Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes

The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10(-6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.     

DNA-binding preferences of bisantrene analogues: relevance to the sequence specificity of drug-mediated topoisomerase II poisoning

To elucidate structure-activity relationships for drugs that are able to poison or inhibit topoisomerase II, we investigated the thermodynamics and stereochemistry of the DNA binding of a number of anthracene derivatives bearing one or two 4, 5-dihydro-1H-imidazol-2-yl-hydrazone side chains (characteristic of bisantrene) at different positions of the planar aromatic system. An aza-bioisostere, which can be considered a bisantrene-amsacrine hybrid, was also tested. The affinity for nucleic acids in different sequence contexts was evaluated by spectroscopic techniques, using various experimental conditions. DNA-melting and DNase I footprinting experiments were also performed. The location and number of the otherwise identical side chains dramatically affected the affinity of the test compounds for the nucleic acid. In addition, the new compounds exhibited different DNA sequence preferences, depending on the locations of the dihydroimidazolyl-hydrazone groups, which indicates a major role for the side-chain position in generating specific contacts with the nucleic acid. Molecular modeling studies of the intercalative binding of the 1- or 9-substituted isomers to DNA fully supported the experimental data, because a substantially more favorable recognition of A-T steps, compared with G-C steps, was found for the 9-substituted derivative, whereas a much closer energy balance was found for the 1-substituted isomer. These results compare well with the alteration of base specificity found for the topoisomerase II-mediated DNA cleavage stimulated by the isomeric drugs. Therefore, DNA-binding specificity appears to represent an important determinant for the recognition of the topoisomerase-DNA cleavable complex by the drug, at least for poisons belonging to the amsacrine-bisantrene family.     

A vertically integrated tool for automated design of /spl Sigma//spl Delta/ modulators

We present a tool that starting from high-level specifications of switched-capacitor (SC) /spl Sigma//spl Delta/ modulators calculates optimum specifications for their building blocks and then optimum sizes for the block schematics. At both design levels, optimization is performed using statistical techniques to enable global design and innovative heuristics for increased computer efficiency as compared with conventional statistical optimization. The tool uses an equation-based approach at the modulator level, a simulation-based approach at the cell level, and incorporates an advanced /spl Sigma//spl Delta/ behavioral simulator for monitoring and design space exploration. We include measurements taken from two silicon prototypes: (1) a 16 b @ 16 kHz output rate second-order /spl Sigma//spl Delta/ modulator; and (2) a 17 b @ 40 kHz output rate fourth-order /spl Sigma//spl Delta/ modulator. Both use SC fully differential circuits and were designed using the proposed tool and manufactured in a 1.2 /spl mu/m CMOS double-metal double-poly technology.<>     

Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions

We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of the literature concerning acute lymphoblastic leukemia and donor leukocyte infusions.     

Investigation of optical losses in photoelastic and ridge waveguides in GaAs-AlGaAs heterostructures

Two approaches have been used to fabricate stable photoelastic waveguides with planarized surfaces on GaAs-AlGaAs heterostructures. The first approach uses tensile Ni/sub 3/GaAs stressors formed by metal-semiconductor reactions. The second approach uses inert, refractory and compressive stressors, such as RF sputtered W and RF co-sputtered WNi films. For comparison purposes, ridge waveguides have also been fabricated using the same heterostructure by a dry etching technique. Optical losses of photoelastic waveguides, measured by Fabry-Perot (FP) method at a wavelength of 1.53 /spl mu/m, are comparable to or better than those of the ridge waveguides. Material loss appears to be the primary loss mechanism in both photoelastic and ridge waveguides. These results indicate that the photoelastic waveguide processing technique reported in this study is a promising alternative to commonly used dry etching techniques for planarization.     

Imitation and pantomime in high-functioning adolescents with autism spectrum disorders

A study was designed to test 2 alternative hypotheses--a symbolic hypothesis and an executive function hypotheses--for the imitation and pantomime deficits found in previous studies of autism. The subjects were 17 adolescent high-functioning subjects with autism spectrum disorders and 15 clinical comparison subjects who were matched on chronological age and verbal IQ. Meaning and sequence were manipulated in facial and manual imitation tasks. Sequence was manipulated in the pantomime and control tasks. Recognition memory and motor control tasks were matched to the experimental tasks. The results provided no support for the symbolic deficit hypothesis; meaning aided rather than hindered the performance of the group with autism. Partial support for the executive deficit hypothesis was found. There were no group differences on motor control tasks, and few on the memory control tasks, arguing against deficits in motor initiation, basic motor coordination, or visual recognition memory.     

Measurement and prediction of pressure drop in two-phase flow

Experimental data for air–water two-phase co-current flow in two different pipe diameters were used to test the prediction of pressure drop by a number of existing theories and correlations. Several models are shown to be useful for prediction, particularly with the stratified regimes which have proved difficult to handle in the past. The model suggested by Olujic proved to be of particular value.     

An assessment of potential nonlinear circuit models for thecharacterization of resonant tunneling diodes

The intrinsically fast process of resonant tunneling through double barrier heterostructures along with the existence of negative differential resistance in the current-voltage characteristic of these structures has led to their implementation as sources for high frequency electromagnetic energy. While sources based upon resonant tunneling diodes (RTDs) have produced frequency of oscillations up to 712 GHz, only microwatt levels of performance has been achieved above 100 GHz. Since stability criteria plays critical role in determining the deliverable power of any oscillator, a physically accurate equivalent-circuit model for the RTD is extremely important for optimizing the dynamics of the device-cavity package. This study identifies a distinctly new equivalent circuit model for characterizing the modes of oscillation in RTD-based sources. Specifically, in order to exhibit the fundamental self-oscillations and the overall I-V characteristics (plateau structure and hysteresis) observed experimentally, an accurate circuit model of the RTD must incorporate: (i) a quantum-well inductance which directly chokes the nonlinear conductance and, (ii) a nonlinear access resistance, associated with the accumulation of charge in the injection region of the double barriers, with a nonlocal dependence on the bias across the double barrier structure     

The effect of bandwidth allocation policies on delay inunidirectional bus networks

We consider the problem of allocating bandwidth fairly to each node in a shared, unidirectional bus network. We focus on the p_i persistent protocol, since these are open loop policies designed to operate well in high speed networks, which have a very large bandwidth-delay product and feedback in the upstream direction is not available in a timely manner. First, we introduce an improvement to the basic p_i persistent protocol, in which we replace random coin tosses with a deterministic counting algorithm, and thereby reduce the delays for all nodes for any given choice of {p_i}. We then describe an exact method for calculating average packet delays and queue lengths in both the p_i persistent and our new deterministic n out of m protocols, based on the regenerative approach of Georgiades et al. (1987). These delay results, together with simulation measurements, show that both of these protocols still waste some bandwidth. After presenting a lower bounding argument to show that some wasted bandwidth is inevitable in all such distributed access control schemes, assuming a passive bus without feedback in the upstream direction, we show that changing the bus to unidirectional point-to-point links between (very simple) active interfaces at each node allows us to construct distributed access schemes that require no upstream feedback and are both work conserving and fair. To illustrate how this can be done, we introduce the p_i preemptive protocol, in which each node randomly inserts its own packets into the traffic arriving from upstream. We derive a simple and effective heuristic for calculating the preemption probability for each node, and use simulation to show how well it equalizes the delays at each node     

Structure and mechanical properties of polyethylene-fullerene composites

The microhardness of films of fullerene-polyethylene composites prepared by gelation from semidilute solution, using ultrahigh molecular weight polyethylene (PE) (6×10⁶), has been determined. The composite materials were characterized by optical microscopy and X-ray diffraction techniques. The microhardness of the films is shown to increase notably with the concentration of fullerene particles within the films. In addition, a substantial hardening of the composites is obtained after annealing the materials at high temperatures (T _a=130 °C) and long annealing times (t _a=10⁵s). The hardening of the composites with annealing temperature has been identified with the thickening of the PE crystalline lamellae. Comparison of X-ray scattering data and the microhardness values upon annealing leads to the conclusion of phase separation of C₆₀ molecules from the polyethylene crystals within the material. The temperature dependence is discussed in terms of the independent contribution of the PE matrix of the C₆₀ aggregates to the hardness value.