The Beginning and Evolution of the Universe

We review the current standard model for the evolution of the Universe from an early inflationary epoch to the complex hierarchy of structure seen today. We summarize and provide key references for the following topics: observations of the expanding Universe; the hot early Universe and nucleosynthesis; theory and observations of the cosmic microwave background; Big Bang cosmology; inflation; dark matter and dark energy; theory of structure formation; the cold dark matter model; galaxy formation; cosmological simulations; observations of galaxies, clusters, and quasars; statistical measures of large-scale structure; and measurement of cosmological parameters. We conclude with discussion of some open questions in cosmology. This review is designed to provide a graduate student or other new worker in the field an introduction to the cosmological literature.Comment: 69 pages. Invited review article for Publications of the Astronomical Society of the Pacific. Supplementary references, tables, and more concise PDF file at http://www.physics.drexel.edu/univers

Exploring types of focused factories in hospital care: a multiple case study

Background: Focusing on specific treatments or diseases is proposed as a way to increase the efficiency of hospital care. The definition of "focus" or "focused factory", however, lacks clarity. Examples in health care literature relate to very different organizations.\ud Our aim was to explore the application of the focused factory concept in hospital care, including an indication of its performance, resulting in a conceptual framework that can be helpful in further identifying different types of focused factories. Thus contributing to the understanding of the diversity of examples found in the literature. - \ud \ud Methods: We conducted a cross-case comparison of four multiple-case studies into hospital care. To cover a broad array of focus, different specialty fields were selected. Each study investigated the organizational context, the degree of focus, and the operational performance. Focus was measured using an instrument translated from industry. Data were collected using both qualitative and quantitative methods and included site visits. A descriptive analysis was performed at the case study and cross-case studies level. - \ud \ud Results: The operational performance per specialty field varied considerably, even when cases showed comparable degrees of focus. Cross-case comparison showed three focus domains. The product domain considered specialty based focused factories that treated patients for a single-specialty, but did not pursue a specific strategy nor adapted work-designs or layouts. The process domain considered delivery based focused factories that treated multiple groups of patients and often pursued strategies to improve efficiency and timeliness and adapted work-designs and physical layouts to minimize delays. The product-process domain considered procedure based focused factories that treated a single well-defined group of patients offering one type of treatment. The strategic focusing decisions and the design of the care delivery system appeared especially important for delivery and procedure based focused factories. - \ud \ud Conclusions: Focus in hospital care relates to limitations on the patient group treated and the range of services offered. Based on these two dimensions, we identified three types of focused factories: specialty based, delivery based, and procedure based. Focus could lead to better operational performance, but only when clear strategic focusing decisions are made

Cyr61/CCN1 Displays High-Affinity Binding to the Somatomedin B 1–44 Domain of Vitronectin

OV) family of extracellular-associated (matricellular) proteins that present four distinct functional modules, namely insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C (vWF), thrombospondin type 1 (TSP), and C-terminal growth factor cysteine knot (CT) domain. While heparin sulphate proteoglycans reportedly mediate the interaction of Cyr61 with the matrix and cell surface, the role of other extracellular associated proteins has not been revealed. at high concentrations attenuate Cyr61 binding to immobilized VTNC, while monomeric VTNC was ineffective. Therefore, immobilization of VTNC exposes cryptic epitopes that recognize Cyr61 with high affinity, as reported for a number of antibodies, β-endorphin, and other molecules. domain suggests that VTNC represent a point of anchorage for CCN family members to the matrix. Results are discussed in the context of the role of CCN and VTNC in matrix biology and angiogenesis

"Sleep disparity" in the population: poor sleep quality is strongly associated with poverty and ethnicity

<p>Abstract</p> <p>Background</p> <p>Little is known about the social determinants of sleep attainment. This study examines the relationship of race/ethnicity, socio-economic status (SES) and other factors upon sleep quality.</p> <p>Methods</p> <p>A cross-sectional survey of 9,714 randomly selected subjects was used to explore sleep quality obtained by self-report, in relation to socioeconomic factors including poverty, employment status, and education level. The primary outcome was poor sleep quality. Data were collected by the Philadelphia Health Management Corporation.</p> <p>Results</p> <p>Significant differences were observed in the outcome for race/ethnicity (African-American and Latino versus White: unadjusted OR = 1.59, 95% CI 1.24-2.05 and OR = 1.65, 95% CI 1.37-1.98, respectively) and income (below poverty threshold, unadjusted OR = 2.84, 95%CI 2.41-3.35). In multivariable modeling, health indicators significantly influenced sleep quality most prominently in poor individuals. After adjusting for socioeconomic factors (education, employment) and health indicators, the association of income and poor sleep quality diminished, but still persisted in poor Whites while it was no longer significant in poor African-Americans (adjusted OR = 1.95, 95% CI 1.47-2.58 versus OR = 1.16, 95% CI 0.87-1.54, respectively). Post-college education (adjusted OR = 0.47, 95% CI 0.31-0.71) protected against poor sleep.</p> <p>Conclusions</p> <p>A "sleep disparity" exists in the study population: poor sleep quality is strongly associated with poverty and race. Factors such as employment, education and health status, amongst others, significantly mediated this effect only in poor subjects, suggesting a differential vulnerability to these factors in poor relative to non-poor individuals in the context of sleep quality. Consideration of this could help optimize targeted interventions in certain groups and subsequently reduce the adverse societal effects of poor sleep.</p

Detection and elimination of cellular bottlenecks in protein-producing yeasts

Yeasts are efficient cell factories and are commonly used for the production of recombinant proteins for biopharmaceutical and industrial purposes. For such products high levels of correctly folded proteins are needed, which sometimes requires improvement and engineering of the expression system. The article summarizes major breakthroughs that led to the efficient use of yeasts as production platforms and reviews bottlenecks occurring during protein production. Special focus is given to the metabolic impact of protein production. Furthermore, strategies that were shown to enhance secretion of recombinant proteins in different yeast species are presented

Genetic Signatures in the Envelope Glycoproteins of HIV-1 that Associate with Broadly Neutralizing Antibodies

A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env) is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen that elicits broadly neutralizing antibodies. To help bridge this gap, we used phylogenetically corrected statistical methods to identify amino acid signature patterns in Envs derived from people who have made potently neutralizing antibodies, with the hypothesis that these Envs may share common features that would be useful for incorporation in a vaccine immunogen. Before attempting this, essentially as a control, we explored the utility of our computational methods for defining signatures of complex neutralization phenotypes by analyzing Env sequences from 251 clonal viruses that were differentially sensitive to neutralization by the well-characterized gp120-specific monoclonal antibody, b12. We identified ten b12-neutralization signatures, including seven either in the b12-binding surface of gp120 or in the V2 region of gp120 that have been previously shown to impact b12 sensitivity. A simple algorithm based on the b12 signature pattern was predictive of b12 sensitivity/resistance in an additional blinded panel of 57 viruses. Upon obtaining these reassuring outcomes, we went on to apply these same computational methods to define signature patterns in Env from HIV-1 infected individuals who had potent, broadly neutralizing responses. We analyzed a checkerboard-style neutralization dataset with sera from 69 HIV-1-infected individuals tested against a panel of 25 different Envs. Distinct clusters of sera with high and low neutralization potencies were identified. Six signature positions in Env sequences obtained from the 69 samples were found to be strongly associated with either the high or low potency responses. Five sites were in the CD4-induced coreceptor binding site of gp120, suggesting an important role for this region in the elicitation of broadly neutralizing antibody responses against HIV-1

Global patterns and drivers of ecosystem functioning in rivers and riparian zones

River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.peerReviewe