bluuebunny/crossref_metadata_2025 huggingface dataset:
Ets protein Elf‐1 bidirectionally suppresses transcriptional activities of the tumor suppressor Tsc2 gene and the repair‐related Nth1 gene
Authors: Honda Satoshi , Kobayashi Toshiyuki , Kajino Kazunori , Urakami Shinji , Igawa Mikio , Hino Okio
Published: July 2003

Alterations in the rat tuberous sclerosis gene (Tsc2) cause renal cell carcinomas (RCCs) with complete penetrance. In this study, it was shown that the minimal core promoters of the rat Tsc2 and endonuclease III 1 (Nth1) genes, lying in a 5′‐to‐5′ arrangement, were localized in a 0.11‐kb region containing two Ets binding sites (EBSs). This region worked as a bidirectional promoter in a single reporter plasmid. Mutational inactivation of each of the two EBSs significantly reduced promoter activity. Moreover, gel shift assays revealed the presence of specific EBSs‐protein complexes. These results demonstrate that some members of the Ets family positively regulate the promoter activities of the Tsc2/Nth1 genes by binding to the EBSs. We identified Elf‐1 as a binding factor for EBSs through super‐shift assays, and detected ∼35 kDa bands with an EBSs‐containing DNA probe by Southwestern blot analysis. Forced expression of Elf‐1 in cells, however, bidirectionally suppressed the activities of the Tsc2/Nth1 promoters. Elf‐1 may be a negative regulator of Tsc2/Nth1 gene expression and may compete against positive regulators for binding to the EBSs. Our observations suggest that mechanisms that inactivate Tsc2 gene expression, such as promoter suppression, may exist. © 2003 Wiley‐Liss, Inc.
Prostate‐specific antitumor activity by probasin promoter‐directed p202 expression
Authors: Wen Yong , Giri Dipak , Yan Duen‐Hwa , Spohn Bill , Zinner Ralph G. , Xia Weiya , Thompson Timothy C. , Matusik Robert J. , Hung Mien‐Chie
Published: July 2003

p202, an interferon (IFN) inducible protein, arrests cell cycle at G1 phase leading to cell growth retardation. We previously showed that ectopic expression of p202 in human prostate cancer cells renders growth inhibition and suppression of transformation phenotype in vitro. In this report, we showed that prostate cancer cells with stable expression of p202 were less tumorigenic than the parental cells. The antitumor activity of p202 was further demonstrated by an ex vivo treatment of prostate cancer cells with p202 expression vector that showed significant tumor suppression in mouse xenograft model. Importantly, to achieve a prostate‐specific antitumor effect by p202, we employed a prostate‐specific probasin (ARR2PB) gene promoter to direct p202 expression (ARR2PB‐p202) in an androgen receptor (AR)–positive manner. The ARR2PB‐p202/liposome complex was systemically administered into mice bearing orthotopic AR‐positive prostate tumors. We showed that parenteral administration of an ARR2PB‐p202/liposome preparation led to prostate‐specific p202 expression and tumor suppression in orthotopic prostate cancer xenograft model. Furthermore, with DNA array technique, we showed that the expression of p202 was accompanied by downregulation of G2/M phase cell‐cycle regulators, cyclin B, and p55cdc. Together, our results suggest that p202 suppresses prostate tumor growth, and that a prostate‐specific antitumor effect can be achieved by systemic administration of liposome‐mediated delivery of ARR2PB‐p202. © 2003 Wiley‐Liss, Inc.
The facility location problem with general cost functions
Authors: Hajiaghayi M. T. , Mahdian M. , Mirrokni V. S.
Published: July 2003

In this paper, we introduce a generalized version of the facility location problem in which the facility cost is a function of the number of clients assigned to the facility. We focus on the case of concave facility cost functions. We observe that this problem can be reduced to the uncapacitated facility location problem. We analyze a natural greedy algorithm for this problem and show that its approximation factor is at most 1.861. We also consider several generalizations and variants of this problem. © 2003 Wiley Periodicals, Inc.
Solving the p‐Center problem with Tabu Search and Variable Neighborhood Search
Authors: Mladenović Nenad , Labbé Martine , Hansen Pierre
Published: July 2003

The p‐Center problem consists of locating p facilities and assigning clients to them in order to minimize the maximum distance between a client and the facility to which he or she is allocated. In this paper, we present a basic Variable Neighborhood Search and two Tabu Search heuristics for the p‐Center problem without the triangle inequality. Both proposed methods use the 1‐interchange (or vertex substitution) neighborhood structure. We show how this neighborhood can be used even more efficiently than for solving the p‐Median problem. Multistart 1‐interchange, Variable Neighborhood Search, Tabu Search, and a few early heuristics are compared on small‐ and large‐scale test problems from the literature. © 2003 Wiley Periodicals, Inc.
Brain aromatase, 5α‐reductase, and 5β‐reductase change seasonally in wild male song sparrows: Relationship to aggressive and sexual behavior
Authors: Soma Kiran K. , Schlinger Barney A. , Wingfield John C. , Saldanha Colin J.
Published: July 2003

In many species, territoriality is expressed only during the breeding season, when plasma testosterone (T) is elevated. In contrast, in song sparrows (Melospiza melodia morphna), males are highly territorial during the breeding (spring) and nonbreeding (autumn) seasons, but not during molt (late summer). In autumn, plasma sex steroids are basal, and castration has no effect on aggression. However, inhibition of aromatase reduces nonbreeding aggression, suggesting that neural steroid metabolism may regulate aggressive behavior. In wild male song sparrows, we examined the neural distribution of aromatase mRNA and seasonal changes in the activities of aromatase, 5α‐, and 5β‐reductase, enzymes that convert T to 17β‐estradiol, 5α‐dihydrotestosterone (5α‐DHT, a potent androgen), or 5β‐DHT (an inactive metabolite), respectively. Enzyme activities were measured in the diencephalon, ventromedial telencephalon (vmTEL, which includes avian amygdala), caudomedial neostriatum (NCM), and the hippocampus of birds captured during spring, molt, or autumn. Aromatase and 5β‐reductase changed seasonally in a region‐specific manner. Aromatase in the diencephalon was higher in spring than in molt and autumn, similar to seasonal changes in male sexual behavior. Aromatase activity in the vmTEL was high in both spring and autumn but significantly reduced at molt, similar to seasonal changes in aggression. 5β‐Reductase was not elevated during molt, suggesting that low aggression during molt is not a result of increased inactivation of androgens. These data highlight the relevance of neural steroid metabolism to the expression of natural behaviors by free‐living animals. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 209–221, 2003
PTPμ‐dependent growth cone rearrangement is regulated by Cdc42
Authors: Rosdahl Jullia A. , Ensslen Sonya E. , Niedenthal Jared A. , Brady‐Kalnay Susann M.
Published: July 2003

PTPμ is expressed in the developing nervous system and promotes growth and guidance of chick retinal ganglion cells. Using a newly developed growth cone rearrangement assay, we examined whether the small G‐proteins were involved in PTPμ‐dependent signaling. The stimulation of retinal cultures with purified PTPμ resulted in a striking morphological change in the growth cone, which becomes dominated by filopodia within 5 min of addition. This rearrangement in response to PTPμ stimulation was mediated by homophilic binding. We perturbed GTPase signaling using Toxin B, which inhibits Cdc42, Rac, and Rho, as well as the toxin Exoenzyme C3 that inhibits Rho. The PTPμ‐induced growth cone rearrangement was blocked by Toxin B, but not by Exoenzyme C3. This result suggests that either Cdc42 or Rac are required but not Rho. To determine which GTPase was involved in PTPμ signaling, we utilized dominant‐negative mutants of Cdc42 and Rac. Dominant‐negative Cdc42 blocked PTPμ‐induced rearrangement, while wild‐type Cdc42 and dominant‐negative Rac did not. Together, these results suggest a molecular signaling cascade beginning with PTPμ homophilic binding at the plasma membrane and the activation of Cdc42, which acts on the actin cytoskeleton to result in rearrangement of the growth cone. © 2003 Wiley Periodicals, Inc. J Neurobiol 56:199–208, 2003
Androgen receptor expression in the developing male and female rat visual and prefrontal cortex
Authors: Nuñez J.L. , Huppenbauer C.B. , McAbee M.D. , Juraska J.M. , DonCarlos L.L.
Published: July 2003

Gonadal steroid hormones are known to influence the development of the cerebral cortex of mammals. Steroid hormone action involves hormone binding to cytoplasmic or nuclear receptors, followed by DNA binding and gene transcription. The goals of the present study were twofold: to determine whether androgen receptors are present during development in two known androgen sensitive regions of the rat cerebral cortex, the primary visual cortex (Oc1) and the anterior cingulate/frontal cortex (Cg1/Fr2); and to determine whether androgen receptor (AR) expression in these regions differs between developing males and females. We used immunocytochemistry to detect AR protein on postnatal days 0, 4, and 10, and in situ hybridization to detect AR mRNA on postnatal day 10 in male and female rats. The level of AR expression was specific to the cortical region, with higher AR immunoreactive cell density and more AR mRNA in Oc1 than in Cg1/Fr2. AR immunoreactive cell density increased with age in both regions. Finally, on postnatal day 10, males had a higher AR immunoreactive cell density and more AR mRNA in Oc1 than did females. Thus, the presence of ARs may allow androgens to directly influence the development the cerebral cortex. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 293–302, 2003
Control of flexor motoneuron activity during single leg walking of the stick insect on an electronically controlled treadwheel
Authors: Peter Gabriel Jens , Scharstein Hans , Schmidt Joachim , Büschges Ansgar
Published: July 2003

In the present study, motoneurons innervating the flexor tibiae muscle of the stick insect (Cuniculina impigra) middle leg were recorded intracellularly while the single leg performed walking‐like movements on a treadwheel. Different levels of belt friction (equivalent to a change in load) were used to study the control of activity of flexor motoneurons. During slow leg movements no fast motoneurons were active, but a recruitment of these neurons could be observed during faster leg movements. The firing rate of slow and fast motoneurons increased with incremented belt friction. Also, the force applied to the treadwheel at different frictional levels was adapted closely to the friction of the treadwheel to be overcome. The motoneurons innervating the flexor tibiae were recruited progressively during the stance phase, with the slow motoneurons being active earlier than the fast (half‐maximal spike frequency after 10–15% and 50–60% of the stance phase, respectively). The resting membrane potential was more hyperpolarized in fast motoneurons (64.6 ± 6.5 mV) than in slow motoneurons (−52.9 ± 5.4 mV). However, the threshold for the initiation of action potentials was not statistically significantly different in both types of flexor motoneurons. Therefore, action potentials were generated in fast motoneurons after a longer period of depolarization and thus later during the stance phase than in slow motoneurons. We show that motoneurons of the flexor tibiae receive substantial common excitatory inputs during the stance phase and that the difference in resting membrane potential between slow and fast motoneurons is likely to play a crucial role in their consecutive recruitment. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 237–251, 2003
Direct injection of venom by a predatory wasp into cockroach brain
Authors: Haspel Gal , Rosenberg Lior Ann , Libersat Frederic
Published: July 2003

In this article, we provide direct evidence for injection of venom by a wasp into the central nervous system of its cockroach prey. Venomous predators use neurotoxins that generally act at the neuromuscular junction, resulting in different types of prey paralysis. The sting of the parasitoid wasp Ampulex compressa is unusual, as it induces grooming behavior, followed by a long‐term lethargic state of its insect prey, thus ultimately providing a living meal for the newborn wasp larvae. These behavioral modifications are induced only when a sting is inflicted into the head. These unique effects of the wasp venom on prey behavior suggest that the venom targets the insect's central nervous system. The mechanism by which behavior modifying compounds in the venom transverse the blood‐brain barrier to induce these central and long‐lasting effects has been the subject of debate. In this article, we demonstrate that the wasp stings directly into the target ganglia in the head of its prey. To prove this assertion, we produced “hot” wasps by injecting them with 14C radiolabeled amino acids and used a combination of liquid scintillation and light microscopy autoradiography to trace radiolabeled venom in the prey. To our knowledge, this is the first direct evidence documenting targeted delivery of venom by a predator into the brain of its prey. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 287‐292, 2003
Protein synthesis at synapse versus cell body: Enhanced but transient expression of long‐term facilitation at isolated synapses
Authors: Liu Ke , Hu Jiang‐Yuan , Wang Denong , Schacher Samuel
Published: July 2003

Protein synthesis at synaptic terminals contributes to LTP in hippocampus and to the formation of new synaptic connections by sensory neurons (SNs) of Aplysia. Here we report that after removal of the SN cell body, isolated SN synapses of Aplysia in culture express protein‐synthesis dependent long‐term facilitation (LTF) produced by 5‐HT that decays rapidly. Changes in expression of a SN‐specific neuropeptide sensorin in isolated SN varicosities parallel the changes in synaptic efficacy. At 24 h after 5‐HT the magnitude of LTF produced at isolated SN synapses was significantly greater than that produced when SN cell bodies were present. LTF was maintained at 48 h at connections with SN cell bodies, but not at isolated SN synapses. The increase in synaptic efficacy at isolated SN synapses at 24 h was blocked by the protein synthesis inhibitor anisomycin. LTF was accompanied by changes in expression of sensorin. The increase in sensorin level at isolated SN varicosities with 5‐HT was blocked by anisomycin or was reversed 48 h after 5‐HT treatment alone. The results suggest that, as is the case for initial synapse formation between SNs and L7, changes in protein synthesis at synaptic terminals may contribute directly to LTF of stable synapses. Changes in expression within the cell body provide additional contributions for long‐term maintenance of the new level of synaptic efficacy that was initiated directly by local changes in protein synthesis at or near synaptic terminals. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 275–286, 2003
Research methods: Managing primary study quality in meta‐analyses
Authors: Conn Vicki S. , Rantz Marilyn J.
Published: July 2003

Meta‐analyses synthesize multiple primary studies and identify patterns of relationships. Differences in primary study methodological quality must be addressed for meta‐analysis to produce meaningful results. No single standard exists for addressing these quality variations. Quality measurement scales are fraught with development and application problems. Several strategies have been proposed to address quality. Researchers can set minimum levels for inclusion or require that certain quality attributes be present. An inclusive method is to weight effect sizes by quality scores. This allows the inclusion of diverse studies but relies on questionable quality measures. By considering quality an empirical question, meta‐analysts can examine associations between quality and effect sizes and thus preserve the purpose of meta‐analysis to systematically examine data. Researchers increasingly are combining strategies to overcome the limitations of using a single approach. Future work to develop valid measures of primary study quality dimensions will improve the ability of meta‐analysis to inform research and nursing practice. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:322–333, 2003
Synthesis and characterization of polyurethane/polybenzoxazine‐based interpenetrating polymer networks (IPNs)
Authors: Cui Yanjun , Chen Ye , Wang Xinling , Tian Guohua , Tang Xiaozhen
Published: July 2003

Sequential interpenetrating polymer networks (IPNs), based on polyurethane and polybenzoxazine, were synthesized. Fourier Transform infrared spectrometry was employed to monitor the formation kinetics, which indicated that only physical bonding existed in the resulting IPNs. Morphological investigations revealed a lightly phase separation behaviour in all of the IPNs studied.

© 2003 Society of Chemical Industry
Study of impact properties and morphology of 4,4′‐diaminodiphenyl methane cured epoxy resin toughened with acrylate‐based liquid rubbers
Authors: Kar S , Gupta D , Banthia AK , Ratna D
Published: July 2003

Randomized carboxyl poly(2‐ethylhexyl acrylate) (A‐1) and randomized epoxy poly(2‐ethylhexyl acrylate) (B‐1) rubbers were synthesized in the form of liquid rubber by a solution polymerization technique. The liquid rubbers A‐1 and B‐1 were characterized by 1H NMR and IR spectroscopic analysis, non‐aqueous titration, viscosity measurements and gel permeation chromatography. The liquid rubbers A‐1 (M̄n = 3900 g mol−1), B‐1 (M̄n = 4100 g mol−1) and a (1:1) mixture of A‐1 and B‐1 were pre‐reacted with epoxy resin separately and the modified epoxy networks were made by curing with high temperature curing agent. The modified epoxy networks were evaluated by unnotched Izod impact testing. The morphology and toughening behaviour were analysed by scanning electron microscopy. Optimum properties were obtained with the mixture of A‐1 and B‐1. Copyright © 2003 Society of Chemical Industry
Spin probe study of semi‐interpenetrating polymer networks based on polyurethane and polymethacrylate functional prepolymers
Authors: Čulin Jelena , Veksli Zorica , Anžlovar Alojz , Žigon Majda
Published: July 2003

The motional transition and heterogeneity of semi‐interpenetrating networks (SIPNs) based on polyurethane (PU) with carboxylic groups and methacrylic copolymer (PM) with tertiary amine groups were studied by the electron spin resonance (ESR) spin probe method. The concentration of functional groups in both prepolymers varied from 0 to 0.45 mmol g−1. Spin‐probed SIPNs show that the temperature‐dependent spectra are sensitive to polymer interactions imposed by functional groups. These interactions determine the free volume distribution in the matrix and temperature at which motional transition takes place. The fraction of free volume increases with functional group concentration and reaches its maximum at 0.25 mmol g−1. Further increases in the functional group concentration reduce the free volume. The results of the networks with strong interactions are discussed in terms of the interference of the plasticizing effect of the PU component and the formation of possible cluster cross‐links, which restricts segmental motions. Copyright © 2003 Society of Chemical Industry
Intumescence in poly(butylene terephthalate): the effect of 2‐methyl‐1,2‐oxaphospholan‐5‐one 2‐oxide and ammonium polyphosphate
Authors: Balabanovich Alexander I , Balabanovich Ala M , Engelmann Jochen
Published: July 2003

The flame‐retardant effect of 2‐methyl‐1,2‐oxaphospholan‐5‐one 2‐oxide (OP) and ammonium polyphosphate (APP) in poly(butylene terephthalate) (PBT) was studied by the limiting oxygen index and the UL94 test. A self‐extinguishing formulation (V‐0 rating) was achieved by the addition of 15 wt% APP and 10 wt% OP. The fire‐retardant effect was attributed to the condensed‐phase mechanism of intumescence. Mechanistic studies were performed using thermogravimetry, IR characterization of solid residues and GC–MS characterization of the gaseous and high‐boiling products. OP–APP was shown to cause ammonolysis of PBT, formation of aromatic nitriles in the high‐boiling products and phosphorus ester groups and polyphosphoric acid–phosphorus pentaoxide in the solid residue. Copyright © 2003 Society of Chemical Industry
Synthesis and characterization of a fully aromatic polyazomethine with rotaxane architecture
Authors: Farcas Aurica , Grigoras Mircea
Published: July 2003

This paper reports the preparation and characterization of a new aromatic polyazomethine with rotaxane architecture. The complex of β‐cyclodextrin and 1,4‐phenylenediamine was treated with N‐n‐butyl‐3,6‐diformylcarbazole, which is large enough to prevent dethreading. The polycondensation reaction was performed in N,N‐dimethylformamide leading to polyazomethine soluble in polar solvents. Measurements made by gel permeation chromatography of the dimethylformamide‐soluble (DMF) soluble polyazomethine show the presence of high molecular weight material. The structure and thermal properties of the resulting polymer were characterized by IR, 1H NMR, TGA and DSC techniques. Copyright © 2003 Society of Chemical Industry
On the linear correlation between microhardness and mechanical properties in polar polymers and blends
Authors: Giménez E , Lagarón JM , Gavara R , Saura JJ
Published: July 2003

The tensile elastic modulus (E), yield stress (σY) and microhardness (MH) of neat and binary and ternary blends of glassy semicrystalline ethylene–vinyl alcohol copolymer (EVOH), a glassy amorphous polyamide and a semicrystalline nylon‐containing ionomer covering a broad range of properties were examined. The tests were carried out on dry and water‐equilibrated samples to produce stiffer and softer materials, respectively. From the results, more accurate linear correlations were found to describe adequately the microhardness, modulus and yield stress of these strongly self‐associated polymers through hydrogen bonding. Copyright © 2003 Society of Chemical Industry
Preparation and properties of acrylonitrile–butadiene copolymer hybrid nanocomposites with organoclays
Authors: Nah Changwoon , Ryu Hyune Jung , Kim Wan Doo , Chang Young‐Wook
Published: July 2003

Acrylonitrile–butadiene rubber (NBR) hybrid nanocomposites with organoclays were prepared by melt mixing, and their properties were compared with those of conventional rubber compounds filled with carbon black and silica. Based on X‐ray diffraction and transmission electron microscopy, the NBR nanocomposites obtained were found to form generally an intercalated structure, although they formed an exfoliated structure when the organoclay content was low enough, <2 parts per 100 rubber. The NBR nanocomposite showed a simultaneous improvement in ultimate strength and stiffness, which is generally in a trade‐off relation in rubbery materials. A characteristic fracture morphology of ‘laminated board‐type’ was observed for NBR nanocomposites instead of typical ‘cross‐hatched’ morphology in conventional rubber composites. The NBR nanocomposites also showed much higher hysteresis and tension set. Copyright © 2003 Society of Chemical Industry
Effect of diisopropyl thiophosphoryl‐N‐oxydiethylene sulfenamide and some disulfidic compounds in the covulcanization of NR–EPDM blends
Authors: Ghosh Arup Kumar , Basu Dipak Kumar
Published: July 2003

Synergistic combinations of diisopropyl thiophosphoryl‐N‐oxydiethylene sulfenamide (DIPTOS) with some disulfide accelerators or sulfur donors improve the physical properties of NR–EPDM blend vulcanizates. Various combinations of DIPTOS with dibenzothiazyl disulfide (MBTS), tetramethyl thiuram disulfide (TMTD), bis(N‐oxydiethylene) disulfide (ODDS) and bis(diisopropyl) thiophosphoryl disulfide (DIPDIS) were used in this study. DIPTOS when used alone produces NR vulcanizates with a moderate range of physical properties, whereas in conjunction with MBTS and DIPDIS it exhibits significant mutual activities. Morphological studies of the tensile‐fractured surfaces of the blend vulcanizates by scanning electron microscopy corroborate the physical data. Copyright © 2003 Society of Chemical Industry
Fullerene membrane transport mediated by γ‐cyclodextrin immobilised in poly(vinyl alcohol) films
Authors: Eddaoudi Hassan , Deratani André , Tingry Sophie , Sinan Fouad , Seta Patrick
Published: July 2003

This paper reports on fullerene C60 and C70 transport across hydrophilic membrane materials consisting of a poly(vinyl alcohol) matrix on which γ‐cyclodextrin moieties were attached as molecular recognition sites. The rate‐limiting step of the membrane transport was demonstrated to be dissociation of the inclusion complex at the stripping interface. Copyright © 2003 Society of Chemical Industry
Study of optically active methacrylates containing 1,1′‐binaphthyl side‐groups polymerized by anionic, group transfer and free radical methods
Authors: Xue Hong , Xu Yong‐An , Song Nai‐Heng , Gao Lian‐Xun , Ding Meng‐Xian
Published: July 2003

Optically active and racemic poly(meth)acrylates with pendant 1,1′‐binaphthalene moiety of 2‐methacryloyloxy‐ and 2‐acryloyloxy‐2′‐methoxy‐1,1′‐binaphthalene (MAMBN and AMBN) were synthesized by anionic, group transfer and free radical polymerization methods. Their polymerizability and chiroptical properties are somewhat different, depending on the three types of polymerization methods used. The yields for poly(MAMBN)s are lower than for poly(AMBN)s. The optical rotation of the optically active polymers is identical to that of the corresponding monomers. The values of specific rotation of optically active poly(AMBN)s are much larger than those of optically active poly(MAMBN)s. © 2002 Society of Chemical Industry
On robust stability of multivariate interval plants
Authors: Kharitonov V. L. , Torres‐Muñoz J. A. , Rodríguez‐Angeles E.
Published: July 2003

In this work we consider the stability property of the feedback connection of a multivariate interval plant with a fixed compensator. Copyright © 2003 John Wiley & Sons, Ltd.
A theoretical framework for gain scheduling
Authors: Fromion Vincent , Scorletti Gérard
Published: July 2003

The weighted incremental norm approach was originally introduced as a natural framework for extending well‐known H∞ linear control concepts into the nonlinear context. In this paper, we investigate the numerous links between this new approach and the classical gain‐scheduling technique. Although based on heuristic rules, gain‐scheduled control is probably the most widespread nonlinear technique. In this paper, we point out that the control objectives of the gain‐scheduled controller design can be expressed as the weighted incremental norm minimization of a nonlinear operator. The result interest is twofold: it first provides a rigorous mathematical formulation of the gain‐scheduling problem. Furthermore, existing gain‐scheduling techniques can be interpreted as approximate solutions to the weighted incremental norm minimization of a nonlinear operator. Copyright © 2003 John Wiley & Sons, Ltd.
RobustH2filtering of linear systems with time delays
Authors: Fridman E. , Shaked U. , Xie L.
Published: July 2003

The problem of robustH2estimation of a combination of states of a stationary linear system with time delays is considered. Since the problem is infinite dimensional in nature, an attempt is being made to develop finite dimensional methods that will guarantee a preassigned estimation accuracy. The approach of minimizing the trace of a matrix that overbounds the exact covariance of the estimation error is considered. Sufficient conditions are given in the form of linear matrix inequalities (LMIs). The results are illustrated by a numerical example. Copyright © 2003 John Wiley & Sons, Ltd.
Cold‐inducible expression of the cell division cycle gene CDC48 and its promotion of cell proliferation during cold acclimation in zebrafish cells1
Authors: Imamura Shintaro , Ojima Nobuhiko , Yamashita Michiaki
Published: July 2003

A member of the ATPases associated with diverse cellular activities (AAA) family, the cell division cycle gene CDC48/VCP (valosin‐containing protein)/p97, was cloned from zebrafish and found to be a major cold‐inducible protein in fish cells. CDC48 mRNA levels increased significantly after reducing the temperature from 30 to 15°C for 25 days. CDC48 protein levels also increased 2.5‐fold after 30 days at cold temperatures. When fish cells overexpressing CDC48 were exposed to a temperature of 15°C, cell proliferation was markedly enhanced in comparison with control cells. By contrast, expression of a mutant molecule with a tyrosine‐805 to alanine substitution at the C‐terminal phosphorylation site inhibited cell proliferation and induced apoptosis at low temperatures. Therefore, CDC48 may promote cell cycling and cell proliferation via C‐terminal tyrosine phosphorylation during cold acclimation in fish cells.
The diverse bacterial origins of the Arabidopsis polyamine biosynthetic pathway
Authors: Illingworth Crista , Mayer Melinda J. , Elliott Katherine , Hanfrey Colin , Walton Nicholas J. , Michael Anthony J.
Published: July 2003

We functionally identified the last remaining step in the plant polyamine biosynthetic pathway by expressing an Arabidopsis thaliana agmatine iminohydrolase cDNA in yeast. Inspection of the whole pathway suggests that the arginine decarboxylase, agmatine iminohydrolase, N‐carbamoylputrescine amidohydrolase route to putrescine in plants was inherited from the cyanobacterial ancestor of the chloroplast. However, the rest of the pathway including ornithine decarboxylase and spermidine synthase was probably inherited from bacterial genes present in the original host cell, common ancestor of plants and animals, that acquired the cyanobacterial endosymbiont. An exception is S‐adenosylmethionine decarboxylase, which may represent a eukaryote‐specific enzyme form.
Detection of an enol intermediate in the hydroperoxide lyase chain cleavage reaction
Authors: Grechkin Alexander N , Mukhtarova Lucia S , Hamberg Mats
Published: July 2003

Guava (Psidium guajava) hydroperoxide lyase (HPL) preparations were incubated with [1‐14C](9Z,11E,13S,15Z)‐13‐hydroperoxy‐9,11,15‐octadecatrienoic acid for 1 min at 0°C, followed by rapid extraction/trimethylsilylation. Analysis of the trimethylsilylated products by gas chromatography–mass spectrometry and radio‐high‐performance liquid chromatography revealed a single predominant 14C‐labelled compound, identified by its 1H‐nuclear magnetic resonance, ultraviolet and mass spectra as the trimethylsilyl ether/ester of (9Z,11E)‐12‐hydroxy‐9,11‐dodecadienoic acid. Longer time incubations afford smaller yield of this enol due to its partial tautomerization into (9Z)‐12‐oxo‐9‐dodecenoic acid. The data obtained demonstrate that formation of (9Z)‐12‐oxo‐9‐dodecenoic acid in the HPL reaction is preceded by unstable enol oxylipin, and further suggest that hemiacetals are the true products of HPL catalysis.
Ground state isomerization of a model green fluorescent protein chromophore
Authors: He Xiang , Bell Alasdair F. , Tonge Peter J.
Published: July 2003

The relationship between ground state cis–trans isomerization and protonation state is explored for a model green fluorescent protein chromophore, 4‐hydroxybenzylidene‐1,2‐dimethylimidazolinone (HBDI). We find that the protonation state has only a modest effect on the free energy differences between cis and trans isomers and on the activation energies for isomerization. Specifically, the experimental free energy differences are 3.3, 8.8, and 9.6 kJ/mol for cationic, neutral, and anionic forms of HBDI, respectively, and the activation energies are 48.9, 54.8, and 54.8 kJ/mol for cationic, neutral, and anionic forms, respectively. Furthermore, these activation energies are much smaller than might be expected based on comparison with similar systems. These results suggest that there may be a sub‐population of the chromophore, which is nearly equally accessible to all three protonation states, through which thermal isomerization may proceed.
The plant cytolytic protein enterolobin assumes a dimeric structure in solution
Authors: Bittencourt Silvia E.T , Silva Luciano P , Azevedo Ricardo B , Cunha Ricardo B , Lima Consuelo M.R , Ricart Carlos A.O , Sousa Marcelo V
Published: July 2003

Enterolobin is a plant cytolytic protein similar to the bacterial cytolysin aerolysin. Biochemical and biophysical techniques were used to verify if enterolobin, like aerolysin, adopts a dimeric structure in solution. SDS–PAGE showed bands corresponding to enterolobin monomer, dimer and oligomers, whilst gel filtration chromatography and electrospray mass spectrometry revealed preferred association of enterolobin as a dimer. Atomic force microscopy (AFM) of enterolobin showed images of a dimer assembly at a concentration as low as 10 μg/ml, similarly to aerolysin. The enterolobin in silico docked structure is coherent with AFM enterolobin dimer shapes.
Amiloride inhibition of the proton‐translocating NADH‐quinone oxidoreductase of mammals and bacteria
Authors: Nakamaru-Ogiso Eiko , Seo Byoung Boo , Yagi Takao , Matsuno-Yagi Akemi
Published: July 2003

The proton‐translocating NADH‐quinone oxidoreductase in mitochondria (complex I) and bacteria (NDH‐1) was shown to be inhibited by amiloride derivatives that are known as specific inhibitors for Na+/H+ exchangers. In bovine submitochondrial particles, the effective concentrations were about the same as those for the Na+/H+ exchangers, whereas in bacterial membranes the inhibitory potencies were lower. These results together with our earlier observation that the amiloride analogues prevent labeling of the ND5 subunit of complex I with a fenpyroximate analogue suggest the involvement of ND5 in H+ (Na+) translocation and no direct involvement of electron carriers in H+ (Na+) translocation.
The ‘antiporter module’ of respiratory chain Complex I includes the MrpC/NuoK subunit – a revision of the modular evolution scheme
Authors: Mathiesen Cecilie , Hägerhäll Cecilia
Published: July 2003

Respiratory chain Complex I or NADH:quinone oxidoreductase catalyzes oxidation of NADH in the mitochondrial matrix or bacterial cytoplasm and reduction of quinone in the membrane, coupled to pumping of 4H+/2e−across the membrane. The same enzyme complex is also capable of the reverse reaction, i.e. ΔμH+‐supported NAD+reduction. The molecular mechanism that couples electron transfer to proton pumping is not understood. The Complex I enzyme, containing 14 protein subunits necessary for function, has evolved from smaller functional building blocks. Three Complex I protein subunits, NuoL, NuoM and NuoN, show primary sequence similarity to one particular class of antiporters, and are thus predicted to play a role in the proton translocation machinery. These antiporters, MrpA and MrpD are encoded by a conserved gene cluster, that contains seven genes. In previous work we have determined that these antiporters come in two subclasses, MrpA‐type and MrpD‐type, and that the Complex I subunit NuoL is more closely related to MrpA and NuoM and N are more closely related to the MrpD antiporter. This implied that both MrpA and MrpD had been recruited to Complex I, rather than arising from gene duplications of one antiporter encoding gene. In this work we show that MrpC and NuoK are homologous proteins. The most plausible explanation for these findings is that a multisubunit antiporter complex was recruited to the ancestral enzyme. We further conclude that the last common ancestor of the Complex I enzyme family and membrane bound NiFe hydrogenases of type 3 and 4 contained the NuoKLMN subunit module.
Targeted inactivation of the hrcA repressor gene in cyanobacteria
Authors: Nakamoto Hitoshi , Suzuki Michiru , Kojima Kouji
Published: July 2003

To determine if the CIRCE/HrcA system operates in cyanobacteria, we have inactivated the hrcA repressor gene in Synechocystis sp. PCC 6803 by gene targeting. In the hrcA mutant, the groESL1 operon and the groEL2 gene, both of which have the CIRCE operator in their upstream regions, were derepressed at 30°C without affecting expression of other major heat‐shock genes. However, expression of these groE genes in the mutant was not fully derepressed. Their transcription increased further upon heat shock, and was initiated from the same sites as those used under normal conditions. This suggests that their expression is regulated by at least two different mechanisms, a negative one controlled by HrcA and an unknown positive one. The heat‐induced expression of clpB1 and htpG was greatly repressed by the absence of HrcA. The hrcA mutant which constitutively overexpressed GroEL displayed improved cellular thermotolerance and also reduced photobleaching of phycocyanin under heat stress conditions.
Insulin regulates the expression of the GLUT5 transporter in L6 skeletal muscle cells
Authors: Hajduch Eric , Litherland Gary J. , Turban Sophie , Brot-Laroche Edith , Hundal Harinder S.
Published: July 2003

Skeletal muscle, a primary insulin target tissue, expresses the GLUT5 fructose transporter. Although insulin has no acute effect on GLUT5 expression and function in muscle, we show here that long‐term (24 h) insulin treatment of L6 muscle cells induces a dose‐dependent increase in GLUT5 protein (by up to two‐fold), leading to a concomitant increase in fructose uptake. The increase in GLUT5 expression and function was suppressed by inhibitors of gene transcription and protein synthesis, suggesting that insulin promotes de novo carrier synthesis. Transfection of the GLUT5 gene promoter fused to luciferase into L6 cells revealed that insulin induced a 1.8‐fold increase in GLUT5 promoter activity. Our findings indicate that insulin is capable of increasing the abundance and functional activity of GLUT5 in skeletal muscle cells and that this is most likely mediated via activation of the GLUT5 promoter.
Are chlorella viruses a rich source of ion channel genes?
Authors: Kang Ming , Moroni Anna , Gazzarrini Sabrina , Van Etten James L.
Published: July 2003

Plaque‐forming dsDNA (>330 kb) viruses that infect certain unicellular, eukaryotic chlorella‐like green algae contain ∼375 protein‐encoding genes. These proteins include a 94 amino acid K+channel protein, called Kcv, as well as two putative ligand‐gated ion channels. The viruses also encode other proteins that could be involved in the assembly and/or function of ion channels, including protein kinases and a phosphatase, polyamine biosynthetic enzymes and histamine decarboxylase.
Possible function for virus encoded K+ channel Kcv in the replication of chlorella virus PBCV‐1
Authors: Mehmel Mario , Rothermel Maike , Meckel Tobias , Van Etten James L , Moroni Anna , Thiel Gerhard
Published: July 2003

The K+ channel Kcv is encoded by the chlorella virus PBCV‐1. There is evidence that this channel plays an essential role in the replication of the virus, because both PBCV‐1 plaque formation and Kcv channel activity in Xenopus oocytes have similar sensitivities to inhibitors. Here we report circumstantial evidence that the Kcv channel is important during virus infection. Recordings of membrane voltage in the host cells Chlorella NC64A reveal a membrane depolarization within the first few minutes of infection. This depolarization displays the same sensitivity to cations as Kcv conductance; depolarization also requires the intact membrane of the virion. Together these data are consistent with the idea that the virus carries functional K+ channels in the virion and inserts them into the host cell plasma membrane during infection.
Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data
Authors: Lear James D
Published: July 2003

The M2 proton channel from influenza A virus forms proton‐selective ion channels, which are the target of the drug amantadine. Here, existing experimental data are quantitatively examined for insights into mechanisms to account for the pH‐ and voltage‐dependences of M2 proton conduction. The analysis shows that a model involving protonation equilibria of His37, including pH‐dependent changes in the relative rates of diffusion on either side of the pore, is quantitatively able to account for recently reported electrophysiological data examining the pH‐ and voltage‐dependences of Rostock and Weybridge strain M2 proton conduction.
Viroporins
Authors: Gonzalez Maria Eugenia , Carrasco Luis
Published: July 2003

Viroporins are a group of proteins that participate in several viral functions, including the promotion of release of viral particles from cells. These proteins also affect cellular functions, including the cell vesicle system, glycoprotein trafficking and membrane permeability. Viroporins are not essential for the replication of viruses, but their presence enhances virus growth. Comprising some 60–120 amino acids, viroporins have a hydrophobic transmembrane domain that interacts with and expands the lipid bilayer. Some viroporins also contain other motifs, such as basic amino acid residues or a domain rich in aromatic amino acids that confers on the protein the ability to interact with the interfacial lipid bilayer. Viroporin oligomerization gives rise to hydrophilic pores at the membranes of virus‐infected cells. As the list of known viroporins steadily grows, recent research efforts focus on deciphering the actions of the viroporins poliovirus 2B, alphavirus 6K, HIV‐1 Vpu and influenza virus M2. All these proteins can enhance the passage of ions and small molecules through membranes depending on their concentration gradient. Future work will lengthen the list of viroporins and will provide a deeper understanding of their mechanisms of action.
Roles of the histidine and tryptophan side chains in the M2 proton channel from influenza A virus
Authors: Takeuchi Hideo , Okada Atsushi , Miura Takashi
Published: July 2003

The M2 protein form influenza A virus forms a tetrameric ion channel, which enables proton passage across biological membranes when the N‐terminal side is acidified. Among the amino acid residues in the transmembrane domain of the M2 protein, His37 and Trp41 are essential for the pH‐regulated proton conductance. Current knowledge about the structures and interactions of His37 and Trp41 suggests a model for the M2 ion channel, in which the channel is closed by a network of His37 hydrogen bonds at neutral pH and is opened by a His37‐Trp41 cation–π interaction at acidic pH.
Vpu from HIV‐1 on an atomic scale: experiments and computer simulations
Authors: Fischer W.B
Published: July 2003

Vpu is an 81 amino acid protein encoded by HIV‐1. Its role is to amplify viral release by two mechanisms: (i) docking to CD4 with the consequence of targeting CD4 for ubiquitine‐mediated degradation, and (ii) formation of ion channels to enhance particle release. The intensive research on its in vivo function, combined with structural investigations, makes this viral membrane protein one of the better characterised membrane proteins. The wealth of structural information enables the use of computational methods to elucidate the mechanisms of function on an atomic scale. The discovery of Vpu and the development of structural models in a chronological order is summarised and first efforts on investigating the mechanics are outlined.
The lichen flora of unprotected soft sea cliffs and slopes
Authors: Gilbert Oliver L.
Published: July 2003

Soft unprotected sea cliffs and slopes were surveyed at forty localities around the English coast and found to support a restricted lichen flora that was zoned in relation to sea-level. Bed rock composition, structural heterogeneity and high levels of instability largely control the terricolous lichen vegetation, which is predominantly composed of calcicoles typical of early successional stages. Cyanobacterial lichens are well represented. The species encountered can be arranged into three provisional assemblages characteristic of alkaline bed rock, acidic bed rock, and turf edges. Few species with maritime affinities were present but this group included rarely recorded species of Pyrenocollema and abundant Lecanora zosterae. Other rare and unusual lichens were present, often at a low density and in only a few localities. The lichen flora of soft cliffs has links with that found on urban wasteland and, remotely, with that of sand dunes.
The lichenicolous fungi of Great Britain and Ireland: an overview and annotated checklist
Authors: Hawksworth David L.
Published: July 2003

Since the last compilation in 1983, the number of lichenicolous fungi (and lichenicolous lichens) recorded in Great Britain and Ireland has increased from 218 to 403 species (a rise of 85%). The introduction includes accounts of: the history of investigation, circumscription, phylogenetic relationships, symbiotic interactions, dispersal and establishment, distribution, culture, host restriction, and identification. The checklist enumerates the recorded species. Information is provided on the systematic position of each genus, together with the authors and dates of publication of all accepted names; synonyms used in the literature of the two countries since 1910 are cross-indexed. References to pertinent literature with descriptions and discussions are included, together with notes on particular species. The list of references cited includes 298 publications. The following new scientific names are introduced: Diederichia gen. nov., and Dactylospora scapanaria (syn. Lecidea scapanaria), Diederichia pseudevemiae (syn. Macrophomina pseudeverniae), Muellerella ventosicola (syn. Microthelia ventosicola) and Nigromacula uniseptata (syn. Vouauxiella uniseptata) combs, nov.
Luminescence chronology of late Pleistocene loess-paleosol and tephra sequences near Fairbanks, Alaska
Authors: Berger Glenn W.
Published: July 2003

Thermoluminescence (TL) and infrared-stimulated luminescence (IRSL) sediment-dating methods have been applied to paleosol- and tephra-bearing loess sequences younger than marine oxygen isotope stage (MIS) 7 at three important sites. TL ages indicate the development of significant paleosols ∼75,000 and ∼30,000 yr ago in the loess sequence at the Gold Hill site. Relatively minor soil development occurred ∼70,000 and ∼48,000 yr ago. Like the ∼75,000-yr-old soil, the 30,000-yr-old soil is apparently of global extent, and consistent in timing with inferred warm intervals elsewhere (e.g., Greenland, Europe, western and central China). At Birch Hill, replicate TL dating of primary loess combined with two earlier TL results from the same site, and with an earlier mean fission-track-glass-shard age of 140,000 ± 10,000 yr for the associated Old Crow tephra, yield a more precise numeric age of 142,300 ± 6600 yr for this Alaska/Yukon chronostratigraphic marker ash bed. Three of the TL ages at the Halfway House site are difficult to interpret, but combined with other evidence, they indicate: (1) the upper 5–6 m of loess from Halfway House is not part of the Gold Hill Loess (equivalent to pre-MIS 5 age) as long thought by T.L. Péwé, but rather is much younger; (2) the regionally significant variegated tephra, found in the Fairbanks and Klondike areas and previously thought to be older than MIS 5, has an age of 77,800 ± 4100 yr (late MIS 5).