Defect formation during binder removal in ethylene vinyl acetate filled system

This paper focuses on determining the criteria for defect formation during the early stages of thermal binder removal within an ethylene vinyl acetate (EVA) polymer filled with submicron SiC ceramic powder. The only product of the early stage thermal degradation reaction of EVA within an inert atmosphere is acetic acid. This single component and well characterized organic reaction product has allowed the defect forming criteria to be definitively examined. It will be shown that bloating occurs in the early stages of binder removal as a result of pressure build-up in the specimen resulting from acetic acid formed from the thermal elimination reaction of EVA. The first part of this paper examines defect formation occurring in the pure polymer within a hot-stage optical microscope. Bubble formation is observed in the pure polymer. Next, bloating occurring in the molded system is examined. The affect of mineral oil on bloating is also discussed as well as the effect that molding pressure has on bloating. It was found that molding pressure effects defect formation. Finally, this paper presents binder removal maps that were developed for specimens up to 8 mm thick. These bloating maps indicate the existence of two primary bloating regimes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44754/1/10853_2004_Article_232418.pd

Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide

Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P≤0.01 and fold change±1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain

Genomic comparisons reveal biogeographic and anthropogenic impacts in the koala (Phascolarctos cinereus): a dietary-specialist species distributed across heterogeneous environments

The Australian koala is an iconic marsupial with highly specific dietary requirements distributed across heterogeneous environments, over a large geographic range. The distribution and genetic structure of koala populations has been heavily influenced by human actions, specifically habitat modification, hunting and translocation of koalas. There is currently limited information on population diversity and gene flow at a species-wide scale, or with consideration to the potential impacts of local adaptation. Using species-wide sampling across heterogeneous environments, and high-density genome-wide markers (SNPs and PAVs), we show that most koala populations display levels of diversity comparable to other outbred species, except for those populations impacted by population reductions. Genetic clustering analysis and phylogenetic reconstruction reveals a lack of support for current taxonomic classification of three koala subspecies, with only a single evolutionary significant unit supported. Furthermore, similar to 70% of genetic variance is accounted for at the individual level. The Sydney Basin region is highlighted as a unique reservoir of genetic diversity, having higher diversity levels (i.e., Blue Mountains region; AvHe(corr)-0.20, PL% = 68.6). Broad-scale population differentiation is primarily driven by an isolation by distance genetic structure model (49% of genetic variance), with clinal local adaptation corresponding to habitat bioregions. Signatures of selection were detected between bioregions, with no single region returning evidence of strong selection. The results of this study show that although the koala is widely considered to be a dietary-specialist species, this apparent specialisation has not limited the koala's ability to maintain gene flow and adapt across divergent environments as long as the required food source is available

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Dimensional changes during binder removal in a mouldable ceramic system

Significant dimensional changes involving linear expansion and shrinkage of 6% occur during heating of a thermoplastic SiC/ethylene vinyl acetate (EVA) mixture. Thermal expansion occurs before weight loss begins, and can be quantitatively explained in terms of the thermal expansion behaviour of the constituents and the crystallization or melting of the semicrystalline polymer. Irreversible anisotropic displacements occur during the first heating cycle due to relaxation of moulding strains. These can be reduced by annealing for periods comparable to the viscoelastic relaxation of the ceramic/polymer system. Shrinkage occurs during the early stages of degradation of EVA. This shrinkage is quantitatively accounted for with volume losses resulting from removal of the EVA. Shrinkage continues as weight loss proceeds and stops only at the point the ceramic particles contact one another. Total displacement behaviour is the sum of the shrinkage from weight loss plus the expansion from thermal expansion of the individual components, and can be quantitatively predicted for simple or multi-step heating schedules.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44747/1/10853_2004_Article_339003.pd

Chemistry of removal of ethylene vinyl acetate binders

The research presented herein has focused on debinding of an ethylene copolymer from a SiC based moulded ceramic green body within an inert atmosphere. Upon heating, the pure polymer undergoes a two-stage thermal degradation process. In the first stage, acetic acid is the only degradation product formed. The effect of the introduction of high surface area powder on the chemistry and kinetics of this first stage reaction was examined. The effluents were captured and analysed in a gas chromatograph/mass spectrometer. The product of the reaction was not altered by introduction of the ceramic powder. However, the kinetics of the reaction were altered. The kinetics of the reaction were determined with the use of thermogravi metric analysis (TGA). The mechanism of mass transport during binder removal was determined by monitoring dimensional changes during binder removal. It was found that one unit volume of shrinkage corresponded with one unit volume of binder removed, indicating that no porosity developed. The escaping acetic acid effluents must diffuse through the liquid polymer filled pores to escape. Bloating was observed in certain conditions and was attributed to the concentration of acetic acid exceeding a critical value, resulting in bubbling.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44746/1/10853_2004_Article_339002.pd

Doxorubicin-induced thiol-dependent alteration of cardiac mitochondrial permeability transition and respiration

Abstract Doxorubicin (DOX) is a highly effective treatment for several forms of cancer. However, clinical experience shows that DOX induces a cumulative and dose-dependent cardiomyopathy that has been ascribed to redox-cycling of the drug on the mitochondrial respiratory chain generating free radicals and oxidative stress in the process. Mitochondrial dysfunction including induction of the mitochondrial permeability transition (MPT) and inhibition of mitochondrial respiration have been implicated as major determinants in the pathogenesis of DOX cardiotoxicity. The present work was aimed at investigating whether the inhibition of mitochondrial respiration occurs secondarily to MPT induction in heart mitochondria isolated from DOX-treated rats and whether one or both consequences of DOX treatment are related with oxidation of protein thiol residues. DOX-induced oxidative stress was associated with the accumulation of products of lipid peroxidation and the depletion of a-tocopherol in cardiac mitochondrial membranes. No changes in mitochondrial coenzyme Q9 and Q10 concentrations were detected in hearts of DOX-treated rats. Cardiac mitochondria from DOX-treated rats were more susceptible to diamide-dependent induction of the MPT. Although DOX treatment did not affect state 4 respiration, state 3 respiration was decreased in heart mitochondria isolated from DOX-treated rats, which was reversed in part by adding either cyclosporin A or dithiothreitol, but not Trolox. The results suggest that in DOX-treated rats, (i) induction of the MPT is at least in part responsible for decreased mitochondrial respiration, (ii) heart mitochondria are more susceptible to diamide induced-MPT, (iii) thiol-dependent alteration of mitochondrial respiration is partially reversible ex vivo with dithiothreitol. Collectively, these data are consistent with the thesis that thiol-dependent alteration of MPT and respiration is an important factor in DOX-induced mitochondrial dysfunction

Enantioselective allylation of α,β-unsaturated aldehydes with allyltrichlorosilane catalyzed by METHOX

α,β-Unsaturated aldehydes 6a-j undergo an enantioselective allylation with allylic trichlorosilanes 2a,b in the presence of METHOX (4) as a Lewis basic catalyst (≤10 mol %) to produce the homoallylic alcohols 7a-l at good to high enantioselectivity (83-96% ee). This study shows that the reactivity scope of METHOX can be extended from aromatic to nonaromatic aldehydes