bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of Vp1 Calcium-Binding Residues in Assembly, Cell Entry, and Nuclear Entry of Simian Virus 40
Authors: Li Peggy P. , Naknanishi Akira , Tran Mary A. , Ishizu Ken-Ichiro , Kawano Masaaki , Phillips Martin , Handa Hiroshi , Liddington Robert C. , Kasamatsu Harumi
Published: June 2003

For polyomaviruses, calcium ions are known to be essential for virion integrity and for the assembly of capsid structures. To define the role of calcium ions in the life cycle of the virus, we analyzed simian virus 40 (SV40) mutants in which structurally deduced calcium-binding amino acids of Vp1 were mutated singly and in combination. Our study provides evidence that calcium ions mediate not only virion assembly but also the initial infection processes of cell entry and nuclear entry. Mutations at Glu48, Glu157, Glu160, Glu216, and/or Glu330 are correlated with different extents of packaging defects. The low packaging ability of mutant E216R suggests the need to position the Glu216 side chain for proper virion formation. All other mutants selected for further analysis produced virus-like particles (VLPs) but were poorly infectious. The VLPs of mutant E330K could not attach to or enter the cell, and mutant E157A-E160A and E216K VLPs entered the cell but failed to enter the nucleus, apparently as a result of premature VLP dissociation. Our results show that five of the seven acidic side chains at the two calcium-binding sites—Glu48 and Glu330 (site 1), Glu157 and Glu160 (site 2), and Glu216 (both sites)—are important for SV40 infection. We propose that calcium coordination imparts not only stability but also structural flexibility to the virion, allowing the acquisition or loss of the ion at the two sites to control virion formation in the nucleus, as well as virion structural alterations at the cell surface and in the cytoplasm early during infection.
Antibody-Dependent Enhancement of Ebola Virus Infection
Authors: Takada Ayato , Feldmann Heinz , Ksiazek Thomas G. , Kawaoka Yoshihiro
Published: June 2003

Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the Zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and by complement component C1q. Our results suggest a novel mechanism of antibody-dependent enhancement of Ebola virus infection, one that would account for the dire outcome of Ebola outbreaks in human populations.
Susceptibility of Immature and Mature Langerhans Cell-Type Dendritic Cells to Infection and Immunomodulation by Human Cytomegalovirus
Authors: Hertel Laura , Lacaille Vashti G. , Strobl Herbert , Mellins Elizabeth D. , Mocarski Edward S.
Published: June 2003

Human cytomegalovirus (CMV) infection initiates in mucosal epithelia and disseminates via leukocytes throughout the body. Langerhans cells (LCs), the immature dendritic cells (DCs) that reside in epithelial tissues, are among the first cells to encounter virus and may play important roles in the immune response, as well as in pathogenesis as hosts for viral replication and as vehicles for dissemination. Here, we demonstrate that CD34+progenitor cell-derived LC-type DCs exhibit a differentiation state-dependent susceptibility to CMV infection. In contrast to the small percentage (3 to 4%) of the immature LCs that supported infection, a high percentage (48 to 74%) of mature, LC-derived DCs were susceptible to infection with endotheliotropic strains (TB40/E or VHL/E) of CMV. These cells were much less susceptible to viral strains AD169varATCC, TownevarRIT3, and Toledo. When exposed to endotheliotropic strains, viral gene expression (IE1/IE2 and other viral gene products) and viral replication proceeded efficiently in LC-derived mature DCs (mDCs). Productive infection was associated with downmodulation of cell surface CD83, CD1a, CD80, CD86, ICAM-1, major histocompatibility complex (MHC) class I, and MHC class II on these cells. In addition, the T-cell proliferative response to allogeneic LC-derived mDCs was attenuated when CMV-infected cultures were used as stimulators. This investigation revealed important characteristics of the interaction between CMV and the LC lineage of DCs, suggesting that LC-derived mDCs are important to viral pathogenesis and immunity through their increased susceptibility to virus replication and virus-mediated immune escape.
Crystallographic Identification of a Noncompetitive Inhibitor Binding Site on the Hepatitis C Virus NS5B RNA Polymerase Enzyme
Authors: Love Robert A. , Parge Hans E. , Yu Xiu , Hickey Michael J. , Diehl Wade , Gao Jingjin , Wriggers Hilary , Ekker Anne , Wang Liann , Thomson James A. , Dragovich Peter S. , Fuhrman Shella A.
Published: June 2003

The virus-encoded nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA-dependent RNA polymerase and is absolutely required for replication of the virus. NS5B exhibits significant differences from cellular polymerases and therefore has become an attractive target for anti-HCV therapy. Using a high-throughput screen, we discovered a novel NS5B inhibitor that binds to the enzyme noncompetitively with respect to nucleotide substrates. Here we report the crystal structure of NS5B complexed with this small molecule inhibitor. Unexpectedly, the inhibitor is bound within a narrow cleft on the protein's surface in the “thumb” domain, about 30 Å from the enzyme's catalytic center. The interaction between this inhibitor and NS5B occurs without dramatic changes to the structure of the protein, and sequence analysis suggests that the binding site is conserved across known HCV genotypes. Possible mechanisms of inhibition include perturbation of protein dynamics, interference with RNA binding, and disruption of enzyme oligomerization.
Nuclear Export of Vpr Is Required for Efficient Replication of Human Immunodeficiency Virus Type 1 in Tissue Macrophages
Authors: Sherman Michael P. , de Noronha Carlos M. C. , Eckstein Lauren A. , Hataye Jason , Mundt Pamela , Williams Samuel A. F. , Neidleman Jason A. , Goldsmith Mark A. , Greene Warner C.
Published: June 2003

Retroviruses must gain access to the host cell nucleus for subsequent replication and viral propagation. Human immunodeficiency virus type 1 (HIV-1) and other primate lentiviruses are distinguished from the gammaretroviruses by their ability to infect nondividing cells such as macrophages, an important viral reservoir in vivo. Rather than requiring nuclear membrane breakdown during cell division, the HIV-1 preintegration complex (PIC) enters the nucleus by traversing the central aqueous channel of the limiting nuclear pore complex. The HIV-1 PIC contains three nucleophilic proteins, matrix, integrase, and Vpr, all of which have been implicated in nuclear targeting. The mechanism by which Vpr can display such nucleophilic properties and yet also be available for incorporation into virions assembling at the plasma membrane is unresolved. We recently characterized Vpr as a nucleocytoplasmic shuttling protein that contains two novel nuclear import signals and an exportin-1-dependent nuclear export signal (NES). We now demonstrate that mutation of this NES impairs the incorporation of Vpr into newly formed virions. Furthermore, we find that the Vpr NES is required for efficient HIV replication in tissue macrophages present in human spleens and tonsils. These findings underscore how the nucleocytoplasmic shuttling of Vpr not only contributes to nuclear import of the HIV-1 PIC but also enables Vpr to be present in the cytoplasm for incorporation into virions, leading to enhancement of viral spread within nondividing tissue macrophages.
Molecular Distinction between Pathogenic and Infectious Properties of the Prion Protein
Authors: Chiesa Roberto , Piccardo Pedro , Quaglio Elena , Drisaldi Bettina , Si-Hoe San Ling , Takao Masaki , Ghetti Bernardino , Harris David A.
Published: June 2003

Tg(PG14) mice express a prion protein (PrP) with a nine-octapeptide insertion associated with a human familial prion disease. These animals spontaneously develop a fatal neurodegenerative disorder characterized by ataxia, neuronal apoptosis, and accumulation in the brain of an aggregated and weakly protease-resistant form of mutant PrP (designated PG14
spon
). Brain homogenates from Tg(PG14) mice fail to transmit disease after intracerebral inoculation into recipient mice, indicating that PG14
spon
, although pathogenic, is distinct from PrP
Sc
, the infectious form of PrP. In contrast, inoculation of Tg(PG14) mice with exogenous prions of the RML strain induces accumulation of PG14
RML
, a PrP
Sc
form of the mutant protein that is infectious and highly protease resistant. Like PrP
Sc
, both PG14
spon
and PG14
RML
display conformationally masked epitopes in the central and octapeptide repeat regions. However, these two forms differ profoundly in their oligomeric states, with PG14
RML
aggregates being much larger and more resistant to dissociation. Our analysis provides new molecular insight into an emerging puzzle in prion biology, the discrepancy between the infectious and neurotoxic properties of PrP.
Human Immunodeficiency Virus Type 2 Reverse Transcriptase Activity in Model Systems That Mimic Steps in Reverse Transcription
Authors: Post Klara , Guo Jianhui , Howard Kathryn J. , Powell Michael D. , Miller Jennifer T. , Hizi Amnon , Le Grice Stuart F. J. , Levin Judith G.
Published: June 2003

Human immunodeficiency virus type 2 (HIV-2) infection is a serious problem in West Africa and Asia. However, there have been relatively few studies of HIV-2 reverse transcriptase (RT), a potential target for antiviral therapy. Detailed knowledge of HIV-2 RT activities is critical for development of specific high-throughput screening assays of potential inhibitors. Here, we have conducted a systematic evaluation of HIV-2 RT function, using assays that model specific steps in reverse transcription. Parallel studies were performed with HIV-1 RT. In general, under standard assay conditions, the polymerase and RNase H activities of the two enzymes were comparable. However, when the RT concentration was significantly reduced, HIV-2 RT was less active than the HIV-1 enzyme. HIV-2 RT was also impaired in its ability to catalyze secondary RNase H cleavage in assays that mimic tRNA primer removal during plus-strand transfer and degradation of genomic RNA fragments during minus-strand DNA synthesis. In addition, initiation of plus-strand DNA synthesis was much less efficient with HIV-2 RT than with HIV-1 RT. This may reflect architectural differences in the primer grip regions in the p66 (HIV-1) and p68 (HIV-2) palm subdomains of the two enzymes. The implications of our findings for antiviral therapy are discussed.
STAT Protein Interference and Suppression of Cytokine Signal Transduction by Measles Virus V Protein
Authors: Palosaari Heidi , Parisien Jean-Patrick , Rodriguez Jason J. , Ulane Christina M. , Horvath Curt M.
Published: June 2003

Measles virus, a paramyxovirus of the
Morbillivirus
genus, is responsible for an acute childhood illness that infects over 40 million people and leads to the deaths of more than 1 million people annually (C. J. Murray and A. D. Lopez, Lancet 349:1269-1276, 1997). Measles virus infection is characterized by virus-induced immune suppression that creates susceptibility to opportunistic infections. Here we demonstrate that measles virus can inhibit cytokine responses by direct interference with host STAT protein-dependent signaling systems. Expression of the measles V protein prevents alpha, beta, and gamma interferon-induced transcriptional responses. Furthermore, it can interfere with signaling by interleukin-6 and the non-receptor tyrosine kinase, v-Src. Affinity purification demonstrates that the measles V protein associates with cellular STAT1, STAT2, STAT3, and IRF9, as well as several unidentified partners. Mechanistic studies indicate that while the measles V protein does not interfere with STAT1 or STAT2 tyrosine phosphorylation, it causes a defect in IFN-induced STAT nuclear accumulation. The defective STAT nuclear redistribution is also observed in measles virus-infected cells, where some of the STAT protein is detected in cytoplasmic bodies that contain viral nucleocapsid protein and nucleic acids. Interference with STAT-inducible transcription may provide a novel intracellular mechanism for measles virus-induced cytokine inhibition that links innate immune evasion to adaptive immune suppression.
Classical Swine Fever Virus Interferes with Cellular Antiviral Defense: Evidence for a Novel Function of Npro
Authors: Ruggli Nicolas , Tratschin Jon-Duri , Schweizer Matthias , McCullough Kenneth C. , Hofmann Martin A. , Summerfield Artur
Published: June 2003

Classical swine fever virus (CSFV) replicates efficiently in cell lines and monocytic cells, including macrophages (MΦ), without causing a cytopathic effect or inducing interferon (IFN) secretion. In the present study, the capacity of CSFV to interfere with cellular antiviral activity was investigated. When the porcine kidney cell line SK-6 was infected with CSFV, there was a 100-fold increased capacity to resist to apoptosis induced by polyinosinic-polycytidylic acid [poly(IC)], a synthetic double-stranded RNA. In MΦ, the virus infection inhibited poly(IC)-induced alpha/beta IFN (type I IFN) synthesis. This interference with cellular antiviral defense correlated with the presence of the viral Nprogene. Mutants lacking the Nprogene (ΔNproCSFV) did not protect SK-6 cells from poly(IC)-induced apoptosis, despite growth properties and protein expression levels similar to those of the wild-type virus. Furthermore, ΔNproCSFV did not prevent poly(IC)-induced type I IFN production in MΦ but rather induced type I IFN in the absence of poly(IC) in both MΦ and the porcine kidney cell line PK-15, but not in SK-6 cells. With MΦ and PK-15, an impaired replication of the ΔNproCSFV compared with wild-type virus was noted. In addition, ΔNproCSFV, but not wild-type CSFV, could interfere with vesicular stomatitis virus replication in PK-15 cells. Taken together, these results provide evidence for a novel function associated with CSFV Nprowith respect to the inhibition of the cellular innate immune system.
Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1
gag
Gene
Authors: Casimiro Danilo R. , Tang Aimin , Chen Ling , Fu Tong-Ming , Evans Robert K. , Davies Mary-Ellen , Freed Daniel C. , Hurni William , Aste-Amezaga Jose M. , Guan Liming , Long Romnie , Huang Lingyi , Harris Virginia , Nawrocki Denise K. , Mach Henryk , Troutman Robert D. , Isopi Lynne A. , Murthy Krishna K. , Rice Karen , Wilson Keith A. , Volkin David B. , Emini Emilio A. , Shiver John W.
Published: June 2003

The cellular immunogenicity of formulated plasmid DNA and replication-defective human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized human immunodeficiency virus type 1
gag
gene was examined in baboons. The Ad5 vaccine was capable of inducing consistently strong, long-lived CD8
+
-biased T-cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune responses were weaker than those elicited by the Ad5 vaccine and highly variable; formulation with chemical adjuvants led to moderate increases in the levels of Gag-specific T cells. Increasing the DNA-primed responses with booster doses of either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in the relative levels of cytotoxic and helper responses. The implications of these results are discussed.
Direct Evidence that C-Peptide Inhibitors of Human Immunodeficiency Virus Type 1 Entry Bind to the gp41 N-Helical Domain in Receptor-Activated Viral Envelope
Authors: Kilgore Nicole R. , Salzwedel Karl , Reddick Mary , Allaway Graham P. , Wild Carl T.
Published: June 2003

While it has been established that peptides modeling the C-helical region of human immunodeficiency virus type 1 gp41 are potent in vivo inhibitors of virus replication, their mechanism of action has yet to be determined. It has been proposed, but never directly demonstrated, that these peptides block virus entry by interacting with gp41 to disrupt the formation or function of a six-helix bundle structure. Using a six-helix bundle-specific monoclonal antibody with isolate-restricted Env reactivity, we provide the first direct evidence that, in receptor-activated viral Env, C-peptide entry inhibitors bind to the gp41 N-helical coiled-coil to form a peptide/protein hybrid structure and, in doing so, disrupt native six-helix bundle formation.
Episomal Persistence of Recombinant Adenoviral Vector Genomes during the Cell Cycle In Vivo
Authors: Ehrhardt Anja , Xu Hui , Kay Mark A.
Published: June 2003

Previously we showed that recombinant adenoviral helper-dependent (HD) vectors result in long-term transgene expression levels in vivo which slowly declined by 95% over a period of 1 year. In this study, we further establish that this was not predominantly immune mediated. To determine if cell turnover was responsible for the loss of transgene expression, we induced rapid hepatocyte cell cycling in mouse liver, by performing a surgical two-thirds partial hepatectomy. We observed a 55 and 65% reduction in transgene expression levels and a 50 and 71% loss of vector genomes for the HD vector and the first-generation adenoviral vector. In sharp contrast, in nonviral, episomal plasmid DNA-injected mice, transgene expression levels and DNA copy numbers decreased by 95 and 99%, respectively. These findings suggest that cell division alone was not the primary reason for the slow decrease in transgene expression levels and that recombinant adenoviral vectors have a more robust mechanism for maintaining persistence during cell cycling. Several potential mechanisms are proposed.
Short-Term Effect of Zidovudine on Plasma and Genital Human Immunodeficiency Virus Type 1 and Viral Turnover in These Compartments
Authors: Mbori-Ngacha Dorothy , Richardson Barbra A. , Overbaugh Julie , Panteleeff Dana DeVange , Nduati Ruth , Steele Matt , John-Stewart Grace
Published: June 2003

The effect of zidovudine on plasma and genital human immunodeficiency virus type 1 (HIV-1) was determined in 42 antiretroviral-naive HIV-1-seropositive women in Nairobi. After 7 days of zidovudine treatment, HIV-1 RNA levels decreased by 0.5 to 1.1 log
10
in plasma and genital secretions. HIV-1 RNA half-life following zidovudine treatment was 4.7, 1.3, and 0.9 days in plasma, cervix, and vagina, respectively, and significantly shorter in genital secretions than in plasma (
P
< 0.001). Defining the short-term effect of zidovudine on plasma and genital HIV-1 is important for improving perinatal HIV-1 interventions.
Effects of stretch on work from fast and slow muscles of mice: damped and undamped energy release
Authors: Syme Douglas A , Grattan Michael J
Published: June 2003

Stretching active muscle increases the work performed during subsequent shortening. The effects of a preceding stretch on work done by the undamped or lightly damped series compliance (SC) and by the contractile component (CC), which includes cross bridges and damped elements, were assessed using mouse soleus (slow) and extensor digitorum longus (fast) muscles with limited tendon. Increasing stretch amplitude (010% fibre length) increased work done by the SC up to a limit, but did not effect work done by the CC. Increasing stretch velocity (10100% Vmax) had almost no effect on work done by either component. Increasing the delay between the end of stretch and onset of shortening (060 ms) caused a decrease in SC work, with no effect on CC work. Recoil of the SC was responsible for 5070% of the total work done during shortening after stretch. Usually only 1040% of the energy imparted during the stretch was recovered as work during subsequent shortening; large stretches and long delays between stretch and shortening further reduced this recovery by one third to one fifth. Results are interpreted in the context of a loss of energy stored in the SC owing to forcible detachment of cross bridges with large stretches and cyclic detachment with long delays.Key words: compliance, stretch, work, muscle, undamped.
The influence of acetaldehyde and glycosaminoglycans upon Factor Xa- and Factor X-deficient plasma
Authors: Brecher Arthur S , Hommema Eric L
Published: June 2003

The comparative effects of glycosaminoglycans and acetaldehyde (AcH)  glycosaminoglycan (GAG) mixtures upon Factor Xa- (FXa) and Factor X-deficient plasma (FXDP) have been studied by activated partial thromboplastin time (APTT) studies. Heparin at 0.025, 0.030, 0.04, and 0.05 U statistically prolonged the APTT when pre-incubated with FXa at 37°C for 3 min prior to addition to FXDP and subsequent addition of Ca2+. Upon addition of 0.25, 0.375, and 0.5 µg heparin-6000 (H6k) to FXa, significant increases in APTT were observed. Similarly, profound increases in APTT were observed when 0.5, 0.75, and 1.0 µg heparin-3000 (H3k) was added to FXa. The chondroitin sulfates (CSA, CSB, CSC) had far less impact upon APTT with the FXaFXDP system. In examining the effects of AcHGAG mixtures upon the clotting factor, it was observed that 44.3 and 443 mM AcH synergistically prolonged the APTT in a statistically significant manner regardless of the order of premixing the three components. Hence, AcH may play a role in prolonging APTT in alcoholics. It synergistically prolonged APTT in concert with GAGs and FXa at the AcH levels used in this study. The effect of the GAGs upon FXDP is far less than its effect upon FXa.Key words: Factor Xa, acetaldehyde, heparin, glycosaminoglycans, blood coagulation.
Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species
Authors: Saez Anabelle M. Opazo , Schellenberg R Robert , Ludwig Mara S , Meiss Richard A , Paré Peter D
Published: June 2003

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus ~60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only ~12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (~22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to ~9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.Key words: isometric force, isotonic shortening, elastance.
Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats
Authors: Das Amitava , Dikshit Madhu , Srivastava Shoba R , Srivastava Umesh K , Nath Chandishwar
Published: June 2003

The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation.Key words: ovariectomy, brain acetylcholinesterase, passive avoidance.
Facilitating an understanding of integrative physiology: emphasis on the composition of body fluid compartments
Authors: Davids Mogamat Razeen , Edoute Yeouda , Jungas Robert L , Cheema-Dhadli Surinder , Halperin Mitchell L
Published: June 2003

As a teaching exercise, we used deductive reasoning and a quantitative analysis to convert a number of facts into a series of concepts to facilitate an understanding of integrative physiology and shed light on the composition of the different body fluid compartments. The starting point was the central need to regenerate ATP to perform biologic work. Because a large quantity of O2must be delivered to cells at a sufficiently high concentration to aid its diffusion into mitochondria, approximately one third of the O2in inspired air was extracted; this led to a PCO2in arterial blood of 40 mmHg (1 mmHg = 133.322 Pa). Blood flow to individual organs must be adjusted precisely to avoid having too low or too high a PO2in mitochondria  the latter augments the formation of reactive O2species. The extracellular fluid (ECF) bicarbonate concentration (EHCO3) must be high to minimize H+buffering by proteins. This high EHCO3sets the ECF concentrations of ionized calcium (Ca2+) and inorganic phosphate (HPO24) because of solubility issues. Three features defined the intracellular fluid (ICF) volume and composition. First, expelling monovalent anions minimized its mass (volume). Second, controlling the tissue PCO2ensured a relatively constant net valence on intracellular proteins. Third, the range of ICF Ca2+concentrations must both induce regulatory signals and avoid Ca3(PO4)2formation. All the above were incorporated into the integrated response that optimized the capacity for vigorous exercise. Key words: acidbase, bicarbonate, calcium, carbon dioxide, exercise, integrative physiology, intracellular fluid pH, oxygen, water.
The effect of epidermal growth factor on the distribution of SGLT-1 in rabbit jejunum
Authors: Chung B M , Wallace L E , Hardin J A , Gall D G
Published: June 2003

The effect of epidermal growth factor (EGF) on the cellular and villous distribution of the sugar transporter SGLT-1 was examined. New Zealand White rabbits (1 kg) were anesthetized, and two jejunal blind loops were isolated and exposed to either 0.9% saline or EGF (60 ng/mL saline), for 1 h. In separate experiments, tissue was harvested for brush border membrane vesicles (BBMV), microsomal membranes, or fixed for immunohistochemistry. SGLT-1 was measured in membrane fractions by Western immunoblot or localized along the villuscrypt axis by immunofluorescent microscopy. EGF increased BBMV SGLT-1 content compared with paired controls. EGF stimulation also induced a corresponding decrease in microsomal SGLT-1 levels and induced the expression of additional SGLT-1 immunoreactivity further down the villus axis. The findings suggest that EGF upregulates intestinal glucose transport by stimulating the translocation of SGLT-1 from an internal microsomal pool into the brush border, thereby recruiting more villus enterocytes into the glucose transporting population.Key words: EGF, epidermal growth factor, SGLT-1, immunofluorescence.
Time- and dose-related effects of gonadotropin-releasing hormone on growth hormone and gonadotropin subunit gene expression in the goldfish pituitary
Authors: Klausen Christian , Chang John P , Habibi Hamid R
Published: June 2003

The goldfish brain contains two molecular forms of gonadotropin-releasing hormone (GnRH): salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II). In a preliminary report, we demonstrated the stimulation of gonadotropin hormone (GtH) subunit and growth hormone (GH) mRNA levels by a single dose of GnRH at a single time point in the goldfish pituitary. Here we extend the work and demonstrate time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH gene expression in vivo and in vitro. The present study demonstrates important differences between the time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH mRNA levels. Using primary cultures of dispersed pituitary cells, the minimal effective dose of cGnRH-II required to stimulate GtH subunit mRNA levels was found to be 10-fold lower than that of sGnRH. In addition, the magnitudes of the increases in GtH subunit and GH mRNA levels stimulated by cGnRH-II were found to be higher than the sGnRH-induced responses. However, no significant difference was observed between sGnRH and cGnRH-II-induced responses in vivo. Time-related studies also revealed significant differences between sGnRH- and cGnRH-II-induced production of GtH subunit and GH mRNA in the goldfish pituitary. In general, the present study provides novel information on time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH mRNA levels and provides a framework for further investigation of GnRH mechanisms of action in the goldfish pituitary.Key words: gonadotropin-releasing hormone, gonadotropin hormone, growth hormone, gene expression, goldfish.
NON-RELATIVISTIC LIMIT OF A DIRAC–MAXWELL OPERATOR IN RELATIVISTIC QUANTUM ELECTRODYNAMICS
Authors: ARAI ASAO
Published: June 2003

The non-relativistic (scaling) limit of a particle-field Hamiltonian H, called a Dirac–Maxwell operator, in relativistic quantum electrodynamics is considered. It is proven that the non-relativistic limit of H yields a self-adjoint extension of the Pauli–Fierz Hamiltonian with spin 1/2 in non-relativistic quantum electrodynamics. This is done by establishing in an abstract framework a general limit theorem on a family of self-adjoint operators partially formed out of strongly anticommuting self-adjoint operators and then by applying it to H.
DECOHERENCE INDUCED TRANSITION FROM QUANTUM TO CLASSICAL DYNAMICS
Authors: BLANCHARD PH. , OLKIEWICZ R.
Published: June 2003

Framework for a general discussion of environmentally induced classical properties, like superselection rules, privileged basis and classical behavior, in quantum systems with both finite and infinite number of degrees of freedom is proposed. A number of examples showing that classical properties do not have to be postulated as an independent ingredient are given. In particular, it is shown that infinite open quantum systems in some cases may behave like simple classical dynamical systems.
LOCALIZATION OF THE NUMBER OF PHOTONS OF GROUND STATES IN NONRELATIVISTIC QED
Authors: HIROSHIMA FUMIO
Published: June 2003

One electron system minimally coupled to a quantized radiation field is considered. It is assumed that the quantized radiation field is massless, and no infrared cutoff is imposed. The Hamiltonian, H, of this system is defined as a self-adjoint operator acting on L2 (ℝ3) ⊗ ℱ ≅ L2 (ℝ3; ℱ), where ℱ is the Boson Fock space over L2 (ℝ3 × {1, 2}). It is shown that the ground state, ψg, of H belongs to [Formula: see text], where N denotes the number operator of ℱ. Moreover, it is shown that for almost every electron position variable x ∈ ℝ3 and for arbitrary k ≥ 0, ‖(1 ⊗ Nk/2) ψg (x)‖ℱ ≤ Dk e-δ|x|m+1 with some constants m ≥ 0, Dk > 0, and δ > 0 independent of k. In particular [Formula: see text] for 0 < β < δ/2 is obtained.
PRESENT AND FUTURE OF HIGH-SPEED COMPOUND SEMICONDUCTOR IC's
Authors: OTSUJI TAIICHI
Published: June 2003

This paper describes state-of-the-art of high-speed electronic device and IC technologies for very high-speed lightwave communications systems. The technology of interest is for over 40-Gbit/s transmitter and receiver operations. Device technology including Si-Ge, GaAs-based, and InP-based heterostructure transistors as well as circuit design technology including analog/digital/mixed-signal and optoelectronic IC's are reviewed. The speed limiting factors are discussed to address the future trends toward 100 Gbit/s and beyond.
A COMPARISON OF SILICON AND III–V TECHNOLOGY PERFORMANCE AND BUILDING BLOCK IMPLEMENTATIONS FOR 10 AND 40 Gb/s OPTICAL NETWORKING ICs
Authors: VOINIGESCU S. P. , McPHERSON D. S. , PERA F. , SZILAGYI S. , TAZLAUANU M. , TRAN H.
Published: June 2003

Scalable models for both active and passive components are essential for the design of highly integrated fiber–optic physical layer ICs. This paper focuses on the various technology options available of 10 Gb/s and 40 Gb/s applications, on how their constituent components are modeled and what the characteristics and requirements are for the basic building blocks. As part of the technology comparison, an overview of the performance of leading edge Si CMOS, SiGe BiCMOS and III–V technologies is presented. Scalable models for SiGe HBTs and GaAs p–HEMTs are then compared with measured data for various device sizes. Inductors, varactors, transmission lines and isolation techniques on Si and III–V substrates are discussed next followed by technology–specific implementations of VCO and digital building blacks. Finally, Transimpedance Limiting Amplifier (TIALA) as well as laser and modulator driver designs in SiGe BiCMOS, InP HBT and GaAs p–HEMT processes using scalable device models are illustrated for 10 and 40 Gb/s fiber-optics applications.
THE TRANSFORMING MMIC
Authors: MARTINEZ EDGAR J.
Published: June 2003

In this paper, we describe two new DARPA initiatives addressing new concepts in compound semiconductor materials and architectures that will radically transform monolithic microwave integrated circuits (MMICs) technology to address future requirements for military and commercial sensors and mobile communication networks.
METAMORPHIC LOW NOISE AMPLIFIERS AND OPTICAL COMPONENTS
Authors: WHELAN C. S. , MARSH P. F. , LEONI R. E. , HOKE W. E. , LARDIZABAL S. M. , LICHWALA S. J. , ZHANG Y. , BALAS P. , KAZIOR T. E.
Published: June 2003

GaAs based metamorphic HEMT (MHEMT) technology has emerged as an attractive, low cost alternative to InP HEMTs. The strain-induced imperfections caused by high indium content layers on GaAs is eliminated in metamorphic devices by providing a properly grown lattice-matching buffer between the substrate and active device layers. With this limitation overcome, it is now possible to provide the superior performance of InP-based devices with the cost advantages of highly manufacturable 4- and 6-inch GaAs wafers that can easily be integrated on existing GaAs fabrication lines. This paper will review device performance as well as state-of-the-art low noise amplifiers fabricated with this technology operating from 1 to 100 GHz. Fiber optic receiver components such as 40 Gb/s optical-to-electrical photodiodes and traveling wave amplifiers fabricated metamorphically will also be discussed. Finally, device and circuit reliability data will be presented demonstrating median-time-to-failure of more than 30 years at 125 C.
GaAs PHEMT CHIP SETS AND IC PROCESSES FOR HIGH-END FIBER OPTIC APPLICATIONS
Authors: LEBLANC REMY , GASMI AHMED , ZAHZOUH MESSAOUD , SMITH DEREK , AUVRAY FRANCIS , MORON JOEL , HOURANY JEAN , DEMANGE DOMINIQUE , THIEDE ANDREAS , ROCCHI MARC
Published: June 2003

Continuous improvement of high bit rate fiber optic networking up to 40 Gb/s, results in increased demand for III/V ICs offering ever lower current input noise, higher output voltage swing, lower jitter and lower DC power consumption. Using production E/D and power sub 0,2 μm GaAs PHEMT processes, transimpedance amplifiers have been developed enabling optical input sensitivity as good as -25 dBm at 2.5 Gb/s and -20 dBm at 40 Gb/s. Similarly laser and modulator drivers have been fabricated with jitter as low as 1,8 ps rms at 10 Gb/s and over 7 V output swing up to 40 GHz. Future generations of products will be implemented using sub 0,1 μm processes based on E/D and power GaAs MHEMTs as well as InP HEMTs maintaining a long tern performance edge over the Silicon counterparts.
INTEGRATED SiGe AND Si DEVICE CAPABILITIES AND TRENDS FOR MULTI-GIGAHERTZ APPLICATIONS
Authors: FREEMAN G. G. , JAGANNATHAN B. , ZAMDMER N. , GROVES R. , SINGH R. , TRETIAKOV Y. , KUMAR M. , JOHNSON J. B. , PLOUCHART J. O. , GREENBERG D. R. , KOESTER S. J. , SCHAUB J. D.
Published: June 2003

Silicon-based devices, including the increasingly available SiGe-based devices, are now demonstrating fT and fMAX values over 200 GHz. These recent advances open the door to a wide range of silicon-based very high frequency, low power and highly integrated solutions. Trends in silicon MOS, SiGe HBT, SiGe MODFET and SiGe strained silicon FETs are reported. Silicon inroads to device functions viewed as the sole realm of III-V technologies are also being demonstrated. Capability and trends of the integrated silicon photodiode are reported here as an example. Integration of these high-speed devices into a complex circuit requires on-chip passive device functionality at such high frequency. Key devices to enable integration are the inductor, varactor, and transmission line, and operation of these devices at high frequency is reported. Further, we discuss noise isolation issues and techniques, which may be used when minimizing cross-talk within a conductive silicon substrate.
A SiGe HBT IC CHIPSET for40-Gb/s OPTICAL TRANSMISSION SYSTEMS
Authors: MASUDA T. , SHIRAMIZU N. , OHUE E. , ODA K. , HAYAMI R. , KONDO M. , ONAI T. , WASHIO K. , OHHATA K. , ARAKAWA F. , TANABE M. , SHIMAMOTO H. , HARADA T.
Published: June 2003

Using a 0.2-μm self-aligned epitaxial-growth silicon-germanium (SiGe) heterojunction bipolar transistor (HBT) technology, we have developed a chipset for 40-Gb/s time-division multiplexing optical transmission systems. In this paper, we describe seven analog and digital ICs: a 45-GHz bandwidth transimpedance amplifier, a 48.7-GHz bandwidth automatic-gain-controllable amplifier, a 40-Gb/s decision circuit, a 40-Gb/s full-wave rectifier, a 40-Gb/s limiting amplifier with a 32-dB gain, a 45-Gb/s 1:4 demultiplexer, and a 45-Gb/s 4:1 multiplexer. To increase bandwidth of the transimpedance amplifier, a common-base input stage is introduced. In order to have high gain and wide bandwidth simultaneously, active load circuits composed of a differential transimpedance amplifier are used for the AGC amplifier, the limiting amplifier, and the decision circuit. Full-rate clocking is employed to reduce the influence caused by clock-duty variation in digital circuits such as the decision circuit, the demultiplexer, and the multiplexer. All ICs were characterized by using on-wafer probes, and some of them were built in brass-packages for bit-error rate measurement.
MICROWAVE GaN-BASED POWER TRANSISTORS ON LARGE-SCALE SILICON WAFERS
Authors: MANOHAR S. , PHAM A. , BROWN J. , BORGES R. , LINTHICUM K.
Published: June 2003

This paper presents the development of microwave Gallium nitride (GaN) heterostructure field-effect transistors (HFETs) on silicon (Si). GaN-on-Si provides a low-cost manufacturable platform that could lead to the commercialization of GaN-based power devices for wireless applications. Small periphery GaN high electron mobility transistors (HEMTs) on Si exhibited a maximum drain current of 900mA/mm, a peak gm of 300 mS/mm, and a microwave output power density of 1.5 W/mm at 2 GHz. Microwave characterization and device modeling of GaN HEMTs on Si are discussed.
RADIATION EFFECTS IN III-V SEMICONDUCTOR ELECTRONICS
Authors: WEAVER B. D. , McMORROW DALE , COHN L. M.
Published: June 2003

Particle irradiation effects in III-V semiconductor devices and selected circuits are reviewed. Radiation effects concerns in III-V devices are associated primarily with displacement damage and single-event upset. In conventional transistors, displacement damage decreases the gain, increases leakage and shifts the collector-emitter offset voltage. In reduced dimensional devices. such as high electron mobility transistors and resonant tunneling diodes, the main displacement damage effect is to reduce current by increasing scattering out of the two-dimensional transport state. The current understanding of single-event effects in III-V circuits and devices, and approaches for mitigating their impact, are also discussed here. Single-event effects are a serious concern for high-speed III-V semiconductor devices operating in radiation-intense environments. GaAs integrated circuits (ICs) based on field effect transistor technology exhibit single-event upset sensitivity to protons and very low linear energy transfer (LET) particles; this sensitivity becomes more significant as clock rates and operating speeds increase.
ON THE PARITY OF PARTITION FUNCTIONS
Authors: BERNDT BRUCE C. , YEE AE JA , ZAHARESCU ALEXANDRU
Published: June 2003

Let S denote a subset of the positive integers, and let pS(n) be the associated partition function, that is, pS(n) denotes the number of partitions of the positive integer n into parts taken from S. Thus, if S is the set of positive integers, then pS(n) is the ordinary partition function p(n). In this paper, working in the ring of formal power series in one variable over the field of two elements Z/2Z, we develop new methods for deriving lower bounds for both the number of even values and the number of odd values taken by pS(n), for n ≤ N. New very general theorems are obtained, and applications are made to several partition functions.
THE STRONG FRANCHETTA CONJECTURE IN ARBITRARY CHARACTERISTICS
Authors: SCHRÖER STEFAN
Published: June 2003

Using Moriwaki's calculation of the ℚ-Picard group for the moduli space of curves, I prove the strong Franchetta Conjecture in all characteristics. That is, the canonical class generates the group of rational points on the Picard scheme for the generic curve of genus g ≥ 3. Similar results hold for generic pointed curves. Moreover, I show that Hilbert's Irreducibility Theorem implies that there are many other nonclosed points in the moduli space of curves with such properties.
HEAT KERNEL ASYMPTOTICS FOR ROOTS OF GENERALIZED LAPLACIANS
Authors: BÄR CHRISTIAN , MOROIANU SERGIU
Published: June 2003

We describe the heat kernel asymptotics for roots of a Laplace type operator Δ on a closed manifold. A previously known relation between the Wodzicki residue of Δ and heat trace asymptotics is shown to hold pointwise for the corresponding densities.
3-FOLD SYMMETRIC PRODUCTS OF CURVES AS HYPERBOLIC HYPERSURFACES IN ℙ4
Authors: CILIBERTO CIRO , ZAIDENBERG MIKHAIL
Published: June 2003

We construct new examples of Kobayashi hyperbolic hypersurfaces in ℙ4. They are generic projections of the triple symmetric product V = C (3) of a generic genus g ≥ 6 curve C, smoothly embedded in ℙ7.
INCIDENCE DIVISOR
Authors: BARLET D. , KADDAR M.
Published: June 2003

Let Z be a complex manifold of dimension n+1 and (Xs)s∈S be an analytic family of n-cycles (not necessarily compact) parametrized by a reduced analytic complex space S. Denote by X the graph of this family and p1 (resp. p2) the canonical projection of S × Z on S (resp. on Z). The construction of Barlet-Magnusson assigns to each n+1-codimensionnal subspace in Z which is assumed to be a local complete intersection and to satisfy:

C1[Formula: see text] is proper and finite on its image which is nowhere dense in S, an effective Cartier divisor ΣY in S. Nice functorial properties of this correspondance are proven.

The purpose of this article is to generalize this result in several directions: using the relative fundamental class of the family (Xs)s∈S in Deligne cohomology, we prove the following results:

(1) ΣY depends only on the cycle underlying the locally complete intersection ideal defining Y in Z

(2) we generalize the construction of the incidence divisor which is Cartier and effective for any cycle Y (no nilpotent structure on Y is needed) satifying the weaker condition

C2[Formula: see text] is proper and generically finite on its image which is nowhere dense in S and we extend the nice functorial properties to this case.
ASYMPTOTIC BEHAVIOR OF HOMOGENEOUS COSMOLOGICAL MODELS ON THE BRANE
Authors: CHAKRABORTY SUBENOY
Published: June 2003

In this work, we have studied the late-time behavior of initially expanding homogeneous cosmological models with a positive cosmological term in Randall–Sundrum brane-world type scenarios. The matter fields are confined in the three-brane, onto which the five-dimensional Weyl tensor has a nonvanishing projection. It is found that all Bianchi models (except IX) exponentially evolve toward the de Sitter solution while the Bianchi IX model also isotropizes but with a restriction on the cosmological parameter.
GAUGED EXTENDED SUPERGRAVITY WITHOUT COSMOLOGICAL CONSTANT: NO-SCALE STRUCTURE AND SUPERSYMMETRY BREAKING
Authors: ANDRIANOPOLI L. , FERRARA S. , D'AURIA R. , LLEDÓ M. A.
Published: June 2003

We consider the interplay of duality symmetries and gauged isometries of supergravity models giving N-extended, spontaneously broken supergravity with a no-scale structure. Some examples motivated by superstring and M-theory compactifications are described.
ANTI-PROTON TO PROTON RATIOS FROM Au + Au COLLISIONS AT $\sqrt{s_{NN}}=200~{\rm GeV}$ BY RQMD
Authors: CHENG YUNHUA , LIU FENG
Published: June 2003

Events of Au + Au collisions from AGS to RHIC energies by RQMD (v2.4) generator are produced. [Formula: see text] ratios as functions of rapidity, transverse momentum and centrality at [Formula: see text] are studied. The dependence on the center of mass energy of [Formula: see text] ratios is presented, compared with the experimental results. It is shown that [Formula: see text] ratio from rescattering RQMD is lower than those of the experiments at RHIC energies. We argue that hadronic rescattering at RHIC energies is suppressed compared to AGS, SPS energies.
BEIJING ELECTRON–POSITRON COLLIDER: RESULTS AND FUTURE PLAN
Authors: CHEN HESHENG
Published: June 2003

The results from BEPC/BES were reviewed. The upgrade program of BEPCII is to build a two-ring collider with the luminosity improvement by two orders of magnitudes. The goal of the BEPCII is the precision measurements in the charm physics and search for new physics.
REMARKS ON THE DECAYS χ'bJ→ωϒ
Authors: VOLOSHIN M. B.
Published: June 2003

The recently observed by CLEO cascade decays ϒ(3S)→γχ'bJ→γωϒ are discussed. It is shown that within the nonrelativistic description of bottomonium in the heavy b quark limit, the ratio of the rates of the transitions χ'bJ→ωϒ with J = 1 and J = 2 should be given by the ratio of the corresponding S wave phase space factors. As a result, the rate of the observed cascade transitions through the χ'b2 resonance should be close to that through the χ'b1. It is suggested that the ratio of the discussed cascade rates can also be tested by measuring a simple angular correlation.
POLYNOMIAL DEFORMATIONS OF sl(2, ℝ) IN A THREE-DIMENSIONAL INVARIANT SUBSPACE OF MONOMIALS
Authors: DEBERGH N. , NDIMUBANDI J. , VAN DEN BOSSCHE B.
Published: June 2003

New finite-dimensional representations of specific polynomial deformations of sl (2, ℝ) are constructed. The corresponding generators can be, in particular, realized through linear differential operators preserving a finite-dimensional subspace of monomials. We concentrate on three-dimensional spaces.