bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute free energies of binding of peptide analogs to the HIV‐1 protease from molecular dynamics simulations
Authors: Bartels Christian , Widmer Armin , Ehrhardt Claus 
Published: June 2005

AbstractThe constants of binding of five peptide analogs to the active site of the HIV‐1 aspartic‐protease are calculated based on a novel sampling scheme that is efficient and does not introduce any approximations in addition to the energy function used to describe the system. The results agree with experiments. The squared correlation coefficient of the calculated vs. the measured values is 0.79. The sampling scheme consists of a series of molecular dynamics integrations with biases. The biases are selected based on an estimate of the probability density function of the system in a way to explore the conformational space and to reduce the statistical error in the calculated binding constants. The molecular dynamics integrations are done with a vacuum potential using a short cutoff scheme. To estimate the probability density of the simulated system, the results of the molecular dynamics integrations are combined using an extension of the weighted histogram analysis method (C. Bartels, Chem. Phys. Letters 331 (2000) 446–454). The probability density of the solvated ligand–protein system is obtained by applying a correction for the use of the short cutoffs in the simulations and by taking into account solvation with an electrostatic term and a hydrophobic term. The electrostatic part of the solvation is determined by finite difference Poisson–Boltzmann calculations; the hydrophobic part of the solvation is set proportional to the solvent accessible surface area. Setting the hydrophobic surface tension parameter equal to 8 mol−1 K−1 A−2, absolute binding constants are in the μM to nM range. This is in agreement with experiments. The standard errors determined from eight repeated binding constant determinations are a factor of 14 to 411. A single determination of a binding constant is done with 499700 steps of molecular dynamics integration and 4500 finite difference Poisson–Boltzmann calculations. The simulations can be analyzed with respect to conformational changes of the active site of the HIV‐1 protease or the ligands upon binding and provide information that complements experiments and can be used in the drug development process. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1294–1305, 2005
Coloring 4‐cycle systems
Authors: Burgess Andrea C. , Pike David A. 
Published: June 2005

AbstractAn m‐cycle system of order n is a partition of the edges of the complete graph Kn into m‐cycles. We investigate k‐colorings of 4‐cycle systems in which no 4‐cycle is monochromatic. For any k ≥ 3, we construct a k‐chromatic 4‐cycle system. We also show that for any k ge; 2, there exists an integer wk such that for all admissible n ≥ wk, there is a k‐chromatic 4‐cycle system of order n. © 2005 Wiley Periodicals, Inc. J Combin Designs
Products of mixed covering arrays of strength two
Authors: Colbourn Charles J. , Martirosyan Sosina S. , Mullen Gary L. , Shasha Dennis , Sherwood George B. , Yucas Joseph L. 
Published: June 2005

AbstractAcovering arrayCA(N;t,k,vis anN × karray such that everyN × tsubarray contains allt‐tuples fromvsymbolsat leastonce, wheretis thestrengthof the array. Covering arrays are used to generate software test suites to cover allt‐sets of component interactions. The particular case whent = 2 (pairwise coverage) has been extensively studied, both to develop combinatorial constructions and to provide effective algorithmic search techniques. In this paper, a simple “cut‐and‐paste” construction is extended to covering arrays in which different columns (factors) admit different numbers of symbols (values); in the process an improved recursive construction for covering arrays witht = 2 is derived. © 2005 Wiley Periodicals, Inc. J Combin Designs 14: 124–138, 2006
Decomposition of complete graphs into 5‐cubes
Authors: Bryant D. , El‐Zanati S. I. , Maenhaut B. , Vanden Eynden C. 
Published: June 2005

AbstractNecessary conditions for the complete graph on n vertices to have a decomposition into 5‐cubes are that 5 divides n − 1 and 80 divides n(n − 1)/2. These are known to be sufficient when n is odd. We prove them also sufficient for n even, thus completing the spectrum problem for the 5‐cube and lending further weight to a long‐standing conjecture of Kotzig. © 2005 Wiley Periodicals, Inc. J Combin Designs 14: 159–166, 2006
Irreducible 2‐fold cycle systems
Authors: Jenkins Peter 
Published: June 2005

AbstractIn this paper, it is shown that for any pair of integers (m,n) with 4 ≤ m ≤ n, if there exists an m‐cycle system of order n, then there exists an irreducible 2‐fold m‐cycle system of order n, except when (m,n) = (5,5). A similar result has already been established for the case of 3‐cycles. © 2005 Wiley Periodicals, Inc. J Combin Designs 14: 324–332, 2006
Recurrent mutations associated with isolation and passage of SARS coronavirus in cells from non‐human primates
Authors: Poon Leo L.M. , Leung Cynthia S.W. , Chan Kwok H. , Yuen Kwok Y. , Guan Yi , Peiris Joseph S.M. 
Published: June 2005

AbstractFour clinical isolates of SARS coronavirus were serially passaged in two primate cell lines (FRhK4 and Vero E6). Viral genetic sequences encoding for structural proteins and open reading frames 6–8 were determined in the original clinical specimen, the initial virus isolate (passage 0) and at passages 5, 10, and 15. After 15 passages, a total of 15 different mutations were identified and 12 of them were non‐synonymous mutations. Seven of these mutations were recurrent mutation and all located at the spike, membrane, and Orf 8a protein encoding sequences. Mutations in the membrane protein and a deletion in ORF 6–8 were already observed in passage 0, suggesting these amino acid substitutions are important in the adaptation of the virus isolate in primate cell culture. A mutation in the spike gene (residue 24079) appeared to be unique to adaptation in FRhK4 cells. It is important to be aware of cell culture associated mutations when interpreting data on molecular evolution of SARS coronavirus. J. Med. Virol. 76:435–440, 2005. © 2005 Wiley‐Liss, Inc.
Prevalence of complete resistance to at least two classes of antiretroviral drugs in treated HIV‐1‐infected patients: A French nationwide study
Authors: Masquelier Bernard , Costagliola Dominique , Schmuck Anne , Cottalorda Jacqueline , Schneider Véronique , Izopet Jacques , Calvez Vincent , Descamps Diane , Poggi Cécile , Brun‐Vézinet Françoise ,   the ANRS resistance study group
Published: June 2005

AbstractThe objective of the study was to estimate the prevalence of HIV‐1 resistance to all drugs belonging to two or more antiretroviral drug (ARV) classes in treated patients in France. All genotyping assays performed in June 2001 and in November 2002 by the ANRS resistance laboratory network were analyzed by the ANRS algorithm. The 17 and 21 centers of the ANRS network participating in the study in 2001 and 2002, respectively, genotyped the viruses in plasma of 456 and 529 patients, respectively. In 2002, the proportions of patients harboring viruses fully resistant to one, two, and three ARV classes were 5.1%, 8.1%, and 2.5%, respectively. These results were similar to those obtained in 2001. In 2002, among the 56 patients with viruses completely resistant to at least two ARV classes, 98%, 96%, and 29% of patients had viruses with complete class resistance to NRTIs, NNRTIs, and PIs, respectively. Complete resistance to PIs was less frequent than full resistance to the other two ARV classes, and ritonavir‐boosted amprenavir and lopinavir/r remained potentially active in respectively 71.4% and 42.9% of these 56 patients. In 2001 and 2002, respectively 30% of the 65 patients and 24% of the 56 patients with viruses completely resistant to at least two ARV classes were at an advanced stage of HIV disease, with CD4+ cell counts below 200/μl and viral loads above 30 000 copies/ml. In France, the prevalence of HIV‐1 viruses completely resistant to two or more ARV classes remained stable between 2001 and 2002. Resistance to RT inhibitors was more frequent than resistance to PIs in patients with viruses completely resistant to two or three classes of ARV. J. Med. Virol. 76:441–446, 2005. © 2005 Wiley‐Liss, Inc.
Diverse pattern of protease inhibitor resistance mutations in HIV‐1 infected patients failing nelfinavir
Authors: Svedhem Veronica , Lindkvist A. , Bergroth T. , Knut Lidman , Sönnerborg A. 
Published: June 2005

AbstractThe aim of the study was to describe the pattern of resistance mutations in human immunodeficiency virus type 1 (HIV‐1) infected patients experiencing their first protease inhibitor (PI) failure on nelfinavir (NFV)‐containing therapy. Earlier PI‐naïve patients (n = 172) with NFV‐containing therapy were therefore retrospectively studied. Plasma HIV RNA from 43 failing patients was sequenced. In addition, virus from the baseline was sequenced in 29 patients. Failure was defined as two consecutive measurements of viral load of >50 copies/ml after 6 months treatment. Subtyping was done in most patients (n = 118). At baseline, the V82A mutation was found in four PI‐naïve patients of whom two failed therapy exhibiting this mutation. At therapy failure, 17 of the 43 (40%) patients had primary PI mutations. In nine subjects, RTI‐mutations only were found and 17 patients had a wild‐type virus. Patients with primary PI and/or RTI mutations had a higher viral load at failure than those who failed with wild‐type virus. A surprisingly diverse pattern of primary PI mutations was seen: M46I (n = 7), D30N (n = 6), L90M (n = 5), and V82A (n = 4). Four patients exhibited more than one primary PI mutation. PI‐naïve patients in Sweden may harbor PI‐resistant virus and resistance testing should be considered before treatment. Patients who fail NFV may develop the M46I mutation, which has been related earlier to mainly other PI. The diverse pattern of the evolved PI‐mutations and the relative low occurrence of the D30N mutation in the material was unexpected and did not seem to be related to the viral subtype. J. Med. Virol. 76:447–451, 2005. © 2005 Wiley‐Liss, Inc.
Subtype analysis and mutations to antiviral drugs in HIV‐1‐infected patients from Mozambique before initiation of antiretroviral therapy: Results from the DREAM programme
Authors: Bellocchi Maria Concetta , Forbici Federica , Palombi Leonardo , Gori Caterina , Coelho Elisabeth , Svicher Valentina , D'Arrigo Roberta , Emberti‐Gialloreti Leonardo , Ceffa Susanna , Erba Fulvio , Marazzi Maria Cristina , Silberstein Francesca Ceccherini , Perno Carlo‐Federico 
Published: June 2005

AbstractPhylogenetic analysis and evaluation of drug‐resistance were carried out upon 59 plasma samples from 58 treatment‐naïve HIV‐1 infected patients from Mozambique, enrolled in a free antiviral‐therapy protocol in the frame of Drug‐Resource‐Enhancement against AIDS and Malnutrition (DREAM) programme. Sequencing of the first 1,300 bases of the pol‐gene shows that all virus strains cluster within clade C, with the exception of a single patient carrying a G‐subtype virus. Relevant mutations in the reverse transcriptase (RT) are rare: 118A/I/L/G (four patients), 179E/D/I (three patients), 333E/D (two patients), 101R, and 210F (one patient each). In Protease (PR), V82I (10.3%) is the only relevant mutation, while natural polymorphisms/secondary mutations are found, some at very high frequency: 20R (25.9%), 36I (91.4%), 36L (8.6%), 60E (31.0%), 63P (29.3%), and 93L (96.6%). Among them, mutations with a frequency >25% were further investigated to assess their covariation pattern with PI resistance associated mutations. The pattern of covariation observed for K20R and D60E (but not L63P and M36I) was different between C and B subtype isolates from PR‐inhibitor‐treated patients. The sequences were also analyzed to calculate the ratio of non‐synonymous to synonymous substitution. The ratio for PR and RT was 0.116 and 0.093, respectively, suggesting a greater conservation in RT than PR in both subtypes B and C HIV strains. Taken together, the results demonstrate a consistent clade‐homogeneity of viral strains circulating in Mozambique, and the very limited presence, in drug‐naïve patients, of mutations associated with resistance to RT‐inhibitors. The high frequency of secondary mutations/polymorphisms in HIV‐PR deserves further studies to evaluate its relevance in clinical settings. J. Med. Virol. 76:452–458, 2005. © 2005 Wiley‐Liss, Inc.
Purification and partial characterization of R5, R5X4, and X4 HIV‐1 subtype C envelope glycoproteins expressed in insect cells
Authors: Nkosi Sibusiso P. , Huismans Henk , Papathanasopoulos Maria A. 
Published: June 2005

AbstractBiological properties of four recombinant HIV‐1 subtype C envelope glycoproteins from viruses with different phenotypic characteristics (CCR5 and/or CXCR4‐utilizing) were investigated. The gp160 genes were cloned, expressed in Spodoptera frugiperda insect cells, purified, and their biological characteristics were examined. The conformational and functional integrity of the HIV‐1 subtype C rgp160 was intact since they reacted with the A32, C11, IgG1b12, 7B2, and 17b conformational dependant monoclonal antibodies (MAb), sCD4, and patient sera. Baculovirus derived rgp160 can be used for further structural, functional, antigenic, and immunological studies. J. Med. Virol. 76:459–463, 2005. © 2005 Wiley‐Liss, Inc.
Development of a sensitive assay for the measurement of antibodies against heat shock protein binding protein 1 (HspBP1): Increased levels of anti‐HspBP1 IgG are prevalent in HIV infected subjects
Authors: Papp Diana , Prohászka Zoltán , Kocsis Judit , Füst George , Bánhegyi Dénes , Raynes Deborah A. , Guerriero Vince 
Published: June 2005

AbstractThe 70 kDa heat shock protein (Hsp70) is generally considered to be an intracellular protein, however, there is evidence that Hsp70 can be found in the extracellular environment. Hsp70 and antibodies against Hsp70 have been reported in human serum. Recent evidence has shown that Hsp70 antibodies are elevated in HIV infected individuals. This study reports on the antibody levels against a co‐chaperone, HspBP1, that regulates Hsp70 activity. We have developed a solid‐phase enzyme linked assay for the determination of anti‐HspBP1 IgG antibodies. We report here that HspBP1 antibodies are present in human serum and the levels are elevated approximately twofold in HIV infected patients. There was no correlation between HspBP1 antibody levels and clinical parameters nor was there a relation between anti‐Hsp70 levels and anti‐HspBP1 levels. The presence of HspBP1 antibodies in human serum suggests that the protein may also be present in the serum. The increased level of HspBP1 antibodies in HIV infected individuals suggests a relationship directly to the virus or indirectly to secondary consequences of HIV infection. J. Med. Virol. 76:464–469, 2005. © 2005 Wiley‐Liss, Inc.
Cervical squamous intra‐epithelial changes and human papillomavirus infection in women infected with human immunodeficiency virus in Pune, India
Authors: Joshi Smita N. , Gopalkrishna V. , Kumar B. Kishore , Dutta Soma , Nyaynirgune Pratima , Thakar Madhuri , Tripathy Srikanth , Mehendale Sanjay , Paranjape Ramesh 
Published: June 2005

AbstractIn view of the dual burden of HIV infection and cervical cancers in India, this study was undertaken to estimate the prevalence of Pap smear abnormalities and human papillomavirus infection among HIV‐infected women. Consecutive HIV‐infected women attending voluntary counseling testing clinics were enrolled. Written informed consent, demographic information, Pap smears, cervical swabs for HPV typing and a blood sample for CD4+ cell count were collected. Treatment for opportunistic and sexually transmitted infections and reproductive tract infections was provided. Women with Pap smear abnormality were referred for further intervention. Between January 2003 and May 2004, 287 HIV‐infected women were enrolled. Pap smear abnormalities were seen in 6.3% women and were more common among women aged 30 and above (P = 0.042) and those who had suffered from opportunistic infections (P = 0.004). In multivariate analysis, Pap smear abnormalities were associated independently with opportunistic infections (P = 0.02, AOR 3.8, 95% CI 1.2–11.5). Of the 100 random cervical specimens screened for HPV 16 and 18 genotypes, 33% (95 CI 23.9–43.1) were positive for HPV 16/18. Of the 122 patients who returned for a follow‐up visit, 5 patients (4.1%) who did not have Pap smear abnormality at baseline, had developed Pap smear abnormality. The incidence of Pap smear abnormalities was 5.5 per 100 person year of follow‐up. In order to prevent thousands of deaths due to cervical cancer in India, there is a need for strengthening the Pap smear screening program and HPV vaccine development. J. Med. Virol. 76:470–475, 2005. © 2005 Wiley‐Liss, Inc.
Complete genome sequence and phylogenetic analysis of hepatitis B virus isolated from turkish patients with chronic HBV infection
Authors: Bozdayi Gülendam , Türkyilmaz A. Resat , Idilman Ramazan , Karatayli Ersin , Rota Seyyal , Yurdaydin Cihan , Bozdayi A. Mithat 
Published: June 2005

AbstractHepatitis viruses are the leading causes of chronic liver disease resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world and also in Turkey. Although Turkey has an intermediate rate of hepatitis B virus (HBV) infection with a prevalence reported as 5%, a complete HBV genome sequence has not been published. In this study, the molecular characterization and phylogenetic analysis are described of 11 complete HBV genomes isolated from 11 naïve patients (5 male, 6 female; ages: 18–54 years old, median 35 years old) with chronic HBV infection. Of 11 patients, 7 and 4 were HBeAg positive/anti‐HBe negative and HBeAg negative/anti‐HBe positive, respectively. All patients had no co‐infection with HCV, HDV, or HIV. HBV DNA was extracted from the sera of the patients. The complete genome was amplified by PCR and cloned into a TA vector. The PCR products were sequenced directly and the complete HBV genome sequences were determined. Ten HBV genomes were 3182 base pairs in length. There was a 183 bp deletion (between nucleotides 2987–3169) in pre‐S region in one HBeAg positive patient. There were two pre‐core stop codons (G1896A) in two HBeAg negative and three core promoter dual mutations (T1762/A1764) in one HBeAg positive and two HBeAg negative patients' HBV genomes. Phylogenetic analysis of all complete genomes yielded that all Turkish sequences were clustered in genotype D branch (ten in subgenotype D1 and one in subgenotype D2). The analysis of S gene amino acid sequences revealed that surface gene subtypes of one and ten HBV strains were subtype ayw3 and ayw2, respectively. This study indicates that Turkish patients with chronic hepatitis B infection show very little genotypic heterogeneity. Genotype D of HBV DNA and subtype ayw2 of surface gene represent almost the whole Turkish patient population infected with HBV. J. Med. Virol. 76:476–481, 2005. © 2005 Wiley‐Liss, Inc.
Intrahepatic cytokine profile in renal‐transplant patients infected by hepatitis C virus
Authors: Kamar Nassim , Rostaing Lionel , Sandres‐Saune Karine , Selves Janick , Barthe Carole , Dubois Martine , Alric Laurent , Durand Dominique , Izopet Jacques 
Published: June 2005

AbstractIn order to examine the immunopathogenesis of hepatitis C virus (HCV)‐related liver injury in renal‐transplant patients, intra‐hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real‐time PCR method of a Th1 cytokine (i.e., interferon (IFN)‐γ), a Th2 cytokines (i.e., interleukine (IL)‐10), a proinflammatory cytokine (i.e., IL‐8), and a potent fibrogenic factor (transforming growth factor [TGF]‐β). There was no significant difference in TGF‐β, IFN‐γ, IL‐10, or IL‐8 levels of expression according to liver‐activity grade, liver‐fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN‐γ/β‐actin mRNA concentration was higher than the IL‐10/β‐actin mRNA concentration in patients with F3 Metavir score. Median IFN‐γ/β‐actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF‐β/β‐actin (r2 = 0.19, P = 0.04) and IL‐8/β‐actin mRNA concentrations (r2 = 0.19, P = 0.03). IFN‐γ/β‐actin mRNA concentration also increased according to the duration of HCV (r2 = 0.19, P = 0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r2 = 0.17, P = 0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients. J. Med. Virol. 76:482–488, 2005. © 2005 Wiley‐Liss, Inc.
Hepatitis C virus‐core and non structural proteins lead to different effects on cellular antioxidant defenses
Authors: Abdalla Maher Y. , Ahmad Iman M. , Spitz Douglas R. , Schmidt Warren N. , Britigan Bradley E. 
Published: June 2005

AbstractChronic hepatitis C virus (HCV) infection leads to increased oxidative stress in the liver. Hepatic antioxidant enzymes provide an important line of defense against oxidative injury. To understand the antioxidant responses of hepatocytes to different HCV proteins, we compared changes in antioxidative enzymes in HCV‐core and HCV‐nonstructural protein expressing hepatocyte cell lines. We found that expression of HCV‐core protein in hepatocyte cell lines leads to increased oxidative stress as determined by increased in the oxidant‐sensitive probe 5‐(and‐6)‐chloromethyl‐2′,7′‐dichlorodihydrofluorescein diacetate (CM‐DCFH2) fluorescence, decreased reduced glutathione (GSH), and increased oxidation of thioredoxin (Trx). Although the expression of HCV‐nonstructural (HCV‐NS) proteins led to increased oxidative stress as well, the antioxidant enzymatic responses were different. Over‐expression of HCV‐NS proteins increased antioxidant enzymes (MnSOD and catalase), heme oxygenase‐1 (HO‐1), and GSH, indicating different mechanism(s) of prooxidative activity than HCV‐core protein. Our findings show that different HCV proteins induce different antioxidant defense responses in hepatocytes. These findings may facilitate understanding the interaction of different HCV proteins with infected liver cells and help identify possible factors contributing to hepatocyte damage during HCV infection. J. Med. Virol. 76:489–497, 2005. © 2005 Wiley‐Liss, Inc.