317 research outputs found
The Interdependent Relationship of a Free Press and an Independent Judiciary in a Constitutional Democracy
For nearly 240 years, we have recognized, at least constitutionally, that it is essential to the very existence of a constitutional democracy that there be an independent judiciary and a free press. What is not often appreciated is how dependent these two vital institutions are upon each other. Certainly, judges and journalists rarely think in such terms. But events occurring at home and around the world in fledgling and failing democracies should heighten our awareness and appreciation for their interdependence, and help us better understand the liberties and fundamental rights they protect
Quantification of Training and Competition Load Across a Season in an Elite Australian Football Club.
Changes in anthropometry, upper-body strength, and nutrient intake in professional Australian football players during a season
©2016 Human Kinetics,Inc. The purpose of this study was to examine the seasonal changes in body composition, nutrition, and upper-body (UB) strength in professional Australian Football (AF) players. The prospective longitudinal study examined changes in anthropometry (body mass, fat-free soft-tissue mass [FFSTM], and fat mass) via dual-energy X-ray absorptiometry 5 times during an AF season (start preseason, midpreseason, start season, midseason, end season) in 45 professional AF players. Dietary intakes and strength (bench press and bench pull) were also assessed at these time points. Players were categorized as experienced (>4 y experience, n = 23) or inexperienced (1 y to develop the appropriate levels of FFSTM in young players and take a long-term view when developing the physical and performance abilities of inexperienced players
Oxysterol-Binding Protein-1 (OSBP1) Modulates Processing and Trafficking of the Amyloid Precursor Protein
BACKGROUND
Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived ligands of the liver X receptors (LXRs) and oxysterol binding proteins, strongly regulate the processing of amyloid precursor protein (APP). Although LXRs have been studied extensively, little is known about the biology of oxysterol binding proteins. Oxysterol-binding protein 1 (OSBP1) is a member of a family of sterol-binding proteins with roles in lipid metabolism, regulation of secretory vesicle generation and signal transduction, and it is thought that these proteins may act as sterol sensors to control a variety of sterol-dependent cellular processes.
RESULTS
We investigated whether OSBP1 was involved in regulating APP processing and found that overexpression of OSBP1 downregulated the amyloidogenic processing of APP, while OSBP1 knockdown had the opposite effect. In addition, we found that OSBP1 altered the trafficking of APP-Notch2 dimers by causing their accumulation in the Golgi, an effect that could be reversed by treating cells with OSBP1 ligand, 25-hydroxycholesterol.
CONCLUSION
These results suggest that OSBP1 could play a role in linking cholesterol metabolism with intracellular APP trafficking and Aβ production, and more importantly indicate that OSBP1 could provide an alternative target for Aβ-directed therapeutic.National Institute on Aging (AG/NS17485
Probabilistic Model Checking for Energy Analysis in Software Product Lines
In a software product line (SPL), a collection of software products is
defined by their commonalities in terms of features rather than explicitly
specifying all products one-by-one. Several verification techniques were
adapted to establish temporal properties of SPLs. Symbolic and family-based
model checking have been proven to be successful for tackling the combinatorial
blow-up arising when reasoning about several feature combinations. However,
most formal verification approaches for SPLs presented in the literature focus
on the static SPLs, where the features of a product are fixed and cannot be
changed during runtime. This is in contrast to dynamic SPLs, allowing to adapt
feature combinations of a product dynamically after deployment. The main
contribution of the paper is a compositional modeling framework for dynamic
SPLs, which supports probabilistic and nondeterministic choices and allows for
quantitative analysis. We specify the feature changes during runtime within an
automata-based coordination component, enabling to reason over strategies how
to trigger dynamic feature changes for optimizing various quantitative
objectives, e.g., energy or monetary costs and reliability. For our framework
there is a natural and conceptually simple translation into the input language
of the prominent probabilistic model checker PRISM. This facilitates the
application of PRISM's powerful symbolic engine to the operational behavior of
dynamic SPLs and their family-based analysis against various quantitative
queries. We demonstrate feasibility of our approach by a case study issuing an
energy-aware bonding network device.Comment: 14 pages, 11 figure
SimNav: Simulink navigation of model clone classes
SimNav is a GUI designed for displaying and navigating clone classes of Simulink models detected by the model clone detector Simone. As an embedded Simulink interface tool, SimNav allows model developers to explore detected clones directly in their own model development environment rather than a separate research tool interface. SimNav allows users to open selected models for side-by-side comparison, in order to visually explore clone classes and view the differences in the clone instances, as well as to explore the context in which the clones exist. This tool paper describes the motivation, implementation, and use cases for SimNav
High prevalence of Plasmodium falciparum gametocyte infections in school-age children using molecular detection: patterns and predictors of risk from a cross-sectional study in southern Malawi
Abstract
Background
In endemic areas, many people experience asymptomatic Plasmodium infections, particularly older children and adults, but their transmission contribution is unknown. Though not the exclusive determinant of infectiousness, transmission from humans to mosquitoes requires blood meals containing gametocytes. Gametocytes often occur at submicroscopic densities, challenging measurement in human populations. More sensitive molecular techniques allow better characterization of gametocyte epidemiologic patterns.
Methods
Approximately 30 households were selected from each of eight sites in southern Malawi during two cross-sectional surveys. Blood was sampled from 623 people during the dry season and 896 the following rainy season. Among people PCR-positive for Plasmodium falciparum, mature gametocytes were detected by qRT-PCR. Regression models evaluated predictors of gametocyte carriage and density in the total population and among those with PCR-positive infections.
Results
The prevalence of gametocyte carriage by molecular testing was 3.5% during the dry season and 8.6% during the rainy season, and by microscopy 0.8 and 3.3%, respectively. Nearly half of PCR-positive infections carried gametocytes, regardless of recent symptom status. Among P. falciparum-infected people, only living in unfinished houses and age were significantly associated with gametocyte presence. Infected people in unfinished houses had higher odds of carrying gametocytes (OR 2.24, 95% CI 1.16–4.31), and 31% (95% CI 3–65%) higher gametocyte density than those in finished houses. School-age children (5–15 years), had higher odds than adults (≥16 years) of having gametocytes when infected (OR 2.77, 95% CI 1.47–5.19), but 31% (95% CI 11–47%) lower gametocyte density. Children <5 years did not have significantly higher odds of gametocyte carriage or density when infected than adults.
Conclusions
School-age children frequently carry gametocytes in communities of southern Malawi and represent an under-recognized reservoir of infection. Malaria elimination strategies should address these frequently asymptomatic reservoirs, especially in highly endemic areas. Improved household construction may also reduce the infectious reservoir.http://deepblue.lib.umich.edu/bitstream/2027.42/134670/1/12936_2016_Article_1587.pd
Intranasal Administration as a Route for Drug Delivery to the Brain: Evidence for a Unique Pathway for Albumin
A variety of compounds will distribute into the brain when placed at the cribriform plate by intranasal (i.n.) administration. In this study, we investigated the ability of albumin, a protein that can act as a drug carrier but is excluded from brain by the blood-brain barrier, to distribute into the brain after i.n. administration. We labeled bovine serum albumin with [125I] ([125I]Alb) and studied its uptake into 11 brain regions and its entry into the blood from 5 minutes to 6 hours after i.n. administration. [125I]Alb was present throughout the brain at 5 minutes. Several regions showed distinct peaks in uptake that ranged from 5 minutes (parietal cortex) to 60 minutes (midbrain). About 2–4% of the i.n. [125I]Alb entered the bloodstream. The highest levels occurred in the olfactory bulb and striatum. Distribution was dose-dependent, with less taken up by whole brain, cortex, and blood at the higher dose of albumin. Uptake was selectively increased into the olfactory bulb and cortex by the fluid-phase stimulator PMA (phorbol 12-myristate 13-acetate), but inhibitors to receptor-mediated transcytosis, caveolae, and phosphoinositide 3-kinase were without effect. Albumin altered the distribution of radioactive leptin given by i.n. administration, decreasing uptake into the blood and by the cerebellum and increasing uptake by the hypothalamus. We conclude that [125I]Alb administered i.n. reaches all parts of the brain through a dose-dependent mechanism that may involve fluid-phase transcytosis and, as illustrated by leptin, can affect the delivery of other substances to the brain after their i.n. administration
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