0045). Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance

Selective Removal of Alkali Metal Cations from Multiply-Charged Ions via Gas-Phase Ion/Ion Reactions Using Weakly Coordinating Anions

Selective removal of alkali metal cations from mixed cation multiply-charged peptide ions is demonstrated here using gas-phase ion/ion reactions with a series of weakly coordinating anions (WCAs), including hexafluorophosphate (PF6 (-)), tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF), tetrakis(pentafluorophenyl)borate (TPPB), and carborane (CHB11Cl11 (-)). In all cases, a long-lived complex is generated by dication/anion condensation followed by ion activation to compare proton transfer with alkali ion transfer from the peptide to the anion. The carborane anion was the only anion studied to undergo dissociation exclusively through loss of the metallated anion, regardless of the studied metal adduct. All other anions studied yield varying abundances of protonated and metallated peptide depending on the peptide sequence and the metal identity. Density functional theory calculations suggest that for the WCAs studied, metal ion transfer is most strongly favored thermodynamically, which is consistent with the experimental results. The carborane anion is demonstrated to be a robust reagent for the selective removal of alkali metal cations from peptide cations with mixtures of excess protons and metal cations