Overexpression of IL-1ra gene up-regulates interleukin-1β converting enzyme (ICE) gene expression: possible mechanism underlying IL-1β-resistance of cancer cells

We investigated the interaction of endogenous interleukin (IL)-1β, IL-1ra, and interleukin-1β converting enzyme (ICE) in four human urological cancer cell lines, KU-19-19, KU-1, KU-2 and KU-19-20. Northern blot analysis showed that IL-1β gene was expressed in all cell lines. On the other hand, in KU-19-19 and KU-19-20, the gene expressions of both IL-1ra and ICE were suppressed. MTT assay revealed that IL-1β (10 ng ml−1) promoted cell growth in KU-19-19 and KU-19-20, while it inhibited in KU-1 and KU-2. An ICE inhibitor, Acetyl-Tyr-Val-Ala-Asp-CHO (YVAD-CHO) blocked IL-1β-induced growth inhibition in KU-1 and KU-2. Overexpression of the secretory type IL-1ra with adenovirus vector (AxIL-1ra) enhanced ICE gene expression, while exogenous IL-1ra (100 ng ml–1) did not enhance it. Furthermore, AxIL-1ra treatment promoted endogenous IL-1β secretion and induced significant growth inhibition and apoptotic cell death on KU-19-19 and KU-19-20. Treatment with either IL-1ra (100 ng ml−1), IL-1β antibody (100 μg ml−1), or YVAD-CHO blocked AxIL-1ra-induced cell death in KU-19-19 and KU-19-20. These results suggest that IL-1β-sensitivity depends on the level of ICE gene expression, which is regulated by the level of endogenous sIL-1ra expression. This is a first report on the intracellular function of sIL-1ra and these findings may provide key insights into the mechanism underlying the viability of cancer cells. © 1999 Cancer Research Campaig

Proteins with Complex Architecture as Potential Targets for Drug Design: A Case Study of Mycobacterium tuberculosis

Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only

National TB prevalence surveys in the COVID-19 era

no abstract availabl

Optical selection of a multiple phase order in the charge density wave condensate o-TaS3 using a spectrally resolved nonequilibrium measurement

We investigate the spectrally resolved transient reflectivity changes Delta R(T,tau,lambda) in the charge density wave (CDW) conductor o-TaS3. A distinct near-infrared resonance in this compound emphasizes the characteristic Delta R(lambda) resonances, and allows a selection of coexisting CDW phases with different nonequilibrium carrier dynamics. Furthermore, the spectrally resolved Delta R(tau) characterizes the collective oscillations associated with the individual states. We believe that this demonstration paves the way for the optical selection of the multiphase order that plays an important role in various macroscopic quantum systems

User's manual for computer simulation and design of the moving-bed coal gasifier. Final report

A computer model of countercurrent moving-bed coal gasifier developed previously has been updated. This manual presents in detail how the computer program developed is used. The unique feature of the present gasifier model is the treatment of the pyrolysis of coal. A semi-empirical approach is taken in the present model to represent the pyrolysis zone of the bed. The pyrolysis reactions are represented by three simple chemical reactions: devolatilization, cracking and carbon deposition with empirically estimated reaction rate constants. The gasification reactions are assumed to be heterogeneous reactions. For fast reactions, diffusion is the rate controlling step while for slow reactions, the surface reactions within the pores of particles is the rate controlling step. Therefore, the rates of gasification reactions used in the model are composed of two terms,the reaction term and the diffusion term. The computer program developed can be used for both simulation and design. It can be used to simulate a gasifier to obtain the gas product distributions and coal conversion and calculate the required bed height for a given carbon conversion. A map of feasible operation ranges can then be constructed for the optimum design of a gasifier. Kinetic parameters for three different kinds of coal are specified in the program. However, the program users may change these parameters according to the guides listed in the manual if the coal used is different. In addition, the reaction rate equations may be replaced if better rate expressions become available. It is important that the user checks the assumptions, the simplifications and the limitations of this computer program before applying in order to assure that the applicability of the model is within the range specified. The scale-up and extrapolation from normal operating conditions should be done with caution and, if possible, verified through additional experimentations

Complex dynamics in a cobweb model with adaptive production adjustment

Chaos occurs in a nonlinear cobweb model with normal demand and supply, naive expectations and adaptive production adjustment. The model differs from existing ones in that it includes adaptive production adjustment instead of adaptive expectations. The model exhibits observable chaos (strange attractors) as well as topological chaos (horseshoes) associated with homoclinic points. As numerical simulations show, the faster suppliers adjust their production and the more inelastic demand is, the more likely the market behaves chaotically. (C) 2000 Elsevier Science B.V. All rights reserved

Stability, chaos and multiple attractors: a single agent makes a difference

This paper provides an example in which a slight behavioral heterogeneity may fundamentally change the dynamical properties of a nonlinear cobweb market with a quadratic cost function and an isoelastic demand function. We consider two types of producers; cautious adapters and naive optimizers. In a market of naive optimizers a single cautious, adapter stabilizes the otherwise exploding market. In a market of cautious adapters a single naive optimizer may destabilize the market; without him there exists at most one periodic attractor in the market but with him there may appear many (and even infinitely many) coexisting periodic attractors. (C) 2002 Elsevier Science B.V. All rights reserved