bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Nuclear Antigen 3C Interacts with and Enhances the Stability of the c-Myc Oncoprotein
Authors: Bajaj Bharat G. , Murakami Masanao , Cai Qiliang , Verma Subhash C. , Lan Ke , Robertson Erle S. 
Published: February 2008

ABSTRACTEpstein-Barr virus (EBV) was the first human DNA virus to be associated with cancer. Its oncogenic potential was further demonstrated by its ability to transform primary B lymphocytes in vitro. EBV nuclear antigen 3C (EBNA3C) is one of a small subset of latent antigens critical for the transformation of human primary B lymphocytes. Although EBNA3C has been shown to modulate several cellular functions, additional targets involved in cellular transformation remain to be explored. EBNA3C can recruit key components of the SCFSkp2ubiquitin ligase complex. In this report, we show that EBNA3C residues 130 to 190, previously shown to bind to the SCFSkp2complex, also can strongly associate with the c-Myc oncoprotein. Additionally, the interaction of EBNA3C with c-Myc was mapped to the region of c-Myc that includes the highly conserved Skp2 binding domain. Skp2 has been shown to regulate c-Myc stability and also has been shown to function as a coactivator of transcription for c-Myc target genes. We now show that the EBV latent oncoprotein EBNA3C can stabilize c-Myc and that the recruitment of both c-Myc and its cofactor Skp2 to c-Myc-dependent promoters can enhance c-Myc-dependent transcription. This same region of EBNA3C also recruits and modulates the activity of retinoblastoma and p27, both major regulators of the mammalian cell cycle. The inclusion of c-Myc in the group of cellular targets modulated by this domain further accentuates the importance of these critical residues of EBNA3C in bypassing the cell cycle checkpoints.
Epstein-Barr Virus Nuclear Antigen 1 Does Not Cause Lymphoma in C57BL/6J Mice
Authors: Kang Myung-Soo , Soni Vishal , Bronson Roderick , Kieff Elliott 
Published: February 2008

ABSTRACT
To test whether transgenic Epstein-Barr virus nuclear antigen 1 (EBNA1) expression in C57BL/6 mouse lymphocytes causes lymphoma, EBNA1 expressed in three FVB lineages at two or three times the level of latent infection was crossed up to six successive times into C57BL/6J mice. After five or six crosses, 14/36, (38%) EBNA1 transgenic mice, 11/31 (36%) littermate EBNA1-negative controls, and 9/25 (36%) inbred C57BL/6J mice housed in the same facility had lymphoma. These data indicate that EBNA1 does not significantly increase lymphoma prevalence in C57BL/6J mice.
Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing
Authors: Salazar-Gonzalez Jesus F. , Bailes Elizabeth , Pham Kimmy T. , Salazar Maria G. , Guffey M. Brad , Keele Brandon F. , Derdeyn Cynthia A. , Farmer Paul , Hunter Eric , Allen Susan , Manigart Olivier , Mulenga Joseph , Anderson Jeffrey A. , Swanstrom Ronald , Haynes Barton F. , Athreya Gayathri S. , Korber Bette T. M. , Sharp Paul M. , Shaw George M. , Hahn Beatrice H. 
Published: February 2008

ABSTRACT

Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 (HIV-1) and in developing vaccines, drugs, or microbicides to prevent infection. Here we describe an experimental approach to analyze HIV-1
env
genes as intact genetic units amplified from plasma virion RNA by single-genome amplification (SGA), followed by direct sequencing of uncloned DNA amplicons. We show that this strategy precludes in vitro artifacts caused by
Taq
-induced nucleotide substitutions and template switching, provides an accurate representation of the
env
quasispecies in vivo, and has an overall error rate (including nucleotide misincorporation, insertion, and deletion) of less than 8 × 10
−5
. Applying this method to the analysis of virus in plasma from 12 Zambian subjects from whom samples were obtained within 3 months of seroconversion, we show that transmitted or early founder viruses can be identified and that molecular pathways and rates of early
env
diversification can be defined. Specifically, we show that 8 of the 12 subjects were each infected by a single virus, while 4 others acquired more than one virus; that the rate of virus evolution in one subject during an 80-day period spanning seroconversion was 1.7 × 10
−5
substitutions per site per day; and that evidence of strong immunologic selection can be seen in Env and overlapping Rev sequences based on nonrandom accumulation of nonsynonymous mutations. We also compared the results of the SGA approach with those of more-conventional bulk PCR amplification methods performed on the same patient samples and found that the latter is associated with excessive rates of
Taq
-induced recombination, nucleotide misincorporation, template resampling, and cloning bias. These findings indicate that HIV-1
env
genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately.
Uncertainties in predicting the impact of climate change on thermal performance of domestic buildings in the UK
Authors: de Wilde Pieter , Rafiq Yaqub , Beck Martin 
Published: February 2008

Buildings typically have a long life span, which can easily reach 50 or 100 years. In the light of expected climate change it is therefore important to look towards the future, and to analyse how buildings will cope with the changes in climate that are predicted by the climatologists. In such long-term predictions of building performance, uncertainties play a large role. This paper describes a preliminary study that aims to better map out the consequences of dealing with a whole range of uncertainties in the specific case of predicting the effect of climate change on the energy use and thermal comfort (overheating) in the large stock of terraced houses in the UK. Uncertainties in climate change prediction are compared with other variable factors like building occupancy patterns, actual thickness of construction materials and HVAC control settings. Uncertainties have been propagated in a transient model of these terraced houses using the transient simulation program EnergyPlus. In order to explore the large range of input variants use has been made of a genetic algorithm. The current search and solution spaces are discussed, putting the impact of climate change in perspective with regards to other changes and developments that might increase or decrease overheating. Overall, the findings indicate that uncertainties in long term thermal performance predictions run high, with standard deviations of over 100%. However, the robustness of the contemporary dwelling design is fortunately high.
A contribution to the audit of an air-conditioning system: modelling, simulation and benchmarking
Authors: André Philippe , Hannay Cleide , Hannay Jules , Lebrun Jean , Lemort Vincent , Teodorese Ion Vladut 
Published: February 2008

This paper intends to show how benchmarks can help in the audit of a HVAC system and how these benchmarks can be generated. The work presented is part of the European `AUDITAC' project. How can an auditor declare that a given HVAC is `consuming too much'? He can't make any judgment, if not having some reference, i.e. some `benchmarks' available. Focus is given here to cooling regime, but even then, heating cannot be forgotten (for example, the remaining heating demand can be satisfied thanks some recovery on the condensers of the chillers). The dramatic question is: what should be the consumption(s) for such a building, in such a climate, with such occupancy, such internal loads and such actual indoor environment? Better than to look for a (very hypothetical) global weather index, similar to heating degree-days, it seems more rational to run a simulation model on a few thousands of hours, corresponding to one (or to several) cooling season(s). Current performances of simulation tools make this approach very expedient. The climate can then be considered as it is, without any simplification. The main simplification is still welcome on the system (building + HVAC) side, in order to get calculation robustness, easy understanding and easy parameter identification. In this perspective, the building has to be subdivided in a very limited number of zones and only a few components of the HVAC system have to be included in the simulation model, with as simple as possible control strategies.
Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438)
Authors: Thompson John A. , Fisher Richard I. , LeBlanc Michael , Forman Stephen J. , Press Oliver W. , Unger Joseph M. , Nademanee Auayporn P. , Stiff Patrick J. , Petersdorf Stephen H. , Fefer Alexander 
Published: February 2008

AbstractTo determine the effect of posttransplantation immunotherapy with IL-2 on the progression-free survival (PFS) and overall survival (OS) of patients with non-Hodgkin lymphoma (NHL) after autologous stem-cell transplantation (PBSCT), patients with previously treated NHL were treated with cyclophosphamide, etoposide, total body irradiation (TBI), and PBSCT. Twenty-eight to 80 days after PBSCT, patients were randomized to IL-2 versus observation. Three hundred seventy-six eligible patients were registered (with 4-year PFS of 34% and 4-year OS of 52%), and 194 eligible patients were randomized to continuous infusion intravenous IL-2 (9 million units/m2/day for 4 days followed 5 days later by 1.6 million units/m2/day for 10 days) versus observation. In randomized patients, there was no significant difference in PFS (hazard ratio of IL-2 to observation = 0.90; P =.56) or in OS (hazard ratio of IL-2 to observation = 0.88; P =.55). There were no deaths related to IL-2 treatment. Grade 4 IL-2–related toxicities (n = 14) were reversible. These results confirm earlier SWOG findings that cyclophosphamide, etoposide, TBI, and PBSCT can be administered to patients with relapsed/refractory NHL with encouraging PFS and OS. Posttransplantation IL-2 given at this dose and schedule of administration had no significant effect on PFS or OS. This study is registered at www.clinicaltrials.gov as NCT00002649.
Genetic susceptibility to progressive massive fibrosis in coal miners
Authors: Yucesoy B. , Johnson V. J. , Kissling G. E. , Fluharty K. , Kashon M. L. , Slaven J. , Germolec D. , Vallyathan V. , Luster M. I. 
Published: February 2008

Progressive massive fibrosis (PMF) is a chronic interstitial lung disease with a complex aetiology that can occur after cumulative dust exposure. A case–control study was conducted to test the hypothesis that single nucleotide polymorphisms (SNPs) within genes involved in inflammatory and fibrotic processes modulate the risk of PMF development.The study population consisted of 648 underground coal miners participating in the National Coal Workers Autopsy Study, of which 304 were diagnosed with PMF. SNPs that influence the regulation of interleukin (IL)-1, IL-6, tumour necrosis factor-α, transforming growth factor-β1, vascular endothelial growth factor (VEGF), epidermal growth factor intercellular cell adhesion molecule (ICAM)-1 and matrix metalloproteinase-2 genes were determined using a 5′-nuclease real-time PCR assay.There were no significant differences in the distribution of any individual SNP or haplotype between the PMF and control groups. However, the polygenotype of VEGF +405/ICAM-1 +241/IL-6 -174 (C-A-G) conferred an increased risk for PMF (odds ratio 3.4, 95% confidence interval 1.3–8.8).The present study suggests that the examined genetic variations that help regulate inflammatory and fibrotic processes are unlikely to strongly influence susceptibility to this interstitial lung disease, although the role of vascular endothelial growth factor, intercellular cell adhesion molecule-1 and interleukin-6 polymorphisms in the development of progressive massive fibrosis may require further investigation.
Tumour necrosis factor gene polymorphisms are associated with COPD
Authors: Gingo M. R. , Silveira L. J. , Miller Y. E. , Friedlander A. L. , Cosgrove G. P. , Chan E. D. , Maier L. A. , Bowler R. P. 
Published: February 2008

Tumour necrosis factor (TNF)-α has been shown to be an important factor in animal models of chronic obstructive pulmonary disease (COPD). However, human studies ofTNFpolymorphisms in COPD have been equivocal.SixTNFsingle nucleotide polymorphisms (-1031C/T, -863C/A, -857C/T, -237G/A, -308G/A and +487G/A) and their haplotypes were investigated in 423 Caucasian smokers (298 patients with spirometric evidence of COPD and 125 without airflow obstruction).The -308 minor allele (A) had a higher odds ratio (OR) of being associated with COPD in multivariate analysis (controlling for age, sex, pack-yrs; OR 1.9, 95% confidence interval (CI) 1.1–3.2) and was also associated with worse forced expiratory volume in one second/forced vital capacity. The -237 minor allele (A) had a lower OR of being associated with COPD (OR 0.40, 95% CI 0.19–0.86). In COPD patients, the -857 minor allele (T) had a lower OR of being associated with severe stages of COPD (Global Initiative for Obstructive Lung Disease stage III and IVversusstage I and II, OR 0.46, 95% CI 0.24–0.88). Other TNF single nucleotide polymorphisms were not associated with COPD but the -1031/-863 haplotype CC/TC had a lower OR in COPD patientsversussmoking controls (OR 0.22, 95% CI 0.05–0.97).The present study adds further evidence that tumour necrosis factor genotypes play a role in susceptibility to cigarette smoke.
Hepatitis B virus infection among pregnant women in Taiwan: Comparison between women born in Taiwan and other southeast countries
Authors: Lin Ching-Chiang , Hsieh Hsiu-Shu , Huang Yu-Jie , Huang Yeou-Lih , Ku Ming-Kun , Hung Hsin-Chia 
Published: February 2008

AbstractBackgroundTaiwan's national vaccination program has successfully decreased the prevalence of hepatitis B infection after twenty years of implementation and might be indirectly beneficial to the second generation. In this study, we compared the hepatitis B infection status of two groups: pregnant Taiwanese women and other Southeast Asian women, who because they had immigrated later in life to Taiwan by marriage to a Taiwanese man, had not been exposed to that vaccination program to evaluate the effect of hepatitis vaccination program on women of child-bearing age and further explored the potential impact of immigration on the hepatitis B public health policy in Taiwan.MethodsData was collected from 10,327 women born in Taiwan and 1,418 women born in other Southeast Asian countries, both groups receiving prenatal examinations at Fooyin University Hospital between 1996 and 2005. The results of serum hepatitis B s-Antigen (HBsAg) and hepatitis B e-Antigen (HBeAg) tests and other demographic data were obtained by medical chart review.ResultsThe pregnant women from Taiwan had a higher HBsAg positive rate (15.5%) but lower HBeAg(+)/HBsAg(+) ratio (32.1%) than the women from other countries (8.9% and 52.4%). For those born before July, 1984, the period of no national vaccination program, Taiwanese women had a higher HBsAg positive rate than other Southeast Asian women (15.7% vs. 8.4%), but for women born after that day and before June 1986, the period of vaccination for high risk newborns, the HBsAg positive rates found to be slightly lower for Taiwanese women than for other Southeast Asian women (11.4% vs. 12.3%) and the difference was more significant (3.1% vs. 28.6%) after June 1986, the period of vaccination for all newborns. While the HBeAg(+)/HBsAg(+) ratios decreased with age in both groups, they were consistently higher in women from other Southeast Asian countries than in women born in Taiwan after age 20.ConclusionIn Taiwan, the neonatal vaccination program that was implemented in 1984 has successfully reduced hepatitis B infection among pregnant women in present day, and is likely to indirectly prevent hepatitis B infection in the next generation. However, the increasing number of pregnant women from other Southeast Asian countries without a national neonatal vaccination program or with a program that was introduced later than the one in Taiwan will likely lessen the positive impact of this program and should be further assessed.
Ginger extract inhibits LPS induced macrophage activation and function
Authors: Tripathi Sudipta , Bruch David , Kittur Dilip S 
Published: February 2008

AbstractBackgroundMacrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation.MethodsMurine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction.ResultsWe observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines) and RANTES, MCP-1 (pro inflammatory chemokines) production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed.ConclusionIn conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.
Statement of the Science Concerning Locoregional Treatments After Preoperative Chemotherapy for Breast Cancer: A National Cancer Institute Conference
Authors: Buchholz Thomas A. , Lehman Constance D. , Harris Jay R. , Pockaj Barbara A. , Khouri Nagi , Hylton Nola F. , Miller Michael J. , Whelan Timothy , Pierce Lori J. , Esserman Laura J. , Newman Lisa A. , Smith Barbara L. , Bear Harry D. , Mamounas Eleftherios P. 
Published: February 2008

Purpose To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. Methods Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. Results High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. Conclusion The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes.
The Imperial Reigns of Leo II
Authors: Croke Brian 
Published: February 2008

Abstract
The boy-emperor Leo II has bequeathed us more than his share of chronological puzzles. He was only seven years old when he died in 474 but he had possessed imperial authority for nearly half his short life. There is uncertainty about the date of his birth, and most of his career as emperor with his grandfather Leo I. If we still had the chronicle of Nestorianos which actually terminated at the death of Leo II we would probably be fully informed on these matters. Instead, several of the relevant documents have been consistently misconstrued, that is, they have been made to fit a predetermined interpretation or order of events. Moreover, one important text has been ignored altogether. The chronology of the boy-emperor's career depends on Seeck's Regesten which has inevitably shaped the coverage in the standard accounts of Bury and Stein. The authority of Seeck also underpins the entry in the Prosopography of the Later Roman Empire which sets out the following chronology of Leo's brief life and imperial career:
467 – birth;
473 – elevated to Caesar by Leo I, October;
474 – elevated to Augustus by Leo I, before 18 January;
474 – death, November.
This investigation is designed to show that the multiple phases in the imperial rule of Leo II have never been properly disentangled. To do so not only brings greater precision to the sequence of events, and to Leo's short career, but also casts light on the wider context of these turbulent few years.