Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology

Characterisation of large changes in wind power for the day-ahead market using a fuzzy logic approach

Wind power has become one of the renewable resources with a major growth in the electricity market. However, due to its inherent variability, forecasting techniques are necessary for the optimum scheduling of the electric grid, specially during ramp events. These large changes in wind power may not be captured by wind power point forecasts even with very high resolution Numerical Weather Prediction (NWP) models. In this paper, a fuzzy approach for wind power ramp characterisation is presented. The main benefit of this technique is that it avoids the binary definition of ramp event, allowing to identify changes in power out- put that can potentially turn into ramp events when the total percentage of change to be considered a ramp event is not met. To study the application of this technique, wind power forecasts were obtained and their corresponding error estimated using Genetic Programming (GP) and Quantile Regression Forests. The error distributions were incorporated into the characterisation process, which according to the results, improve significantly the ramp capture. Results are presented using colour maps, which provide a useful way to interpret the characteristics of the ramp events

Discrimination Training with Multimodal Stimuli Changes Activity in the Mushroom Body of the Hawkmoth Manduca sexta

The mushroom bodies of the insect brain play an important role in olfactory processing, associative learning and memory. The mushroom bodies show odor-specific spatial patterns of activity and are also influenced by visual stimuli.Functional imaging was used to investigate changes in the in vivo responses of the mushroom body of the hawkmoth Manduca sexta during multimodal discrimination training. A visual and an odour stimulus were presented either together or individually. Initially, mushroom body activation patterns were identical to the odour stimulus and the multimodal stimulus. After training, however, the mushroom body response to the rewarded multimodal stimulus was significantly lower than the response to the unrewarded unimodal odour stimulus, indicating that the coding of the stimuli had changed as a result of training. The opposite pattern was seen when only the unimodal odour stimulus was rewarded. In this case, the mushroom body was more strongly activated by the multimodal stimuli after training. When no stimuli were rewarded, the mushroom body activity decreased for both the multimodal and unimodal odour stimuli. There was no measurable response to the unimodal visual stimulus in any of the experiments. These results can be explained using a connectionist model where the mushroom body is assumed to be excited by olfactory stimulus components, and suppressed by multimodal configurations.Discrimination training with multimodal stimuli consisting of visual and odour cues leads to stimulus specific changes in the in vivo responses of the mushroom body of the hawkmoth

High-temperature performance of ferritic steels in fireside corrosion regimes: temperature and deposits

The paper reports high temperature resistance of ferritic steels in fireside corrosion regime in terms of temperature and deposits aggressiveness. Four candidate power plant steels: 15Mo3, T22, T23 and T91 were exposed under simulated air-fired combustion environment for 1000 h. The tests were conducted at 600, 650 and 700 °C according to deposit-recoat test method. Post-exposed samples were examined via dimensional metrology (the main route to quantify metal loss), and mass change data were recorded to perform the study of kinetic behavior at elevated temperatures. Microstructural investigations using ESEM-EDX were performed in order to investigate corrosion degradation and thickness of the scales. The ranking of the steels from most to the least damage was 15Mo3 > T22 > T23 > T91 in all three temperatures. The highest rate of corrosion in all temperatures occurred under the screening deposit

Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern

<p>Abstract</p> <p>Background</p> <p>Initial assessment of dyspepsia often includes noninvasive testing for <it>Helicobacter pylori </it>infection. Commercially available tests vary widely in cost and accuracy. Although there is extensive literature on the cost-effectiveness of <it>H. pylori </it>treatment, there is little information comparing the cost-effectiveness of various currently used, noninvasive testing strategies.</p> <p>Methods</p> <p>A Markov simulation was used to calculate cost per symptom-free year and cost per correct diagnosis. Uncertainty in outcomes was estimated using probabilistic sensitivity analysis.</p> <p>Results</p> <p>Under the baseline assumptions, cost per symptom-free year was $122 for empiric proton pump inhibitor (PPI) trial, and costs for the noninvasive test strategies ranged from$123 (stool antigen) to $129 (IgG/IgA combined serology). Confidence intervals had significant overlap.</p> <p>Conclusions</p> <p>Under our assumptions for how testing for <it>H. pylori </it>infection is employed in United States medical practice, the available noninvasive tests all have similar cost-effectiveness between one another as well as with empiric PPI trial.</p

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Barrier dysfunction or drainage reduction: differentiating causes of CSF protein increase

BACKGROUND Cerebrospinal fluid (CSF) protein analysis is an important element in the diagnostic chain for various central nervous system (CNS) pathologies. Among multiple existing approaches to interpreting measured protein levels, the Reiber diagram is particularly robust with respect to physiologic inter-individual variability, as it uses multiple subject-specific anchoring values. Beyond reliable identification of abnormal protein levels, the Reiber diagram has the potential to elucidate their pathophysiologic origin. In particular, both reduction of CSF drainage from the cranio-spinal space as well as blood-CNS barrier dysfunction have been suggested ρas possible causes of increased concentration of blood-derived proteins. However, there is disagreement on which of the two is the true cause. METHODS We designed two computational models to investigate the mechanisms governing protein distribution in the spinal CSF. With a one-dimensional model, we evaluated the distribution of albumin and immunoglobulin G (IgG), accounting for protein transport rates across blood-CNS barriers, CSF dynamics (including both dispersion induced by CSF pulsations and advection by mean CSF flow) and CSF drainage. Dispersion coefficients were determined a priori by computing the axisymmetric three-dimensional CSF dynamics and solute transport in a representative segment of the spinal canal. RESULTS Our models reproduce the empirically determined hyperbolic relation between albumin and IgG quotients. They indicate that variation in CSF drainage would yield a linear rather than the expected hyperbolic profile. In contrast, modelled barrier dysfunction reproduces the experimentally observed relation. CONCLUSIONS High levels of albumin identified in the Reiber diagram are more likely to originate from a barrier dysfunction than from a reduction in CSF drainage. Our in silico experiments further support the hypothesis of decreasing spinal CSF drainage in rostro-caudal direction and emphasize the physiological importance of pulsation-driven dispersion for the transport of large molecules in the CSF

Genotyping of Bacillus cereus Strains by Microarray-Based Resequencing

The ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. In this regard, Bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the B. cereus group that can cause diverse diseases. We employed custom-designed resequencing arrays (RAs) based on the genome sequence of Bacillus anthracis to generate 422 kb of genomic sequence from a panel of 41 Bacillus cereus sensu lato strains. Here we show that RAs represent a “one reaction” genotyping technology with the ability to discriminate between highly similar B. anthracis isolates and more divergent strains of the B. cereus s.l. Clade 1. Our data show that RAs can be an efficient genotyping technology for pre-screening the genetic diversity of large strain collections to selected the best candidates for whole genome sequencing

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

HER1-Targeted 86Y-Panitumumab Possesses Superior Targeting Characteristics than 86Y-Cetuximab for PET Imaging of Human Malignant Mesothelioma Tumors Xenografts

Malignant mesothelioma (MM), a rare form of cancer is often associated with previous exposure to fibrous minerals, such as asbestos. Asbestos exposure increases HER1-activity and expression in pre-clinical models. Additionally, HER1 over-expression is observed in the majority of MM cases. In this study, the utility of HER1-targeted chimeric IgG(1), cetuximab, and a human IgG(2), panitumumab, radiolabeled with (86)Y, were evaluated for PET imaging to detect MM non-invasively in vivo, and to select an antibody candidate for radioimmunotherapy (RIT).Radioimmunoconjugates (RICs) of cetuximab and panitumumab were prepared by conjugation with CHX-A''-DTPA followed by radiolabeling with (86)Y. The HER1 expression of NCI-H226, NCI-H2052, NCI-H2452 and MSTO-211H human mesothelioma cells was characterized by flow cytometry. In vivo biodistribution, pharmacokinetic analysis, and PET imaging were performed in tumor bearing athymic mice.In vivo studies demonstrated high HER1 tumor uptake of both RICs. Significant reduction in tumor uptake was observed in mice co-injected with excess mAb (0.1 mg), demonstrating that uptake in the tumor was receptor specific. Significant differences were observed in the in vivo characteristics of the RICs. The blood clearance T(½)α of (86)Y-cetuximab (0.9-1.1 h) was faster than (86)Y-panitumumab (2.6-3.1 h). Also, the tumor area under the curve (AUC) to liver AUC ratios of (86)Y-panitumumab were 1.5 to 2.5 times greater than (86)Y-cetuximab as observed by the differences in PET tumor to background ratios, which could be critical when imaging orthotopic tumors and concerns regarding radiation doses to normal organs such as the liver.This study demonstrates the more favorable HER1-targeting characteristics of (86)Y-panitumumab than (86)Y-cetuximab for non-invasive assessment of the HER1 status of MM by PET imaging. Due to lower liver uptake, panitumumab based immunoconjugates may fare better in therapy than corresponding cetuximab based immunoconjugates