bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphogranuloma Venereum in Australia: AnorectalChlamydia trachomatisSerovar L2b in Men Who Have Sex with Men
Authors: Stark D. , van Hal S. , Hillman R. , Harkness J. , Marriott D. 
Published: January 2007

ABSTRACTLymphogranuloma venereum (LGV) is a sexually transmitted infection that is causing an ongoing epidemic in men who have sex with men (MSM) in Europe, the United Kingdom, and North America. Twenty-nine rectal swabs positive forChlamydia trachomatiswere analyzed by real-time PCR for the presence of LGV serovars. Genotyping revealed an identical L2b serovar from four specimens. All patients were MSM and human immunodeficiency virus infected. Three of the four presented with severe ulcerative proctitis. We report a cluster of rectal LGV serovar L2b infections in Sydney, Australia.
Virus-Like Particle Vaccine Induces Protective Immunity against Homologous and Heterologous Strains of Influenza Virus
Authors: Quan Fu-Shi , Huang Chunzi , Compans Richard W. , Kang Sang-Moo 
Published: January 2007

ABSTRACTRecurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated. In this study, we developed VLPs containing influenza virus A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung proinflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers and neutralizing activity against PR8 and A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no proinflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months postimmunization. Influenza VLPs induced mucosal immunoglobulin G and cellular immune responses, which were reactivated rapidly upon virus challenge. Long-lived antibody-secreting cells were detected in the bone marrow of immunized mice. Immune sera administered intranasally were able to confer 100% protection from a lethal challenge with PR8 or WSN, which provides further evidence that anti-HA antibodies are primarily responsible for preventing infection. Taken together, these results indicate that nonreplicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.
Vaccine-Induced T Cells Control Reversion of AIDS Virus Immune Escape Mutants
Authors: Fernandez Caroline S. , Smith Miranda Z. , Batten C. Jane , De Rose Robert , Reece Jeanette C. , Rollman Erik , Venturi Vanessa , Davenport Miles P. , Kent Stephen J. 
Published: January 2007

ABSTRACT

Many current-generation human immunodeficiency virus (HIV) vaccines induce specific T cells to control acute viremia, but their utility following infection with escape mutant virus is unclear. We studied reversion to wild type of an escape mutant simian-HIV in major histocompatibility complex-matched vaccinated pigtail macaques. High levels of vaccine-induced CD8
+
T cells strongly correlated with maintenance of escape mutant virus during acute infection. Interestingly, in animals with lower CD8
+
T-cell levels, transient reversion to wild-type virus resulted in better postacute control of viremia. Killing of wild-type virus facilitated by transient reversion outweighs the benefit of a larger CD8
+
T-cell response that only maintains the less fit escape mutant virus. These findings have important implications for the further development of T-cell-based HIV vaccines where exposure to escape mutant viruses is common.
Spindles of an Entomopoxvirus Facilitate Its Infection of the Host Insect by Disrupting the Peritrophic Membrane
Authors: Mitsuhashi Wataru , Kawakita Hiromu , Murakami Ritsuko , Takemoto Yutaka , Saiki Tomoaki , Miyamoto Kazuhisa , Wada Sanae 
Published: January 2007

ABSTRACT

The mode of action by which entomopoxvirus (EPV) spindles, proteinaceous crystalline bodies produced by EPVs, enhance EPV infection has not been clarified. We fed
Anomala cuprea
EPV (AcEPV) spindles to host insects; subsequent scanning electron microscopy revealed the disruption of the peritrophic membranes (PMs) of these insects. The PM is reportedly a barrier against the infection of some insects by viruses. Quantitative PCR of AcEPV DNA in the ectoperitrophic area revealed that PM disruption facilitated the passage of EPVs through the PM toward the initial infection site, the midgut epithelium. These results indicate that EPV spindles enhance infection by EPVs by disrupting the PM in the host insects. Fusolin is almost exclusively the constituent protein of the spindles and is the enhancing factor of the infectivity of nucleopolyhedroviruses (NPVs) and possibly that of EPVs. Spheroid is another type of proteinaceous crystalline structure produced by EPVs.
Pseudaletia separata
EPV (PsEPV) spheroids reportedly contain considerable amounts of fusolin and enhance NPV infection. We assessed the ability of AcEPV spheroids to enhance EPV infectivity and their effect on the PM and carried out immunological experiments; these experiments showed that AcEPV spheroids contain little or no fusolin and are biologically inactive, in contrasts to the situation in PsEPV.
Respiratory Syncytial Virus NS1 Protein Degrades STAT2 by Using the Elongin-Cullin E3 Ligase
Authors: Elliott Joanne , Lynch Oonagh T. , Suessmuth Yvonne , Qian Ping , Boyd Caroline R. , Burrows James F. , Buick Richard , Stevenson Nigel J. , Touzelet Olivier , Gadina Massimo , Power Ultan F. , Johnston James A. 
Published: January 2007

ABSTRACT
Respiratory syncytial virus (RSV) infection causes bronchiolitis and pneumonia in infants. RSV has a linear single-stranded RNA genome encoding 11 proteins, 2 of which are nonstructural (NS1 and NS2). RSV specifically downregulates STAT2 protein expression, thus enabling the virus to evade the host type I interferon response. Degradation of STAT2 requires proteasomal activity and is dependent on the expression of RSV NS1 and NS2 (NS1/2). Here we investigate whether RSV NS proteins can assemble ubiquitin ligase (E3) enzymes to target STAT2 to the proteasome. We demonstrate that NS1 contains elongin C and cullin 2 binding consensus sequences and can interact with elongin C and cullin 2 in vitro; therefore, NS1 has the potential to act as an E3 ligase. By knocking down expression of specific endogenous E3 ligase components using small interfering RNA, NS1/2, or RSV-induced STAT2, degradation is prevented. These results indicate that E3 ligase activity is crucial for the ability of RSV to degrade STAT2. These data may provide the basis for therapeutic intervention against RSV and/or logically designed live attenuated RSV vaccines.
Control of Human Immunodeficiency Virus Type 1 Is Associated with HLA-B*13 and Targeting of Multiple Gag-Specific CD8+T-Cell Epitopes
Authors: Honeyborne Isobella , Prendergast Andrew , Pereyra Florencia , Leslie Alasdair , Crawford Hayley , Payne Rebecca , Reddy Shabashini , Bishop Karen , Moodley Eshia , Nair Kriebashnie , van der Stok Mary , McCarthy Noel , Rousseau Christine M. , Addo Marylyn , Mullins James I. , Brander Christian , Kiepiela Photini , Walker Bruce D. , Goulder Philip J. R. 
Published: January 2007

ABSTRACTTo better understand relationships between CD8+T-cell specificity and the immune control of human immunodeficiency virus type 1 (HIV-1), we analyzed the role of HLA-B*13, an allele associated with low viremia, in a cohort of 578 C clade-infected individuals in Durban, South Africa. Six novel B*13-restricted cytotoxic T lymphocyte epitopes were defined from analyses of 37 B*13-positive subjects, including three Gag epitopes. These B*13-restricted epitopes contribute to a broad Gag-specific CD8+response that is associated with the control of viremia. These data are consistent with data from studies of other HLA-class I alleles associated with HIV control that have shown that the targeting of multiple Gag epitopes is associated with relative suppression of viremia.
THE DYNAMICS OF GAMES OF INNOVATION
Authors: MILLER ROGER , OLLEROS XAVIER 
Published: January 2007

Many executives see innovation as an unmanageable process, riddled with risks. The research we conducted with the Industrial Research Institute, interviewing over 200 vice-presidents of research and development and chief technical officers in many sectors around the world, yields a more nuanced view. Innovation becomes manageable once managers move away from normative prescriptions that view the process as uniform and recognise that different rules and practices apply to different circumstances.Our argument is that clusters of interdependent firms contributing to the building of a set of interacting products and services tend to self-organise themselves into distinct and relatively persistent "games of innovation". Such games operate at a meso level of analysis, grouping together many complementary agents, such as competitors, suppliers, public regulators, universities, innovation-support agencies, and venture capitalists. Six games of innovation, each with a distinct set of rules for innovating, have been identified around value-creation exchanges between buyers and sellers. Three games focus on market creation: "patent-driven discovery", "systems integration" and "platform orchestration". Market maintenance games are "cost-based competition", "systems extension and engineering" and "customised mass production".The perspective proposed in this paper recognises that heterogeneous innovation patterns and strategies can coexist within a single industrial sector and that the same game can be played in many sectors. Specific conditions call for distinct rules and practices. Customer expectations, for example, are central in some games but almost irrelevant in others. Rules for managing innovation are neither generic best practices that can be applied universally nor narrow industry recipes. They are game- and role-specific ways to create and capture market value.
Multiple Gene Expression Classifiers from Different Array Platforms Predict Poor Prognosis of Colorectal Cancer
Authors: Lin Yu-Hsin , Friederichs Jan , Black Michael A. , Mages Jörg , Rosenberg Robert , Guilford Parry J. , Phillips Vicky , Thompson-Fawcett Mark , Kasabov Nikola , Toro Tumi , Merrie Arend E. , van Rij Andre , Yoon Han-Seung , McCall John L. , Siewert Jörg Rüdiger , Holzmann Bernhard , Reeve Anthony E. 
Published: January 2007

AbstractPurpose: This study aimed to develop gene classifiers to predict colorectal cancer recurrence. We investigated whether gene classifiers derived from two tumor series using different array platforms could be independently validated by application to the alternate series of patients.Experimental Design: Colorectal tumors from New Zealand (n = 149) and Germany (n = 55) patients had a minimum follow-up of 5 years. RNA was profiled using oligonucleotide printed microarrays (New Zealand samples) and Affymetrix arrays (German samples). Classifiers based on clinical data, gene expression data, and a combination of the two were produced and used to predict recurrence. The use of gene expression information was found to improve the predictive ability in both data sets. The New Zealand and German gene classifiers were cross-validated on the German and New Zealand data sets, respectively, to validate their predictive power. Survival analyses were done to evaluate the ability of the classifiers to predict patient survival.Results: The prediction rates for the New Zealand and German gene-based classifiers were 77% and 84%, respectively. Despite significant differences in study design and technologies used, both classifiers retained prognostic power when applied to the alternate series of patients. Survival analyses showed that both classifiers gave a better stratification of patients than the traditional clinical staging. One classifier contained genes associated with cancer progression, whereas the other had a large immune response gene cluster concordant with the role of a host immune response in modulating colorectal cancer outcome.Conclusions: The successful reciprocal validation of gene-based classifiers on different patient cohorts and technology platforms supports the power of microarray technology for individualized outcome prediction of colorectal cancer patients. Furthermore, many of the genes identified have known biological functions congruent with the predicted outcomes.
An Integrated Clinical-Genomics Approach Identifies a Candidate Multi-Analyte Blood Test for Serous Ovarian Carcinoma
Authors: Meinhold-Heerlein Ivo , Bauerschlag Dirk , Zhou Yingyao , Sapinoso Lisa M. , Ching Keith , Frierson Henry , Bräutigam Karen , Sehouli Jalid , Stickeler Elmar , Könsgen Dominique , Hilpert Felix , von Kaisenberg Constantin S. , Pfisterer Jacobus , Bauknecht Thomas , Jonat Walter , Arnold Norbert , Hampton Garret M. 
Published: January 2007

Abstract
Purpose: Cancer of the ovary confers the worst prognosis among women with gynecologic malignancies, underscoring the need to develop new biomarkers for detection of early disease, particularly those that can be readily monitored in the blood.
Experimental Design: We developed an algorithm to identify secreted proteins encoded among ∼22,500 genes on commercial oligonucleotide arrays and applied it to gene expression profiles of 67 stage I to IV serous papillary carcinomas and 9 crudely enriched normal ovarian tissues, to identify putative diagnostic markers. ELISAs were used to validate increased levels of secreted proteins in patient sera encoded by genes with differentially high expression.
Results: We identified 275 genes predicted to encode secreted proteins with increased/decreased expression in ovarian cancers (&lt;0.5- or &gt;2-fold, P &lt; 0.001). The serum levels of four of these proteins (matrix metalloproteinase-7, osteopontin, secretory leukoprotease inhibitor, and kallikrein 10) were significantly elevated in a series of 67 independent patients with serous ovarian carcinomas compared with 67 healthy controls (P &lt; 0.001, Wilcoxon rank sum test). Optimized support vector machine classifiers with as few as two of these markers (osteopontin or kallikrein 10/matrix metalloproteinase-7) in combination with CA-125 yielded sensitivity and specificity values ranging from 96% to 98.7% and 99.7% to 100%, respectively, with the ability to discern early-stage disease from normal, healthy controls.
Conclusions: Our data suggest that this assay combination warrants further investigation as a multi-analyte diagnostic test for serous ovarian adenocarcinoma.
Gene Expression Signature and the Prediction of Ulcerative Colitis–Associated Colorectal Cancer by DNA Microarray
Authors: Watanabe Toshiaki , Kobunai Takashi , Toda Etsuko , Kanazawa Takamitsu , Kazama Yoshihiro , Tanaka Junichiro , Tanaka Toshiaki , Yamamoto Yoko , Hata Keisuke , Kojima Tetsu , Yokoyama Tadashi , Konishi Tsuyoshi , Okayama Yoshihiro , Sugimoto Yoshikazu , Oka Toshinori , Sasaki Shin , Ajioka Yohichi , Muto Tetsuichiro , Nagawa Hirokazu 
Published: January 2007

Abstract
Purpose: Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients.
Experimental Design: Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group).
Results: By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor–related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8% and 98.1%, respectively.
Conclusions: These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.
Human Glioma Cell Sensitivity to the Sequence-Specific Alkylating Agent Methyl-Lexitropsin
Authors: Bobola Michael S. , Varadarajan Sridhar , Smith Nolan W. , Goff Ryan D. , Kolstoe Douglas D. , Blank A. , Gold Barry , Silber John R. 
Published: January 2007

Abstract
Purpose: Defining the cytotoxicity of individual adducts in DNA is necessary for mechanistic understanding of human brain tumor resistance to therapeutic alkylating agents and for design of DNA repair-related antiresistance strategies. Our purpose is to characterize the sensitivity of human glioma cells to methyl-lexitropsin (Me-lex), a sequence-specific alkylator that produces 3-methyladenine (3-meA) as the predominant (&gt;90%) DNA lesion.
Experimental Design: We quantitated the Me-lex cytotoxicity of 10 human glioma cell lines that differ in O6-methylguanine (O6-meG)-DNA methyltransferase (MGMT) and mismatch repair activity. We used antisense suppression of alkyladenine DNA glycosylase (AAG) and Ape1 to assess the contribution of 3-meA and abasic sites to lethality and measured abasic sites.
Results: (a) The LD10 for Me-lex varied widely among the cell lines. (b) MGMT-proficient lines were more resistant than MGMT-deficient lines, an unexpected finding because Me-lex produces very little O6-meG. (c) Suppression of AAG increased Me-lex killing and reduced abasic site content. (d) Suppression of Ape1 increased Me-lex killing and increased abasic site content. (e) Ablation of MGMT had no effect on Me-lex cytotoxicity.
Conclusions: (a) Me-lex is cytotoxic in human glioma cells and AAG promotes resistance, indicating that 3-meA is a lethal lesion in these cells. (b) Abasic sites resulting from 3-meA repair are cytotoxic and Ape1 promotes resistance to these derivative lesions. (c) A factor(s) associated with MGMT expression, other than repair of O6-meG, contributes to Me-lex resistance. (d) Me-lex may have clinical utility in the adjuvant therapy of gliomas. (e) AAG and Ape1 inhibitors may be useful in targeting alkylating agent resistance.
Cyclophosphamide Enhances the Antitumor Efficacy of Adoptively Transferred Immune Cells through the Induction of Cytokine Expression, B-Cell and T-Cell Homeostatic Proliferation, and Specific Tumor Infiltration
Authors: Bracci Laura , Moschella Federica , Sestili Paola , La Sorsa Valentina , Valentini Mara , Canini Irene , Baccarini Sara , Maccari Sonia , Ramoni Carlo , Belardelli Filippo , Proietti Enrico 
Published: January 2007

Abstract
Purpose: Immunotherapy is a promising antitumor strategy, which can be successfully combined with current anticancer treatments, as suggested by recent studies showing the paradoxical chemotherapy-induced enhancement of the immune response. The purpose of the present work is to dissect the biological events induced by chemotherapy that cooperate with immunotherapy in the success of the combined treatment against cancer. In particular, we focused on the following: (a) cyclophosphamide-induced modulation of several cytokines, (b) homeostatic proliferation of adoptively transferred lymphocytes, and (c) homing of transferred lymphocytes to secondary lymphoid organs and tumor mass.
Experimental Design: Here, we used the adoptive transfer of tumor-immune cells after cyclophosphamide treatment of tumor-bearing mice as a model to elucidate the mechanisms by which cyclophosphamide can render the immune lymphocytes competent to induce tumor rejection.
Results: The transfer of antitumor immunity was found to be dependent on CD4+ T cells and on the cooperation of adoptively transferred cells with the host immune system. Of note, tumor-immune lymphocytes migrated specifically to the tumor only in mice pretreated with cyclophosphamide. Cyclophosphamide treatment also promoted homeostatic proliferation/activation of transferred B and T lymphocytes. Optimal therapeutic responses to the transfer of immune cells were associated with the cyclophosphamide-mediated induction of a “cytokine storm” [including granulocyte macrophage colony-stimulating factor, interleukin (IL)-1β, IL-7, IL-15, IL-2, IL-21, and IFN-γ], occurring during the “rebound phase” after drug-induced lymphodepletion.
Conclusions: The ensemble of these data provides a new rationale for combining immunotherapy and chemotherapy to induce an effective antitumor response in cancer patients.
Cumulative Incidence in Competing Risks Data and Competing Risks Regression Analysis
Authors: Kim Haesook T. 
Published: January 2007

Abstract
Competing risks occur commonly in medical research. For example, both treatment-related mortality and disease recurrence are important outcomes of interest and well-known competing risks in cancer research. In the analysis of competing risks data, methods of standard survival analysis such as the Kaplan-Meier method for estimation of cumulative incidence, the log-rank test for comparison of cumulative incidence curves, and the standard Cox model for the assessment of covariates lead to incorrect and biased results. In this article, we discuss competing risks data analysis which includes methods to calculate the cumulative incidence of an event of interest in the presence of competing risks, to compare cumulative incidence curves in the presence of competing risks, and to perform competing risks regression analysis. A hypothetical numeric example and real data are used to compare those three methods in the competing risks data analysis to their respective counterparts in the standard survival analysis. The source and magnitude of bias from the Kaplan-Meier estimate is also detailed.