A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha 3 domain mutants of MHC class I/peptide complex

In this study, we have compared the effector functions and fate of a number of human CTL clones in vitro or ex vivo following contact with variant peptides presented either on the cell surface or in a soluble multimeric format. In the presence of CD8 coreceptor binding, there is a good correlation between TCR signaling, killing of the targets, and Fast-mediated CTL apoptosis. Blocking CD8 binding using (alpha3 domain mutants of MHC class I results in much reduced signaling and reduced killing of the targets. Surprisingly, however, Fast expression is induced to a similar degree on these CTLs, and apoptosis of CTL is unaffected. The ability to divorce these events may allow the deletion of antigen-specific and pathological CTL populations without the deleterious effects induced by full CTL activation.

ATM, a central controller of cellular responses to DNA damage

Mutations in the ATM gene lead to the genetic disorder ataxia-telangiectasia. ATM encodes a protein kinase that is mainly distributed in the nucleus of proliferating cells. Recent studies reveal that ATM regulates multiple cell cycle checkpoints by phosphorylating different targets at different stages of the cell cycle. ATM also functions in the regulation of DNA repair and apoptosis, suggesting that it is a central regulator of responses to DNA double-strand breaks.

Probabilistic modelling of CO2 corrosion laboratory data using neural networks

The present paper addresses two major concerns that were identified when developing neural network based prediction models and which can limit their wider applicability in the industry. The first problem is that it appears neural network models are not readily available to a corrosion engineer. Therefore the first part of this paper describes a neural network model of CO2 corrosion which was created using a standard commercial software package and simple modelling strategies. It was found that such a model was able to capture practically all of the trends noticed in the experimental data with acceptable accuracy. This exercise has proven that a corrosion engineer could readily develop a neural network model such as the one described below for any problem at hand, given that sufficient experimental data exist. This applies even in the cases when the understanding of the underlying processes is poor. The second problem arises from cases when all the required inputs for a model are not known or can be estimated with a limited degree of accuracy. It seems advantageous to have models that can take as input a range rather than a single value. One such model, based on the so-called Monte Carlo approach, is presented. A number of comparisons are shown which have illustrated how a corrosion engineer might use this approach to rapidly test the sensitivity of a model to the uncertainities associated with the input parameters. (C) 2001 Elsevier Science Ltd. All rights reserved.

Interference rejection capabilities of different types of array antennas in cellular systems

The suitable use of array antennas in cellular systems results in improvement in the signal-to-interference ratio (StR), This property is the basis for introducing smart or adaptive antenna systems. in general, the SIR depends on the array configuration and is a function of the direction of the desired user and interferers. Here, the SIR performance for linear and circular arrays is analysed and compared.

Modelling of microstructure formation and evolution during solidification

A comprehensive probabilistic model for simulating microstructure formation and evolution during solidification has been developed, based on coupling a Finite Differential Method (FDM) for macroscopic modelling of heat diffusion to a modified Cellular Automaton (mCA) for microscopic modelling of nucleation, growth of microstructures and solute diffusion. The mCA model is similar to Nastac's model for handling solute redistribution in the liquid and solid phases, curvature and growth anisotropy, but differs in the treatment of nucleation and growth. The aim is to improve understanding of the relationship between the solidification conditions and microstructure formation and evolution. A numerical algorithm used for FDM and mCA was developed. At each coarse scale, temperatures at FDM nodes were calculated while nucleation-growth simulation was done at a finer scale, with the temperature at the cell locations being interpolated from those at the coarser volumes. This model takes account of thermal, curvature and solute diffusion effects. Therefore, it can not only simulate microstructures of alloys both on the scale of grain size (macroscopic level) and the dendrite tip length (mesoscopic level), but also investigate nucleation mechanisms and growth kinetics of alloys solidified with various solute concentrations and solidification morphologies. The calculated results are compared with values of grain sizes and solidification morphologies of microstructures obtained from a set of casting experiments of Al-Si alloys in graphite crucibles.

A probabilistic analysis of Clostridium perfringens growth during food service operations

The purpose of this study was threefold: first, the study was designed to illustrate the use of data and information collected in food safety surveys in a quantitative risk assessment. In this case, the focus was on the food service industry; however, similar data from other parts of the food chain could be similarly incorporated. The second objective was to quantitatively describe and better understand the role that the food service industry plays in the safety of food. The third objective was to illustrate the additional decision-making information that is available when uncertainty and variability are incorporated into the modelling of systems. (C) 2002 Elsevier Science B.V. All rights reserved.

Cellular responses to Schistosoma japonicum cathepsin D aspartic protease

Lymphocyte proliferation and cytokine production were measured in groups of mice vaccinated (but not subsequently challenge infected) with recombinant forms of Schistosoma japonicum cathepsin D aspartic protease, rSjASP1 (expressed in bacteria; enzymatically inactive) and rSjASP2 (expressed in insect cells; enzymatically active). Both forms of the schistosome enzyme induced significant proliferation of splenocytes recovered from vaccinated mice, and expression of interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 mRNA in these cells was detected using reverse transcriptase-polymerase chain reaction. Secretion of IFN-gamma, IL-4 and IL-10 by splenocytes from vaccinated mice was confirmed and quantified using enzyme-linked immunosorbent assay. IFN-gamma was the most abundant cytokine produced, followed by IL-4 and IL-10 in rank order. These findings indicated that vaccination of mice with the schistosome protease induces a mixed Th1/Th2 cytokine response, which may explain the modest level of protection after challenge infection in cathepsin d-vaccinated mice, reported previously.

Movement through slits: cellular migration via the Slit family

First isolated in the fly and now characterised in vertebrates, the Slit proteins have emerged as pivotal components controlling the guidance of axonal growth cones and the directional migration of neuronal precursors. As well as extensive expression during development of the central nervous system (CNS), the Slit proteins exhibit a striking array of expression sites in non-neuronal tissues, including the urogenital system, limb primordia and developing eye. Zebrafish Slit has been shown to mediate mesodermal migration during gastrulation, while Drosophila slit guides the migration of mesodermal cells during myogenesis. This suggests that the actions of these secreted molecules are not simply confined to the sphere of CNS development, but rather act in a more general fashion during development and throughout the lifetime of an organism. This review focuses on the non-neuronal activities of Slit proteins, highlighting a common role for the Slit family in cellular migration.

On measuring quality of a probabilistic commodity forecast for a system that incorporates seasonal climate forecasts

Regional commodity forecasts are being used increasingly in agricultural industries to enhance their risk management and decision-making processes. These commodity forecasts are probabilistic in nature and are often integrated with a seasonal climate forecast system. The climate forecast system is based on a subset of analogue years drawn from the full climatological distribution. In this study we sought to measure forecast quality for such an integrated system. We investigated the quality of a commodity (i.e. wheat and sugar) forecast based on a subset of analogue years in relation to a standard reference forecast based on the full climatological set. We derived three key dimensions of forecast quality for such probabilistic forecasts: reliability, distribution shift, and change in dispersion. A measure of reliability was required to ensure no bias in the forecast distribution. This was assessed via the slope of the reliability plot, which was derived from examination of probability levels of forecasts and associated frequencies of realizations. The other two dimensions related to changes in features of the forecast distribution relative to the reference distribution. The relationship of 13 published accuracy/skill measures to these dimensions of forecast quality was assessed using principal component analysis in case studies of commodity forecasting using seasonal climate forecasting for the wheat and sugar industries in Australia. There were two orthogonal dimensions of forecast quality: one associated with distribution shift relative to the reference distribution and the other associated with relative distribution dispersion. Although the conventional quality measures aligned with these dimensions, none measured both adequately. We conclude that a multi-dimensional approach to assessment of forecast quality is required and that simple measures of reliability, distribution shift, and change in dispersion provide a means for such assessment. The analysis presented was also relevant to measuring quality of probabilistic seasonal climate forecasting systems. The importance of retaining a focus on the probabilistic nature of the forecast and avoiding simplifying, but erroneous, distortions was discussed in relation to applying this new forecast quality assessment paradigm to seasonal climate forecasts. Copyright (K) 2003 Royal Meteorological Society.

Capacity Enhancement Using MIMO Antenna Arrays in Realistic Macro-Cellular Urban Environment

In MIMO systems the antenna array configuration in the BS and MS has a large influence on the available channel capacity. In this paper, we first introduce a new Frequency Selective (FS) MIMO framework for macro-cells in a realistic urban environment. The MIMO channel is built over a previously developed directional channel model, which considers the terrain and clutter information in the cluster, line-of-sight and link loss calculations. Next, MIMO configuration characteristics are investigated in order to maximize capacity, mainly the number of antennas, inter-antenna spacing and SNR impact. Channel and capacity simulation results are presented for the city of Lisbon, Portugal, using different antenna configurations. Two power allocations schemes are considered, uniform distribution and FS spatial water-filling. The results suggest optimized MIMO configurations, considering the antenna array size limitations, specially at the MS side.

DRhoGEF2 regulates cellular tension and cell pulsations in the Amnioserosa during Drosophila dorsal closure

Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction.

Probabilistic linkage in household survey on hospital care usage

OBJECTIVE: To evaluate the potential advantages and limitations of the use of the Brazilian hospital admission authorization forms database and the probabilistic record linkage methodology for the validation of reported utilization of hospital care services in household surveys. METHODS: A total of 2,288 households interviews were conducted in the county of Duque de Caxias, Brazil. Information on the occurrence of at least one hospital admission in the year preceding the interview was obtained from a total of 10,733 household members. The 130 records of household members who reported at least one hospital admission in a public hospital were linked to a hospital database with 801,587 records, using an automatic probabilistic approach combined with an extensive clerical review. RESULTS: Seventy-four (57%) of the 130 household members were identified in the hospital database. Yet only 60 subjects (46%) showed a record of hospitalization in the hospital database in the study period. Hospital admissions due to a surgery procedure were significantly more likely to have been identified in the hospital database. The low level of concordance seen in the study can be explained by the following factors: errors in the linkage process; a telescoping effect; and an incomplete record in the hospital database. CONCLUSIONS: The use of hospital administrative databases and probabilistic linkage methodology may represent a methodological alternative for the validation of reported utilization of health care services, but some strategies should be employed in order to minimize the problems related to the use of this methodology in non-ideal conditions. Ideally, a single identifier, such as a personal health insurance number, and the universal coverage of the database would be desirable.

Increase of the delivered energy probability in DES using a fuzzy probabilistic modeling

The paper proposes a methodology to increase the probability of delivering power to any load point by identifying new investments in distribution energy systems. The proposed methodology is based on statistical failure and repair data of distribution components and it uses a fuzzy-probabilistic modeling for the components outage parameters. The fuzzy membership functions of the outage parameters of each component are based on statistical records. A mixed integer nonlinear programming optimization model is developed in order to identify the adequate investments in distribution energy system components which allow increasing the probability of delivering power to any customer in the distribution system at the minimum possible cost for the system operator. To illustrate the application of the proposed methodology, the paper includes a case study that considers a 180 bus distribution network.