Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.     

A PC-based simulation package for supporting end-user demand sideenergy management strategies

A simulation package designated at SIMCA-E² (simulation for management, control and analysis of electricity end-use) is described. The package covers a wide area of applications-namely, the testing and performance evaluation of demand controllers and demand control algorithms, computer-aided analysis of data from energy audits, generation of alternative scenarios according to different consumption patterns and/or different contractual terms with the utility, and computer-aided teaching of demand-side management techniques and strategies. The package is written in Pascal and runs on IBM PC-AT, XT, or compatible computers. It may be used with different graphic cards     

Structure and expression of the mouse L23mrp gene downstream of the imprinted H19 gene: biallelic expression and lack of interaction with the H19 enhancers

Previous studies have identified populations of dopamine neurons in the midbrain that colocalize cholecystokinin some of which project to the nucleus accumbens and caudate-putamen. The contribution of dopamine-colocalized peptide to the total releasable pool of cholecystokinin in these brain regions was investigated using microdialysis. Dopamine, dihydroxyphenylacetic acid and cholecystokinin immunoreactive levels in dialysates of the posterior medial nucleus accumbens and medial caudate-putamen were determined following 6-hydroxydopamine lesions of the ventral tegmental area and substantia nigra or transection of the medial forebrain bundle. An 89-99% depletion in basal extracellular dihydroxyphenylacetic acid and an 87-99% decrease in veratridine-evoked extracellular dopamine levels was observed in the nucleus accumbens and caudate-putamen, 4 weeks after 6-hydroxydopamine lesion. No statistically significant difference was observed between lesioned and control animals in the basal or veratridine-evoked extracellular level of cholecystokinin immunoreactivity in either region. Similarly, transection of the medial forebrain bundle failed to significantly deplete the releasable pool of cholecystokinin immunoreactivity in the nucleus accumbens or caudate nucleus despite 89-99% depletions of dopamine and its metabolite. These data suggest that midbrain dopamine or non-dopaminergic cells are not the primary source of releasable cholecystokinin in the posterior medial nucleus accumbens and medial caudate-putamen measured by microdialysis.     

Nitrosourea pharmacodynamics in relation to the central nervous system

Time-response curves were established for the effect of 3 doses of pimozide, a potent and specific dopamine receptor blocker, on deprivation-induced drinking in rats. Injections occurred once every 3 days at intervals of 2, 4, 8, and 16 hr prior to the daily 15 min drinking period. Pimozide produced a significant attenuation in the amount of water normally consumed (on nondrug days) whose degree varied with the proximity of the injection to the drinking period. Only the 2 higher doses (0.5 and 1.0 mg/kg) produced a significant dose dependent effect which was strongest at the 2 hr interval and which gradually weakened by the 8th post injection hr. The relevance of these findings for a direct versus an indirect action of the drug on water intake is discussed.     

Vector Fields: an Interactive Tool for Animation, Modeling and Simulation with Physically Based 3D Particle Systems and Soft Objects

Vectorfields have traditionally been used in computer graphics as a means of visualizing models over time. This paper presents a system which extends the use of vector fields as an interactive tool for physically based three dimensional particle systems and soft objects. The techniques implemented in the system provide the user with new flexibility in animation, modeling and simulation. This paper describes bounded interactive vectorfields and how they can be used to manipulate particle systems and a class of soft objects. Applications to animation, modeling and simulation are also presented.     

The partitioning of phosphoramide mustard and its aziridinium ions among alkylation and P-N bond hydrolysis reactions

NMR (1H and 31P) and HPLC techniques were used to study the partitioning of phosphoramide mustard (PM) and its aziridinium ions among alkylation and P-N bond hydrolysis reactions as a function of the concentration and strength of added nucleophiles at 37 degrees C and pH 7.4. With water as the nucleophile, bisalkylation accounted for only 10-13% of the product distribution given by PM. The remainder of the products resulted from P-N bond hydrolysis reactions. With 50 mM thiosulfate or 55-110 mM glutathione (GSH), bisalkylation by a strong nucleophile increased to 55-76%. The rest of the PM was lost to either HOH alkylation or P-N bond hydrolysis reactions. Strong experimental and theoretical evidence was obtained to support the hypothesis that the P-N bond scission observed at neutral pH does not occur in the parent PM to produce nornitrogen mustard; rather it is an aziridinium ion derived from PM which undergoes P-N bond hydrolysis to give chloroethylaziridine. In every buffer studied (bis-Tris, lutidine, triethanolamine, and Tris), the decomposition of PM (with and without GSH) gave rise to 31P NMR signals which could not be attributed to products of HOH or GSH alkylation or P-N bond hydrolysis. The intensities of these unidentified signals were dependent on the concentration of buffer.     

Kinetics of the methanogenic fermentation of acetate

The kinetics of methanogenesis from a stirred batch-fed calcium acetate enrichment culture have been studied. A detailed kinetic analysis of the culture allowed four distinct phases to be distinguished. Phase 1 was a period of very rapid increase (from low initial values) in the rate of methanogenesis upon addition of acetate, and was not thought to be associated with cell growth. In Phase 2 the rate of methanogenesis increased exponentially with time reflecting exponential growth. Phase 3 was characterised by an approximately constant rate of methane production, and is discussed in relation to the uncoupling of growth and methanogenesis. Phase 4 is a period of rapid decline associated with depletion of acetate. The apparent size of the population of the acetate-utilising methanogenic bacteria subsequently declined, with a specific decay constant of 0.4 ± 0.1 d^?1. The significance of these phases, in particular 2 and 3, for industrial anaerobic digestion is discussed.     

Psychological factors in the prediction of Lyme disease course

We developed methodology for prospective randomized effectiveness studies using a demonstration project at a multispecialty practice, health maintenance organization, and hospital in academic medical center. An operational unit called the effectiveness registry was developed to design and support comparisons of potential practice improvements with standard care. The studies differ from observational effectiveness studies in that they provide long-term follow-up of randomized comparison groups. Physician involvement in data collection is limited. No tests or observations are made other than those required for clinical care. Follow-up and data collection are modeled after tumor registry procedures. Patients who refuse randomization enter the study in whichever treatment arm they choose. The protocol for each study is approved by the institutional review board (IRB) before recruitment begins, and all patients, randomized and nonrandomized, sign an informed consent document. Between its beginning on October 7, 1993 and April 7, 1997, the IRB approved 14 trials. Four were terminated after entering at most a few patients. Recruitment is complete in four trials and continues in six. Randomization was accepted by 74% (596/804) of the patients. Over 800 patients in 10 studies are being followed at least annually. Major peer-reviewed journals have accepted reports of initial findings for two studies. Prospective randomized effectiveness studies are feasible in the multipractice setting and have potential to provide useful and reliable assessment of treatment outcomes. Collaborative arrangements between several institutions are needed to provide larger sample sizes.     

Dynamic finite element analysis of viscoelastic composite plates in the time domain

Numerical procedures for analysing transient responses of anisotropic viscoeiastic composite plates have been developed in the time domain using variational principles and a direct time integration method. Recursion relationships have been formulated in order to reduce computer storage substantially. The method developed herein requires only two previous lime solutions to evaluate the next time solution and the necessary storage is independent of the number of the time steps. Verification studies were conducted to evaluate the accuracy and convergence of the present numerical algorithm and they show that the numerical solutions agree well with analytical ones. As examples, dynamic transient responses of viscoeiastic composite plates subjected to unit step loads were calculated using the presently developed procedure.