Molecular modeling on some human interleukins sharing gamma c of interleukin-2 receptor, and structure-function relationships

Five models for human interleukin-7 (HIL-7), HIL-9, HIL-13, HIL-15 and HIL-17 have been generated by SYBYL software package. The primary models were optimized using molecular dynamics and molecular mechanics methods. The final models were optimized using a steepest descent algorithm and a subsequent conjugate gradient method. The complexes with these interleukins and the common gamma chain of interleukin-2 receptor (IL-2R) were constructed and subjected to energy minimization. We found residues, such as Gln127 and Tyr103, of the common gamma chain of IL-2R are very important. Other residues, e.g. Lys70, Asn128 and Glu162, are also significant. Four hydrophobic grooves and two hydrophilic sites converge at the active site triad of the gamma chain. The binding sites of these interleukins interaction with the common gamma chain exist in the first helical and/or the fourth helical domains. Therefore, we conclude that these interleukins binds to the common gamma chain of IL-2R by the first and the fourth helix domain. Especially at the binding sites of some residues (lysine, arginine, asparagine, glutamic acid and aspartic acid), with a discontinuous region of the common gamma chain of IL-2R, termed the interleukins binding sites (103-210). The study of these sites can be important for the development of new drugs. (C) 2000 Elsevier Science B.V. All rights reserved.

The non-local nature of structure functions

Kolmogorov's two-thirds, ((Δv) 2) ∼ e 2/ 3r 2/ 3, and five-thirds, E ∼ e 2/ 3k -5/ 3, laws are formally equivalent in the limit of vanishing viscosity, v → 0. However, for most Reynolds numbers encountered in laboratory scale experiments, or numerical simulations, it is invariably easier to observe the five-thirds law. By creating artificial fields of isotropic turbulence composed of a random sea of Gaussian eddies whose size and energy distribution can be controlled, we show why this is the case. The energy of eddies of scale, s, is shown to vary as s 2/ 3, in accordance with Kolmogorov's 1941 law, and we vary the range of scales, γ = s max/s min, in any one realisation from γ = 25 to γ = 800. This is equivalent to varying the Reynolds number in an experiment from R λ = 60 to R λ = 600. While there is some evidence of a five-thirds law for g > 50 (R λ > 100), the two-thirds law only starts to become apparent when g approaches 200 (R λ ∼ 240). The reason for this discrepancy is that the second-order structure function is a poor filter, mixing information about energy and enstrophy, and from scales larger and smaller than r. In particular, in the inertial range, ((Δv) 2) takes the form of a mixed power-law, a 1+a 2r 2+a 3r 2/ 3, where a 2r 2 tracks the variation in enstrophy and a 3r 2/ 3 the variation in energy. These findings are shown to be consistent with experimental data where the polution of the r 2/ 3 law by the enstrophy contribution, a 2r 2, is clearly evident. We show that higherorder structure functions (of even order) suffer from a similar deficiency.

On the functions of products

Understanding the performance and manner of functioning of existing products is at the base of new product development activities. In engineering design the term function is generally used to refer to the technical actions performed by a product. However, products accomplish a wider range of goals. This research explores the opportunity to describe and model, through the concept of function, product actions across four dimensions including technical, aesthetic, social and economic. The research demonstrates that non-technical functions can be represented through active verbs and nouns and modelled using a method known as the Function Analysis Diagram (FAD). The research argues that when technical, aesthetic, social and economic perspectives on product development are considered as different types of function, stakeholders have a common language to communicate which can benefit design collaboration.

700V smart trench IGBT with monolithic over-voltage and over-current protecting functions

An advanced 700V Smart Trench IGBT with monolithically integrated over-voltage and over-current protecting circuits is presented in this paper. The proposed Smart IGBT comprises a sense IGBT, a low voltage lateral n-channel MOSFET (M 1), an avalanche diode (D av), and poly-crystalline Zener diodes (ZD) and resistor (R poly). Mix-mode transient simulations with MEDICI have proven the functionalities of the protecting circuits when the device is operating under abnormal conditions, such as Unclamped Inductive Switching (UIS) and Short Circuit (SC) condition. A Trench IGBT process is used to fabricate this device with total 11 masks including one metal mask only. The characterizations of the fabricated device exhibit the clamping capability of the avalanche diode and voltage pull-down ability of the MOSFET. © 2012 IEEE.

Gamma-ray spectroscopy at TRIUMF-ISAC

The 8π spectrometer at TRIUMF-ISAC consists of 20 Compton-suppressed germanium detectors and various auxiliary devices. The Ge array, once used for studies of nuclei at high angular momentum, has been transformed into the world's most powerful device dedicated to radioactive-decay studies. Many improvements in the spectrometer have been made, including a high-throughput data acquisition system, installation of a moving tape collector, incorporation of an array of 20 plastic scintillators for β-particle tagging, 5 Si(Li) detectors for conversion electrons, and 10 BaF2 detectors for fast-lifetime measurements. Experiments can be performed where data from all detectors are collected simultaneously, resulting in a very detailed view of the nucleus through radioactive decay. A number of experimental programmes have been launched that take advantage of the versatility of the spectrometer, and the intense beams available at TRIUMF-ISAC. © 2006 American Institute of Physics.

Characterising the neutron and gamma responses of the NPL liquid scintillation detectors.

The absolute responses of the NPL liquid scintillation spectrometers to monoenergetic neutrons and gammas were measured at various energies in the ranges 1.2 - 17 MeV approximately for neutrons and 0.28 - 1.8 MeV for gammas. Additional measurements of the proton light output function were also carried out. Calculated responses were then obtained for the larger detector using the programs NRESP7 and PHRESP, and compared with the absolute measurements. Finally, response matrices for this detector were generated using responses calculated at closely spaced energies.

Lyapunov functions for stable cascades and applications to global stabilization

This paper generalizes recent Lyapunov constructions for a cascade of two nonlinear systems, one of which is stable rather than asymptotically stable. A new cross-term construction in the Lyapunov function allows us to replace earlier growth conditions by a necessary boundedness condition. This method is instrumental in the global stabilization of feedforward systems, and new stabilization results are derived from the generalized construction.

Testing of the multi-objective alliance algorithm on benchmark functions

A new version of the Multi-objective Alliance Algorithm (MOAA) is described. The MOAA's performance is compared with that of NSGA-II using the epsilon and hypervolume indicators to evaluate the results. The benchmark functions chosen for the comparison are from the ZDT and DTLZ families and the main classical multi-objective (MO) problems. The results show that the new MOAA version is able to outperform NSGA-II on almost all the problems.

The search for the IFN-gamma receptor in fish: Functional and expression analysis of putative binding and signalling chains in rainbow trout Oncorhynchus mykiss

Interferons (IFNs), consisting of three major subfamilies, type I, type II (gamma) and type III (lambda) IFN, activate vertebrate antiviral defences once bound to their receptors. The three IFN subfamilies bind to different receptors, IFNAR1 and IFNAR2 for type I IFNs, IFN gamma R1 and IFN gamma R2 for type II IFN, and IL-28R1 and IL-10R2 for type III IFNs. In fish, although many types I and II IFN genes have been cloned, little is known about their receptors. In this report, two putative IFN-gamma receptor chains were identified and sequenced in rainbow trout (Oncorhynchus mykiss), and found to have many common characteristics with mammalian type II IFN receptor family members. The presented gene synteny analysis, phylogenetic tree analysis and ligand binding analysis all suggest that these molecules are the authentic IFN gamma Rs in fish. They are widely expressed in tissues, with IFN gamma R1 typically more highly expressed than IFN gamma R2. Using the trout RTG-2 cell line it was possible to show that the individual chains could be differentially modulated, with rIFN-gamma and rIL-1 beta down regulating IFN gamma R1 expression but up regulating IFN gamma R2 expression. Overexpression of the two receptor chains in RTG-2 cells revealed that the level of IFN gamma R2 transcript was crucial for responsiveness to rIFN-gamma, in terms of inducing gamma IP expression. Transfection experiments showed that the two putative receptors specifically bound to rIFN-gamma. These findings are discussed in the context of how the IFN gamma R may bind IFN-gamma in fish and the importance of the individual receptor chains to signal transduction. (c) 2009 Elsevier Ltd. All rights reserved.

Comparative study and expression analysis of the interferon gamma gene locus cytokines in Xenopus tropicalis

Using bioinformatics approach, the genome locus containing interleukin (IL)-22, IL-26, and interferon gamma (IFN-gamma) genes has been identified in the amphibian, Xenopus tropicalis. Like that in other vertebrates such as fish, birds, and mammals, the Xenopus IL-22, IL-26, and IFN-gamma are clustered in the same chromosome and the adjacent genes are conserved. The genomic structures of the Xenopus IL-22, IL-26, and IFN-gamma gene were identical to that of their mammalian counterparts. The Xenopus IL-22 and IL-26 genes contained five exons and four introns while the Xenopus IFN-gamma gene consisted of four exons and three introns. The Xenopus IL-22, IL-26, and IFN-gamma share 14.1-41.6%, 14.6-31.2%, and 23.7-36.5% identity to their counterparts in other species, respectively. Reverse-transcription polymerase chain reaction (PCR) and real-time quantitative PCR analyses revealed that the expression of IL-22, IL-26, and IFN-gamma genes was significantly upregulated after simulation with bacterial polyliposaccharide and/or synthetic double-stranded poly(I:C), suggesting these cytokines like those in other vertebrates play an important role in regulating immune response in Xenopus.

Molecular cloning and characterization of common carp (Cyprinus carpio L.) TCR gamma and CD3 gamma/delta chains

Partial cDNA sequences of TCR gamma and CD3 gamma/delta were isolated from the thymus of common carp (Cyprinus carpio L.) by the method of suppression subtractive hybridization (SSH). Subsequently the full length cDNAs of carp TCR gamma and CD3 gamma/delta were obtained by means of 3' RACE and 5' RACE, respectively. The full length of carp TCR gamma chain is 1368 bp and encodes 326 amino acids including a signal peptide region of 19 amino acids and a transmembrane region of 23 amino acids at the C-terminal region from aa 291 to 313. The V region of carp TCR gamma contains 109 amino acids, the core motif FGXG in J segment was also found in carp TCR gamma. The C region of carp TCR gamma contains the characteristic CX6PX6WX45C motif. The CP region of carp TCR C gamma contains 37 amino acids. The full length of carp CD3 gamma/delta is 790 bp and encodes 175 amino acids including a signal peptide region of 17 amino acids and a transmembrane region of 23 amino acids from aa 93 to 115. Similar to other known CD3 gamma/delta s, four cysteine residues in the extracellular domain and an immunoreceptor tyrosine-based activation motif ITAM (YxxL/Ix6-8YxxL/I) in the intracellular domain are also included in carp CD3 gamma/delta. Differing from other known CD3 gamma/delta s, carp CD3 gamma/delta tacks the CXXCXE motif in the extracellular domain. RTPCR analysis demonstrated that the expression of TCR gamma gene was mainly in the thymus and gill of 6-month carp, but in 18-month carp, TCR gamma gene was detected in all the examined tissues. The expression of CD3 gamma/delta gene was detected in all examined tissues of 6 and 18-month carp; among them, the highest expression level was in the thymus of 6-month carp. In situ hybridization showed that CD3 gamma/delta-expressing cells were widely distributed in the head kidney, spleen and kidney of carp, whereas in the thymus, they were densely distributed in the lymphoid outer zone and scattered in the epithelioid inner zone. (c) 2007 Published by Etsevier Ltd.

Effects of the "all-fish" growth hormone transgene expression on non-specific immune functions of common carp, Cyprinus carpio L.

This study investigated non-specific immune functions of the F-2 generation of "all-fish" growth hormone transgenic carp, Cyprinus carpio L. Lysozyme activity was 145.0 (+/- 30.7) U ml(-1) in the transgenic fish serum and 105.0 (+/- 38.7) U ml(-1) in age-matched non-transgenic control fish serum, a significant difference (P < 0.01). The serum bactericidal activity in the transgenics was significantly higher than that in the controls (P < 0.05), with the percentage serum killing of 59.5% (6.83%) and 50.8% (8.67%), respectively. Values for leukocrit and phagocytic percent of macrophages in head kidney were higher in transgenics than controls (P < 0.05). However, the phagocytic indices in the transgenics and the controls were not different. In addition, the mean body weight of the transgenics was 63.4 (6.65) g, much higher than that of the controls [39.2 (+/- 3.30) g, P < 0.01]. The absolute weight of spleen of the transgenics [0.13 (+/- 0.03) g] was higher than that of the controls [0.08 (+/- 0.02) g, P < 0.01]. However, there was no difference in the relative weight of spleen between the transgenics and the controls, with the spleen mass index being 0.21% (+/- 0.02%) and 0.20% (+/- 0.03%), respectively. This study suggests that the "all-fish" growth hormone transgene expression could stimulate not only the growth but also the non-specific immune functions of carp. (c) 2006 Published by Elsevier B.V.

Effects of intraperitoneal injection of cortisol on nonspecific immune functions of Ctenopharyngodon idella

After grass carps Ctenopharyngodon idellus were injected with cortisol, with (CBC) and without (C) a cocoa butter carrier, the effects of both slowly and rapidly acting exogenous cortisol oil their non-specific immune functions were investigated. On the one hand, after injection with CBC, the cortisol concentration and lysozyme activity in fish serum were enhanced and were sustained at high levels for a long period (30 days). The killing activity in the serum declined with time, and phagocytosis of head kidney macrophages diminished significantly (P < 0.05 or P < 0.01). The leukocrit values in the high dose group (31-8 mg cortisol fish(-1)) increased over time, however, with the maximum average being 5.6% at day 30. The spleen mass index in the high dose group was 0.93 x 10(-3) after 30 days, notably lower (P < 0.05) than that in the control group. In addition, a decrease in resistance to Aeronionas hydrophilo infection in cortisol-treated fish was shown, with the final cumulative mortalities being 54.5 and 66.7% in the low and high dose groups, respectively. On the other hand, there was a decrease in both serum cortisol concentration and lysozyme activity of the experimental fish within 2 weeks after injection with C, where plasma bactericidal activities in the high dose group (31-8 mg cortisol fish(-1)) were remarkably lower (P < 0.01) than those in the control group at each sampling, but were increased slightly over time. The results of which were different from those in the CBC trial. Phagocytic activity of head kidney macrophages and spleen mass index decreased significantly (P < 0.05), while there were increases in leukocrit value and cumulative mortality due to A. hydrophila. The results of which were similar to those in the CBC trial. This study indicated that the injection of cortisol depressed the non-specific immune functions of the grass carp and increased its susceptibility to disease. (c) 2005 The Fisheries Society of the British Isles.