Inhibition of human mesangial cell proliferation by targeting T-Type calcium channels

Background: Aberrant glomerular mesangial cell (MC) proliferation is a common finding in renal diseases. T-type calcium channels (T-CaCN) play an important role in the proliferation of a number of cell types, including vascular smooth muscle cells. The hypothesis that T-CaCN may play a role in the proliferation of human MC was investigated. Methods: The presence of T-CaCN in primary cultures of human MC was examined using voltage clamping and by RT-PCR. The effect of calcium channel inhibitors, and of siRNA directed against the Cav3.2 T-CaCN isoform, on MC proliferation was assessed using the microculture tetrazolium assay and nuclear BrdU incorporation. Results: Human MC express only the Cav3.2 T-CaCN isoform. Co-incubation of MC with a T-CaCN inhibitor (mibefradil, TH1177 or Ni2+) results in a concentration-dependent attenuation of proliferation. This effect cannot be attributed to direct drug-induced cytotoxicity or apoptosis and is not seen with verapamil, an L-type channel blocker. Transfection of MC with siRNA results in knockdown of T-CaCN Cav3.2 mRNA and a clear attenuation of MC proliferation. Conclusions: These results demonstrate for the first time an important role for T-CaCN in human MC proliferation. This could potentially lead to a novel therapy in the treatment of proliferative renal diseases.

The effect of intensive case management on the relatives of patients with severe mental illness

Objective: Relatives play a vital role in caring for patients with severe mental illness but receive inadequate support from psychiatric services. Evidence suggests that although intensive case management is directed primarily at patients, relatives may benefit a's well. This study examined whether relatives of patients who were receiving intensive case management had more contact with mental health professionals than relatives of patients who were receiving standard case management. It also examined whether relatives of patients receiving intensive case management appraised caregiving less negatively and experienced less psychological distress than relatives of patients receiving standard case management. Methods: The sample was drawn from the pool of patients participating in the UK700 randomized controlled trial of intensive case management. Prospective data on contact between case managers and the relatives of 146 patients were collected over a two-year period. At a two-year follow-up assessment, relatives of 116 patients were. interviewed with the Experience of Caregiving Inventory and the 12-item General Health Questionnaire. Results: Considerably more relatives of patients receiving intensive case management had contact with a case manager during the study period than relatives of patients receiving standard case management (70 percent compared with 45 percent). However, relatives of patients receiving intensive case management did not-appraise caregiving less negatively or experience less psychological distress than relatives of patients who were receiving. standard case management. Conclusions: Reducing case managers' caseloads alone. will not guarantee adequate support for relatives.. Instead, providing more support will need to be an explicit aim, and staff will require specific additional training to achieve it.

Twentieth century secular decrease in the atmospheric potential gradient

Current flowing in the global atmospheric electrical circuit (AEC) substantially decreased during the twentieth century. Fair-weather potential gradient (PG) observations in Scotland and Shetland show a previously unreported annual decline from 1920 to 1980, when the measurements ceased. A 25% reduction in PG occurred in Scotland 1920–50, with the maximum decline during the winter months. This is quantitatively explained by a decrease in cosmic rays (CR) increasing the thunderstorm-electrosphere coupling resistance, reducing the ionospheric potential VI. Independent measurements of VI also suggest a reduction of 27% from 1920–50. The secular decrease will influence fair weather atmospheric electrical parameters, including ion concentrations and aerosol electrification. Between 1920–50, the PG showed a negative correlation with global temperature, despite the positive correlation found recently between surface temperature and VI. The 1980s stabilisation in VI may arise from compensation of the continuing CR-induced decline by increases in global temperature and convective electrification.

Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal raman spectroscopy

The stratum corneum (SC) barrier typically consists of layers of corneocytes embedded in a lipid continuum that regulates barrier function. The lipid domain containing ceramides, cholesterol, and free fatty acids provides the major pathway for most drugs permeating across SC. Penetration enhancers diminish the SC barrier function. The classic enhancer is dimethyl sulfoxide (DMSO). Its mechanisms of action remain unclear, although DMSO disrupts lipid organisation and may displace protein-bound water. Here we use confocal Raman spectroscopy to probe molecular interactions between a finite (depleting) dose of DMSO and SC, as functions of depth and time, providing novel information about residence time and location of DMSO in human SC in vivo

A comparison of the performance of Kalpana and Meteosat-7 WV radiances in the ECMWF NWP model

The Kalpana Very High Resolution Radiometer (VHRR) water vapour (WV) channel is very similar to the WV channel of the Meteosat Visible and Infrared Radiation Imager (MVIRI) on Meteosat-7, and both satellites observe the Indian subcontinent. Thus it is possible to compare the performance of VHRR and MVIRI in numerical weather prediction (NWP) models. In order to do so, the impact of Kalpana- and Meteosat-7-measured WV radiances was evaluated using analyses and forecasts of moisture, temperature, geopotential and winds, using the European Centre for Medium-range Weather Forecasts (ECMWF) NWP model. Compared with experiments using Meteosat-7, the experiments using Kalpana WV radiances show a similar fit to all observations and produce very similar forecasts.

Infotainment across access devices: the perceptual impact of multimedia QoS

The introduction of multimedia on pervasive and mobile communication devices raises a number of perceptual quality issues. However, limited work has been done examining the 3-way interaction between use of equipment, user perceptual quality and quality of service. Our work measures user perceptual quality with the quality of perception (QoP) metrics which comprises levels of informational transfer (objective) and user satisfaction (subjective) when users are presented with multimedia video clips at three different frame rates, using four different display devices. Finally, our results will show that variation in frame-rate does not impact a user’s level of information assimilation (IA), however, does impact a users’ perception of multimedia video ‘quality’.

Silica templating of a self-assembling peptide amphiphile that forms nanotapes

The peptide amphiphile C16-KTTKS templates silica polymerization, enabling the production of silica nanotape structures, imaged via electron microscopy (TEM and SEM). X-ray scattering shows that the nanotapes comprise stacked layers, as for the parent peptide amphiphile, but with a substantially increased layer spacing resulting from silica polymerization.

Multi‐method global sensitivity analysis (MMGSA) for modelling floodplain hydrological processes

When studying hydrological processes with a numerical model, global sensitivity analysis (GSA) is essential if one is to understand the impact of model parameters and model formulation on results. However, different definitions of sensitivity can lead to a difference in the ranking of importance of the different model factors. Here we combine a fuzzy performance function with different methods of calculating global sensitivity to perform a multi-method global sensitivity analysis (MMGSA). We use an application of a finite element subsurface flow model (ESTEL-2D) on a flood inundation event on a floodplain of the River Severn to illustrate this new methodology. We demonstrate the utility of the method for model understanding and show how the prediction of state variables, such as Darcian velocity vectors, can be affected by such a MMGSA. This paper is a first attempt to use GSA with a numerically intensive hydrological model.

Multi-method global sensitivity analysis (MMGSA) for modelling floodplain hydrological processes

When studying hydrological processes with a numerical model, global sensitivity analysis (GSA) is essential if one is to understand the impact of model parameters and model formulation on results. However, different definitions of sensitivity can lead to a difference in the ranking of importance of the different model factors. Here we combine a fuzzy performance function with different methods of calculating global sensitivity to perform a multi-method global sensitivity analysis (MMGSA). We use an application of a finite element subsurface flow model (ESTEL-2D) on a flood inundation event on a floodplain of the River Severn to illustrate this new methodology. We demonstrate the utility of the method for model understanding and show how the prediction of state variables, such as Darcian velocity vectors, can be affected by such a MMGSA. This paper is a first attempt to use GSA with a numerically intensive hydrological model