Chemical inhibitors when timing is critical: a pharmacological concept for the maturation of T cell contacts

Cellular signal transduction proceeds through a complex network of molecular interactions and enzymatic activities. The timing of these molecular events is critical for the propagation of a signal and the generation of a specific cellular response. To define the timing of signalling events, we introduce the combination of high-resolution confocal microscopy with the application of small-molecule inhibitors at various stages of signal transduction in T cells. Inhibitors of Src-family tyrosine kinases and actin dynamics were employed to dissect the role of the lymphocyte-specific tyrosine kinase Lck in the formation and maintenance of T cell receptor/CD3-dependent contacts. Anti-CD3epsilon-coated coverslips served as a highly defined stimulus. The kinetics of the recruitment of the yellow fluorescent protein-tagged signalling protein ZAP-70 were detected by high-resolution confocal microscopy. The analysis revealed that at 5 min after receptor engagement, Lck activity was required for maintenance of contacts. In contrast, after 20 min of receptor engagement, the contacts were Lck-independent. The relevance of the timing of inhibitor application provides a pharmacological concept for the maturation of T cell-substrate contacts.     

Copolyester studies. I. Preparation and characterization of tetramethylene terephthalate–tetramethylene sebacate copolymers

Tetramethylene terephthalate–tetramethylene sebacate copolymers containing up to 20 mol % sebacate have been prepared and characterized. Molecular weights and distributions have been evaluated using viscometry and gel-permeation chromatography. Compositions have been established by NMR spectroscopy. Thermal properties have been studied by differential scanning calorimetry and dynamic mechanical methods. Melting and glass-transition temperatures and moduli are discussed in terms of the structural differences, particularly the effect of composition on chain flexibility. Density and thermal methods of crystallinity determination are critically discussed for these systems.     

The behaviour of PbO2 in concentrated sulphuric acid

Linear sweep experiments on Pb in H₂SO₄ at concentrations in excess of 5 mol dm^–3 have been conducted using computer controlled techniques. Measurements have indicated that the maximum charge in the PbO₂ reduction peak occurs at 5 mol dm^–3, the available capacity decreasing with the concentration of H₂SO₄.     

PHASE-SPACE DIFFUSION EQUATIONS FOR SINGLE BROWNIAN PARTICLE MOTION NEAR SURFACES

In numerous physical processes involving the motion of micron and submicron sized particles near surfaces, such as the filtration of hydrosols and aerosols, the particle motion is the net result of the combined effects of fluid convection, external forces, particle inertia, Brownian particle motion, and particle-surface fluid dynamic interactions. The most general method of describing particle motion under the combined action of these effects is through the so-called Fokker-Planck equation. In the absence of particle-surface fluid dynamic interactions, the Fokker-Planck equation is well-known, and it has been applied in a general way to problems involving the adsorption or deposition of Brownian particles onto surfaces through a solution technique known as the Brownian dynamics simulation method.

In this study, the Fokker-Planck equation for Brownian particle motion near surfaces is generalized to include particle-surface fluid dynamic interactions. The Fokker-Planck equation is shown to follow from the Liouville equation for the Brownian particle and n-fluid molecules present in the system, thus, establishing a firm theoretical foundation for the Fokker-Planck equation and the various other phase-space diffusion equations that follow from it.

Based on diagonalization of the Fokker-Planck equation, its short-time behavior is also derived here which enables a generalization of the Brownian dynamics method for the study of particle motion near surfaces including fluid dynamic interactions. Additionally, a perturbation solution of the Fokker-Planck equation under the conditions of small, but finite particle Stokes number is also derived. These solutions are shown to agree with previously given representations of the Smoluchowski or convective-diffusion equation for Brownian particle motion near surfaces, as well as with inertial corrections to the Smoluchowski equation available in the literature. This latter equation is also generalized here to include particle-surface fluid dynamic interactions.     

Adsorption of Cationic Dyes by Acrylic Films II—Kinetics of Dyeing

Concentration distributions of basic dyes in a film of acrylic polymer have been determined using a microdensitometric technique. The diffusion coefficients calculated from them are dependent on concentration. An explanation of the dependence is offered based on the ionic transfer of hydrogen (or sodium) ions for dye. From the concentration dependence an average diffusion coefficient was calculated and found to agree with that calculated from rates of dyeing. Rates of dyeing of a binary mixture have demonstrated the competitive effect predicted by the diffusion equation derived for the individual dyes.     

Note: flowing ion population from a resonance cavity source

The experimental low energy plasma for hemispherical analyzers nominal testing thermal plasma facility of Dartmouth College uses a microwave plasma source which generates an ionosphere-like plasma through a two-step process. The plasma is initially generated inside a cylindrical, insulated, resonance cavity. This initial plasma must pass through a sheath in order to enter the main experimental region. This process imparts a significant flow velocity to the ions which has been neglected in previous analysis of this plasma source. We predict the flow energy of the ions to be between 12-15 eV depending on conservation laws and show agreement with experimental results.     

Performance bounds in linear control of unstable MIMO systems with pole location constraint

This paper proposes a methodology to compute quadratic performance bounds when the closed loop poles of a discrete-time multivariable control loop are confined to a disk, centred at the origin, and with radius less than one. The underlying philosophy in this constraint is to avoid certain undesirable dynamic features which arise in quadratic optimal designs. An expression for the performance loss due to the pole location constraint is also provided. Using numerical examples, we show that the performance loss is compensated by an improved transient performance, specially visible in the control signals.     

Top-down vs bottom-up methodologies in multi-agent system design

Traditionally, two alternative design approaches have been available to engineers: top-down and bottom-up. In the top-down approach, the design process starts with specifying the global system state and assuming that each component has global knowledge of the system, as in a centralized approach. The solution is then decentralized by replacing global knowledge with communication. In the bottom-up approach, on the other hand, the design starts with specifying requirements and capabilities of individual components, and the global behavior is said to emerge out of interactions among constituent components and between components and the environment. In this paper we present a comparative study of both approaches with particular emphasis on applications to multi-agent system engineering and robotics. We outline the generic characteristics of both approaches from the MAS perspective, and identify three elements that we believe should serve as criteria for how and when to apply either of the approaches. We demonstrate our analysis on a specific example of load balancing problem in robotics. We also show that under certain assumptions on the communication and the external environment, both bottom-up and top-down methodologies produce very similar solutions.