Delivery of human apolipoprotein (apo) E to liver by an [E1(-), E3(-), polymerase(-), pTP(-)] adenovirus vector containing a liver-specific promoter inhibits atherogenesis in immunocompetent apoE-deficient mice

Recombinant adenovirus (rAd)-mediated apoE gene transfer to the liver of apoE(-/-) mice is anti-atherogenic. However, first generation rAd vectors were associated with immune clearance of transduced hepatocytes, while an improved [E1(-), E3(-) polymerase(-)] adenovirus vector that persisted in the liver, had transient effects due to cellular shutdown of the cytomegalovirus (CMV) promoter (Ad-CMV-apoE). Here, we utilise an improved class of rAd vector with multiple deletions in the E1, E3, polymerase and pTP (pre-terminal protein) genes, which contains a modular synthetic liver-specific promoter (LSP) to drive expression of the human apoE cDNA (Ad-LSP-apoE) for hepatic gene transfer. Approximately 1 year old apoE(-/-) mice were injected intravenously with 4x10(10) virus particles of either Ad-LSP-apoE or Ad-CMV-apoE. Animals were monitored for plasma apoE, total plasma cholesterol and plasma lipoprotein distribution. The effect of Ad-LSP-apoE on atheroma progression was assessed in animals killed at 8 and 28 weeks after the injections. Ad-LSP-apoE vector administration gave sustained, though low, levels of plasma apoE throughout the study period without inducing a humoral immune response, but failed to reduce plasma cholesterol or normalize the adverse lipoprotein profile. Animals killed 8 weeks after the injections, demonstrated no significant retardation of atherosclerosis, whereas aortic lesions in those killed at 28 weeks were significantly reduced by 30% ( P< 0.006) compared to untreated animals. In summary, the combination of a multiply deleted rAd vector with a liver-specific promoter provided sustained low levels of plasma apoE, resulting in significant retardation of aortic atherosclerotic lesions

Effect of Wheelchair Running on Recovery of Blood Lactate and Physical Performance after High-Intensity Intermittent Exercise – An Experimental Trial

Background and Purpose: Repetitive sprint sport players perform high intensity exercise only for a small percentage of a total game and such periods are often instrumental in determining the eventual outcome. Recovery is a key factor for performance, and constant lack of recovery or insufficient recovery turns into overtraining which is detrimental in achieving peak performance. The purpose was to find out the effect of wheelchair running on the physical performance recovery after high-intensity intermittent exercise. Method: Ten sportsmen having the age range from 20 to 29, VO2max Ranges from 60.51 to 64.29 were randomly divided into experimental and control groups. After filling pre-participation questionnaire and 30-min of supine rest, Blood lactate and the field tests for the measurement of static balance, power, speed and agility were applied. The subjects were made to run in the treadmill and to increase the intensity to reach the Target Heart Rate (THR). After 1-min the subjects were given rest for 15-s and after that they started exercise again and thus the subjects completed several bouts of such exercises until exhaustion followed by either Passive rest or wheelchair running for the duration of 10 minutes. Parameters were measures after completed the exercise bout and after the recovery. Results: After the recovery in experimental group significant improvement found only in blood lactate (p<0.01) and no significant changes found in other parameters while in control group no significant changes found in all parameters. There was no significant difference found in all the parameters including blood lactate between the groups. Conclusion: Both wheelchair running and passive recovery are same in the efficiency of blood lactate removal and restoration of physical performance following intense intermittent exercise

Annoyance due to railway vibration at different times of the day

The time of day when vibration occurs is considered as a factor influencing the human response to vibration. The aim of the present paper is to identify the times of day during which railway vibration causes the greatest annoyance, to measure the differences between annoyance responses for different time periods and to obtain estimates of the time of day penalties. This was achieved using data from case studies comprised of face-to-face interviews and internal vibration measurements (N=755). Results indicate that vibration annoyance differs with time of day and that separate time of day weights can be applied when considering exposure–response relationships from railway vibration in residential environments

Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy.

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy

Improving Search through A3C Reinforcement Learning based Conversational Agent

We develop a reinforcement learning based search assistant which can assist users through a set of actions and sequence of interactions to enable them realize their intent. Our approach caters to subjective search where the user is seeking digital assets such as images which is fundamentally different from the tasks which have objective and limited search modalities. Labeled conversational data is generally not available in such search tasks and training the agent through human interactions can be time consuming. We propose a stochastic virtual user which impersonates a real user and can be used to sample user behavior efficiently to train the agent which accelerates the bootstrapping of the agent. We develop A3C algorithm based context preserving architecture which enables the agent to provide contextual assistance to the user. We compare the A3C agent with Q-learning and evaluate its performance on average rewards and state values it obtains with the virtual user in validation episodes. Our experiments show that the agent learns to achieve higher rewards and better states.Comment: 17 pages, 7 figure

Human response to vibration in residential environments, technical report 1 : measurement of vibration exposure

The Technical Report 1 describes the research undertaken to develop a method by which human exposure to vibration in residential environments can be assessed. That work has been carried out by the University of Salford supported by the Department of environment food and rural affairs (Defra). The overall aim of the project is to derive exposure-response relationships for human vibration in residential environments. This document in particular focuses on the equipment and methodology employed to measure vibration from different sources. The main objective of this report is to describe the practical experience of implementing a vibration measurement protocol. Reported here are findings obtained in the field measurements and a description of a feasible method for measuring vibration for different sources. In addition, controlled tests performed to determine the suitability of the vibration mounting for various practical situations are reported

Human response to vibration in residential environments (NANR209), executive summary

The aim of the Defra-funded project NANR209 ‘Human response to vibration in residential environments’ was to develop exposure-response relationships for vibration experienced in residential environments from sources outside of the residents’ control. The project was performed at the University of Salford between January 2008 and March 2011. The final report was published on the Defra website on 6th September 2012. The NANR209 Final Report consists of the following documents: • Executive summary • Final project report • Technical report 1: Measurement of vibration exposure • Technical report 2: Measurement of response • Technical report 3: Calculation of vibration exposure • Technical report 4: Measurement and calculation of noise exposure • Technical report 5: Analysis of the social survey findings • Technical report 6: Determination of exposure-response relationships This document is the Executive summary