Geometric properties of a prestressed segmented spherical shell

Design and construction of plastic model of prestressed segmented spherical shel

Development of a HgCdTe photomixer and impedance matched GaAs FET amplifier

A research program for the development of a 10.6 micron HgCdTe photodiode/GaAs field effect transistor amplifier package for use at cryogenic temperatures (77k). The photodiode/amplifier module achieved a noise equivalent power per unit bandwidth of 5.7 times 10 to the 20th power W/Hz at 2.0 GHz. The heterodyne sensitivity of the HgCdTe photodiode was improved by designing and building a low noise GaAs field effect transistor amplifier operating at 77K. The Johnson noise of the amplifier was reduced at 77K, and thus resulted in an increased photodiode heterodyne sensitivity

Fitness benefits of prolonged post-reproductive lifespan in women

Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction

High‐Frequency Dissolved Organic Carbon and Nitrate Measurements Reveal Differences in Storm Hysteresis and Loading in Relation to Land Cover and Seasonality

Storm events dominate riverine loads of dissolved organic carbon (DOC) and nitrate and are expected to increase in frequency and intensity in many regions due to climate change. We deployed three high‐frequency (15 min) in situ absorbance spectrophotometers to monitor DOC and nitrate concentration for 126 storms in three watersheds with agricultural, urban, and forested land use/land cover. We examined intrastorm hysteresis and the influences of seasonality, storm size, and dominant land use/land cover on storm DOC and nitrate loads. DOC hysteresis was generally anticlockwise at all sites, indicating distal and plentiful sources for all three streams despite varied DOC character and sources. Nitrate hysteresis was generally clockwise for urban and forested sites, but anticlockwise for the agricultural site, indicating an exhaustible, proximal source of nitrate in the urban and forested sites, and more distal and plentiful sources of nitrate in the agricultural site. The agricultural site had significantly higher storm nitrate yield per water yield and higher storm DOC yield per water yield than the urban or forested sites. Seasonal effects were important for storm nitrate yield in all three watersheds and farm management practices likely caused complex interactions with seasonality at the agricultural site. Hysteresis indices did not improve predictions of storm nitrate yields at any site. We discuss key lessons from using high‐frequency in situ optical sensors

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Gender shift in realisation of preferred type of gp practice: longitudinal survey over the last 25 years

<p>Abstract</p> <p>Background</p> <p>An increasing number of newly trained Dutch GPs prefer to work in a group practice and as a non-principal rather than in a single-handed practice. In view of the greater number of female doctors, changing practice preferences, and discussions on future workforce problems, the question is whether male and female GPs were able to realise their initial preferences in the past and will be able to do so in the future.</p> <p>Methods</p> <p>We have conducted longitudinal cohort study of all GPs in the Netherlands seeking a practice between 1980 and 2004. The Netherlands Institute of Health Services Research (NIVEL) in Utrecht collected the data used in this study by means of a postal questionnaire. The overall mean response rate was 94%.</p> <p>Results</p> <p>Over the past 20 years, an increasing proportion of GPs, both male and female, were able to achieve their preference for working in a group practice and/or in a non-principal position. Relatively more women than men have settled in group practices, and more men than women in single-handed practices; however, the practice preference of men and women is beginning to converge. Dropout was highest among the GPs without any specific practice preference.</p> <p>Conclusion</p> <p>The overwhelming preference of male and female GPs for working in group practices is apparently being met by the number of positions (principal or non-principal) available in group practices. The preference of male and female GPs regarding the type of practice and job conditions is expected to converge further in the near future.</p

An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

<p>Abstract</p> <p>Background</p> <p>The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A_2Aadenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.</p> <p>Methods</p> <p>Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (<it>Escherichia coli </it>or <it>Staphylococcus aureus</it>) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A_2AAR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days.</p> <p>Results</p> <p>There was a significant survival benefit in mice infected with live <it>E. coli </it>(100% vs. 20%, <it>p </it>= 0.013) or <it>S. aureus </it>(60% vs. 20%, <it>p </it>= 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, <it>p </it>= 0.005). The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (<it>p </it>< 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (<it>p </it>< 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.</p

Identification of pediatric septic shock subclasses based on genome-wide expression profiling

<p>Abstract</p> <p>Background</p> <p>Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling.</p> <p>Methods</p> <p>Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization.</p> <p>Results</p> <p>Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, <it>P </it>< 0.05) identified 6,934 differentially regulated genes. K-means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the three subclasses. Leave one out cross-validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C.</p> <p>Conclusion</p> <p>Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.</p

A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans

The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans