bluuebunny/crossref_metadata_2025 huggingface dataset:
Amino Acid Substitutions at Position 190 of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Increase Susceptibility to Delavirdine and Impair Virus Replication
Authors: Huang Wei , Gamarnik Andrea , Limoli Kay , Petropoulos Christos J. , Whitcomb Jeannette M.
Published: December 2002

Suboptimal treatment of human immunodeficiency virus type 1 (HIV-1) infection with nonnucleoside reverse transcriptase inhibitors (NNRTI) often results in the rapid selection of drug-resistant virus. Several amino acid substitutions at position 190 of reverse transcriptase (RT) have been associated with reduced susceptibility to the NNRTI, especially nevirapine (NVP) and efavirenz (EFV). In the present study, the effects of various 190 substitutions observed in viruses obtained from NNRTI-experienced patients were characterized with patient-derived HIV isolates and confirmed with a panel of isogenic viruses. Compared to wild-type HIV, which has a glycine at position 190 (G190), viruses with 190 substitutions (A, C, Q, S, V, E, or T, collectively referred to as G190X substitutions) were markedly less susceptible to NVP and EFV. In contrast, delavirdine (DLV) susceptibility of these G190X viruses increased from 3 to 300-fold (hypersusceptible) or was only slightly decreased. The replication capacity of viruses with certain 190 substitutions (C, Q, V, T, and E) was severely impaired and was correlated with reduced virion-associated RT activity and incomplete protease (PR) processing of the viral p55

gag

polyprotein. These defects were the result of inadequate p160

gagpol

incorporation into virions. Compensatory mutations within RT and PR improved replication capacity, p55

gag

processing, and RT activity, presumably through increased incorporation of p160

gagpol

into virions. We observe an inverse relationship between the degree of NVP and EFV resistance and the impairment of viral replication in viruses with substitutions at 190 in RT. These observations may have important implications for the future design and development of antiretroviral drugs that restrict the outgrowth of resistant variants with high replication capacity.
Kaposi's Sarcoma-Associated Herpesvirus Induces the Phosphatidylinositol 3-Kinase-PKC-ζ-MEK-ERK Signaling Pathway in Target Cells Early during Infection: Implications for Infectivity
Authors: Naranatt Pramod P. , Akula Shaw M. , Zien Christopher A. , Krishnan Harinivas H. , Chandran Bala
Published: December 2002

Human herpesvirus 8 (HHV-8) is implicated in the pathogenesis of Kaposi's sarcoma. HHV-8 envelope glycoprotein B (gB) possesses the RGD motif known to interact with integrin molecules, and HHV-8 infectivity was inhibited by RGD peptides, by antibodies against α3 and β1 integrins, and by soluble α3β1 integrin (S. M. Akula, N. P. Pramod, F.-Z. Wang, and B. Chandran, Cell 108:407-419, 2002). Anti-gB antibodies immunoprecipitated the virus α3 and β1 complexes, and virus-binding studies suggest a role for α3β1 in HHV-8 entry. HHV-8 infection induced the integrin-mediated activation of focal adhesion kinase (FAK), implicating a role for integrin and the associated signaling pathways in HHV-8 entry into the target cells. Immediately after infection, target cells exhibited morphological changes and cytoskeletal rearrangements, suggesting the induction of signal pathways. As early as 5 min postinfection, HHV-8 activated the MEK-ERK1/2 pathway. The focal adhesion components phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase C-ζ (PKC-ζ) were recruited as upstream mediators of the HHV-8-induced ERK pathway. Anti-HHV-8 gB-neutralizing antibodies and soluble α3β1 integrin inhibited the virus-induced signaling pathways. Early kinetics of the cellular signaling pathway and its activation by UV-inactivated HHV-8 suggest a role for virus binding and/or entry but not viral gene expression in this induction. Studies with human α3 integrin-transfected Chinese hamster ovary cells and FAK-negative mouse DU3 cells suggest that the α3β1 integrin and FAK play roles in the HHV-8 mediated signal induction. Inhibitors specific for PI 3-kinase, PKC-ζ, MEK, and ERK significantly reduced the virus infectivity without affecting virus binding to the target cells. Examination of viral DNA entry suggests a role for PI 3-kinase in HHV-8 entry into the target cells and a role for PKC-ζ, MEK, and ERK at a post-viral entry stage of infection. These findings implicate a critical role for integrin-associated mitogenic signaling in HHV-8's infection of target cells and suggest that, by orchestrating the signal cascade, HHV-8 may create an appropriate intracellular environment to facilitate the infection.
Persistent Sin Nombre Virus Infection in the Deer Mouse (
Peromyscus maniculatus
) Model: Sites of Replication and Strand-Specific Expression
Authors: Botten Jason , Mirowsky Katy , Kusewitt Donna , Ye Chunyan , Gottlieb Keith , Prescott Joseph , Hjelle Brian
Published: December 2002

To address Sin Nombre (SN) virus persistence in deer mice, we sacrificed experimentally infected deer mice at eight time points from day 21 to day 217 postinoculation (p.i.) and examined their tissues for viral nucleocapsid (N) antigen expression and both negative-strand (genomic) and positive-strand (replicative/mRNA) viral S segment RNA titers. All the animals that we inoculated developed persistent infections, and SN virus could be isolated from tissues throughout the course of infection. The transition from an acute to a persistent pattern of infection appeared to occur between days 60 and 90 p.i. Beginning on day 60 p.i., the heart, brown adipose tissue (BAT), and lung retained antigen expression and genomic viral RNA the most frequently. We found a statistically significant association among the presence of replicative RNA in the heart, lung, and BAT, widespread antigen expression (in ≥5 tissues), and RNA viremia. Of these three tissues, the heart retained negative-strand RNA and viral N antigen the most consistently (in 25 of 26 animals). During persistence, there were two distinct patterns of infection: restricted versus disseminated tissue involvement. Mice with the restricted pattern exhibited N antigen expression in ≤3 tissues, an absence of viral RNA in the blood, neutralizing antibody titers of ≤1:1,280 (
P
= 0.01), and no replicative RNA in the heart, lung, or BAT. Those with the “disseminated” pattern showed N antigen expression in ≥5 tissues, neutralizing antibody titers of 1:160 to 1:20,480, replicative RNA in the heart, lung, and BAT at a high frequency, and RNA viremia. Virus could be isolated consistently only from mice that demonstrated the disseminated pattern. The heart, lung, and BAT are important sites for the replication and maintenance of SN virus during persistent infection.
Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells
Authors: DeFilippis Rosa Anna , Goodwin Edward C. , Wu Lingling , DiMaio Daniel
Published: December 2002

Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins, and repression of HPV gene expression causes the cells to cease proliferation and undergo senescence. However, it is not known whether both HPV proteins are required to maintain the proliferative state of cervical cancer cells, or whether mutations that accumulate during carcinogenesis eliminate the need for one or the other of them. To address these questions, we used the bovine papillomavirus E2 protein to repress the expression of either the E6 protein or the E7 protein encoded by integrated HPV18 DNA in HeLa cervical carcinoma cells. Repression of the E7 protein activated the Rb pathway but not the p53 pathway and triggered senescence, whereas repression of the E6 protein activated the p53 pathway but not the Rb pathway and triggered both senescence and apoptosis. Telomerase activity, cyclin-dependent kinase activity, and expression of c-myc were markedly inhibited by repression of either E6 or E7. These results demonstrate that continuous expression of both the E6 and the E7 protein is required for optimal proliferation of cervical carcinoma cells and that the two viral proteins exert distinct effects on cell survival and proliferation. Therefore, strategies that inhibit the expression or activity of either viral protein are likely to inhibit the growth of HPV-associated cancers.
Development of a Dual Recombinant Vaccine To Protect Small Ruminants against Peste-des-Petits-Ruminants Virus and Capripoxvirus Infections
Authors: Berhe G. , Minet C. , Le Goff C. , Barrett T. , Ngangnou A. , Grillet C. , Libeau G. , Fleming M. , Black D. N. , Diallo A.
Published: December 2002

A recombinant capripoxvirus vaccine containing a cDNA of the peste-des-petits-ruminants virus (PPRV) fusion protein gene was constructed. A quick and efficient method was used to select a highly purified recombinant virus clone. A trial showed that a dose of this recombinant as low as 0.1 PFU protected goats against challenge with a virulent PPRV strain.
Proline 78 Is Crucial for Human Immunodeficiency Virus Type 1 Nef To Down-Regulate Class I Human Leukocyte Antigen
Authors: Yamada Takeshi , Kaji Naotoshi , Odawara Takashi , Chiba Joe , Iwamoto Aikichi , Kitamura Yoshihiro
Published: December 2002

Human immunodeficiency virus type 1 Nef down-regulates human leukocyte antigen class I (HLA-I) in T lymphocytes, and the down-regulation involves the Nef proline-rich domain (PRD) containing four prolines at positions 69, 72, 75, and 78. We used a Sendai virus vector with
nef
and examined regulation by Nef of HLA-I and CD4 in suspension cultures of cells such as T lymphocytes. Analyses of a series of PRD substitution mutants indicated that, because the substitution of Pro78 with Ala abolished down-regulation of HLA-I but not of CD4, Pro78 is important for HLA-I down-regulation in T lymphocytes.
Simian Virus 40 Sequences in Human Lymphoblastoid B-Cell Lines
Authors: Dolcetti Riccardo , Martini Fernanda , Quaia Michele , Gloghini Annunziata , Vignocchi Beatrice , Cariati Roberta , Martinelli Marcella , Carbone Antonino , Boiocchi Mauro , Tognon Mauro
Published: December 2002

Human Epstein-Barr virus-immortalized lymphoblastoid B-cell lines tested positive by PCR for simian virus 40 (SV40) DNA (22 of 42 cell lines, 52.3%). B lymphocytes or tissues from which B-cell lines derived were also SV40 positive. In situ hybridization showed that SV40 DNA was present in the nucleus of a small fraction (1/250) of cells. SV40 T-antigen mRNA was detected by reverse transcription-PCR. Lymphoblastoid B-cell lines (
n
= 4) infected with SV40 remained SV40 positive for 4 to 6 months. SV40-positive B-cell lines were more tumorigenic in SCID mice than were SV40-negative cell lines (4 of 5 [80%] SV40-positive cell lines versus 2 of 4 [50%] SV40-negative cell lines). These results suggest that SV40 may play a role in the early phases of human lymphomagenesis.
Cofactors for Human Immunodeficiency Virus Type 1 cDNA Integration In Vitro
Authors: Gao Kui , Gorelick Robert J. , Johnson Donald G. , Bushman Frederic
Published: December 2002

We have investigated the function of two DNA binding proteins that stimulate human immunodeficiency virus type 1 cDNA integration in vitro, the cellular HMGa1 protein and the viral nucleocapsid (NC) protein. Of the three forms of NC (NCp7, NCp9, and NCp15), we find that NCp9 is the most effective at increasing integration in vitro; thus, processing of NC may potentially modulate its activities during infection. We also found that maximal stimulation by NCp9 required roughly enough NC to coat the reactant DNAs whereas less HMGa1 was required, and the reactions displayed different optima for divalent metal cofactors and order of addition. These findings reveal probable distinct mechanisms of action in vitro.
Novel Viral Disease Control Strategy: Adenovirus Expressing Alpha Interferon Rapidly Protects Swine from Foot-and-Mouth Disease
Authors: Chinsangaram Jarasvech , Moraes Mauro P. , Koster Marla , Grubman Marvin J.
Published: December 2002

We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN-α/β). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN-α or IFN-β (Ad5-pIFNα or Ad5-pIFNβ). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 10
9
PFU of a control Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed typical signs of foot-and-mouth disease (FMD), including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 10
9
PFU of Ad5-pIFNα were completely protected when challenged 24 h later with FMDV. These animals showed no clinical signs of FMD and no viremia and did not develop antibodies against viral nonstructural proteins, suggesting that complete protection from infection was achieved.
The N-Terminal Domain of the Murine Coronavirus Spike Glycoprotein Determines the CEACAM1 Receptor Specificity of the Virus Strain
Authors: Tsai Jean C. , Zelus Bruce D. , Holmes Kathryn V. , Weiss Susan R.
Published: December 2002

Using isogenic recombinant murine coronaviruses expressing wild-type murine hepatitis virus strain 4 (MHV-4) or MHV-A59 spike glycoproteins or chimeric MHV-4/MHV-A59 spike glycoproteins, we have demonstrated the biological functionality of the N-terminus of the spike, encompassing the receptor binding domain (RBD). We have used two assays, one an in vitro liposome binding assay and the other a tissue culture replication assay. The liposome binding assay shows that interaction of the receptor with spikes on virions at 37°C causes a conformational change that makes the virions hydrophobic so that they bind to liposomes (B. D. Zelus, J. H. Schickli, D. M. Blau, S. R. Weiss, and K. V. Holmes, J. Virol. 77: 830-840, 2003). Recombinant viruses with spikes containing the RBD of either MHV-A59 or MHV-4 readily associated with liposomes at 37°C in the presence of soluble mCEACAM1
a
, except for S
4
R, which expresses the entire wild-type MHV-4 spike and associated only inefficiently with liposomes following incubation with soluble mCEACAM1
a
. In contrast, soluble mCEACAM1
b
allowed viruses with the MHV-A59 RBD to associate with liposomes more efficiently than did viruses with the MHV-4 RBD. In the second assay, which requires virus entry and replication, all recombinant viruses replicated efficiently in BHK cells expressing mCEACAM1
a
. In BHK cells expressing mCEACAM1
b
, only viruses expressing chimeric spikes with the MHV-A59 RBD could replicate, while replication of viruses expressing chimeric spikes with the MHV-4 RBD was undetectable. Despite having the MHV-4 RBD, S
4
R replicated in BHK cells expressing mCEACAM1
b
; this is most probably due to spread via CEACAM1 receptor-independent cell-to-cell fusion, an activity displayed only by S
4
R among the recombinant viruses studied here. These data suggest that the RBD domain and the rest of the spike must coevolve to optimize function in viral entry and spread.
Reactivation of Lytic Replication from B Cells Latently Infected with Epstein-Barr Virus Occurs with High S-Phase Cyclin-Dependent Kinase Activity while Inhibiting Cellular DNA Replication
Authors: Kudoh Ayumi , Fujita Masatoshi , Kiyono Tohru , Kuzushima Kiyotaka , Sugaya Yutaka , Izuta Shunji , Nishiyama Yukihiro , Tsurumi Tatsuya
Published: December 2002

Productive infection and replication of herpesviruses usually occurs in growth-arrested cells, but there has been no direct evidence in the case of Epstein-Barr virus (EBV), since an efficient lytic replication system without external stimuli does not exist for the virus. Expression of the EBV lytic-switch transactivator BZLF1 protein in EBV-negative epithelial tumor cell lines, however, is known to arrest the cell cycle in G
0
/G
1
by induction of the tumor suppressor protein p53 and the cyclin-dependent kinase (CDK) inhibitors p21
WAF-1/CIP-1
and p27
KIP-1
, followed by the accumulation of a hypophosphorylated form of the Rb protein. In order to determine the effect of the onset of lytic viral replication on cellular events in latently EBV-infected B LCLs, a tightly controlled induction system of the EBV lytic-replication program by inducible BZLF1 protein expression was established in B95-8 cells. The induction of lytic replication completely arrested cell cycle progression and cellular DNA replication. Surprisingly, the levels of p53, p21
WAF-1/CIP-1
, and p27
KIP-1
were constant before and after induction of the lytic program, indicating that the cell cycle arrest induced by the lytic program is not mediated through p53 and the CDK inhibitors. Furthermore, although cellular DNA replication was blocked, elevation of cyclin E/A expression and accumulation of hyperphosphorylated forms of Rb protein were observed, a post-G
1
/S phase characteristic of cells. Thus, while the EBV lytic program promoted specific cell cycle-associated activities involved in the progression from G
1
to S phase, it inhibited cellular DNA synthesis. Such cellular conditions appear to especially favor viral lytic replication.
Association between Virus-Specific T-Cell Responses and Plasma Viral Load in Human Immunodeficiency Virus Type 1 Subtype C Infection
Authors: Novitsky V. , Gilbert P. , Peter T. , McLane M. F. , Gaolekwe S. , Rybak N. , Thior I. , Ndung'u T. , Marlink R. , Lee T. H. , Essex M.
Published: December 2002

Virus-specific T-cell immune responses are important in restraint of human immunodeficiency virus type 1 (HIV-1) replication and control of disease. Plasma viral load is a key determinant of disease progression and infectiousness in HIV infection. Although HIV-1 subtype C (HIV-1C) is the predominant virus in the AIDS epidemic worldwide, the relationship between HIV-1C-specific T-cell immune responses and plasma viral load has not been elucidated. In the present study we address (i) the association between the level of plasma viral load and virus-specific immune responses to different HIV-1C proteins and their subregions and (ii) the specifics of correlation between plasma viral load and T-cell responses within the major histocompatibility complex (MHC) class I HLA supertypes. Virus-specific immune responses in the natural course of HIV-1C infection were analyzed in the gamma interferon (IFN-γ)-enzyme-linked immunospot assay by using synthetic overlapping peptides corresponding to the HIV-1C consensus sequence. For Gag p24, a correlation was seen between better T-cell responses and lower plasma viral load. For Nef, an opposite trend was observed where a higher T-cell response was more likely to be associated with a higher viral load. At the level of the HLA supertypes, a lower viral load was associated with higher T-cell responses to Gag p24 within the HLA A2, A24, B27, and B58 supertypes, in contrast to the absence of such a correlation within the HLA B44 supertype. The present study demonstrated differential correlations (or trends to correlation) in various HIV-1C proteins, suggesting (i) an important role of the HIV-1C Gag p24-specific immune responses in control of viremia and (ii) more rapid viral escape from immune responses to Nef with no restraint of plasma viral load. Correlations between the level of IFN-γ-secreting T cells and viral load within the MHC class I HLA supertypes should be considered in HIV vaccine design and efficacy trials.
Ubiquitin Ligase Activities of
Bombyx mori
Nucleopolyhedrovirus RING Finger Proteins
Authors: Imai Noriko , Matsuda Noriyuki , Tanaka Keiji , Nakano Akihiko , Matsumoto Shogo , Kang WonKyung
Published: December 2002

The genome of
Bombyx mori
nucleopolyhedrovirus (BmNPV) is predicted to contain six RING finger proteins: IAP1, ORF35, IAP2, CG30, IE2, and PE38. Several other members of the RING finger family have recently been shown to have the ubiquitin-ligase (E3) activity. We thus examined whether BmNPV RING finger proteins have the E3 activity. In vitro ubiquitination assay with the rabbit reticulocyte lysates and BmNPV RING finger proteins fused with maltose-binding protein (MBP) showed that four of them (IAP2, IE2, PE38, and CG30) were polyubiquitinated in the presence of zinc ion. Furthermore, MBP-IAP2, MBP-IE2, and MBP-PE38 were able to reconstitute ubiquitination activity in cooperation with the Ubc4/5 subfamily of ubiquitin-conjugating enzymes. Mutational analysis also showed that ubiquitination activity of MBP-IAP2, MBP-IE2, and MBP-PE38 were dependent on their RING finger motif. Therefore, these results suggest that IAP2, IE2, and PE38 may function as E3 enzymes during BmNPV infection.
A Protective Role of Locally Administered Immunostimulatory CpG Oligodeoxynucleotide in a Mouse Model of Genital Herpes Infection
Authors: Harandi Ali M. , Eriksson Kristina , Holmgren Jan
Published: December 2002

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODNs) are known as potent activators of the immune system and inducers of several Th1-associated immunomodulatory cytokines. We therefore investigated whether such a CpG-containing ODN (CpG ODN) given mucosally in the female genital tract could enhance innate immunity and protect against genital herpes infection. Groups of C57BL/6 mice were treated intravaginally with either CpG ODN or a non-CpG ODN control in the absence of any antigen either 2 days before or 4 h after an intravaginal challenge with a normally lethal dose of herpes simplex virus type 2 (HSV-2). Mice treated with CpG ODN exhibited significantly decreased titers of HSV-2 in their vaginal fluids compared with non-CpG ODN-treated mice. Furthermore, CpG ODN pretreatment significantly protected against development of disease and death compared to non-CpG ODN pretreatment. Most strikingly, CpG ODN conferred protection against disease and death even when given after the viral challenge. The CpG ODN-induced protection was associated with a rapid production of gamma interferon (IFN-γ), interleukin-12 (IL-12), IL-18, and RANTES in the genital tract mucosa following CpG ODN treatment. The observed protection appeared to be dependent on IFN-γ, IL-12, IL-18, and T cells, as CpG ODN pretreatment did not confer any significant protection in mice deficient in IFN-γ, IL-12, IL-18, or T cells. Further, a complete protective immunity to reinfection was elicited in CpG ODN-treated, HSV-2-challenged mice, suggesting a role for mucosally administered CpG ODN in inducing the development of an acquired immune response in addition to its potent stimulation of innate immunity.
Human T-Cell Leukemia Virus Type 1 Envelope-Mediated Syncytium Formation Can Be Activated in Resistant Mammalian Cell Lines by a Carboxy-Terminal Truncation of the Envelope Cytoplasmic Domain
Authors: Kim Felix J. , Manel Nicolas , Boublik Yvan , Battini Jean-Luc , Sitbon Marc
Published: December 2002

Human T-cell leukemia virus (HTLV) envelope (Env) glycoproteins induce fusion, leading to rampant syncytium formation in a broad range of cell lines. Here, we identified murine, hamster, canine, and porcine cell lines that are resistant to HTLV-1 Env-induced syncytium formation. This resistance was not due to the absence of functional receptors for HTLV Env, as these cells were susceptible to infection with HTLV Env-pseudotyped virions. As murine leukemia virus (MLV) Env and HTLV Env present close structural homologies (F. J. Kim, I. Seiliez, C. Denesvre, D. Lavillette, F. L. Cosset, and M. Sitbon, J. Biol. Chem.
275:
23417-23420, 2000), and because activation of syncytium formation by MLV Env generally requires cleavage of the R peptide in the cytoplasmic domain of the Env transmembrane (TM) component, we assessed whether truncation of the cytoplasmic domain of HTLV Env would alleviate this resistance. Indeed, in all resistant cell lines, truncation of the last 8 amino acids of the HTLV Env cytoplasmic domain (HdC8) was sufficient to overcome resistance to HTLV Env-induced syncytium formation. Furthermore, HdC8-mediated cell-to-cell infection titers varied according to the target cell lines and could be significantly higher than that observed with HTLV Env on HeLa cells. These data indicate that a determinant located within the 8 carboxy-terminal cytoplasmic amino acids of TM plays a distinct role in HTLV Env-mediated cell-to-cell infection and syncytium formation.
Quantitative Detection of Hepadnavirus-Infected Lymphoid Cells by In Situ PCR Combined with Flow Cytometry: Implications for the Study of Occult Virus Persistence
Authors: Mulrooney Patricia M. , Michalak Tomasz I.
Published: December 2002

The detection of small amounts of viral pathogens in infected cells by classical PCR is hampered by a partial loss of virus nucleic acid due to extraction and by difficulties in discrimination between truly intracellular virus genome material and that possibly adhered to the cell surface. These impediments limit reliable identification of virus traces within infected cells, which are typically encountered in latent and persistent occult infections. In this study, hepadnavirus-specific in situ PCR combined with the enzymatic elimination of extracellular virus and flow cytometry permitted detection of viral genomes in lymphoid cells without nucleic acid isolation and allowed quantification of infected cells during the course of persistent infection with woodchuck hepatitis virus (WHV). The validity of the procedure was confirmed by hybridization analysis of the in situ-amplified viral sequences. The results showed that hepadnavirus can be directly detected within lymphoid cells not only in serologically accountable infection, but also years after recovery from viral hepatitis and in the course of primary occult virus carriage. Percentages of infected peripheral lymphoid cells in symptomatic WHV hepatitis fluctuate between 3.4 and 20.4% (mean ± standard error of the mean, 9.6% ± 1.7%), whereas those in persistent, serologically mute WHV infection range from 1.1 to 14.6% (mean ± standard error of the mean, 4.8% ± 0.8%) (
P
= 0.005). The data obtained provide further evidence that WHV infection continues indefinitely in the lymphatic system independently of whether it is symptomatic or concealed. They document that hepadnavirus can be detected in a significant proportion of circulating lymphoid cells in both immunovirologically apparent as well as occult persistent infection.
Increased Mucosal Transmission but Not Enhanced Pathogenicity of the CCR5-Tropic, Simian AIDS-Inducing Simian/Human Immunodeficiency Virus SHIV
SF162P3
Maps to Envelope gp120
Authors: Hsu Mayla , Harouse Janet M. , Gettie Agegnehu , Buckner Clarisa , Blanchard James , Cheng-Mayer Cecilia
Published: December 2002

Through rapid serial transfer in vivo, the chimeric CCR5-tropic simian/human immunodeficiency virus SHIV
SF162
evolved from a virus that is nonpathogenic and poorly transmissible across the vaginal mucosa to a variant that still maintains CCR5 usage but which is now pathogenic and establishes intravaginal infection efficiently. To determine whether envelope glycoprotein gp120 is responsible for increased pathogenesis and transmissibility of the variant SHIV
SF162P3
, we cloned and sequenced the dominant envelope gene (encoding P3 gp120) and characterized its functions in vitro. Chimeric SHIV
SF162
virus expressing P3 gp120 of the pathogenic variant, designated SHIV
SF162PC
, was also constructed and assessed for its pathogenicity and mucosal transmissibility in vivo. We found that, compared to wild-type SHIV
SF162
gp120, P3 gp120 conferred in vitro neutralization resistance and increased entry efficiency of the virus but was compromised in its fusion-inducing capacity. In vivo, SHIV
SF162PC
infected two of two and two of three rhesus macaques by the intravenous and intravaginal routes, respectively. Nevertheless, although peak viremia reached 10
6
to 10
7
RNA copies per ml of plasma in some infected animals and was associated with depletion of gut-associated CD4
+
lymphocytes, none of the animals maintained a viral set point that would be predictive of progression to disease. Together, the data from this study suggest a lack of correlation between entry efficiency and cytopathic properties of envelope glycoproteins with viral pathogenicity. Furthermore, whereas
env
gp120 contains the determinant for enhanced mucosal transmissibility of SHIV
SF162P3
, the determinant(s) of its increased virulence may require additional sequence changes in
env
gp41 and/or maps to other viral genes.
Reducing work related psychological ill health and sickness absence: a systematic literature review
Authors: Michie S , Williams S
Published: December 2002

A literature review revealed the following: key work factors associated with psychological ill health and sickness absence in staff were long hours worked, work overload and pressure, and the effects of these on personal lives; lack of control over work; lack of participation in decision making; poor social support; and unclear management and work role. There was some evidence that sickness absence was associated with poor management style. Successful interventions that improved psychological health and levels of sickness absence used training and organisational approaches to increase participation in decision making and problem solving, increase support and feedback, and improve communication. It is concluded that many of the work related variables associated with high levels of psychological ill health are potentially amenable to change. This is shown in intervention studies that have successfully improved psychological health and reduced sickness absence.
CONFORMAL SYMMETRY OF SUPERSTRINGS ON AdS3 × S3 × T4 AND D1/D5 System
Authors: ALI ABBAS
Published: December 2002

Conformal field theory of the D1/D5 system and superstrings on AdS3 × S3 × T4 is studied with particular attention to the worldsheet fields corresponding to the T4 part. A solution to the space–time N = 4 superconformal symmetry doubling and other problems is proposed. It is argued that the relevant space–time symmetry should be based on the middle N = 4 superconformal algebra. It is discussed as to why this superconformal structure has been missed so far.
LEPTON NUMBER AND LEPTON FLAVOR VIOLATIONS IN SEESAW MODELS
Authors: FALCONE D.
Published: December 2002

We discuss the impact of fermion mass matrices on some lepton number violating processes, namely baryogenesis via leptogenesis and neutrinoless double beta decay, and on some lepton flavor violating processes, namely radiative lepton decays in supersymmetric seesaw models.
THE SIGNIFICANCE OF VALENCE ELECTRON CONCENTRATION ON THE FORMATION MECHANISM OF SOME TERNARY ALUMINUM-BASED QUASICRYSTALS
Authors: ATHANASIOU N. S. , POLITIS C. , SPIRLET J. C. , BASKOUTAS S. , KAPAKLIS V.
Published: December 2002

In the present study we report on the formation mechanism of some binary Al-TM and ternary Al-Cu-TM (TM = transition metal) quasicrystals. We have found that the formation mechanism of quasicrystalline phases in the binary Al-TM system takes place at extremely high solidification rates, is linked to the location of the transition metal in the periodic table, depends upon the atomic radius ratio of the constituents, is composition sensitive, and as a result is strongly affected by the effective atomic radius ratio (a eff ). Applying empirical criteria on the formation of ternary Al-Cu-TM quasicrystals we were able to calculate the composition range at which the formation tendency and stability of quasicrystalline phases is enhanced. The method presented can be viewed as an empirical criterion to find new and high quality quasicrystalline materials and to optimize the quasicrystalline material composition. Furthermore, it was observed that the stabilization mechanism of the quasicrystalline Al-Cu-(Fe, Co, Ru, Rh, Os, Ir) phases takes place when the atomic ratio (TM+Cu)/Al ranges from 0.46 to 0.69 and for a eff values between 4.10 and 7.30. At the same valence electron concentration, metastable icosahedral Al-Cu-(Cr, Mn) phases are formed at relatively smaller atomic ratios (TM+Cu)/Al and having higher a eff values in comparison to those of the stable D- and I-phases.
TWO ANALYTICAL TECHNIQUES FOR THE DETERMINATION OF THE ABSOLUTE ATOM CONCENTRATION USING ELECTRON ENERGY LOSS SPECTROSCOPY (EELS)
Authors: HADJI N.
Published: December 2002

Two analytical techniques for the determination (within the limits of validity of the free electron model) of the absolute atom concentration (AAC) are reported in details. One of these may be useful for the determination of a AAC for chemical elements (e.g. hydrogen) which are not easy to detect. EELS is used.
OPERATOR METHOD FOR A NONCONSERVATIVE HARMONIC OSCILLATOR WITH AND WITHOUT SINGULAR PERTURBATION
Authors: CHOI JEONG RYEOL , KWEON BO HA
Published: December 2002

We used dynamical invariant operator method to find the quantum mechanical solution of a harmonic plus inverse harmonic oscillator with time-dependent coefficients. The eigenvalue of invariant operator is obtained and is constant with time. We constructed lowering and raising operators from the invariant operator. The solution of Schrödinger equation is obtained using operator method. We have also used ladder operators to obtain various expectation values of the time-dependent system. The results in this manuscript are not only more general than the existing results in the literatures but also well match with others.
IMPEDANCE AND MODULUS SPECTROSCOPY OF (Na1/2Bi1/2)1-xCaxTiO3 CERAMICS
Authors: SARADHI B. V. BAHUGUNA , SRINIVAS K. , BHIMASANKARAM T.
Published: December 2002

Impedance spectroscopy studies of calcium doped (Ca=0.01, 0.05, 0.1) sodium bismuth titanate (NBT), that is, ( Na 1/2 Bi 1/2)1-x Ca x TiO 3 (NBCT) solid solution are studied as a function of temperature (RT — 575°C) and frequency (100 Hz–1 MHz). The electrical properties and equivalent circuit parameters of Ca doped NBT, and it's bulk and grain boundary effects are studied with impedance spectroscopy as a non-destructive testing tool.
LONGITUDINAL DYNAMICAL SPIN SUSCEPTIBILITY IN HEISENBERG FERROMAGNETS
Authors: PANTIĆ M. R.
Published: December 2002

We study the longitudinal dynamical spin susceptibility [Formula: see text] within the framework of Heisenberg model in the ferromagnetic phase, where no external field exists. On the basis of memory function formalism within the framework of the irreducible Green's functions we obtained the self-consistent equations for [Formula: see text] in mode coupling approximation. The expression for the longitudinal spin susceptibility is valid in the whole range of system frequencies. Its validity in the range of low and high frequencies was discussed in particular for the magnetic systems in ferromagnetic phase.
EXTINCTION DYNAMICS AND EVOLUTION OF A SURVIVABILITY-BASED MULTI-LEVEL FOOD-WEB MODEL
Authors: BERGER B. W. , BOULTER C. J.
Published: December 2002

A multi-level evolution model where forced extinctions occur throughout the system based on a species fitness value (or survivability) is developed that is essentially the fusion of the evolution model of Bak and Sneppen and the food-web model of Amaral and Meyer. This model is found to describe the fossil record and behave as a self-organized critical system with a power law exponent of approximately 2, but is also found to be remarkably similar to a model that causes the forced extinctions randomly throughout the system. To explain this result we show that fitness is nearly randomly distributed with a slight peak in forced extinction (due to fitness) in the middle levels. These findings lend strong support to the hypothesis that coextinction effects (propagated through a food-web) provide a robust explanation of the fossil record, independent of the mechanism for species competition.
THE FERMION-BOSON MAPPING APPLIED TO LAGRANGIAN MODELS FOR CHARGE-DENSITY-WAVES IN ONE-DIMENSIONAL SYSTEMS
Authors: BELVEDERE L. V. , AMARAL R. L. P. G. , DE QUEIROZ A. F.
Published: December 2002

We use the two-dimensional Fermion-Boson mapping to perform a field theory analysis of the effective Lagrangian model for incommensurate charge-density waves (ICDW) in one-dimensional systems. We consider an approach in which both the phase of the complex phonon field and the electron field are dynamical degrees of freedom contributing to the quantum dynamics and symmetry-related features of the ICDW phenomenon. We obtain the bosonized and fermionized versions of the effective electron–phonon Lagrangian. The phase of the phonon field and the phase of the bosonized chiral density of the electron field condense as a soliton order parameter, carrying neither the charge nor the chirality of the electron–phonon system, leading to a periodic sine-Gordon potential. The phonon field is fermionized in terms of a chiral fermionic condensate and the effective model is mapped into the chiral Gross–Neveu (GN) model with two Fermi field species. The linked electron–phonon symmetry of the ICDW system is mapped into the chiral symmetry of the GN model. Within the functional integral formulation, we obtain for the vacuum expectation value of the phonon field < ϕ > = 0 and < ϕ ϕ* > ≠ 0, due to the charge selection rule associated with the chiral electron–phonon symmetry. We show that the two-point correlation function of the phonon field satisfies the cluster decomposition property, as required by the chiral symmetry of the underlying GN model. The quantum description of the ICDW corresponds to charge transport through the lattice, due to the propagation of a "Goldstone mode" carrying the effective charge of the electron–phonon system, is accomplished by an electron–lattice energy redistribution. This accounts for a dynamical Peierls's energy gap generation.
QUANTUM DYNAMICS OF A SINGLE COOPER-PAIR BOX WITH A SINGLE-MODE CAVITY FIELD
Authors: ZHANG MENG , ZOU JIAN , SHAO BIN
Published: December 2002

We consider a single Cooper-pair box biased by a classical voltage and also irradiated by a single-mode quantized field. We investigate the quantum dynamics of the Cooper-pair box and show that the collapse and revival phenomena can exist in this system, which is sensitive to the detuning between the Josephson energy EJ and cavity field frequency ω.
VERY NARROW RESONANCES IN SPHERICAL PROTON EMITTING NUCLEI
Authors: LEITE T. N. , TERUYA N. , DIAS H.
Published: December 2002

The separation energy and half-life of some heavy proton emitting nuclei, and the single-particle structure of unbound 11 N , have been evaluated by implementing a careful numerical treatment to solve the Schrödinger equation in a continuum discretization context. The basic scheme behind the method consists in using the ground-state proton emitter in connection with an isolated single-particle resonance.
EXACT SOLUTIONS OF THE DIRAC EQUATION WITH A COULOMB PLUS SCALAR POTENTIAL IN 2 + 1 DIMENSIONS
Authors: DONG SHI-HAI , GU XIAO-YAN , MA ZHONG-QI , DONG SHISHAN
Published: December 2002

The exact solutions of the (2+1)-dimensional Dirac equation with a Coulomb potential and a scalar one are analytically presented by studying the second-order differential equations obtained from a pair of coupled first-order ones. The eigenvalues are studied in some detail.
NEGATIVE NORM STATES IN DE SITTER SPACE AND QFT WITHOUT RENORMALIZATION PROCEDURE
Authors: TAKOOK MOHAMMAD VAHID
Published: December 2002

In recent papers,1,2 it has been shown that the presence of negative norm states or negative frequency solutions are indispensable for a fully covariant quantization of the minimally coupled scalar field in de Sitter space. Their presence, while leaving unchanged the physical content of the theory, offers the advantage of eliminating any ultraviolet divergence in the vacuum energy2 and infrared divergence in the two point function.3 We attempt here to extend this method to the interacting quantum field in Minkowski space-time. As an illustration of the procedure, we consider the λϕ4 theory in Minkowski space-time. The mathematical consequences of this method is the disappearance of the ultraviolet divergence to the one-loop approximation. This means, the effect of these auxiliary negative norm states is to allow an automatic renormalization of the theory in this approximation.
EFFECTS OF THE SIDE-PATH MODEL ON THE MUON TOTAL STICKING COEFFICIENT AND CYCLING RATE IN D/T μCF
Authors: KALANTARI S. Z. , SOHANI M.
Published: December 2002

In this paper we explore the effects of the meta-stable states of dtμ* molecules on crucial parameters in μCF such as total sticking coefficient and muon cycling rate. For this purpose we establish a new approach in the study of the determination of the q1s parameter and the relative population of muonic atoms by solving the kinetics of μCF. We have answered the basic questions about the muon total sticking including the side-path effects.
C0 COVERAGE-MEASURE AND TESTING-DOMAIN METRICS BASED ON A SOFTWARE RELIABILITY GROWTH MODEL
Authors: FUJIWARA TAKAJI , YAMADA SHIGERU
Published: December 2002

Generally, a software development manager is performing the testing-progress management by using various CASE tools. These CASE tools support testing activities of Windows applications or embedded software systems. Then, by using various testing coverage-measures, the testing-progress management can be recognized visually. However, in the system-testing phase, it is impossible to measure them of software systems which have been becoming large-scale and complicated recently. Therefore, the manager has to determine the testing termination time in consideration of the convergence situation of the cumulative number of detected faults and the prespecified delivery time to the users. These determination method have ambiguity based on the manager's experience or intuition. In this paper, we investigate the relationship between the testing-domain rate derived from a testing-domain dependent software reliability growth model and the testing-path coverage. Then, we show that the testing-domain rate, which is defined as the increasing ratio of the testing-paths in the modules and functions in the software system to be influenced by executed test-cases, is useful as an alternative measure of testing-coverage metrics. Further, this model is applied to the fault data observed in an actual software project, and the comparisons of goodness-of-fit with the conventional software reliability growth models are performed. Finally, in numerical illustrations, we discuss the software reliability analysis and the usefulness of the testing-domain rate, and propose a new testing-path coverage rate.
AN INNOVATIVE TECHNIQUE FOR QUALITY CONTROL OF GEAR PUMPS
Authors: FANTI GIULIO , BASSO ROBERTO , BERNARDI MICHELE , VERZA UMBERTO
Published: December 2002

This paper describes an innovative technique for the quality control of gear pumps based on the frequency analysis of the oscillations of the discharge pressure using a new mathematical tool called "the spectrum of the power cepstrum." It consists in applying Fourier transform of the pressure data sampled in the time domain three times consecutively. The innovative technique makes it possible to obtain an acceptance mask for a set of gear pumps in the same series, in which the class and entity of a defect can be detected.
STATISTICAL MODEL FOR VEHICLE BODY-IN-PRIME STATIC STIFFNESS TARGET SETTING
Authors: GOMEZ-LEVI GIANNA , KUO EVERETT , WANG NANXIN
Published: December 2002

The vehicle body-in-prime static stiffness can significantly affect vehicle NVH, ride and handling, and durability performance. Stiffness target setting is a crucial step in a vehicle design and development process. Traditionally, benchmarking data and CAE models are used to help identify and set the target, yet they have proven to be time consuming and very subjective. On the other hand, statistical models obtained through data mining or meta-modeling have been tested and applied to various problems, including design optimization. In the present paper, we attempt to utilize this technology for providing more objective vehicle static stiffness targets. Stiffness data characteristics of various vehicle classes are benchmarked. Different statistical modeling techniques are examined using the data to set stiffness targets. The validity and limitations of these techniques are also discussed.
GLOBAL ALTERNATION-INDUCED PATTERNS
Authors: BUCETA J. , LINDENBERG KATJA , PARRONDO J. M. R.
Published: December 2002

We present a review of a recently proposed mechanism for pattern formation in which deterministic or random global alternation of dynamics, neither of which exhibits patterns, induces stationary or oscillatory ordered structures. We illustrate the mechanism by means of Swift-Hohenberg-like models and implement a theoretical analysis in terms of mode amplitude equations. Numerical simulations on 1-d and 2-d lattices support our findings.
Parametrically excited nonlinear systems: a comparison of two methods
Authors: El-Bassiouny A. F.
Published: December 2002

Subharmonic resonance of two‐degree‐of‐freedom systems with cubic nonlinearities to multifrequency parametric excitations in the
presence of three‐to‐one internal resonance is investigated. Two
approximate methods (the multiple scales and the generalized
synchronization) are used to construct a first‐order nonlinear
ordinary differential equations governing the modulation of the
amplitudes and phases. Steady state solutions and their stability
are computed for selected values of the system parameters. The
results obtained by the two methods are in excellent agreement.
Numerical solutions are carried out and graphical representations
of the results are presented and discussed.
Sufficient conditions for univalence in ℂ n
Authors: Rãducanu Dorina
Published: December 2002

The method of subordination chains is used to establish new univalence criteria for holomorphic mappings in the unit ball of ℂ n. Various criteria involving the first and the second derivative of a holomorphic mapping in the unit ball of ℂ n are developed.
Powersum formula for polynomials whose distinct roots are differentially independentover constants
Authors: Nahay John Michael
Published: December 2002

We prove that the author′s powersum formula yields a
nonzero expression for a particular linear ordinary differential
equation, called a resolvent, associated with a
univariate polynomial whose coefficients lie in a differential
field of characteristic zero provided the distinct roots of the
polynomial are differentially independent over constants. By
definition, the terms of a resolvent lie in the differential field
generated by the coefficients of the polynomial, and each of the
roots of the polynomial are solutions of the resolvent. One
example shows how the powersum formula works. Another example
shows how the proof that the formula is not zero works.
Transitivity in uniform approach theory
Authors: Lee Y. J. , Windels B.
Published: December 2002

We introduce a notion of transitivity for approach uniformities and approach uniform convergence spaces, yielding reflective subconstructs of AUnif
and AUCS. Further, we investigate how these new categories are related to uACHY, uACHY U , and uMET, and we show that these relationships are similar to those in the classical case.
On the notion of L 1‐completeness of a stochastic flow on a manifold
Authors: Gliklikh Yu. E. , Morozova L. A.
Published: December 2002

We introduce the notion of L 1‐completeness for a stochastic flow on manifold and prove a necessary and sufficient condition for a flow to be L 1‐complete. L 1‐completeness means that the flow is complete (i.e., exists on the given time
interval) and that it belongs to some sort of L 1‐functional space, natural for manifolds where no Riemannian metric is specified.
Sign‐changing and multiple solutions for the p‐Laplacian
Authors: Carl Siegfried , Perera Kanishka
Published: December 2002

We obtain a positive solution, a negative solution, and a sign‐changing solution for a class of p‐Laplacian problems with jumping nonlinearities using variational and super‐subsolution methods.