A Computational Approach to Analyze the Mechanism of Action of the Kinase Inhibitor Bafetinib

Prediction of drug action in human cells is a major challenge in biomedical research. Additionally, there is strong interest in finding new applications for approved drugs and identifying potential side effects. We present a computational strategy to predict mechanisms, risks and potential new domains of drug treatment on the basis of target profiles acquired through chemical proteomics. Functional protein-protein interaction networks that share one biological function are constructed and their crosstalk with the drug is scored regarding function disruption. We apply this procedure to the target profile of the second-generation BCR-ABL inhibitor bafetinib which is in development for the treatment of imatinib-resistant chronic myeloid leukemia. Beside the well known effect on apoptosis, we propose potential treatment of lung cancer and IGF1R expressing blast crisis

Effectiveness of an implementation optimisation intervention aimed at increasing parent engagement in HENRY, a childhood obesity prevention programme - the Optimising Family Engagement in HENRY (OFTEN) trial: study protocol for a randomised controlled trial

Background: Family-based interventions to prevent childhood obesity depend upon parents’ taking action to improve diet and other lifestyle behaviours in their families. Programmes that attract and retain high numbers of parents provide an enhanced opportunity to improve public health and are also likely to be more cost-effective than those that do not. We have developed a theory-informed optimisation intervention to promote parent engagement within an existing childhood obesity prevention group programme, HENRY (Health Exercise Nutrition for the Really Young). Here, we describe a proposal to evaluate the effectiveness of this optimisation intervention in regard to the engagement of parents and cost-effectiveness. Methods/design: The Optimising Family Engagement in HENRY (OFTEN) trial is a cluster randomised controlled trial being conducted across 24 local authorities (approximately 144 children’s centres) which currently deliver HENRY programmes. The primary outcome will be parental enrolment and attendance at the HENRY programme, assessed using routinely collected process data. Cost-effectiveness will be presented in terms of primary outcomes using acceptability curves and through eliciting the willingness to pay for the optimisation from HENRY commissioners. Secondary outcomes include the longitudinal impact of the optimisation, parent-reported infant intake of fruits and vegetables (as a proxy to compliance) and other parent-reported family habits and lifestyle. Discussion: This innovative trial will provide evidence on the implementation of a theory-informed optimisation intervention to promote parent engagement in HENRY, a community-based childhood obesity prevention programme. The findings will be generalisable to other interventions delivered to parents in other community-based environments. This research meets the expressed needs of commissioners, children’s centres and parents to optimise the potential impact that HENRY has on obesity prevention. A subsequent cluster randomised controlled pilot trial is planned to determine the practicality of undertaking a definitive trial to robustly evaluate the effectiveness and cost-effectiveness of the optimised intervention on childhood obesity prevention

Direct solar ultraviolet irradiance over Nainital, India, in the central Himalayas for clear-sky day conditions during December 2004

From a high-altitude station, Nainital, India (29.4 degrees N, 79.5 degrees E, 1958 masl), located in the central part of lower Himalayas, the observations made during December 2004 using a pair of Sun photometers (Microtops II) at wavelengths ranging from 305 to 1020 nm are reported. The observed parameters are the direct solar UV irradiance, column ozone, water vapor, and aerosol optical depths (AOD). The results are presented for the full day clear-sky conditions that prevailed for about 16 days during the whole month. It is found that Nainital is a comparatively pristine site with average AOD at 500 nm ranging between 0.03 and 0.09 and Angstrom exponent generally close to 1. The high AOD values occurred on 2 and 25 December due to winds from populated north Indian plains as revealed by the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) backward trajectory model. The total column ozone varies between 251 and 308 DU during the entire period of observations. The maximum diurnal UV irradiance values in the 2.4 nm bandwidth centered at 305.5, 312.5, and 320.0 nm varied between 0.027 and 0.049, 0.15 and 0.20, and 0.29 and 0.37 W m(-2), respectively. The measured UV irradiances are compared with the Tropospheric Ultraviolet Visible (TUV) radiation model and show a good agreement

Aerosol contents at an altitude of ~2 km in central Himalayas

Aerosols, both natural and anthropogenic, play an important role in the atmospheric science, by imparting radiative forcing and perturbing the radiative balance of the Earth atmosphere system as well as by degrading the environment. To understand the effect of aerosols on our geo/biosphere system, it is essential to characterize their physical and chemical properties regionally because of the regional nature of their properties and the short lifetime. As most of the aerosol sources are of terrestrial origin the variability of their properties will be very large close to the surface. At higher altitudes, above the mixing region, and in the free troposphere, the aerosol characteristics have a more synoptic perspective; would be indicative of the background level and are useful to understand long-term impacts. Such systematic measurements of aerosols at high altitudes are practically non-existing in India. Realising the potential and need for such studies, an activity has been initiated at Manora Peak, Nainital in the Shivalik Hills of Central Himalayas at an altitude of $\sim$2 km. The present paper provides the preliminary results of these aerosol measurements. These daytime measurements are compared with the existing earlier nighttime measurements

Aerosol characteristics at a high-altitude location during ISRO-GBP Land Campaign-II

We present detailed analysis of the extensively measured aerosol parameters at the Aryabhatta Research Institute of Observational Sciences (ARIES), Manora Peak Nainital, during ISRO-GBP Land Campaign-II. This land campaign was focused on the winter month of December 2004, using eight fixed stations distinctly located over the Gangetic belt in the North Indian corridor, where thick fog conditions generally prevail during winter. Among these stations, Manora Peak was selected due to its high-altitude location, at an altitude of ~2 km, having a pristine location in the Shivalik Ranges of Central Himalayas and allowing a free tropospheric site. In this perspective, observations of aerosol optical depths (AODs), black carbon (BC) mass concentration, total columnar ozone (TCO), mass loading of total suspended particulates (TSP), and number concentration of near-surface aerosols have been carried out from Manora Peak. These experiments barring AODs, were made for the first time at this location. The monthly mean AOD at 500 nm was found to be 0.056 (±0.037). Temporal as well as the diurnal variation of BC mass concentration show almost similar variation as that of aerosol number (>0.3 µm) concentration, having relatively low values during night and early morning periods, and gradually increasing as the day advances reaching its maximum level around 1600 h local time. The monthly mean BC concentration was found to be 1.36 (±0.99) µg m-3. Mass loading of TSP was in the range 20-40 µg m-3, with a mean value of 27.1 (± 8.3) µg m-3. During the period under study, average BC mass fraction at Nainital was found to be ~6.3±2%. The monthly mean TCO was found to be 268 ±22 DU. The diurnal variation of BC mass concentration shows a typical behaviour compared with other low-altitude stations, where simultaneous measurements were made by other investigators during the campaign. This behaviour in the diurnal trend of aerosols is due to the topography and the boundary-layer dynamics over the high-altitude station of ARIES at Nainital

Spatial distribution and vertical structure of the MABL aerosols over Bay of Bengal during winter: results from W-ICARB experiment

The first ever in-situ measurements of size-segregated vertical profiles of aerosol in the marine atmospheric boundary layer (MABL) over the Bay of Bengal (BoB), made at five different locations during the winter Integrated Campaign of Aerosols, gases and Radiation Budget (W_ICARB) experiment is presented which showed large spatial variability in aerosol properties over BoB with high aerosol concentration over northern BoB &gt;500 cm<SUP>−3</SUP>) and low aerosol concentration (≤100 cm<SUP>−3</SUP>) over southern BoB with a moderate aerosol concentration (250–450 cm<SUP>−3</SUP>) over far east BoB. The altitude variation of aerosol number density is found to be steady in the convective boundary layer (up to ∼400 m) at all locations over BoB and above that the aerosol concentration is found to decrease, except at far eastern BoB. Over far eastern BoB, the altitude distribution of aerosol number concentration showed an increase at ∼600 m. Examination of the simultaneous air mass back trajectories along with the observations aerosol size distribution indicates that while the aerosols advected from IGP have a strong natural (coarse mode) component where as those from the east-Asia region are in general accumulation mode (anthropogenic) dominant