bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immutability specification and its applications
Authors: Pechtchanski Igor , Sarkar Vivek 
Published: February 2005

AbstractA location is said to be immutable if its value and the values of selected locations reachable from it are guaranteed to remain unchanged during a specified time interval. We introduce a framework for immutability specification, and discuss its application to code optimization. Compared with a final declaration, an immutability assertion in our framework can express a richer set of immutability properties along three dimensions—lifetime, reachability and context. We present a framework for processing and verifying immutability annotations in Java, as well as extending optimizations so as to exploit immutability information. Preliminary experimental results show that a significant number (61%) of read accesses could potentially be classified as immutable in our framework. Further, use of immutability information yields substantial reductions (33–99%) in the number of dynamic read accesses, and also measurable speedups in the range of 5–10% for certain benchmark programs. Copyright © 2005 John Wiley & Sons, Ltd.
No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes
Authors: Johanson E. H. , Jansson P.‐A. , Gustafson B. , Sandqvist M. , Taskinen M.‐R. , Smith U. , Axelsen M. 
Published: February 2005

AbstractBackgroundTo study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes.MethodsSix women and 10 men, with at least one first‐degree relative with type 2 diabetes were included (Age: 48 ± 7 years, BMI: 27.5 ± 2.8 kg m−2, P‐triglycerides: 1.3 ± 0.4 mmol L−1, P‐cholesterol: 5.4 ± 0.6 mmol L−1, B‐glucose: 4.6 ± 0.3 mmol L−1). They each had two 8‐h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First‐phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg−1 body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m−2 min−1).ResultsThe 1‐h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 ± 81 vs 376 ± 58 pmol L−1, p < 0.001), as well as the response during the first two hours (IAUC: 41 243 ± 5844 vs 29 956 ± 4662 pmol L−1 min, p < 0.01). Accordingly, nateglinide lowered the 8‐h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB‐48) and endogenous (apoB‐100) lipoproteins was not reduced by nateglinide.ConclusionsAcute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes. Copyright © 2005 John Wiley & Sons, Ltd.
TGF‐β‐treated microglia induce oligodendrocyte precursor cell chemotaxis through the HGF‐c‐Met pathway
Authors: Lalive Patrice H. , Paglinawan Rey , Biollaz Gregoire , Kappos Elisabeth A. , Leone Dino P. , Malipiero Ursula , Relvas Joao B. , Moransard Martijn , Suter Tobias , Fontana Adriano 
Published: February 2005

AbstractIn acute experimental autoimmune encephalomyelitis (EAE), demyelination is induced by myelin‐specific CD4+ T lymphocytes and myelin‐specific antibodies. Recovery from the disease is initiated by cytokines which suppress T cell expansion and the production of myelin‐toxic molecules by macrophages. Th2/3 cell‐derived signals may also be involved in central nervous system (CNS) repair. Remyelination is thought to be initiated by the recruitment and differentiation of oligodendrocyte precursor cells (OPC) in demyelinated CNS lesions. Here, we report that unlike Th1 cytokines (TNF‐α, IFN‐γ), the Th2/3 cytokine TGF‐β induces primary microglia from C57BL/6 mice to secrete a chemotactic factor for primary OPC. We identified this factor to be the hepatocyte growth factor (HGF). Our studies show that TGF‐β‐1‐2‐3 as well as IFN‐β induce HGF secretion by microglia and that antibodies to the HGF receptor c‐Met abrogate OPC chemotaxis induced by TGF‐β2‐treated microglia. In addition we show spinal cord lesions in EAE induced in SJL/J mice to contain both OPC and HGF producing macrophages in the recovery phase, but not in the acute stage of disease. Taken these findings, TGF‐β may play a pivotal role in remyelination by inducing microglia to release HGF which is both a chemotactic and differentiation factor for OPC.
Serum amyloid A activates NF‐κB and proinflammatory gene expression in human and murine intestinal epithelial cells
Authors: Jijon Humberto B. , Madsen Karen L. , Walker John W. , Allard Brigitte , Jobin Christian 
Published: February 2005

AbstractSerum amyloid A (SAA) is an acute‐phase protein whose levels positively correlate with disease activity in inflammatory bowel diseases. In this study we investigated the impact of SAA on NF‐κB signaling and proinflammatory gene expression in intestinal epithelial cells (IEC). Human HT‐29 and Caco‐2 monolayers were stimulated with recombinant SAA and NF‐κB activation/NF‐κB‐dependent gene expression measured. Adenoviral dominant negative mutants IκB‐α (Ad5IκBAA) were utilized to determine the contribution of NF‐κB signaling pathway to SAA‐dependent gene expression. Intestinal explant and primary IEC derived from κB‐EGFP transgenic mice were exposed to SAA and NF‐κB‐dependent enhanced green fluorescent protein (EGFP) fluorescence measured. SAA induced IκB‐α degradation, RelA serine 536 (S536) phosphorylation, NF‐κB transcriptional activity, RelA recruitment to the IL‐8 gene promoter and endogenous gene expression (IL‐8, COX‐2) in HT‐29 cells. Further, Ad5IκBAA abrogated SAA‐induced RelA nuclear translocation, NF‐κB transcriptional activity and IL‐8 gene expression. SAA‐dependent IL‐8 gene expression required activation of the MAPK ERK, p38 and JNK in HT‐29 cells. Finally, SAA induced EGFP expression in intestinal explants isolated from κB‐EGFP transgenic mice and enhanced RelA and IκBα phosphorylation in primary IEC. This indicates that SAA potentially participate in the inflammatory process by virtue of its ability to activate proinflammatory signaling in IEC.
Ex vivo expansion of human cytomegalovirus‐specific cytotoxic T cells by recombinant polyepitope: implications for HCMV immunotherapy
Authors: Rist Michael , Cooper Leanne , Elkington Rebecca , Walker Susan , Fazou Chrysa , Tellam Judy , Crough Tania , Khanna Rajiv 
Published: February 2005

AbstractStem cell transplantation (SCT) remains the most effective curative therapy for the majority of hematopoietic malignancies. Unfortunately, SCT is limited by its toxicity and infectious complications that result from profound immunosuppression. In particular, acquisition of exogenous or reactivation of endogenous human cytomegalovirus (HCMV) is common after SCT. More recently, reconstitution of host immunity through augmentation of anti‐HCMV T cell responses has been proposed as an exciting candidate therapy to avoid the requirement for antiviral drug use. Here we have developed a novel antigen presentation system based on a replication‐deficient adenovirus that encodes multiple HLA class I‐restricted epitopes from eight different antigens of HCMV as a polyepitope (referred to as AdCMVpoly). Ex vivo stimulation of peripheral blood mononuclear cells with AdCMVpoly consistently showed rapid stimulation and expansion of multiple epitope‐specific T cells that recognized endogenously processed epitopes presented on virus‐infected cells. Interestingly, the AdCMVpoly expression system is capable of expanding antigen‐specific T cells even in the absence of CD4+ T cells. These studies show the effectiveness of a polyepitope antigen presentation system for reproducible expansion of antigen‐specific T cells from immunocompetent and immunocompromised settings.
Efficient homologous prime‐boost strategies for T cell vaccination based on virus‐like particles
Authors: Schwarz Katrin , Meijerink Edwin , Speiser Daniel E. , Tissot Alain C. , Cielens Indulis , Renhof Regina , Dishlers Andris , Pumpens Paul , Bachmann Martin F. 
Published: February 2005

AbstractInduction of high frequencies of specific T cells by vaccination requires prime‐boost regimens. To reach optimal immune responses, it is necessary to use different vectors for priming and boosting as e.g. DNA vaccination followed by boosting with a recombinant viral vector. Here, we show that vaccines based on virus‐like particles (VLP) displaying peptide epitopes are equally effective to induce CTL responses if used in a homologous or heterologous prime‐boost setting. Strikingly, high frequencies (>20% of CD8+ cells) of protective CTL could be induced and maintained by weekly injection of VLP. Thus, the use of VLP may avoid the requirement for complicated heterologous prime‐boost regimens, facilitating the development of effective T cell‐based vaccines.
Inverse correlation between IL‐7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation
Authors: Lang Karl S. , Recher Mike , Navarini Alexander A. , Harris Nicola L. , Löhning Max , Junt Tobias , Probst Hans Christian , Hengartner Hans , Zinkernagel Rolf M. 
Published: February 2005

AbstractPersistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8+ T cells. We demonstrate here that persistent antigen suppressed IL‐7Rα expression and this correlated with T cell exhaustion and reduced expression of the anti‐apoptotic molecule B cell leukemia/lymphoma 2 (Bcl‐2). In contrast, exposure to short‐lived antigen only temporarily suppressed IL‐7Rα expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL‐7Rα expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.
CoII Complexes of Triazine‐Based Tridentate Ligands with Positive and Attractive CoII/III Redox Couples
Authors: Medlycott Elaine A. , Theobald Isabelle , Hanan Garry S. 
Published: February 2005

AbstractCoII complexes based on the triazine ligand 2,4‐di(2'‐pyridyl)‐6‐(p‐R‐C6H4)‐1,3,5‐triazine have been synthesized and characterized. Cyclic voltammetry shows that the CoII/III redox couple is more positive than previously described Co complexes of tridentate ligands. The CoII/III redox couple may be varied depending on the nature of the substituent on the phenyl ring of the triazine ligand. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Survival outcome of patients with nasopharyngeal carcinoma with first local failure: A study by the Hong Kong Nasopharyngeal Carcinoma Study Group
Authors: Yu Kwok Hung , Leung Sing Fai , Tung Stewart Yuk , Zee Benny , Chua Daniel T. T. , Sze Wai Man , Law Stephen C. K. , Kam Michael K. M. , Leung To Wai , Sham Jonathan S. T. , Lee Anne W. M. , Au Joseph S. K. , Hui Edwin P. , Sze Wing Kin , Cheng Ashley C. K. , Yau T. K. , Ngan Roger K. C. , Wong Frank C. S. , Au Gordon K. H. , Chan Anthony T. C. 
Published: February 2005

AbstractBackground.The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS.Methods.Between January 1996 and December 2000, 2915 patients received primary radiotherapy (RT) with or without chemotherapy for nonmetastatic NPC. At a median follow‐up of 3.1 years, 319 patients had developed local failure as the first failure, with or without synchronous regional/distant failure. OS was calculated from the start of primary RT. Univariate and multivariate analyses were performed to identify prognostic factors for OS in patients with isolated local failure.Results.The T classification distribution of the local failure (rT classification) was as follows: 68 (21%) rT1 to T2a, 92 (29%) rT2b, 82 (26%) rT3, and 77 (24%) rT4. The rT classification was the same as the initial T classification in 82% of patients. Two hundred seventy‐five patients (86%) had isolated local failure, and 232 (84%) of them did not have any distant metastasis or regional failure develop during follow‐up. Salvage treatment was given to 200 patients (73%) with isolated local failure. One hundred fifty‐nine patients (80%) received reirradiation (108 external beam RT [EBRT], 44 brachytherapy, and seven EBRT plus brachytherapy), 22 patients (11%) underwent nasopharyngectomy with or without postoperative RT, and 19 patients (9%) were treated with chemotherapy alone. Four patients died of RT complications, and one died of chemotherapy toxicity in the absence of active NPC. The 3‐year actuarial OS for patients with isolated local failure was 74%. On multivariate analysis, advanced initial T classification (hazard ratio [HR], 1.44; p = .0006) and the use of salvage treatment (HR, 0.54; p = .0038) were independent prognostic factors. For the subgroups of patients who had the same recurrent and initial T classification, salvage treatment was associated with improved OS only in the subgroup with T1 to T2 local failure (n = 127; p = 0.0446), but not in the subgroups with T3 (n = 48) or T4 (n = 54) disease.Conclusions.Most patients with first local failure have localized disease. Salvage treatment is feasible in most of the patients with clinically isolated local failure. Patients who had early initial T classification have a more favorable prognosis. Subgroup analysis suggests that salvage treatment only prolongs survival in patients with T1 to T2 recurrent disease. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Dichloroacetate‐induced developmental toxicity and production of reactive oxygen species in zebrafish embryos
Authors: Hassoun Ezdihar , Kariya Chirag , Williams Frederick E. 
Published: February 2005

AbstractDichloroacetate (DCA) is one of the toxic by products that are formed during the chlorine disinfection process of drinking water. In this study, the developmental toxicity of DCA has been determined in zebrafish (Danio rerio) embryos. Embryos were exposed to different concentrations (4, 8, 16, and 32 mM) of the compound at the 4 h postfertilization (hpf) stage of development, and were observed for different developmental toxic effects at 8, 24, 32, 55, 80, and 144 hpf. Exposure of embryos to 8–32 mM of DCA resulted in significant increases in the heart rate and blood flow of the 55 and 80 hpf embryos that turned into significant decreases at the 144 hpf time point. At 144 hpf, malformations of mouth structure, notochord bending, yolk sac edema and behavioral effects including perturbed swimming and feeding behaviors were also observed. DCA was also found to produce time‐ and concentration‐dependent increases in embryonic levels of superoxide anion (O) and nitric oxide (NO), at various stages of development. The results of the study suggest that DCA‐induced developmental toxic effects in zebrafish embryos are associated with production of reactive oxygen species in those embryos. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:52–58, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20051
Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene‐induced porphyria
Authors: Chaufan Gabriela , Corvi Maria M. , Viale Leonor C. San Martín de , Cárdenas María Luz , Molina María del Carmen Ríos de 
Published: February 2005

AbstractUroporphyrinogen decarboxylase is an essential enzyme in all organisms and functions in the heme biosynthetic pathway, catalyzing the decarboxylation of the four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work examines whether the four sequential decarboxylations occur at the same active site, and explores whether hexachlorobenzene‐induced porphyria affects the behavior of the enzyme. For this purpose, kinetic competition studies were done with mixtures of uroporphyrinogen III and pentacarboxyporphyrinogen III. With the enzyme from normal rats, a constant velocity was obtained with all the mixtures, indicating that uroporphyrinogen and pentacarboxy‐porphyrinogen react at the same active site, i.e. the first and fourth decarboxylations occur at the same site. In contrast, in experiments with enzyme from rats with hexachlorobenzene‐induced porphyria, the total rate for mixtures was always lower than the reference rate; and a curve with a deep minimum was obtained, indicating that the two reactions occur at functionally different sites, but with cross‐inhibition. This suggests that the modifications induced in the enzyme by hexachlorobenzene cause the two active sites to become nonequivalent and functionally different. The question is discussed how the hexachlorobenzene treatment may produce this abnormal kinetic behavior, and alternative hypotheses are considered. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:19–24, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20055
Transmembrane electropotential changes in amphibian eggs at ovulation, activation and first cleavage
Authors: Morrill Gene A. , Watson Donald E. 
Published: February 2005

AbstractElectropotential differences between the cell interior and the external medium have been studied with intracellular microelectrodes in ovarian oocytes, ovulated unfertilized eggs and fertilized eggs of R. pipiens. In ovarian oocytes the cytoplasm was 50 to 80 mV negative, relative to isotonic Ringer's solution. In contrast, electrode penetration of the oocyte nucleus in situ indicated that the nucleoplasm was about 25 mV positive, relative to the cytoplasm. After ovulation, the cortical cytoplasm became 20 to 50 mV positive with regard to an external solution of 0.1 strength Ringer's solution (ca. pond water). Penetration of the cytoplasm at levels from 0.3 to 0.6 mm below the egg surface revealed an inner zone with a potential which was about 15 mV negative, relative to the cortical cytoplasm. A slow hyperpolarization of the cortical membrane occurred at activation, with the potential returning to that of the ovulated unfertilized egg within ten minutes. After fertilization, the egg cytoplasm remained positive until the first cleavage. As division proceeded, the cytoplasm slowly depolarized and became 50 to 60 mV negative, relative to 0.1 strength Ringer's solution.
Membranes of animal cells. I. Methods of isolation of the surface membrane
Authors: Warren L. , Glick M. C. , Nass M. K. 
Published: February 2005

AbstractProcedures have been devised for the isolation of the surface membranes of mouse fibroblasts (L cell) and a variety of other cells. The surface membranes are stabilized by various reagents in a hypotonic solution and are then removed intact or as large fragments with a Dounce homogenizer. The membranes are purified by differential centrifugation on solutions of sucrose or glycerol or on a column of fine glass beads. A trilaminar pattern can be seen in thin sections of the membrane in the electron microscope. Sufficient material can be conveniently obtained for chemical analyses.
Electrical activity and structural correlates of giant nerve fibers in Kuruma shrimp (Penaeus japonicus)
Authors: Kusano Kiyoshi 
Published: February 2005

AbstractMorphology and recordings of electrical activity of Kuruma shrimp (Penaeus japonicus) giant medullated nerve fibers were carried out. A pair of giant fibers with external diameter of about 120 μ and 10 μ in myelin thickness were found in the ventral nerve cord. The diameter of the axon is about 10 μ. Thus there is a wide gap between the axon and the external myelin sheath. Each axon is doubly coated directly by Schwann cells and indirectly by the myelin sheath layer which is produced by those Schwann cells.Impulse conduction velocities of these giant fibers showed a range between 90–210 m/sec at about 22°C. Large action potentials (up to 113 mV, rise time of 0.16–0.3 msec, maximum rate of rise of 650–1250 V/sec, half decay time of 0.2–0.3 msec, maximum rate of fall of 250–450 V/sec and total duration of less than 1.5 msec) could be obtained by inserting microelectrodes or by longitudinal insertion of 25 μ diameter capillary electrodes into the gap but no DC‐potential difference was observed across the myelin sheath. Transmyelin electrical parameters were very favorable for fast impulse conduction: myelin resistance of 3 × 104 Ω cm2; time constant of 0.38 msec; myelin capacitance of 1.35 × 10−8 F/cm2; gap fluid resistivity of 23 Ω cm. The existence of nodes of Ranvier could not be demonstrated morphologically, but electrophysiological evidence suggests that a type of saltatory conduction occurs in these giant fibers.
Enzyme activity during the growth and aging of human cells in vitro
Authors: Cristofalo V. J. , Parris N. , Kritchevsky David 
Published: February 2005

AbstractAcid phosphatase, alkaline phosphatase, and lactic dehydrogenase activities have been compared in normal human diploid cell strains and in SV40‐transformed heteroploid cell lines derived from them. A higher level of acid phosphatase activity was observed in diploid cultures derived from adult lung than in cultures derived from fetal lung of similar passage levels. The alkaline phosphatase activity of normal diploid fibroblasts was significantly higher than that of SV40‐transformed cell lines derived from them. Generally, the lactic dehydrogenase activities of all these cell cultures were similar.Human diploid cells in culture “age,” in the sense that their ability to proliferate decreases with time during serial subcultivation. Evaluation of the activities of these three enzymes during the “aging” process showed that, although alkaline phosphatase and lactic dehydrogenase activities were similar in “young” and “senescent” cells, acid phosphatase showed a small but significant increase in the senescent cells.
Correlation between cell enlargement and nucleic acid and protein content of hela cells in unbalanced growth produced by inhibitors of DNA synthesis
Authors: Cohen Larry S. , Studzinski George P. 
Published: February 2005

AbstractHeLa cells in monolayer cultures were treated with the following inhibitors of DNA synthesis: mitomycin C, nitrogen mustard, fluorodeoxyuridine, hydroxyurea, arabinofuranosylcytosine and high concentrations of thymidine. The concentration of each inhibitor used was, in most cases, just sufficient to arrest cell multiplication and all produced unbalanced growth in the sense that the synthesis of RNA and protein were only partially inhibited while DNA synthesis stopped. This resulted in approximately 100% increases in RNA and protein content per cell in 48 hours and, since cell volume also increased by 100% during this time, the concentration of RNA and protein per unit cell volume remained constant. It was concluded that cell protein content may be used as an accurate index of variation in cell size in HeLa cells treated with inhibitors of DNA synthesis.
Osmotic regulation in hydra: Sodium and calcium localization and source of electrical potential
Authors: Macklin Martin 
Published: February 2005

AbstractCa45 and Na22 radioautographs using freeze‐substitution with 2‐ethoxyethanol have been prepared for hydra. They reveal a heavy accumulation of Ca and Na along the mesoglea. Microelectrode probes indicate that the positive resting potential in the hydra gut may be resolved into a series of three steps. These results in hydra epithelium suggest that hydra concentrate ions across the outer epidermal cell layer in much the same way that Na is transported across frog skin.