Interleukin 13 inhibits growth of human renal cell carcinoma cells independently of the p140 interleukin 4 receptor chain

Interleukin-13 (IL-13) is a cytokine produced primarily by activated T lymphocytes. It exerts a variety of effects on different cell types, including monocytes, B lymphocytes, mast cells, and keratinocytes. The effects of IL-13 on target cells are often similar to the effects of IL-4, which is another cytokine product of activated T lymphocytes. We recently described the expression of intermediate- to high-affinity receptors for IL-13 (IL-13R) on renal cell carcinoma (RCC) cells. In the present study, we examined the effect of IL-13 on the growth of RCC cells as measured by [3H]thymidine uptake and a clonogenic assay. In addition, we used an IL-4R-specific antibody to examine the specificity of IL-4R and IL-13R binding and function. We observed that IL-13 inhibited RCC cell proliferation by up to 50% and colony formation by up to 32% when compared with cells cultured in medium alone. A combination of IL-4 and IL-13 did not have an additive or synergistic effect on the growth of RCC cells. These cells expressed mRNA for IL-13 and secreted immunoreactive IL-13 protein in culture. The growth-inhibitory effects of IL-13 were specific, because they were not affected by antibodies to IL-4 or to the 140-kilodalton subunit of IL-4R. Furthermore, polyclonal antibodies to IL-4R failed to inhibit the binding of 125I-IL-13 to RCC cells. These results indicate that IL-13 has significant antiproliferative effects on human RCC cells, and the inhibition of IL-13 effects by anti-IL-4R antibody previously reported in lymphoid cells does not occur in RCC cells.     

Mechanism of constitutive activation of the AT1 receptor: influence of the size of the agonist switch binding residue Asn(111)

The AT1 receptor is a G-protein-coupled receptor (GPCR); its activation from the basal state (R) requires an interaction between Asn111 in transmembrane helix III (TM-III) of the receptor and the Tyr4 residue of angiotensin II (Ang II). Asn111 to Gly111 mutation (N111G) results in constitutive activation of the AT1 receptor (Noda et al. (1996) Biochemistry, 35, 16435-16442). We show here that replacement of the AT1 receptors TM-III with a topologically identical 16-residue segment (Cys101-Val116) from the AT2 receptor induces constitutive activity, although Asn111 is preserved in the resulting chimera, CR18. Effects of CR18 and N111G mutations are neither additive nor synergistic. The conformation(s) induced in either mutant mimics the partially activated state (R'), and transition to the fully activated R conformation in both no longer requires the Tyr4 of Ang II. Both the R state of the receptor and the Tyr4 Ang II dependence of receptor activation can be reinstated by introduction of a larger sized Phe side chain at the 111 position in CR18, suggesting that the CR18 mutation generated an effect similar to the reduction of side chain size in the N111G mutation. Consistently in the native AT1 receptor, R' conformation is generated by replacement with residues smaller but not larger than the Asn111. However, size substitution of several other TM-III residues in both receptors did not affect transitions between R, R', and R states. Thus, the property responsible for Asn111 function as a conformational switch is neither polarity nor hydrogen bonding potential but the side chain size. We conclude that the fundamental mechanism responsible for constitutive activation of the AT1 receptor is to increase the entropy of the key agonist-switch binding residue, Asn111. As a result, the normally agonist-dependent R --> R' transition occurs spontaneously. This mechanism may be applicable to many other GPCRs.     

Effect of corrugation frequencies on natural convective heat transfer and flow characteristics in a square enclosure of vee-corrugated vertical walls

A numerical investigation has been carried out on natural convective heat transfer and fluid flow in a square cavity with vee-corrugated vertical surfaces. This study covers the range of corrugation frequency from 1 to 3 and Grashof number from 10³ to 10⁵. The corrugation amplitude has been fixed at 5% of the enclosure height. The vorticity stream function formulation with the control volume based finite element method has been used to analyse the effects of corrugation frequency and Grashof number. The investigation shows that the overall heat transfer through the enclosure increases with the increase of corrugation for low Grashof number; but the trend is reversed for high Grashof number.     

Preparation and characterization of polyether‐based polyurethane dolomite composite

A polyether polyol‐based two‐component polyurethane composite was prepared by a reaction of polypropylene glycol (PPG) and diethylene glycol (DEG) used as a crosslinker. The final reaction for the preparation of composite is carried out with processed polyether polyol and diphenylmethane 4,4′‐diisocyanate (MDI). The physicochemical properties of processed polyether polyol have been measured, such as viscosity, moisture content, and hydroxyl value. The composite has been formed with loading of inorganic filler dolomite [MgCa(CO₃)₂] with different filler ratios. It shows good adhesive strength and mechanical properties. Composite samples have also been studied for the effects of acids and bases, swelling in solvents, physical and mechanical properties such as compression strength, shore hardness A and D, tensile strength, and elongation. Some electrical properties have also been studied, viz. thermal conductivity, volume resistivity, and dielectric strength. A comparison of prepared polyether‐based polyurethane composite with some conventional polymeric materials suggests their suitability for various applications. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2337–2342, 2007     

Triply‐promoted ethene epoxidation: NOx promotion of the Ag‐catalysed reaction in the presence of alkali and chlorine under electrochemical control

Potassium, electrochemically supplied from K β"‐alumina to a silver thin film catalyst in the presence of ppm levels of NO_x, strongly promotes the selectivity of ethene epoxidation. However, in the absence of gaseous NO_x, alkali catastrophically suppresses both activity and selectivity. Addition of surface chlorine via ppm levels of ethylene dichloride further enhances the promotional effect of alkali + NO yielding the highest selectivity of all. The minimum necessary and sufficient conditions for the appearance of NO_x promotion are submonolayer quantities of alkali on the metal surface, and ppm levels of gaseous NO_x. This revised version was published online in August 2006 with corrections to the Cover Date.     

Stress reactions of children and adolescents in war and siege conditions

OBJECTIVE: This was a study of posttraumatic stress symptoms in children and adolescents during siege conditions in Sarajevo. METHOD: Seven hundred ninety-one students aged 7-15 years were surveyed to assess symptoms of posttraumatic stress and level of deprivation. RESULTS: Girls reported more stress than boys. Loss of family members and deprivation of basic needs were associated with more symptoms. CONCLUSIONS: Personal experiences of siege are related to increased stress.     

Multiobjective mixed symmetric duality involving cones

A pair of multiobjective mixed symmetric dual programs is formulated over arbitrary cones. Weak, strong, converse and self-duality theorems are proved for these programs under K-preinvexity and K-pseudoinvexity assumptions. This mixed symmetric dual formulation unifies the symmetric dual formulations of Suneja et al. (2002) [14] and Khurana (2005) [15].     

Autonomic cloud resource provisioning and scheduling using meta-heuristic algorithm

We investigate that resource provisioning and scheduling is a prominent problem due to heterogeneity as well as dispersion of cloud resources. Cloud service providers are building more and more datacenters due to demand of high computational power which is a serious threat to environment in terms of energy requirement. To overcome these issues, we need an efficient meta-heuristic technique that allocates applications among the virtual machines fairly and optimizes the quality of services (QoS) parameters to meet the end user objectives. Binary particle swarm optimization (BPSO) is used to solve real-world discrete optimization problems but simple BPSO does not provide optimal solution due to improper behavior of transfer function. To overcome this problem, we have modified transfer function of binary PSO that provides exploration and exploitation capability in better way and optimize various QoS parameters such as makespan time, energy consumption, and execution cost. The computational results demonstrate that modified transfer function-based BPSO algorithm is more efficient and outperform in comparison with other baseline algorithm over various synthetic datasets.

     

Effects of angiotensin II generated by an angiotensin converting enzyme-independent pathway on left ventricular performance in the conscious baboon

Human chymase is a serine proteinase that converts angiotensin (Ang) I to Ang II independent of angiotensin converting enzyme (ACE) in vitro. The effects of chymase on systemic hemodynamics and left ventricular function in vivo were studied in nine conscious baboons instrumented with a LV micromanometer and LV minor axis and wall thickness sonomicrometer crystal pairs. Measurements were made at baseline and after [Pro11DAla12] Ang I, a specific substrate for human chymase, was given in consecutive fashion as a 0.1 mg bolus, an hour-long intravenous infusion of 5 mg, a 3 mg bolus, and after 5 mg of an Ang II receptor antagonist. [Pro11DAla12]Ang I significantly increased LV systolic and diastolic pressure, LV end-diastolic and end systolic dimensions and the time constant of LV relaxation and significantly decreased LV fractional shortening and wall thickening. Administration of a specific Ang II receptor antagonist reversed all the hemodynamic changes. In separate studies, similar results were obtained in six of the baboons with ACE blockade (20 mg, intravenous captopril). Post-mortem studies indicated that chymase-like activity was widely distributed in multiple tissues. Thus, in primates, Ang I is converted into Ang II by an enzyme with chymase-like activity. This study provides the first in vivo evidence of an ACE-independent pathway for Ang II production.     

Intelligent network: a key platform for PCS interworking andinteroperability

The Tl and TIA standards committees in the United States have worked jointly on the development of the first phase of personal communication services (PCS) standards, which were approved in December 1995. PCS systems based on these standards are currently under development. As these systems are deployed, the variety of wireless systems will grow, making interworking and interoperability a key challenge. This article provides an overview of PCS standards and explores how the different types of wireless systems (PCS and cellular) will utilize the capabilities of the intelligent network to provide seamless roaming