Simulation of receptor triggering by kinetic segregation shows role of oligomers and close-contacts

The activation of T cells, key players of the immune system, involves local evacuation of phosphatase CD45 from a region of the T cell's surface, segregating it from the T cell receptor. What drives this evacuation? In the presence of antigen, what ensures evacuation happens in the sub-second timescales necessary to initiate signaling? In the absence of antigen, what mechanisms ensure evacuation does not happen spontaneously, which could cause signaling errors? Phenomena known to influence spatial organization of CD45 or similar surface molecules include diffusive motion in the lipid bilayer, oligomerization reactions, and mechanical compression against a nearby surface, such as that of the cell presenting antigen. Computer simulations can investigate hypothesized spatiotemporal mechanisms of T cell signaling. The challenge to computational studies of evacuation is that the base process, spontaneous evacuation by simple diffusion, is in the extreme rare event limit, meaning direct stochastic simulation is unfeasible. Here we combine particle-based spatial stochastic simulation with the Weighted Ensemble method for rare events to compute the mean first-passage time for cell surface availability by surface reorganization of CD45. We confirm mathematical estimates that, at physiological concentrations, spontaneous evacuation is extremely rare, roughly 300 years. We find that dimerization decreases the time required for evacuation. A weak bi-molecular interaction (dissociation constant estimate 460 microMolar) is sufficient for an order of magnitude reduction of spontaneous evacuation times, and oligomerization to hexamers reduces times to below 1 second. This introduces a mechanism whereby CD45 oligomerization could be accessible to an engineered therapeutic. For large regions of close-contact, such as those induced by large microvilli, molecular size and compressibility imply a nonzero re-entry probability 60 %, decreasing evacuation times. Simulations show that these reduced evacuation times are still unrealistically long, suggesting that a yet-to-be-described mechanism, besides compressional exclusion at a close contact, drives evacuation.

An accurate lumped convective plus radiative heat exchanger model for performance-based modelling

There are several thermo-fluid process modelling tools available on the market which can be used to analyze the off-design performance of thermal plants. These tools all offer the user with a simple convective heat exchanger component that requires the design-base process conditions as inputs. The tools would then calculate an effective overall heat transfer factor (UA) and make use of gas flow mass ratios to scale the UA value for off-design conditions. The models employed in these tools assume that the contribution of gas radiation is insignificant, hence only applies convection scaling laws. This paper presents an improved model which considers the contribution of the gas and particle radiation, as is often encountered in the first few heaters in coal fired boilers and heat recovery steam generators. A more fundamental scaling law is applied for the convection scaling and incorporates a cleanliness factor which allows for the consideration of fouling of the heater surfaces. The model’s performance was validated against a discretized tube-level heater model that solves the fundamental convection and radiation terms. The model is accurate within 1% for the cases considered, as compared to more than 20% error if radiation contribution is not considered.

Comparison of Power Distribution, Losses and Efficiencies of a Steam Turbine with and without Extractions

The paper presents an analysis of two steam turbine operation regimes - regime with all steam extractions opened (base process) and regime with all steam extractions closed. Closing of all steam extractions significantly increases turbine real developed power for 5215.88 kW and increases turbine energy and exergy losses with simultaneous decrease of turbine energy and exergy efficiencies for more than 2%. First extracted steam mass flow rate has a dominant influence on turbine power losses (in comparison to turbine maximum power when all of steam extractions are closed). Cumulative power losses caused by steam mass flow rate extractions are the highest in the fourth turbine segment and equal to 1687.82 kW.

Characterisation of aptamer-anchored poly(EDMA-co-GMA) monolith for high throughput affinity binding

Immobilisation of aptameric ligands on solid stationary supports for effective binding of target molecules requires understanding of the relationship between aptamer-polymer interactions and the conditions governing the mass transfer of the binding process. Herein, key process parameters affecting the molecular anchoring of a thrombin-binding aptamer (TBA) onto polymethacrylate monolith pore surface, and the binding characteristics of the resulting macroporous aptasensor were investigated. Molecular dynamics (MD) simulations of the TBA-thrombin binding indicated enhanced Guanine 4 (G4) structural stability of TBA upon interaction with thrombin in an ionic environment. Fourier-transform infrared spectroscopy and thermogravimetric analyses were used to characterise the available functional groups and thermo-molecular stability of the immobilised polymer generated with Schiff-base activation and immobilisation scheme. The initial degradation temperature of the polymethacrylate stationary support increased with each step of the Schiff-base process: poly(Ethylene glycol Dimethacrylate-co-Glycidyl methacrylate) or poly(EDMA-co-GMA) [196.0 °C (±1.8)]; poly(EDMA-co-GMA)-Ethylenediamine [235.9 °C (±6.1)]; poly(EDMA-co-GMA)-Ethylenediamine-Glutaraldehyde [255.4 °C (±2.7)]; and aptamer-modified monolith [273.7 °C (±2.5)]. These initial temperature increments reflected in the associated endothermic energies were determined with differential scanning calorimetry. The aptameric ligand density obtained after immobilisation was 480 pmol/μL. Increase in pH and ionic concentration affected the surface charge distribution and the binding characteristics of the aptamer-modified disk-monoliths, resulting in the optimum binding pH and ionic concentration of 8.0 and 5 mM Mg2+, respectively. These results are critical in understanding and setting parametric constraints indispensable to develop and enhance the performance of aptasensors.

CATALYSTS OF ACID-BASE PROCESS ON THE BASIS OF THE MODIFIED CARBON FIBER

The functionalization of the carbon fiber based on polyacrylonitrile with sulfur-containing groups of high acidity was carried out in order to obtain the acid-base processes catalysts. Fibers were treated with sulfur vapors in the temperature range of 400-800°C, followed by surface oxidation with 30% hydrogen peroxide solution. Modified samples were investigated by chemical analysis, thermo-programmed desorption with mass spectrometric registration of products, IR spectroscopy and thermogravimetry. It is shown that the obtained materials contain SO3H-functional groups and oxygen-containing groups (carboxyl, lactone, phenolic, etc.) formed in the surface layer during the oxidation of the fiber surface. The chemical analysis showed that the concentration of sulfur in the samples of the modified fiber is 1.6-6.5 mmol/g. The synthesized samples have a satisfactory thermal stability. The synthesized catalysts were investigated in the model reaction - gas phase dehydration of isopropyl alcohol. It was found that obtained SO3H-containing carbon fibers were catalytically active and had high propylene selectivity. For all the samples obtained there is a complete conversion of alcohol into propylene. The activity of modified carbon fiber samples in the reaction indicated is a fairly high, temperatures of the total conversion of alcohol into propylene are in the range of 160-190°C. During the study of synthesized catalysts in several cycles of catalysis it have been shown that within repeated use (3 cycles) of all modified fiber samples, the yield of propylene does not decrease, the activity remains stable - the temperature of the dehydration reaction remains unchanged or increases insignificantly (by 5-10ºС). The temperatures of complete conversion of isopropyl alcohol in propylene for synthesized catalysts are lower than the temperatures of destruction maxima of surface sulfogroups. Thus, modified carbon fibers can be used as low-temperature catalysts of acid-base processes, in particular dehydration of alcohols.

Performance Evaluation of a New Hybrid Multivariate Meteorological Model Analysis: A Simulation Study

Simulation is used to measure the robustness and the efficiency of the forecasting techniques performance over complex systems. A method for simulating multivariate time series was presented in this study using vector autoregressive base-process. By applying the methodology to the multivariable meteorological time series, a simulation study was carried out to check for the model performance. MAPE and MAE performance measurements were used and the results show that the proposed method that consider persistency in volatility gives better performance and the accuracy error is six time smaller than the normal hybrid model.

RISK ANALYSIS OF DATABASE PRIVELEGE IMPLEMENTATION IN SQL INJECTION CASE

Software is important thing that needed by enterprises to support business. When developers build software, security must be concerned as important element. In bad condition, security incidents can make financial loss to organizaion so it need mitigation actions to minimize risk. Security testing and risk analysis become base process to choose good mitigation method. Implementation of database privilege become one of mitigation methods that can be used in SQL injection attack case. Based on DREAD analysis, it can decrease risk of SQL injection attack from high to medium ranking.