Fundamental Study of nanostructured electro-catalysts with reduced noble metal content for PEM based water electrolysis

Identification and development of non-noble metal based electro-catalysts or electro-catalysts with significant reduction of expensive noble metal contents (E.g. IrO2, Pt) with comparable electrochemical performance as the standard noble metal/metal oxide for proton exchange membrane (PEM) based water electrolysis would constitute a major breakthrough in the generation of hydrogen by water electrolysis. Accomplishing such a system would not only result reduction of the overall capital costs of PEM based water electrolyzers, but also help attain the targeted hydrogen production cost [< $ 3.0 / gallon gasoline equivalent (gge)] comparable to conventional liquid fuels. In line with these goals, it was demonstrated that fluorine doped IrO2 thin films and nanostructured high surface area powders display remarkably higher electrochemical activity, and comparable durability as pure IrO2 electro-catalyst for the oxygen evolution reaction (OER) in PEM based water electrolysis. Furthermore, corrosion resistant SnO2 and NbO2 support has been doped with F and coupled with IrO2 or RuO2 for use as an OER electro-catalyst. A solid solution of SnO2:F or NbO2:F with only 20 - 30 mol.% IrO2 or RuO2 yielding a rutile structure in the form of thin films and bulk nanoparticles displays similar electrochemical activity and stability as pure IrO2/RuO2. This would lead to more than 70 mol.% reduction in the noble metal oxide content. Novel nanostructured ternary (Ir,Sn,Nb)O2 thin films of different compositions have also been studied. It has been shown that (Ir0.40Sn0.30Nb0.30)O2 shows similar electrochemical activity and enhanced chemical robustness as compared to pure IrO2. F doping of the ternary (Ir,Sn,Nb)O2 catalyst helps in further decreasing the noble metal oxide content of the catalyst. As a result, these reduced noble metal oxide catalyst systems would potentially be preferred as OER electro-catalysts for PEM electrolysis. The excellent performance of the catalysts coupled with its robustness would make them great candidates for contributing to significant reduction in the overall capital costs of PEM based water electrolyzers. This thesis provides a detailed fundamental study of the synthesis, materials, characterization, theoretical studies and detailed electrochemical response and potential mechanisms of these novel electro-catalysts for OER processes

Discovery, Characterization, and Structure–Activity Relationships of an Inhibitor of Inward Rectifier Potassium (Kir) Channels with Preference for Kir2.3, Kir3.X, and Kir7.1

The inward rectifier family of potassium (Kir) channels is comprised of at least 16 family members exhibiting broad and often overlapping cellular, tissue, or organ distributions. The discovery of disease-causing mutations in humans and experiments on knockout mice has underscored the importance of Kir channels in physiology and in some cases raised questions about their potential as drug targets. However, the paucity of potent and selective small-molecule modulators targeting specific family members has with few exceptions mired efforts to understand their physiology and assess their therapeutic potential. A growing body of evidence suggests that G protein-coupled inward rectifier K (GIRK) channels of the Kir3.X subfamily may represent novel targets for the treatment of atrial fibrillation. In an effort to expand the molecular pharmacology of GIRK, we performed a thallium (Tl+) flux-based high-throughput screen of a Kir1.1 inhibitor library for modulators of GIRK. One compound, termed VU573, exhibited 10-fold selectivity for GIRK over Kir1.1 (IC50 = 1.9 and 19 μM, respectively) and was therefore selected for further study. In electrophysiological experiments performed on Xenopus laevis oocytes and mammalian cells, VU573 inhibited Kir3.1/3.2 (neuronal GIRK) and Kir3.1/3.4 (cardiac GIRK) channels with equal potency and preferentially inhibited GIRK, Kir2.3, and Kir7.1 over Kir1.1 and Kir2.1.Tl+ flux assays were established for Kir2.3 and the M125R pore mutant of Kir7.1 to support medicinal chemistry efforts to develop more potent and selective analogs for these channels. The structure–activity relationships of VU573 revealed few analogs with improved potency, however two compounds retained most of their activity toward GIRK and Kir2.3 and lost activity toward Kir7.1. We anticipate that the VU573 series will be useful for exploring the physiology and structure–function relationships of these Kir channels

Central aortic valve coaptation area during diastole as seen by 64-multidetector computed tomography (MDCT)

As multiple new procedures now require better visualization of the aortic valve, we sought to better define the central aortic valve coaptation area seen during diastole on multi-detector row cardiac computed tomography (MDCT). 64-MDCT images of 384 symptomatic consecutive patients referred for coronary artery disease evaluation were included in the study. Planimetric measurements of this area were performed on cross-sectional views of the aortic valve at 75% phase of the cardiac cycle. Planimetric measurement of central regurgitation orifice area (ROA) seen in patients with aortic regurgitation and Hounsfield units of the central aortic valve coaptation area were performed. Mean area of the central aortic valve coaptation area was 5.34 ± 5.19 mm2 and Hounsfield units in this area were 123.69 ± 31.31 HU. The aortic valve coaptation area (mm2) measurement in patients without AR was: 4.90 ± 0.17 and in patients with AR: 10.53 ± 0.26 (P = <0.05). On Bland–Altman analysis a very good correlation between central aortic valve coaptation area and central ROA was found (r = 0.80, P = <0.001). Central aortic valve coaptation area is a central area present at the coaptation of nodules of arantius of aortic cusps during diastole; it is incompetent and increased in size in patients with aortic regurgitation

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Left ventricular volume: an optimal parameter to detect systolic dysfunction on prospectively triggered 64-multidetector row computed tomography: another step towards reducing radiation exposure

In this study, we define the correlation between LV volumes (both LV end-diastolic volume [LVEDV] and LV end-systolic volume [LVESV]) and ejection fraction (EF) on 64 slice multi-detector computed tomography (MDCT). We also determine the accuracy of all the LV volume (LVV) parameters to detect LV systolic dysfunction (LVSD) and investigate the feasibility of using LVV as a surrogate of LVSD on prospectively gated imaging to prevent the radiation exposure of retrospective imaging. 568 patients undergoing 64-detector MDCT were divided into 2 groups: Group 1—subjects without any heart disease and LVEF ≥ 50%; and Group 2—patients with coronary artery disease and LVEF < 50% (defined as LVSD). The LVV (LV cavity only) and Total LV volume (cavity + LV mass) at end-systole and end-diastole (LVESV, Total LVESV, LVEDV and Total LVEDV) were measured. The upper limit values (mean + 2 SD) of all LVV parameters in Group 1 were used as the reference criterion to diagnose LVSD in Group 2. An exponential correlation was found between LVEF and all the LVV parameters. The specificity to detect LVSD in Group 2 was >90% and the sensitivity was 88.9, 83.3, 61.3 and 74.9% by using LVESV, Total LVESV, LVEDV and Total LVEDV, respectively. Systolic and diastolic LV volumes had a high correlation with LVEF and a high accuracy to detect LVSD. Thus, on prospectively triggered imaging, ventricular volumes can predict patients with reduced LVEF, and appropriate referrals can be made

Non-contrast cardiac computed tomography can accurately detect chronic myocardial infarction: Validation study

BackgroundThis study evaluates whether non-contrast cardiac computed tomography (CCT) can detect chronic myocardial infarction (MI) in patients with irreversible perfusion defects on nuclear myocardial perfusion imaging (MPI).MethodsOne hundred twenty-two symptomatic patients with irreversible perfusion defect (N = 62) or normal MPI (N = 60) underwent coronary artery calcium (CAC) scanning. MI on these non-contrast CCTs was visually detected based on the hypo-attenuation areas (dark) in the myocardium and corresponding Hounsfield units (HU) were measured.ResultsNon-contrast CCT accurately detected MI in 57 patients with irreversible perfusion defect on MPI, yielding a sensitivity of 92%, specificity of 72%, negative predictive value (NPV) of 90%, and a positive predictive value (PPV) of 77%. On a per myocardial region analysis, non-contrast CT showed a sensitivity of 70%, specificity of 85%, NPV of 91%, and a PPV of 57%. The ROC curve showed that the optimal cutoff value of LV myocardium HU to predict MI on non-contrast CCT was 21.7 with a sensitivity of 97.4% and specificity of 99.7%.ConclusionNon-contrast CCT has an excellent agreement with MPI in detecting chronic MI. This study highlights a novel clinical utility of non-contrast CCT in addition to assessment of overall burden of atherosclerosis measured by CAC

Long-term health status and trajectories of seriously injured patients: A population-based longitudinal study

Improved understanding of the quality of survival of patients is crucial in evaluating trauma care, understanding recovery patterns and timeframes, and informing healthcare, social, and disability service provision. We aimed to describe the longer-term health status of seriously injured patients, identify predictors of outcome, and establish recovery trajectories by population characteristics.A population-based, prospective cohort study using the Victorian State Trauma Registry (VSTR) was undertaken. We followed up 2,757 adult patients, injured between July 2011 and June 2012, through deaths registry linkage and telephone interview at 6-, 12-, 24-, and 36-months postinjury. The 3-level EuroQol 5 dimensions questionnaire (EQ-5D-3L) was collected, and mixed-effects regression modelling was used to identify predictors of outcome, and recovery trajectories, for the EQ-5D-3L items and summary score. Mean (SD) age of participants was 50.8 (21.6) years, and 72% were male. Twelve percent (n = 333) died during their hospital stay, 8.1% (n = 222) of patients died postdischarge, and 155 (7.0%) were known to have survived to 36-months postinjury but were lost to follow-up at all time points. The prevalence of reporting problems at 36-months postinjury was 37% for mobility, 21% for self-care, 47% for usual activities, 50% for pain/discomfort, and 41% for anxiety/depression. Continued improvement to 36-months postinjury was only present for the usual activities item; the adjusted relative risk (ARR) of reporting problems decreased from 6 to 12 (ARR 0.87, 95% CI: 0.83-0.90), 12 to 24 (ARR 0.94, 95% CI: 0.90-0.98), and 24 to 36 months (ARR 0.95, 95% CI: 0.95-0.99). The risk of reporting problems with pain or discomfort increased from 24- to 36-months postinjury (ARR 1.06, 95% CI: 1.01, 1.12). While loss to follow-up was low, there was responder bias with patients injured in intentional events, younger, and less seriously injured patients less likely to participate; therefore, these patient subgroups were underrepresented in the study findings.The prevalence of ongoing problems at 3-years postinjury is high, confirming that serious injury is frequently a chronic disorder. These findings have implications for trauma system design. Investment in interventions to reduce the longer-term impact of injuries is needed, and greater investment in primary prevention is needed