Dissecting the genetic components of a quantitative trait locus for blood pressure and renal pathology on rat chromosome 3

Background: We have previously confirmed the importance of rat chromosome 3 (RNO3) genetic loci on blood pressure elevation, pulse pressure (PP) variability and renal pathology during salt challenge in the stroke-prone spontaneously hypertensive (SHRSP) rat. The aims of this study were to generate a panel of RNO3 congenic sub-strains to genetically dissect the implicated loci and identify positional candidate genes by microarray expression profiling and analysis of next-generation sequencing data. Method and results: A panel of congenic sub-strains were generated containing Wistar-Kyoto (WKY)-introgressed segments of varying size on the SHRSP genetic background, focused within the first 50 Mbp of RNO3. Haemodynamic profiling during salt challenge demonstrated significantly reduced systolic blood pressure, diastolic blood pressure and PP variability in SP.WKYGla3a, SP.WKYGla3c, SP.WKYGla3d and SP.WKYGla3e sub-strains. Only SBP and DBP were significantly reduced during salt challenge in SP.WKYGla3b and SP.WKYGla3f sub-strains, whereas SP.WKYGla3g rats did not differ in haemodynamic response to SHRSP. Those sub-strains demonstrating significantly reduced PP variability during salt challenge also demonstrated significantly reduced renal pathology and proteinuria. Microarray expression profiling prioritized two candidate genes for blood pressure regulation (Dnm1, Tor1b), localized within the common congenic interval shared by SP.WKYGla3d and SP.WKYGla3f strains, and one candidate gene for salt-induced PP variability and renal pathology (Rabgap1), located within the region unique to the SP.WKYGla3d strain. Comparison of next-generation sequencing data identified variants within additional positional genes that are likely to affect protein function. Conclusion: This study has identified distinct intervals on RNO3-containing genes that may be important for blood pressure regulation and renal pathology during salt challenge

Numerical simulations of a two-dimensional lattice grain boundary model

We present detailed Monte Carlo results for a two-dimensional grain boundary model on a lattice. The effective Hamiltonian of the system results from the microscopic interaction of grains with orientations described by spins of unit length, and leads to a nearest-neighbour interaction proportional to the absolute value of the angle between the grains. Our analysis of the correlation length xi and susceptibility chi in the high-temperature phase favour a Kosterlitz-Thouless-like (KT) singularity over a second-order phase transition. Unconstrained KT fits of chi and xi confirm the predicted value for the critical exponent nu, while the values of eta deviate from the theoretical prediction. Additionally we apply finite-size scaling theory and investigate the question of multiplicative logarithmic corrections to a KT transition. As for the critical exponents our results are similar to data obtained from the XY model, so that both models probably lie in the same universality class.Comment: 13 pages, Latex, 7 figures, to appear in Physica

Predicting Ebola Severity: A Clinical Prioritization Score for Ebola Virus Disease.

Despite the notoriety of Ebola virus disease (EVD) as one of the world's most deadly infections, EVD has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. With increasingly sensitive EVD diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment. This retrospective cohort study analyses the clinical characteristics of 158 EVD(+) patients at the GOAL-Mathaska Ebola Treatment Centre, Sierra Leone. The prognostic potential of each characteristic was assessed and incorporated into a statistically weighted disease score. The mortality rate among EVD(+) patients was 60.8% and highest in those aged <5 or >25 years (p<0.05). Death was significantly associated with malaria co-infection (OR = 2.5, p = 0.01). However, this observation was abrogated after adjustment to Ebola viral load (p = 0.1), potentially indicating a pathologic synergy between the infections. Similarly, referral-time interacted with viral load, and adjustment revealed referral-time as a significant determinant of mortality, thus quantifying the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Disorientation was the strongest unadjusted predictor of death (OR = 13.1, p = 0.014) followed by hiccups, diarrhoea, conjunctivitis, dyspnoea and myalgia. Including these characteristics in multivariate prognostic scores, we obtained a 91% and 97% ability to discriminate death at or after triage respectively (area under ROC curve). This study proposes highly predictive and easy-to-use prognostic tools, which stratify the risk of EVD mortality at or after EVD triage

Predicting Ebola infection: A malaria-sensitive triage score for Ebola virus disease.

The non-specific symptoms of Ebola Virus Disease (EVD) pose a major problem to triage and isolation efforts at Ebola Treatment Centres (ETCs). Under the current triage protocol, half the patients allocated to high-risk "probable" wards were EVD(-): a misclassification speculated to predispose nosocomial EVD infection. A better understanding of the statistical relevance of individual triage symptoms is essential in resource-poor settings where rapid, laboratory-confirmed diagnostics are often unavailable. This retrospective cohort study analyses the clinical characteristics of 566 patients admitted to the GOAL-Mathaska ETC in Sierra Leone. The diagnostic potential of each characteristic was assessed by multivariate analysis and incorporated into a statistically weighted predictive score, designed to detect EVD as well as discriminate malaria. Of the 566 patients, 28% were EVD(+) and 35% were malaria(+). Malaria was 2-fold more common in EVD(-) patients (p<0.05), and thus an important differential diagnosis. Univariate analyses comparing EVD(+) vs. EVD(-) and EVD(+)/malaria(-) vs. EVD(-)/malaria(+) cohorts revealed 7 characteristics with the highest odds for EVD infection, namely: reported sick-contact, conjunctivitis, diarrhoea, referral-time of 4-9 days, pyrexia, dysphagia and haemorrhage. Oppositely, myalgia was more predictive of EVD(-) or EVD(-)/malaria(+). Including these 8 characteristics in a triage score, we obtained an 89% ability to discriminate EVD(+) from either EVD(-) or EVD(-)/malaria(+). This study proposes a highly predictive and easy-to-use triage tool, which stratifies the risk of EVD infection with 89% discriminative power for both EVD(-) and EVD(-)/malaria(+) differential diagnoses. Improved triage could preserve resources by identifying those in need of more specific differential diagnostics as well as bolster infection prevention/control measures by better compartmentalizing the risk of nosocomial infection

Environmental and behavioural drivers of Antarctic krill distribution at the South Orkney Islands: A regional perspective

Antarctic krill (Euphausia superba) is a key species in the marine ecosystem of the Southern Ocean, but is also the target of a commercial fishery, with an important fishing ground in the South Orkney Islands region. The potential for competition for krill between predators and the fishery requires risk management strategies for the fishery, underpinned by an understanding of the key physical and behavioural drivers of krill movement and retention in target areas. Here, we present the results of a regional modelling study, combining a high-resolution ocean-sea ice model and an individual-based model parameterised for krill, to elucidate the roles of oceanographic variability and krill behaviour on patterns of transport and retention on and around the South Orkney Plateau. Simulations suggest that oceanic transport from sources around the Antarctic Peninsula is restricted by the northward flowing Antarctic Slope Current. Around the South Orkney Plateau, anticyclonic flows associated with the Weddell Front and the shelf edge transport krill rapidly towards the main fishing grounds to the northwest of the plateau. Transport onto the shelf and subsequent retention are influenced by the strength and direction of regional winds; weaker on-shelf transport and shorter retention times are associated with stronger westerly and northerly winds. The incorporation of sea-ice associated behaviour, whereby krill are moved with sea ice when sea ice is present, significantly modifies the patterns from purely oceanic transport; it reduces the influence of strong regional oceanic flows and increases transport of krill to the South Orkneys region from the Antarctic Peninsula. The inclusion of diel vertical migration also modifies predicted patterns from oceanic transport, but to a lesser extent, and moderates the impact of including sea-ice associated behaviour. We highlight the importance of understanding the behaviour of krill, including age-dependent behavioural changes in response to sea ice conditions, for modelling and management of Antarctic krill populations

The Influences of Diesel Particulate Filter Installation on Air Pollutant Emissions for Used Vehicles

Three kinds of diesel particulate filters (DPFs) were installed on used diesel-powered vehicles to investigate their influences on air pollutant emissions. The air pollutant emissions were measured before, after and running for specific distances to assess the deterioration effect. The emission measurement was performed on a chassis dynamometer. The results show that emissions of smoke, CO and HC are all reduced after DPF installation. After 20000 km driving, the emission concentrations of the above 3 criteria air pollutants do not increase in comparison with that right after installation. When DPFs are installed, the emissions of PAHs (polycyclic aromatic hydrocarbons) are reduced by 85.6-89.4% and 69.0-89.2% for heavy-duty diesel vehicles (HDVs) and light-duty diesel vehicles (LDVs), respectively. After driving 20000 km for HDVs and 2500 km for LDVs, PAH emissions do not increase in comparison with that right after installation, indicating that the DPFs do not deteriorate after driving for the test mileages. The lower molecular weight PAHs predominates in the exhaust both before and after DPF installation. The results also show the reduction rate is higher for higher molecular weight PAHs due to their tendency to adsorb on particulate

Quantum-fluctuation-induced collisions and subsequent excitation gap of an elastic string between walls

An elastic string embedded between rigid walls is simulated by means of the density-matrix renormalization group. The string collides against the walls owing to the quantum-mechanical zero-point fluctuations. Such ``quantum entropic'' interaction has come under thorough theoretical investigation in the context of the stripe phase observed experimentally in doped cuprates. We found that the excitation gap opens in the form of exponential singularity DeltaE ~ exp(-Ad^sigma) (d: wall spacing) with the exponent sigma =0.6(3), which is substantially smaller than the meanfield value sigma=2. That is, the excitation gap is much larger than that anticipated from meanfield, suggesting that the string is subjected to robust pinning potential due to the quantum collisions. This feature supports Zaanen's ``order out of disorder'' mechanism which would be responsible to the stabilization of the stripe phase

Expression of human apolipoprotein B100 in transgenic mice. Editing of human apolipoprotein B100 mRNA

Apolipoprotein B (apoB) is a large glycoprotein that circulates in plasma as a major constituent of numerous lipoproteins. ApoB exists in two forms: apoB48 and apoB100. ApoB48 is identical in sequence to the N-terminal region of apoB100 and is generated by sequence-specific mRNA editing of the apoB100 transcript. Here, we describe the development of a line of mice expressing a human apoB transgene driven by promoter/enhancer sequences from the transthyretin gene. In these mice, immunodetectable human apoB100 is synthesized by the liver, kidney, and brain. Human apoB100 is found in low concentration (approximately 0.1 mg/dl) in the plasma of the transgenic mice and circulates in the low density lipoprotein fraction. The hepatic human apoB100 transcripts undergo mRNA editing at only slightly lower efficiency than the endogenous mouse apoB100 message. Therefore, there is no absolute species specificity to the apoB100 mRNA editing process

Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a)

The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants, \u3b2-VLDL, LDL, oxidized LDL, and Lp(a)]. Here we describe the development of transgenic mice expressing high levels of human apo-B48 and apo-B100. A 79.5-kb human genomic DNA fragment containing the entire human apo-B gene was isolated from a P1 bacteriophage library and microinjected into fertilized mouse eggs. 16 transgenic founders expressing human apo-B were generated, and the animals with the highest expression had plasma apo-B100 levels nearly as high as those of normolipidemic humans ( 3c50 mg/dl). The human apo-B100 in transgenic mouse plasma was present largely in lipoproteins of the LDL class as shown by agarose gel electrophoresis, chromatography on a Superose 6 column, and density gradient ultracentrifugation. When the human apo-B transgenic founders were crossed with transgenic mice expressing human apo(a), the offspring that expressed both transgenes had high plasma levels of human Lp(a). Both the human apo-B and Lp(a) transgenic mice will be valuable resources for studying apo-B metabolism and the role of apo-B and Lp(a) in atherosclerosis

Azimuthal Correlations in the Target Fragmentation Region of High Energy Nuclear Collisions

Results on the target mass dependence of proton and pion pseudorapidity distributions and of their azimuthal correlations in the target rapidity range $-1.73 \le \eta \le 1.32$ are presented. The data have been taken with the Plastic-Ball detector set-up for 4.9 GeV p + Au collisions at the Berkeley BEVALAC and for 200 $A\cdot$GeV/$c$ p-, O-, and S-induced reactions on different nuclei at the CERN-SPS. The yield of protons at backward rapidities is found to be proportional to the target mass. Although protons show a typical ``back-to-back'' correlations, a ``side-by-side'' correlation is observed for positive pions, which increases both with target mass and with impact parameter of a collision. The data can consistently be described by assuming strong rescattering phenomena including pion absorption effects in the entire excited target nucleus.Comment: 7 pages, figures included, complete postscript available at ftp://qgp.uni-muenster.de/pub/paper/azi-correlations.ps submitted to Phys. Lett.