bluuebunny/crossref_metadata_2025_split huggingface dataset:
The York Play: Expanding the Boundaries of Civic Drama1
Authors: Christie Sheila 
Published: March 2007

AbstractWhile current scholarship on late medieval, civic cycle drama warns against assuming an either antagonistic or unifying function of that drama, scholars continue to reinscribe a conflictual relationship negotiated through cycle production. Examining assumptions about both participants and the pageant route, this article reveals how pre‐conceived notions of the York cycle's cultural function have limited our interpretations of the text and context. The article concludes with a brief case study which demonstrates that, during a time of economic recession, sources of pageant funding expanded to include all civic labourers, altering the very conception of ‘civic’ negotiated by and through the play.
Transient Overdrive Pacing Upon Standing Prevents Orthostatic Hypotension in Elderly Pacemaker Patients with Chronotropic Incompetence
Authors: TSE HUNG‐FAT , LAU CHU‐PAK , PARK EULJOON , BORNZIN GENE A. , YU CANNAS , BENSER MICHAEL E. , BLOOMFIELD DANIEL M. , PADELETTI LUIGI 
Published: March 2007

Background: Elderly pacemaker patients with chronotropic incompetence (CI) may experience orthostatic hypotension (OH) upon standing. The objective of this study was to determine whether a transient increase in heart rate (HR) by overdrive pacing upon standing prevents OH in elderly pacemaker patients.
Methods: We studied the effect of transient overdrive pacing upon standing in mitigating the drop in blood pressure (BP) in 62 pacemaker patients (77 ± 6 years, 32 F) implanted with DDD pacemaker for sick sinus syndrome (n = 40) or atrioventricular block (n = 22). All patients underwent two standing procedures in random order: a control, with backup (60 bpm) pacing and another with overdrive DDD pacing (at 35 bpm above their baseline rate) for 2 minutes upon standing. Systolic (SBP) and diastolic blood pressure (DBP) and HR were measured while supine (baseline) and 1, 2, and 3 minutes after standing. OH was defined as a drop in SBP ≥20 mmHg or DBP ≥10 mmHg during standing. Chronotropic incompetence (CI) was defined as an absence of HR increase of ≥10 bpm during standing.
Results: A total of 17 (27%) patients developed OH upon standing during backup pacing. Baseline clinical characteristics (age, sex, prevalence of diabetes, use of vasoactive medications, and sick sinus syndrome) were similar between patients with or without OH. In patients with or without OH, transient overdrive pacing upon standing increased HR and DBP as compared with baseline (P < 0.05). However, in patients with OH, transient overdrive pacing did not prevent decrease in SBP upon standing and avoided the development of OH in only 10/17 patients (59%). Among those patients with OH, 10/17 (59%) patients had CI. In OH patients with CI, transient overdrive pacing upon standing maintained SBP and DBP as compared to baseline and prevented OH in the majority of patients (80%). By contrast, transient overdrive pacing in OH patients without CI had no significant effect on the decrease in SBP upon standing and prevented OH in only 20% of patients.
Conclusions: OH is common (27%) in the elderly pacemaker population. In a subgroup of these patients, CI may be responsible for the occurrence of OH, and OH can be prevented by transient overdrive pacing upon standing.
Rail Safety and Rail Privatization
Authors: Evans Andrew 
Published: March 2007

Abstract
Privatisation of the state-owned British railway system was completed in 1997. The following 6 years saw four serious fatal train accidents, leading to 49 deaths. These were the train collisions at Southall in 1997 and Ladbroke Grove in 1999, each caused by trains passing red signals, and the derailments at Hatfield in 2000 and Potters Bar in 2002, each caused by defective track. Has safety been compromised by the sell-off of the railways? Andrew Evans looks at the evidence and asks has privatisation led to more accidents?
Carbon Assimilation Profiles as a Tool for Identification of Zygomycetes
Authors: Schwarz Patrick , Lortholary Olivier , Dromer Françoise , Dannaoui Eric 
Published: March 2007

ABSTRACT

Identification of Zygomycetes is difficult and time-consuming by standard microbiological procedures. Carbon assimilation profiles are commonly used for yeast-and bacterial-species identification but rarely for filamentous-fungus identification. Carbon assimilation profiles were evaluated using the commercialized kits ID32C and API 50 CH, which contain 31 and 49 tests, respectively, to serve as simple tools for species identification of Zygomycetes in clinical microbiology laboratories. Fifty-seven strains belonging to 15 species and varieties of Zygomycetes, including
Rhizopus
,
Absidia
,
Mucor
, and
Rhizomucor
species, were tested for intra- and interspecies variability based on their carbon assimilation profiles. Using ID32C strips, 6 tests were always positive, 7 were never positive, and 18 showed consistently different results between species. With API 50 CH strips, 15 tests were positive for all species, 13 were never positive, and 21 showed different results between species. Nevertheless, assimilation patterns were highly variable among
Rhizopus oryzae
isolates, and it was not possible to define a specific carbon assimilation profile. With both ID32C and API CH 50 strips, intraspecies variation was found to be low, while large differences were found between genera and species. The clustering of isolates based on their carbon assimilation profiles was in accordance with DNA-based phylogeny of Zygomycetes. In conclusion, carbon assimilation profiles allowed precise and accurate identification of most Zygomycetes to the species level.
Development and Evaluation of an Oligonucleotide Ligation Assay for Detection of Drug Resistance-Associated Mutations in the Human Immunodeficiency Virus Type 2
pol
Gene
Authors: Jallow Sabelle , Kaye Steve , Schutten Martin , Brandin Eleonor , Albert Jan , McConkey Samuel J. , Corrah Tumani , Whittle Hilton , Vanham Guido , Rowland-Jones Sarah , Janssens Wouter 
Published: March 2007

ABSTRACT
Human immunodeficiency virus type 2 (HIV-2) is naturally resistant to several antiretroviral drugs, including all of the non-nucleoside reverse transcriptase inhibitors and the entry inhibitor T-20, and may have reduced susceptibility to some protease inhibitors. These resistance properties make treatment of HIV-2 patients difficult, with very limited treatment options. Therefore, early detection of resistance mutations is important for understanding treatment failures and guiding subsequent therapy decisions. With the Global Fund Initiative, a substantial number of HIV-2 patients in West Africa will receive antiretroviral therapy. Therefore, development of cheaper and more sustainable resistance assays, such as the oligonucleotide ligation assay (OLA), is a priority. In this study, we designed oligonucleotide probes to detect the Q151M mutation, associated with phenotypic resistance to zidovudine, didanosine, zalcitabine, and stavudine, and the M184V mutation, associated with phenotypic resistance to lamivudine and emtricitabine, in HIV-2. The assay was successfully developed and evaluated with 122 samples from The Gambia, Guinea Bissau, The Netherlands, and Sweden. The overall sensitivity of the assay was 98.8%, with 99.2% for Q151M and 98.4% for M184V. OLA results were compared with sequencing to give high concordances of 98.4% (Q151M) and 97.5% (M184V). OLA demonstrated a higher sensitivity for detection of minor variants as a mixture of wild-type and mutant viruses in cases when sequencing detected only the major population. In conclusion, we have developed a simple, easy-to-use, and economical assay for genotyping of drug resistance in HIV-2 that is more sustainable for use in resource-poor settings than is consensus sequencing.
Effect of Plasmid DNA Vaccine Design and In Vivo Electroporation on the Resulting Vaccine-Specific Immune Responses in Rhesus Macaques
Authors: Luckay Amara , Sidhu Maninder K. , Kjeken Rune , Megati Shakuntala , Chong Siew-Yen , Roopchand Vidia , Garcia-Hand Dorys , Abdullah Rashed , Braun Ralph , Montefiori David C. , Rosati Margherita , Felber Barbara K. , Pavlakis George N. , Mathiesen Iacob , Israel Zimra R. , Eldridge John H. , Egan Michael A. 
Published: March 2007

ABSTRACTSince human immunodeficiency virus (HIV)-specific cell-mediated immune (CMI) responses are critical in the early control and resolution of HIV infection and correlate with postchallenge outcomes in rhesus macaque challenge experiments, we sought to identify a plasmid DNA (pDNA) vaccine design capable of eliciting robust and balanced CMI responses to multiple HIV type 1 (HIV-1)-derived antigens for further development. Previously, a number of two-, three-, and four-vector pDNA vaccine designs were identified as capable of eliciting HIV-1 antigen-specific CMI responses in mice (M. A. Egan et al., Vaccine 24:4510-4523, 2006). We then sought to further characterize the relative immunogenicities of these two-, three-, and four-vector pDNA vaccine designs in nonhuman primates and to determine the extent to which in vivo electroporation (EP) could improve the resulting immune responses. The results indicated that a two-vector pDNA vaccine design elicited the most robust and balanced CMI response. In addition, vaccination in combination with in vivo EP led to a more rapid onset and enhanced vaccine-specific immune responses. In macaques immunized in combination with in vivo EP, we observed a 10- to 40-fold increase in HIV-specific enzyme-linked immunospot assay responses compared to those for macaques receiving a 5-fold higher dose of vaccine without in vivo EP. This increase in CMI responses translates to an apparent 50- to 200-fold increase in pDNA vaccine potency. Importantly, in vivo EP enhanced the immune response against the less immunogenic antigens, resulting in a more balanced immune response. In addition, in vivo EP resulted in an approximate 2.5-log10increase in antibody responses. The results further indicated that in vivo EP was associated with a significant reduction in pDNA persistence and did not result in an increase in pDNA associated with high-molecular-weight DNA relative to macaques receiving the pDNA without EP. Collectively, these results have important implications for the design and development of an efficacious vaccine for the prevention of HIV-1 infection.
Cross-Clade Inhibition of Recombinant Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus SIVcpz Reverse Transcriptases by RNA Pseudoknot Aptamers
Authors: Held Daniel M. , Kissel Jay D. , Thacker Sarah J. , Michalowski Daniel , Saran Dayal , Ji Jianfei , Hardy Richard W. , Rossi John J. , Burke Donald H. 
Published: March 2007

ABSTRACT
Reverse transcriptase (RT) remains a primary target in therapies directed at human immunodeficiency virus type 1 (HIV-1). RNA aptamers that bind RT from HIV-1 subtype B have been shown to protect human cells from infection and to reduce viral infectivity, but little is known about the sensitivity of the inhibition to amino sequence variations of the RT target. Therefore, we assembled a panel of 10 recombinant RTs from phylogenetically diverse lentiviral isolates (including strains of HIV-1, simian immunodeficiency virus SIVcpz, and HIV-2). After validating the panel by measuring enzymatic activities and inhibition by small-molecule drugs, dose-response curves for each enzyme were established for four pseudoknot RNA aptamers representing two structural subfamilies. All four aptamers potently inhibited RTs from multiple HIV-1 subtypes. For aptamers carrying family 1 pseudoknots, natural resistance was essentially all-or-none and correlated with the identity of the amino acid at position 277. In contrast, natural resistance to aptamers carrying the family 2 pseudoknots was much more heterogeneous, both in degree (gradation of 50% inhibitory concentrations) and in distribution across clades. Site-directed and subunit-specific mutagenesis identified a common R/K polymorphism within the p66 subunit as a primary determinant of resistance to family 1, but not family 2, pseudoknot aptamers. RNA structural diversity therefore translates into a nonoverlapping spectrum of mutations that confer resistance, likely due to differences in atomic-level contacts with RT.
Progression of Fibrosis during Chronic Hepatitis C Is Associated with Rapid Virus Evolution
Authors: Wang Xiao-Hong , Netski Dale M. , Astemborski Jacquie , Mehta Shruti H. , Torbenson Michael S. , Thomas David L. , Ray Stuart C. 
Published: March 2007

ABSTRACT
Hepatic fibrosis is the primary mediator of disease due to chronic infection with hepatitis C virus (HCV). HCV exists as a quasispecies in each infected individual, and longitudinal viral sequence changes may reveal viral dynamics and the selection pressures applied by the host immune system. Thus, we hypothesized that patterns of sequence change might reveal the immunopathogenesis of fibrosis progression. We tested this hypothesis by studying individuals enrolled in a prospective study of chronic HCV-related hepatic fibrosis with little or no fibrosis at first biopsy (stage 0 or 1) and a second planned liver biopsy sample obtained 4 years later. Serum was obtained from five individuals with fast progression (FP; defined as a >2-stage change between visits) and 10 carefully matched individuals with slow progression (SP; defined as a <2-stage change between visits). We sequenced multiple cloned hemigenomic cDNAs from each person spanning six genes (core through NS3). Phylogenetic analysis revealed temporal shifts in phylogenetic clustering over time, suggesting frequent quasispecies replacement rather than simple diversification. In addition, mixed infections were detected in three subjects, with coexistence in two subjects (one FP, one SP) of subtypes 1a and 1b throughout the 4-year biopsy interval. Subjects with FP had a higher rate of evolution than subjects with SP, with a preponderance of synonymous changes, suggesting purifying selection, except in hypervariable region 1, where positive selection pressure is frequently detected. Thus, in a small but carefully matched cohort we found evidence for rapid neutral evolution of HCV in persons with rapid progression of hepatic fibrosis, suggesting higher turnover of infected cells.
Enhanced Detection of Human Immunodeficiency Virus Type 1 (HIV-1) Nef-Specific T Cells Recognizing Multiple Variants in Early HIV-1 Infection
Authors: Malhotra Uma , Li Fusheng , Nolin Jessica , Allison Megan , Zhao Hong , Mullins James I. , Self Steve , McElrath M. Juliana 
Published: March 2007

ABSTRACTA human immunodeficiency virus (HIV)-preventive vaccine will likely need to induce broad immunity that can recognize antigens expressed within circulating strains. To understand the potentially relevant responses that T-cell based vaccines should elicit, we examined the ability of T cells from early infected persons to recognize a broad spectrum of potential T-cell epitopes (PTE) expressed by the products encoded by the HIV type 1 (HIV-1)nefgene, which is commonly included in candidate vaccines. T cells were evaluated for gamma interferon (IFN-γ) secretion using two peptide panels: subtype B consensus (CON) peptides and a novel peptide panel providing 70% coverage of PTE in subtype B HIV-1 Nef. Eighteen of 23 subjects’ T cells recognized HIV-1 Nef. In one subject, Nef-specific T cells were detected with the PTE but not with the CON peptides. The greatest frequency of responses spanned Nef amino acids 65 to 103 and 113 to 147, with multiple epitope variants being recognized. Detection of both the epitope domain number and the response magnitude was enhanced using the PTE peptides. On average, we detected 2.7 epitope domains with the PTE peptides versus 1.7 domains with the CON peptides (P= 0.0034). The average response magnitude was 2,169 spot-forming cells (SFC)/106peripheral blood mononuclear cells (PBMC) with the PTE peptides versus 1,010 SFC/106PBMC with CON peptides (P= 0.0046). During early HIV-1 infection, Nef-specific T cells capable of recognizing multiple variants are commonly induced, and these responses are readily detected with the PTE peptide panel. Our findings suggest that Nef responses induced by a given vaccine strain before HIV-1 exposure may be sufficiently broad to recognize most variants within subtype B HIV-1.
The CD8+T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus
Authors: Kotturi Maya F. , Peters Bjoern , Buendia-Laysa Fernando , Sidney John , Oseroff Carla , Botten Jason , Grey Howard , Buchmeier Michael J. , Sette Alessandro 
Published: March 2007

ABSTRACTCD8+T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2bmice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8+CD44hiT-cell response to LCMV in H-2bmice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-γ) induction from CD8+T cells derived from LCMV-infected H-2bmice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8+CD44hiresponse. Thus, bystander T-cell activation does not contribute appreciably to the CD8+CD44hipool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8+T cells, whereas IFN-γ production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8+T-cell response is more complex than previously appreciated.
Cardiorespiratory fitness and metabolic syndrome: US National Health and Nutrition Examination Survey 1999–2002
Authors: Brien Susan E. , Janssen Ian , Katzmarzyk Peter T. 
Published: March 2007

Increasing physical activity is recommended as a therapeutic lifestyle change in the treatment of metabolic syndrome (MetS); however, little evidence exists for a relationship between cardiorespiratory fitness (CRF) and MetS in representative samples. Using data from the US National Health and Nutrition Examination Survey, 1999–2002, the relationship between CRF and MetS was examined in 692 men and 608 women between the ages of 18 and 49 y who were free of major disease and disability. In men, the odds of MetS were significantly lower in moderate and high CRF categories versus the low CRF category, whereas in women there were no significant relationships between CRF and MetS.
Standard Treatments Induce Antigen-Specific Immune Responses in Prostate Cancer
Authors: Nesslinger Nancy J. , Sahota Robert A. , Stone Brad , Johnson Kayli , Chima Navraj , King Caitlin , Rasmussen Devon , Bishop Darcy , Rennie Paul S. , Gleave Martin , Blood Paul , Pai Howard , Ludgate Charles , Nelson Brad H. 
Published: March 2007

Abstract
Purpose: Prostate tumors express antigens that are recognized by the immune system in a significant proportion of patients; however, little is known about the effect of standard treatments on tumor-specific immunity. Radiation therapy induces expression of inflammatory and immune-stimulatory molecules, and neoadjuvant hormone therapy causes prominent T-cell infiltration of prostate tumors. We therefore hypothesized that radiation therapy and hormone therapy may initiate tumor-specific immune responses.
Experimental Design: Pretreatment and posttreatment serum samples from 73 men with nonmetastatic prostate cancer and 50 cancer-free controls were evaluated by Western blotting and SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen arrays to examine whether autoantibody responses to tumor proteins arose during the course of standard treatment.
Results: Western blotting revealed the development of treatment-associated autoantibody responses in patients undergoing neoadjuvant hormone therapy (7 of 24, 29.2%), external beam radiation therapy (4 of 29, 13.8%), and brachytherapy (5 of 20, 25%), compared with 0 of 14 patients undergoing radical prostatectomy and 2 of 36 (5.6%) controls. Responses were seen within 4 to 9 months of initiation of treatment and were equally prevalent across different disease risk groups. Similarly, in the murine Shionogi tumor model, hormone therapy induced tumor-associated autoantibody responses in 5 of 10 animals. In four patients, SEREX immunoscreening of a prostate cancer cDNA expression library identified several antigens recognized by treatment-associated autoantibodies, including PARP1, ZNF707 + PTMA, CEP78, SDCCAG1, and ODF2.
Conclusion: We show for the first time that standard treatments induce antigen-specific immune responses in prostate cancer patients. Thus, immunologic mechanisms may contribute to clinical outcomes after hormone and radiation therapy, an effect that could potentially be exploited as a practical, personalized form of immunotherapy.
The Association Between Measures of Progression and Survival in Castrate-Metastatic Prostate Cancer
Authors: Scher Howard I. , Warren Mary , Heller Glenn 
Published: March 2007

Abstract
Purpose: To explore the association between progression-free survival and overall survival time in patients with castration-resistant prostate cancer treated with microtubule-targeted therapies.
Experimental Design: We retrospectively studied patients treated in three trials evaluating a taxane or an epothilone for progressive castration-resistant prostate cancer. Study subjects were 98 patients with bone metastases; 63 of them also had soft tissue lesions. All scans were reviewed independently. Associations of radiographic progression-free survival and prostate-specific antigen (PSA) progression-free survival with survival time were measured using Kendall's τ, adjusted for right censoring. A smoothing procedure was applied to estimate Kendall's τ within each neighborhood of the follow-up process.
Results: The overall associations between progression-free survival time and overall survival time were moderate: 0.4 for radiographic progression-free survival and 0.33 for PSA progression-free survival. The association between radiographic progression-free survival and overall survival was weakest early in the follow-up process, whereas the PSA association was weakest when the progression-free survival–related event (PSA progression, death, or censoring) occurred after 6 months from the start of treatment.
Conclusions: Current measures of progression-free survival time for men with castration-resistant prostate cancer are not strongly concordant with survival time. Factors that attenuate the association include interval censoring and the discontinuation of therapy early in the follow-up due to imaging changes that may not reflect true failure of the treatment. For radiographic progression-free survival, the association may be increased by requiring confirmation of progression with a second scan, as is routinely done when assessing response.
Friendship through Fourteenth-Century Fissures: Dai Liang, Wu Sidao and Ding Henian
Authors: Gerritsen Anne 
Published: March 2007

AbstractThis essay analyzes one set of male bonds—the relationships between three men in the Yuan-Ming transition—to understand the range of meanings assigned to the practice of friendship in the fourteenth century. Through the exchange of writings, the three men constructed a friendship based on shared cultural ideas that was more valuable to them than the ethnic, regional, and political differences between them. At a time when the violence and disruptions associated with the Yuan-Ming transition and the lack of access to examinations and the civil service created a crisis in masculinity, these friendships allowed them to create a space where masculine values could be shared and expressed.