bluuebunny/crossref_metadata_2025_split huggingface dataset:
Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?
Authors: Vogel Thorsten U. , Friedrich Thomas C. , O'Connor David H. , Rehrauer William , Dodds Elizabeth J. , Hickman Heather , Hildebrand William , Sidney John , Sette Alessandro , Hughes Austin , Horton Helen , Vielhuber Kathy , Rudersdorf Richard , de Souza Ivna P. , Reynolds Matthew R. , Allen Todd M. , Wilson Nancy , Watkins David I. 
Published: October 2002

ABSTRACTIt is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79GY9), and one from the Nef protein (Nef159-167YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35SL8, which reproducibly selects for escape variants during acute infection, and Gag181-189CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.
Characterization of a Putative α-Helix across the Capsid-SP1 Boundary That Is Critical for the Multimerization of Human Immunodeficiency Virus Type 1 Gag
Authors: Liang Chen , Hu Jing , Russell Rodney S. , Roldan Ariel , Kleiman Lawrence , Wainberg Mark A. 
Published: October 2002

ABSTRACT

A 14-amino-acid spacer peptide termed SP1 that separates the capsid (CA) and nucleocapsid (NC) sequences plays an active role in the assembly of human immunodeficiency virus type 1. This activity of SP1 involves its amino-terminal residues that, together with adjacent CA residues, constitute a putative α-helical structure spanning Gag residues from positions 359 to 371. In this study, we have determined that the virus assembly determinants within this putative α-helix were residues H359, K360, A361, L364, A367, and M368, of which K360 and A367 contribute to virus production to lesser extents. Notably, changes of the two basic amino acids H359 and K360 to arginine (R) impaired virus production, whereas mutations L364I and M368I, in contrast to L364A and M368A, generated near-wild-type levels of virus particles. This suggests that within Gag complexes, amino acids H359 and K360 are involved in stricter steric interactions than L364 and M368. Since L364 and M368 are separated by four residues and thus presumably located on the same side of the helical surface, they may initiate synergistic hydrophobic interactions to stabilize Gag association. Further analysis in the context of the protease-negative mutation D185H confirmed the key roles of amino acids H359, A361, L364, and M368 in virus assembly. Importantly, when transfected cells were subjected to Dounce homogenization and the cell lysates were treated by ultracentrifugation at 100,000 ×
g
, Gag molecules containing each of the H359A, A361V, L364A, and M368A mutations were found mainly in the supernatant fraction (S100), whereas approximately 80% of wild-type Gag proteins were found in the pellet. Therefore, these four mutations must have prevented Gag from generating large complexes.
Characterization of Porcine Endogenous Retrovirus γ
pro-pol
Nucleotide Sequences
Authors: Klymiuk Nikolai , Müller Mathias , Brem Gottfried , Aigner Bernhard 
Published: October 2002

ABSTRACT

Endogenous retroviral sequences in the pig genome (PERV) represent a potential infectious risk in xenotransplantation. All known infectious PERV have been asssigned to the PERV γ1 family, consisting of the subfamilies A, B, and C. The aim of the study was the concise examination of PERV γ by the analysis of the retroviral
pro
-
pol
sequences. The analysis of 52
pro
-
pol
clones amplified in this study revealed eight PERV γ families. In addition to four already-described families (γ1, γ4, γ5, γ6), four novel families (γ7, γ8, γ9, γ10) were identified. Quantitative analysis of the novel PERV γ sequences in selected breeds revealed variations in the endogenous retroviral load. Open reading frames (ORF) in the amplified proviral fragment were only found for PERV γ1. In addition, novel ORF-containing PERV γ1 clones consisting of hybrid sequences were revealed. Sequence comparison from published full-length PERV γ1 clones of the PERV subfamilies A, B, and C resulted in a lack of strict correlation of the classification of
pro
-
pol
and
env
. The results indicated the occurrence of causative recombination events between retroviral genomes. Thus, our study on PERV γ provides new data for the evaluation and selection of pigs intended to be used in xenotransplantation.
What Can History Teach Us? A Retrospective Examination of Long-Term Energy Forecasts for the United States
Authors: Craig Paul P. , Gadgil Ashok , Koomey Jonathan G. 
Published: October 2002

▪ Abstract  This paper explores how long-term energy forecasts are created and why they are useful. It focuses on forecasts of energy use in the United States for the year 2000 but considers only long-term predictions, i.e., those covering two or more decades. The motivation is current interest in global warming forecasts, some of which run beyond a century. The basic observation is that forecasters in the 1950–1980 period underestimated the importance of unmodeled surprises. A key example is the failure to foresee the ability of the United States economy to respond to the oil embargos of the 1970s by increasing efficiency. Not only were most forecasts of that period systematically high, but forecasters systematically underestimated uncertainties. Long-term energy forecasts must make assumptions about both technologies and social systems. At their most successful, they influence how people act by showing the consequences of not acting. They are useful when they provide insights to energy planners, influence the perceptions of the public and the energy policy community, capture current understanding of underlying physical and economic principles, or highlight key emerging social or economic trends.It is true that at best we see dimly into the future, but those who acknowledge their duty to posterity will feel impelled to use their foresight upon what facts and guiding principles we do possess. Though many data are at present wanting or doubtful, our conclusions may be rendered so far probable as to lead to further inquiries… ( 1 ), p. 4.
Predictors and outcomes of scleroderma renal crisis: The high‐dose versus low‐dose D‐penicillamine in early diffuse systemic sclerosis trial
Authors: DeMarco Paul J. , Weisman Michael H. , Seibold James R. , Furst Daniel E. , Wong Weng Kee , Hurwitz Eric L. , Mayes Maureen , White Barbara , Wigley Fredrick , Barr Walter , Moreland Larry , Medsger Thomas A. , Steen Virginia , Martin Richard W. , Collier David , Weinstein Arthur , Lally Edward , Varga John , Weiner Steven R. , Andrews Brian , Abeles Micha , Clements Philip J. 
Published: November 2002

AbstractObjectiveThe reported frequency of scleroderma M01‐R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15–20%. Early use of angiotensin‐converting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc.MethodsWe retrospectively evaluated the cohort of SSc patients who participated in the High‐Dose Versus Low‐Dose D‐Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled.ResultsOne hundred thirty‐four SSc patients entered the observation period a mean ± SD of 0.8 ± 0.3 years after onset of SSc. SRC occurred in 18 patients a mean ± SD of 0.9 ± 1.1 years after entry. During a mean ± SD 4.0 ± 1.1 years of followup after entry, 9 of the 18 patients died (mean ± SD 0.6 ± 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of ≥20 (P < 0.01), enlarged cardiac silhouette on radiograph (P = 0.04), large joint contractures (wrist, elbow, knee) (P = 0.008), and prednisone use at entry (P = 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P = 0.012) in the 6 months before onset of SRC.ConclusionSRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort. Predictors of SRC identified in this study included higher than average skin score, prednisone use at study entry, large joint contractures, and heart enlargement. Our data suggest, however, that low‐dose prednisone alone was not associated with the onset of SRC, except in the appropriate clinical setting. Although ACE inhibitors and dialysis are now readily available, SRC continues to be associated with poor survival (in this study, 50% of patients with SRC died).
Linear optimal control applied to instabilities
in spatially developing boundary layers
Authors: HÖGBERG MARKUS , HENNINGSON DAN S. 
Published: November 2002

The work presented extends previous research on linear controllers in temporal channel flow to spatially evolving boundary layer flow. The flows studied are those on an
infinite swept wedge described by the Falkner–Skan–Cooke (FSC) velocity profiles,
including the special case of the flow over a flat plate. These velocity profiles are used
as the base flow in the Orr–Sommerfeld–Squire equations to compute the optimal
feedback control through blowing and suction at the wall utilizing linear optimal control theory. The control is applied to a parallel FSC flow with unstable perturbations.
Through an eigenvalue analysis and direct numerical simulations (DNS), it is shown
that instabilities are stabilized by the controller in the parallel case. The localization
of the convolution kernels for control is also shown for the FSC profiles.Assuming that non-parallel effects are small a technique is developed to apply
the same controllers to a DNS of a spatially evolving flow. The performance of
these controllers is tested in a Blasius flow with both a Tollmien–Schlichting (TS)
wave and an optimal spatial transiently growing perturbation. It is demonstrated
that TS waves are stabilized and that transient growth is lowered by the controller.
Then the control is also applied to a spatial FSC flow with unstable perturbations
leading to saturated cross-flow vortices in the uncontrolled case. It is demonstrated
that the linear controller successfully inhibits the growth of the cross-flow vortices to
a saturated level and thereby delays the possibility of transition through secondary
instabilities. It is also demonstrated that the controller works for relatively high levels
of nonlinearity, and for stationary as well as time-varying perturbations.
Telechelic cis‐1,4‐oligoisoprenes through the selective oxidolysis of epoxidized monomer units and polyisoprenic monomer units in cis‐1,4‐polyisoprenes
Authors: Gillier‐Ritoit Sandrine , Reyx Danièle , Campistron Irène , Laguerre Albert , Pal Singh Raj 
Published: November 2002

AbstractTelechelic cis‐1,4‐oligoisoprenes were prepared by the selective cleavage of weak epoxidized units (E) in epoxidized cis‐1,4‐polyisoprenes (EPIs) and by the random cleavage of isoprenic units (I) in cis‐1,4‐polyisoprene (PI). In both cases, cleavage by periodic acid (H5IO6) in tetrahydrofuran led to aldehydic and ketonic chain ends. Through variations in the E/(I + E) molar percentage (E%) in the cleavage of EPI and through variations in the H5IO6/I molar percentage (PA%) in the cleavage of PI, a polydispersity index near 2 and a number‐average molecular weight of 2 – 20 × 103 were obtained. The correlation of the degree of scission with E% and PA%, combined with kinetic, led to the proposal of a two‐step mechanism for the H5IO6 cleavage of double bonds. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 42–46, 2003
Diimide hydrogenation of isoprene–styrene diblock copolymers
Authors: Phinyocheep Pranee , Pasiri Sureemas , Tavichai Orasa 
Published: November 2002

AbstractIsoprene–styrene diblock copolymers of various molecular weights were prepared by anionic polymerization with n‐BuLi in cyclohexane. Hydrogenation of the unsaturated backbone of the block copolymers was performed with diimide generated in situ by the thermolysis of p‐toluenesulfonylhydrazide (TSH). The reaction was carried out in xylene at 135°C. A molar ratio of TSH to double bonds equal to 4:1 was found to be the optimum ratio, which provided the highest percentage of hydrogenation. The percentage of hydrogenation analyzed by 1H‐NMR, IR spectroscopy, and iodine value (the Wijs method) were compared. Evidence from 1H‐NMR also revealed a change in the ratio of the cis–trans configuration after hydrogenation. The thermal stability of the hydrogenated products was improved as shown by the results from thermogravimetric analysis. From differential scanning calorimetry measurements, the glass‐transition temperatures of the hydrogenated products were found to increase about 10–20°C above those of the original block copolymers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 76–82, 2003
Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism
Authors: Berckmans René J. , Nieuwland Rienk , Tak Paul Peter , Böing Anita N. , Romijn Fred P. H. T. M. , Kraan Maarten C. , Breedveld Ferdinand C. , Hack C. Erik , Sturk Augueste 
Published: November 2002

AbstractObjectiveTo determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.MethodsMicroparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n = 10) and patients with other forms of arthritis (non‐RA; n = 10) and in plasma from healthy subjects (n = 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F1+2 (by enzyme‐linked immunosorbent assay [ELISA]) and thrombin–antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo.ResultsPlasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non‐RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F1+2 (median 66 nM) and TAT complex (median 710 μg/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 μg/liter, respectively) as well as the controls (1.0 nM and 2.9 μg/liter, respectively).ConclusionSynovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII–dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.
Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes
Authors: Sen Malini , Reifert Jack , Lauterbach Kevin , Wolf Vladimir , Rubin Jeffrey S. , Corr Maripat , Carson Dennis A. 
Published: November 2002

AbstractObjectiveThe enhanced release of extracellular matrix proteins by fibroblast‐like synoviocytes (FLS) from rheumatoid arthritis (RA) patients is suggestive of joint remodeling. Because Wnt proteins play a critical role in joint development, we investigated whether up‐regulated Wnt signaling plays a role in the enhanced synthesis of extracellular matrix proteins. The purpose of the present experiments was to determine the role of Wnt‐1–like molecules in the expression of matrix proteins by RA FLS and to ascertain the effects of Wnt antagonists on RA FLS function and survival.MethodsTransfection with a reporter plasmid (TOPflash) was performed to assess whether Wnt signaling is active in RA FLS. Wnt signaling was up‐regulated in normal FLS by transfection with a Wnt‐1 expression plasmid and was down‐regulated in RA FLS by transfection with dominant‐negative lymphoid enhancer factor 1 (LEF‐1)/T cell factor 4 (TCF‐4) and secreted Frizzled receptor protein 1 (sFRP‐1) expression plasmids. Recombinant sFRP‐1 and anti–Wnt‐1 antibody were also administered to RA FLS to block Wnt signaling.ResultsRA FLS had constitutive activation of the canonical Wnt signaling pathway. Transfection of normal FLS with a Wnt‐1 expression vector enhanced not only fibronectin, but also pro–matrix metalloproteinase 3 (proMMP‐3) expression. In a complementary manner, interference with Wnt signaling using anti–Wnt‐1 antibody, the Wnt antagonist sFRP‐1, or dominant‐negative vectors that inhibited the transcription factors TCF‐4/LEF‐1 blocked the expression of fibronectin by RA FLS and reduced cell survival. Anti–Wnt‐1 antibody and sFRP‐1 also blocked the expression of proMMP‐3.ConclusionOur results indicate that the canonical Wnt pathway regulates fibronectin and metalloproteinase expression in RA FLS.
Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus
Authors: Kogure Toshiaki , Takasaki Yoshinari , Takeuchi Ken , Yamada Hirofumi , Nawata Masuyuki , Ikeda Keigo , Matsushita Masakazu , Matsudaira Ran , Kaneda Kazuhiko , Terasawa Katsutoshi , Hashimoto Hiroshi 
Published: November 2002

AbstractObjectiveTo analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation.MethodsPCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti‐PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK‐PCNA) were purified using anti‐PCNA serum AK. The reactions to these antigens of 10 anti‐PCNA–positive and 40 anti‐PCNA–negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme‐linked immunosorbent assays (ELISAs).ResultsWith one exception (serum OK), anti‐PCNA–positive sera reacted exclusively with only the 34‐kd polypeptide. In contrast, 14 of 40 anti‐PCNA–negative sera reacted with multiple proteins within PCNA complexes. Most anti‐PCNA–positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK‐PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58‐kd polypeptide and the 34‐kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes.ConclusionIntermolecular–intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.
Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus
Authors: Reichlin Morris , Fesmire James , Quintero‐Del‐Rio Ana I. , Wolfson‐Reichlin Marianne 
Published: November 2002

AbstractObjectiveTo demonstrate the binding of bovine lipoprotein lipase (LPL) by IgG from sera obtained from patients with systemic lupus erythematosus (SLE) and other rheumatic diseases, and the relationship of anti‐LPL to triglyceride levels in SLE.MethodBinding of LPL by IgG from sera obtained from patients with SLE and other rheumatic diseases was measured by an enzyme‐linked immunosorbent assay technique. Lipid profiles for fasting blood samples obtained from SLE patients and control subjects were determined.ResultsSera obtained from 105 patients with SLE were assessed for reactivity with LPL, and 49 (47%) of the results were positive. Sera obtained from patients with rheumatoid arthritis (RA) (n = 80), Sjögren's syndrome (n = 30), polymyositis and dermatomyositis (n = 30), and progressive systemic sclerosis (n = 31) were also studied, and 10 (13%), 3 (10%), 12 (40%), and 13 (42%), respectively, were positive for reactivity with LPL. It was determined that all affinity‐purified anti–double‐stranded DNA (dsDNA) antibodies and 4 of 5 monoclonal anti‐dsDNA antibodies bound to LPL. The binding of IgG depleted of anti‐dsDNA to LPL indicates a second anti‐LPL activity in SLE. Measurements of fasting lipid levels in SLE patients with anti‐LPL revealed a strong positive correlation of antibody levels and total serum triglycerides, apolipoprotein B, and apolipoprotein E concentrations.ConclusionAntibodies to LPL occurred in 47% of SLE patients and in a similar percentage of patients with polymyositis or systemic sclerosis. The prevalence of these antibodies was less in patients with RA or Sjögren's syndrome. It is hypothesized that the elevated triglyceride levels in SLE patients are in part attributable to anti‐LPL, and this lipid abnormality could contribute to the premature atherosclerosis known to be present in patients with SLE.
Interpreting 2hJ(F,N), 1hJ(H,N) and 1J(F,H) in the hydrogen‐bonded FH–collidine complex
Authors: Del Bene Janet E. , Bartlett Rodney J. , Elguero José 
Published: November 2002

AbstractAb initio EOM‐CCSD calculations were performed to determine 19F,1H, 19F,15N and 1H,15N spin–spin coupling constants in model complexes FH–NH3 and FH–pyridine as a function of the F—H and F—N distances. The absolute value of 1J(F,H) decreases and that of 1hJ(H,N) increases rapidly along the proton‐transfer coordinate, even in the region of the proton‐shared F—H—N hydrogen bond. In contrast, 2hJ(F,N) remains essentially constant in this region. These results are consistent with the recently reported experimental NMR spectra of FH–collidine which show that 1hJ(H,N) increases and 1J(F,H) decreases, while 2hJ(F,N) remains constant as the temperature of the solution decreases. They suggest that the FH–collidine complex is stabilized by a proton‐shared hydrogen bond over the range of experimental temperatures investigated, being on the traditional side of quasi‐symmetric at high temperatures, and on the ion‐pair side at low temperatures. Copyright © 2002 John Wiley & Sons, Ltd.