EVALUATING NOVEL RISK FACTOR ASSOCIATIONS FOR SUBCLINICAL CARDIOVASCULAR DISEASE

Globally, cardiovascular disease (CVD) is the leading cause of death. Increased risk for CVD can be attributed to smoking, high blood pressure, poor lipid profiles, obesity and psychosocial factors. Markers of subclinical CVD are non-invasive measures that detect early atherosclerotic changes. The purpose of this dissertation was to evaluate novel risk factor associations for subclinical CVD in three distinct populations. The protective effect of HDL-c for subclinical CVD was diminished in a population of postmenopausal women compared to premenopausal women. Furthermore, the concentration of small HDL particles was higher among postmenopausal women. Lipid profile changes with the menopausal transition may in part explain the increased risk of CVD seen after menopause.The protective effect of education for subclinical CVD was evident only among females from an Afro-Caribbean population. Educational differences in SBP and lipids varied for males and females providing insight into potential mechanisms for the education-subclinical CVD relationship observed on the island of Tobago.Tonic cardiac sympathetic activity and parasympathetic reactivity were independent predictors of subclinical CVD in a population of overweight and obese young adults. The effect of C-reactive protein (CRP) on subclinical CVD is potentially explained by the autonomic anti-inflammatory mechanisms linking heart rate variability and CRP. Identifying novel risk factor associations for subclinical CVD in various populations supports the important public health objective of reducing the global burden of CVD morbidity and mortality through early detection of atherosclerosis

The Changing Role of RSEs over the Lifetime of Parsl

This position paper describes the Parsl open source research software project and its various phases over seven years. It defines four types of research software engineers (RSEs) who have been important to the project in those phases; we believe this is also applicable to other research software projects.Comment: 3 page

Bivalve facilitation mediates seagrass recovery from physical disturbance in a temperate estuary

Rapid global degradation of coastal habitats can be attributed to anthropogenic activities associated with coastal development, aquaculture, and recreational surface water use. Restoration of degraded habitats has proven challenging and costly, and there is a clear need to develop novel approaches that promote resilience to human-caused disturbances. Positive interactions between species can mitigate environmental stress and recent work suggests that incorporating positive interactions into restoration efforts may improve restoration outcomes. We hypothesized that the addition of a potential facultative mutualist, the native hard clam (Mercenaria mercenaria), could enhance seagrass bed recovery from disturbance. We conducted two experiments to examine the independent and interacting effects of hard clam addition and physical disturbance mimicking propeller scarring on mixed community Zostera marina and Halodule wrightii seagrass beds in North Carolina. Adding clams to seagrass beds exposed to experimental disturbance generally enhanced seagrass summer growth rates and autumn shoot densities. In contrast, clam addition to non-disturbed seagrass beds did not result in any increase in seagrass growth rates or shoot densities. Clam enhancement of autumn percent cover relative to areas without clam addition was most prominent after Hurricane Dorian, suggesting that clams may also enhance seagrass resilience to repeated disturbances. By June of the next growing season, disturbed areas with clam additions had greater percent cover of seagrass than disturbed areas without clam additions. Beds that were disturbed in April had higher percent cover than areas disturbed in June of the previous growing season. Our results suggest that the timing and occurrence of physical disturbances may modify the ability of clams to facilitate seagrass resiliency and productivity. Understanding when and how to utilize positive, interspecific interactions in coastal restoration is key for improving restoration success rates.ECU Open Access Publishing Support Fun

Anode Biofilm Transcriptomics Reveals Outer Surface Components Essential for High Density Current Production in Geobacter sulfurreducens Fuel Cells

The mechanisms by which Geobacter sulfurreducens transfers electrons through relatively thick (>50 µm) biofilms to electrodes acting as a sole electron acceptor were investigated. Biofilms of Geobacter sulfurreducens were grown either in flow-through systems with graphite anodes as the electron acceptor or on the same graphite surface, but with fumarate as the sole electron acceptor. Fumarate-grown biofilms were not immediately capable of significant current production, suggesting substantial physiological differences from current-producing biofilms. Microarray analysis revealed 13 genes in current-harvesting biofilms that had significantly higher transcript levels. The greatest increases were for pilA, the gene immediately downstream of pilA, and the genes for two outer c-type membrane cytochromes, OmcB and OmcZ. Down-regulated genes included the genes for the outer-membrane c-type cytochromes, OmcS and OmcT. Results of quantitative RT-PCR of gene transcript levels during biofilm growth were consistent with microarray results. OmcZ and the outer-surface c-type cytochrome, OmcE, were more abundant and OmcS was less abundant in current-harvesting cells. Strains in which pilA, the gene immediately downstream from pilA, omcB, omcS, omcE, or omcZ was deleted demonstrated that only deletion of pilA or omcZ severely inhibited current production and biofilm formation in current-harvesting mode. In contrast, these gene deletions had no impact on biofilm formation on graphite surfaces when fumarate served as the electron acceptor. These results suggest that biofilms grown harvesting current are specifically poised for electron transfer to electrodes and that, in addition to pili, OmcZ is a key component in electron transfer through differentiated G. sulfurreducens biofilms to electrodes

Improving efficiency of analysis jobs in CMS

Hundreds of physicists analyze data collected by the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider using the CMS Remote Analysis Builder and the CMS global pool to exploit the resources of the Worldwide LHC Computing Grid. Efficient use of such an extensive and expensive resource is crucial. At the same time, the CMS collaboration is committed to minimizing time to insight for every scientist, by pushing for fewer possible access restrictions to the full data sample and supports the free choice of applications to run on the computing resources. Supporting such variety of workflows while preserving efficient resource usage poses special challenges. In this paper we report on three complementary approaches adopted in CMS to improve the scheduling efficiency of user analysis jobs: automatic job splitting, automated run time estimates and automated site selection for jobs

Functional consequences of postnatal interventions in a mouse model of Fragile X syndrome

BackgroundFragile X syndrome (FXS) is a leading genetic cause of autism and intellectual disability with cortical hyperexcitability and sensory hypersensitivity attributed to loss and hypofunction of inhibitory parvalbumin-expressing (PV) cells. Our studies provide novel insights into the role of excitatory neurons in abnormal development of PV cells during a postnatal period of inhibitory circuit refinement.MethodsTo achieve Fragile X mental retardation gene (Fmr1) deletion and re-expression in excitatory neurons during the postnatal day (P)14-P21 period, we generated CreCaMKIIa/Fmr1Flox/y (cOFF) and CreCaMKIIa/Fmr1FloxNeo/y (cON) mice, respectively. Cortical phenotypes were evaluated in adult mice using biochemical, cellular, clinically relevant electroencephalogram (EEG) and behavioral tests.ResultsWe found that similar to global Fmr1 KO mice, the density of PV-expressing cells, their activation, and sound-evoked gamma synchronization were impaired in cOFF mice, but the phenotypes were improved in cON mice. cOFF mice also showed enhanced cortical gelatinase activity and baseline EEG gamma power, which were reduced in cON mice. In addition, TrkB phosphorylation and PV levels were lower in cOFF mice, which also showed increased locomotor activity and anxiety-like behaviors. Remarkably, when FMRP levels were restored in only excitatory neurons during the P14-P21 period, TrkB phosphorylation and mouse behaviors were also improved.ConclusionsThese results indicate that postnatal deletion or re-expression of FMRP in excitatory neurons is sufficient to elicit or ameliorate structural and functional cortical deficits, and abnormal behaviors in mice, informing future studies about appropriate treatment windows and providing fundamental insights into the cellular mechanisms of cortical circuit dysfunction in FXS

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies