bluuebunny/crossref_metadata_2025_split huggingface dataset:
Destabilization of YopE by the Ubiquitin-Proteasome Pathway Fine-Tunes Yop Delivery into Host Cells and Facilitates Systemic Spread of
Yersinia enterocolitica
in Host Lymphoid Tissue
Authors: Gaus Kristin , Hentschke Moritz , Czymmeck Nicole , Novikova Lena , Trülzsch Konrad , Valentin-Weigand Peter , Aepfelbacher Martin , Ruckdeschel Klaus 
Published: December 2010

ABSTRACT

Pathogenic
Yersinia
species inject a panel of Yop virulence proteins by type III protein secretion into host cells to modulate cellular defense responses. This enables the survival and dissemination of the bacteria in the host lymphoid tissue. We have previously shown that YopE of the
Y. enterocolitica
serogroup O8 is degraded in the host cell through the ubiquitin-proteasome pathway. YopE normally manipulates rearrangements of the actin cytoskeleton and triggers phagocytosis resistance. To shed light into the physiological role of YopE inactivation, we mutagenized the lysine polyubiquitin acceptor sites of YopE in the
Y. enterocolitica
serogroup O8 virulence plasmid. The resulting mutant strain escaped polyubiquitination and degradation of YopE and displayed increased intracellular YopE levels, which was accompanied by a pronounced cytotoxic effect on infected cells. Despite its intensified activity on cultured cells, the
Yersinia
mutant with stabilized YopE showed reduced dissemination into liver and spleen following enteral infection of mice. Furthermore, the accumulation of degradation-resistant YopE was accompanied by the diminished delivery of YopP and YopH into cultured,
Yersinia
-infected cells. A role of YopE in the regulation of Yop translocation has already been described. Our results imply that the inactivation of YopE by the proteasome could be a tool to ensure intermediate intracellular YopE levels, which may effectuate optimized Yop injection into host cells. In this regard,
Y. enterocolitica
O8 appears to exploit the host ubiquitin proteasome system to destabilize YopE and to fine-tune the activities of the Yop virulence arsenal on the infected host organism.
Dataset acquisition to support geoscience
Authors: Giles J. R. A. , Marsh S. H. , Napier B. 
Published: December 2010

Abstract

Environmental scientists are both producers and consumers of data. Numerous studies have shown that significant amounts of scientists’ time can be consumed in acquiring, managing and transforming data prior to their use. To facilitate the work of its scientists, the British Geological Survey (BGS) has identified a series of national datasets that are required by scientists across the organization. The BGS then seeks to acquire and manage these centrally, and to supply them to the scientists in formats that they normally use. Making these datasets readily available helps to:

enhance the quality of the science;

promote interdisciplinary working;

reduce costs.
The accuracy of ASTER digital elevation models: a comparison with NEXTMap Britain
Authors: Hall M. , Tragheim D. G. 
Published: December 2010

Abstract
In many overseas geological surveying projects an accurate elevation model is often required for analysis, image orthorectification, navigation and the generation of contours. Acquiring an accurate elevation model can be a difficult and expensive task. One possible solution is to generate a digital elevation model (DEM) from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite imagery. However, to fully understand the potential of ASTER DEMs the accuracy of these models needs to be established. The DEM was created using the Sulsoft ASTER DTM add-on ENVI module.
NEXTMap provides an ideal reference dataset for comparison. In this study the accuracy of an ASTER generated DEM was assessed for a 50×50 km area in central Wales. A total of 2.4 million points were compared.

Visual and statistical assessments were made, including profile and contour comparisons, allowing the spatial variation in accuracy to be explored. A mean vertical difference of –0.98 m and a standard deviation of
c
. 9 m were calculated. This suggests that 95% of the ASTER DEM points are within ±20 m of the NEXTMap DEM. Considering these accuracy levels, contours from ASTER can be generated at 40 m intervals.
Alias analysis for optimization of dynamic languages
Authors: Gorbovitski Michael , Liu Yanhong A. , Stoller Scott D. , Rothamel Tom , Tekle Tuncay K. 
Published: December 2010

Dynamic languages such as Python allow programs to be written more easily using high-level constructs such as comprehensions for queries and using generic code. Efficient execution of programs then requires powerful optimizations - incrementalization of expensive queries and specialization of generic code. Effective incrementalization and specialization of dynamic languages require precise and scalable alias analysis.
This paper describes the development and experimental evaluation of a may-alias analysis for a full dynamic object-oriented language, for program optimization by incrementalization and specialization. The analysis is flow-sensitive; we show that this is necessary for effective optimization of dynamic languages. It uses precise type analysis and a powerful form of context sensitivity, called trace sensitivity, to further improve analysis precision. It uses a compressed representation to significantly reduce the memory used by flow-sensitive analyses.We evaluate the effectiveness of this analysis and 17 variants of it for incrementalization and specialization of Python programs, and we evaluate the precision, memory usage, and running time of these analyses on programs of diverse sizes. The results show that our analysis has acceptable precision and efficiency and represents the best trade-off between them compared to the variants.
N -Acetyltransferase 2 Polymorphisms and Susceptibility to Infant Leukemia with Maternal Exposure to Dipyrone during Pregnancy
Authors: Zanrosso Crisiane Wais , Emerenciano Mariana , Gonçalves Bruno Alves de Aguiar , Faro Alessandra , Koifman Sérgio , Pombo-de-Oliveira Maria S. 
Published: December 2010

Abstract
Background: Maternal exposure to dipyrone during pregnancy has been associated with risk of infant leukemia (IL). N-Acetyltransferase 2 (NAT2) enzyme acetylates dipyrone, resulting in a detoxified metabolite. We performed genotyping to identify the distribution of NAT2 polymorphisms in duo samples from mothers and children previously investigated in a case-controlled study of IL.
Methods: Samples from 132 IL, 131 age-matched controls, mothers of cases (n = 86), and mothers of controls (n = 36) were analyzed. PCR-RFLP assays were used to determine the NAT2 variants 191G&gt;A, 282C&gt;T, 341T&gt;C, 481C&gt;T, 590G&gt;A, 803A&gt;G, and 857G&gt;A. The test for case-control differences in the distribution of genotypes was based on χ2 statistics. Unconditional logistic regression was used to examine the association between maternal exposure to dipyrone during the index pregnancy, IL, and NAT2 phenotypes. Crude and adjusted odds ratios (OR) are given with the 95% confidence interval (95% CI).
Results:NAT2 slow-acetylation haplotypes were associated with IL (OR, 8.90; 95% CI, 1.71-86.7). An association between IL and NAT2 phenotype was observed in IL whether the mothers reported dipyrone exposures (OR, 4.48; 95% CI, 1.88-10.7) or not (OR, 4.27; 95% CI, 1.75-10.5). The combination of NAT2 slow/slow (mother/child) phenotypes confers a higher risk of IL (OR, 30.0; 95% CI, 5.87-279.7).
Conclusion: NAT2 slow-acetylation profiles are associated with IL regardless of maternal exposure to dipyrone during pregnancy.
Impact: Further recommendations about medicine exposures during pregnancy should take into account that infants with the maternal NAT2 slow-acetylation genotypes might be particularly vulnerable to greater risk. Cancer Epidemiol Biomarkers Prev; 19(12); 3037–43. ©2010 AACR.
Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium
Authors: Wolpin Brian M. , Kraft Peter , Xu Mousheng , Steplowski Emily , Olsson Martin L. , Arslan Alan A. , Bueno-de-Mesquita H. Bas , Gross Myron , Helzlsouer Kathy , Jacobs Eric J. , LaCroix Andrea , Petersen Gloria , Stolzenberg-Solomon Rachael Z. , Zheng Wei , Albanes Demetrius , Allen Naomi E. , Amundadottir Laufey , Austin Melissa A. , Boutron-Ruault Marie-Christine , Buring Julie E. , Canzian Federico , Chanock Stephen J. , Gaziano J. Michael , Giovannucci Edward L. , Hallmans Göran , Hankinson Susan E. , Hoover Robert N. , Hunter David J. , Hutchinson Amy , Jacobs Kevin B. , Kooperberg Charles , Mendelsohn Julie B. , Michaud Dominique S. , Overvad Kim , Patel Alpa V. , Sanchéz Maria-José , Sansbury Leah , Shu Xiao-Ou , Slimani Nadia , Tobias Geoffrey S. , Trichopoulos Dimitrios , Vineis Paolo , Visvanathan Kala , Virtamo Jarmo , Wactawski-Wende Jean , Watters Joanne , Yu Kai , Zeleniuch-Jacquotte Anne , Hartge Patricia , Fuchs Charles S. 
Published: December 2010

Abstract
Background: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A1 versus A2 variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A1 allele would confer greater risk than A2 allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk.
Methods: We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression.
Results: An increased risk was observed in participants with A1 but not A2 alleles. Compared with subjects with genotype O/O, genotypes A2/O, A2/A1, A1/O, and A1/A1 had ORs of 0.96 (95% CI, 0.72–1.26), 1.46 (95% CI, 0.98–2.17), 1.48 (95% CI, 1.23–1.78), and 1.71 (95% CI, 1.18–2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A1, and A2 were 1.00 (95% CI, 0.87–1.14), 1.38 (95% CI, 1.20–1.58), and 0.96 (95% CI, 0.77–1.20); P, O01 versus O02 = 0.94, A1 versus A2 = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63).
Conclusions: Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk.
Impact: These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34. Cancer Epidemiol Biomarkers Prev; 19(12); 3140–9. ©2010 AACR.
Body Mass Index, Hormone Replacement Therapy, and Endometrial Cancer Risk: A Meta-Analysis
Authors: Crosbie Emma J. , Zwahlen Marcel , Kitchener Henry C. , Egger Matthias , Renehan Andrew G. 
Published: December 2010

Abstract
Background: Body mass index (BMI) is a risk factor for endometrial cancer. We quantified the risk and investigated whether the association differed by use of hormone replacement therapy (HRT), menopausal status, and histologic type.
Methods: We searched MEDLINE and EMBASE (1966 to December 2009) to identify prospective studies of BMI and incident endometrial cancer. We did random-effects meta-analyses, meta-regressions, and generalized least square regressions for trend estimations assuming linear, and piecewise linear, relationships.
Results: Twenty-four studies (17,710 cases) were analyzed; 9 studies contributed to analyses by HRT, menopausal status, or histologic type, all published since 2003. In the linear model, the overall risk ratio (RR) per 5 kg/m2 increase in BMI was 1.60 (95% CI, 1.52–1.68), P &lt; 0.0001. In the piecewise model, RRs compared with a normal BMI were 1.22 (1.19–1.24), 2.09 (1.94–2.26), 4.36 (3.75–5.10), and 9.11 (7.26–11.51) for BMIs of 27, 32, 37, and 42 kg/m2, respectively. The association was stronger in never HRT users than in ever users: RRs were 1.90 (1.57–2.31) and 1.18 (95% CI, 1.06–1.31) with P for interaction = 0.003. In the piecewise model, the RR in never users was 20.70 (8.28–51.84) at BMI 42 kg/m2, compared with never users at normal BMI. The association was not affected by menopausal status (P = 0.34) or histologic type (P = 0.26).
Conclusions: HRT use modifies the BMI-endometrial cancer risk association.
Impact: These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association, whilst the presence of residual risk in HRT users points to the role of additional systems. Cancer Epidemiol Biomarkers Prev; 19(12); 3119–30. ©2010 AACR.
Prevalence of BRCA1 and BRCA2 Mutations in Women with Breast Carcinoma In Situ and Referred for Genetic Testing
Authors: Hall Michael J. , Reid Julia E. , Wenstrup Richard J. 
Published: December 2010

Abstract
Ductal and lobular carcinoma in situ (CIS) accounted for 62,280 (24.5%) of all new breast cancer diagnoses in 2009. BRCA1/2 mutations confer an extremely high risk of breast cancer, and management guidelines for BRCA1/2 mutation carriers advise close follow-up, intensive screening, and consideration of prophylactic surgery to lower this risk. The limited relevant previous data are not definitive in establishing the prevalence of BRCA1/2 mutations in breast CIS patients, creating uncertainty as to whether referral for cancer risk assessment and genetic testing is appropriate for this group. Therefore, we conducted a cross-sectional analysis of the Myriad Genetics BRCA1/2 database to determine the prevalence of these mutations in breast CIS patients. All statistical tests were 2-sided, and confidence intervals (CI) are reported at the 95% level (α = 0.05). The source population was 64,717 consecutive women who were not Ashkenazi Jewish, underwent BRCA1/2 testing, and provided a personal and family history of invasive breast and ovarian cancer; 7,295 (11.3%) reported a diagnosis of CIS (ductal or lobular) and had an overall 5.9% prevalence of mutated BRCA1/2 (mBRCA). Subgrouped by history (personal or family) of invasive breast and/or ovarian cancer, these CIS patients had the following prevalences of mBRCA: (1) no personal or family history, 2.3%; (2) personal history, 5.2%; (3) family history, 5%; and (4) personal and family history, 10.3%. mBRCA risk was significantly higher in women with early-onset (&lt;50 years old) CIS than with late-onset (≥50 years old) CIS [odds ratio (OR) = 1.5; 95% CI = 1.1–2.1). Disease onset at less than 40 years age was associated with an even higher mBRCA risk (OR = 1.8; 95% CI = 1.3–2.3). By far the largest analysis of BRCA1/2 mutation prevalence in non-Ashkenazi Jewish breast CIS patients, this study shows that early-onset CIS is associated with mBRCA1/2 in patients referred for genetic testing. When a family history of breast and/or ovarian cancer are also present, testing women with early-onset CIS may increase both the likelihood of detecting BRCA1/2 mutations and opportunities for carriers to consider additional cancer prevention strategies. Cancer Prev Res; 3(12); 1579–85. ©2010 AACR.
Chitin or Chitin-Like Glycans as Targets for Late-Term Cancer Chemoprevention
Authors: Wattenberg Lee W. , Patterson Steven , Antonides Jennifer D. 
Published: December 2010

AbstractA consistent observation in studies of carcinogenesis is that some glycans are expressed differently in cancer cells than in normal cells. A well-known example is the aberrant β1–6 N-acetyl-d-glucosamine branching associated with metastasis and poor prognosis in many cancers. This commentary proposes that, although not found in normal mammalian cells, a chitin (β-1,4-linked N-acetyl-d-glucosamine) or a chitin-like polysaccharide (e.g., hyaluronan) may exist as a cancer-associated glycan, which can be targeted by the novel pyrimidine nucleotide derivative SP-1015 (designed as a chitin synthase inhibitor). Preliminary chemoprevention data of our group showed SP-1015 in the diet can inhibit benzo(a)pyrene-induced neoplasia in the forestomach of female A/J mice, and, of importance, this activity occurred at late stages in carcinogenesis. While no effect was seen in the murine lung, this may be due to the low bioavailability of the compound. A different route of administration (e.g. inhalation of an aerosol) may have potential to inhibit pulmonary carcinogenesis. We hypothesize that inhibitors of chitin or chitin-like glycan formation may be effective chemopreventive agents and suggest that further work is needed to study these novel targets for cancer prevention. Cancer Prev Res; 3(12); 1519–22. ©2010 AACR.
Transition of a Clinical Trial into Translational Research: The Prostate Cancer Prevention Trial Experience
Authors: Goodman Phyllis J. , Tangen Catherine M. , Kristal Alan R. , Thompson Ian M. , Lucia M. Scott , Platz Elizabeth A. , Figg William D. , Hoque Ashraful , Hsing Ann , Neuhouser Marian L. , Parnes Howard L. , Reichardt Juergen K.V. , Santella Regina M. , Till Cathee , Lippman Scott M. 
Published: December 2010

Abstract
Large clinical trials provide a tremendous opportunity to integrate correlative, comprehensive biological studies with invaluable repositories of biospecimens and clinical and other data from the trial. The Prostate Cancer Prevention Trial (PCPT) was a phase III randomized, double-blind, placebo-controlled clinical trial of finasteride in 18,882 men. Clinical data and blood and tissue specimens were collected at baseline and throughout the study, offering an opportunity to create a program project to investigate hypotheses related to the biology underlying the PCPT findings as well as the etiology and risk of prostate cancer. The transition of the randomized PCPT into this translational and epidemiologic scientific investigation required extensive planning and coordination. Five individual but interrelated projects were brought together with the underlying program theme of the genetic, metabolic, and environmental factors associated with the risks of overall and high-grade prostate cancer and how these factors affected the efficacy of finasteride in preventing cancer. All projects with serum-based measures use a single, shared, nested case–control sample of participants so that each subject provides a more complete biomarker and genetic profile for the evaluation of joint effects of these factors. Strengths of this program include the following: 1) the control group contains only men who are negative for biopsy-detected cancer, 2) the statistical methods to evaluate associations of risk factors with disease are shared across all projects, 3) the large number of cancer cases with fully characterized genetic, metabolic, and behavioral exposures, 4) a central pathology core histopathologically classified the prostate cancer, and 5) cancer cases identified during the PCPT reflect the characteristics of cases currently being detected in the prostate-specific antigen screening era, leading to contemporary and highly relevant results. This article describes the comprehensive methodology and multidisciplinary collaborations, both national and international, essential to a major risk-modeling research program. We provide a framework for doing collaborative research in an international setting structured around a common theme of a clinical trial. Cancer Prev Res; 3(12); 1523–33. ©2010 AACR.
Association between Folate Levels and CpG Island Hypermethylation in Normal Colorectal Mucosa
Authors: Wallace Kristin , Grau Maria V. , Levine A. Joan , Shen Lanlan , Hamdan Randala , Chen Xinli , Gui Jiang , Haile Robert W. , Barry Elizabeth L. , Ahnen Dennis , McKeown-Eyssen Gail , Baron John A. , Issa Jean Pierre J. 
Published: December 2010

Abstract
Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association of blood folate levels and dietary and lifestyle factors with CpG island (CGI) methylation in normal colorectal mucosa. Subjects were enrolled in a multicenter chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1,000 biopsy specimens from 389 patients, 501 samples from the right colon and 499 from the rectum at the follow-up colonoscopy. We measured DNA methylation of estrogen receptor alpha (ERα) and secreted frizzled related protein-1 (SFRP1), using bisulfite pyrosequencing. We used generalized estimating equations regression analysis to examine the association between methylation and selected variables. For both ERα and SFRP1, percentage methylation was significantly higher in the rectum than in the right colon (P = 0.001). For each 10 years of age, we observed a 1.7% increase in methylation level for ERα and a 2.9% increase for SFRP1 (P &lt; 0.0001). African Americans had a significantly lower level of ERα and SFRP1 methylation than Caucasians and Hispanics. Higher RBC folate levels were associated with higher levels of both ERα (P = 0.03) and SFRP1 methylation (P = 0.01). Our results suggest that CGI methylation in normal colorectal mucosa is related to advancing age, race, rectal location, and RBC folate levels. These data have important implications regarding the safety of supplementary folate administration in healthy adults, given the hypothesis that methylation in normal mucosa may predispose to colorectal neoplasia. Cancer Prev Res; 3(12); 1552–64. ©2010 AACR.
Update on Cancer Prevention Research in the United States and China: The 2009 China—U.S. Forum on Frontiers of Cancer Research
Authors: Bode Ann M. , Cao Ya , Dong Zigang 
Published: December 2010

AbstractCancer is one of the major physical, social, and economic burdens and public health threats worldwide. Citizens everywhere face the challenge of dealing with the costs and devastation of this dreadful disease regardless of country of residence. In October 2009, a joint China—U.S. forum focusing on cancer prevention was held in Changsha, China. The goal of this timely joint conference was to provide a forum for the exchange of the most recent and relevant information on cancer control, translational cancer prevention research, and clinical trials in China and the United States. The scientifically driven symposium comprised didactic sessions that included discussions focused on identifying and validating effective chemopreventive agents and their molecular and cellular targets. A major highlight of the meeting was the participation of Chinese and American experts from Xiangya Medical School, Central South University and the Center for Health Policy and Management (China), and the National Institutes of Health (NIH, United States), who provided a unique insight into each country's public efforts and progress in cancer prevention. Participants clearly agreed that our current understanding of the many factors influencing cancer causation indicates that as much as two thirds or more of human cancers can be prevented. This perspective presents an overview of the progress being made in cancer prevention in China and the United States. Cancer Prev Res; 3(12); 1630–7. ©2010 AACR.