bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of hMLH1 Missense Mutations in East Asian Patients with Suspected Hereditary Nonpolyposis Colorectal Cancer
Authors: Fan Yimei , Wang Wei , Zhu Ming , Zhou Jiji , Peng Jingyuan , Xu Lizhi , Hua Zichun , Gao Xiang , Wang Yaping 
Published: December 2007

Abstract
Purpose: Germ line mutations in the DNA mismatch repair gene hMLH1 are a frequent cause of hereditary nonpolyposis colorectal cancer and about one-third of these are missense mutations. Several missense mutations in hMLH1 have frequently been detected in East Asian patients with suspected hereditary nonpolyposis colorectal cancer, but their pathogenic role has not been extensively assessed. The aim of this study was to perform functional analyses of these variants and their association with gastrointestinal cancer in East Asians.
Experimental Design: Altogether, 10 hMLH1 variants were analyzed by yeast two-hybrid and coimmunoprecipitation assays.
Results: The carboxyl-terminal replacements Q542L, L549P, L574P, and P581L in hMLH1 resulted in complete loss of activity in both yeast two-hybrid and coimmunoprecipitation tests and thus might be considered as pathogenic. The amino-terminal variants S46I, G65D, G67R, and R217C did not affect complex formation with hPMS2 in coimmunoprecipitation, but partly or fully lost their activity in yeast two-hybrid assay, and we suggested that these variants might reduce the efficiency of the heterodimer to go into the nucleus and thus the mismatch repair function might be blocked or reduced. The V384D and the Q701K variant resulted in the interaction of hMLH1 with hPMS2 at reduced efficiency and might raise the gastrointestinal cancer risk of the mutation carriers.
Conclusions: This work availably evaluated the functional consequences of some missense mutations not previously determined in the hMLH1 gene and might be useful for the clinical diagnosis of hereditary gastrointestinal cancer, especially in East Asians.
BRCA1 mRNA Expression Levels Predict for Overall Survival in Ovarian Cancer after Chemotherapy
Authors: Quinn Jennifer E. , James Colin R. , Stewart Gail E. , Mulligan Jude M. , White Patricia , Chang Gary K.F. , Mullan Paul B. , Johnston Patrick G. , Wilson Richard H. , Harkin D. Paul 
Published: December 2007

Abstract
Purpose: We investigated whether BRCA1 mRNA expression levels may represent a biomarker of survival in sporadic epithelial ovarian cancer following chemotherapy treatment.
Experimental Design: The effect of loss of BRCA1 expression on chemotherapy response in ovarian cancer was measured in vitro using dose inhibition assays and Annexin V flow cytometry. Univariate and multivariate analyses were done to evaluate the relationship between BRCA1 mRNA expression levels and survival after chemotherapy treatment in 70 fresh frozen ovarian tumors.
Results: We show that inhibition of endogenous BRCA1 expression in ovarian cancer cell lines results in increased sensitivity to platinum therapy and decreased sensitivity to antimicrotubule agents. In addition, we show that patients with low/intermediate levels of BRCA1 mRNA have a significantly improved overall survival following treatment with platinum-based chemotherapy in comparison with patients with high levels of BRCA1 mRNA (57.2 versus 18.2 months; P = 0.0017; hazard ratio, 2.9). Furthermore, overall median survival for higher-BRCA1-expressing patients was found to increase following taxane-containing chemotherapy (23.0 versus 18.2 months; P = 0.12; hazard ratio, 0.53).
Conclusions: We provide evidence to support a role for BRCA1 mRNA expression as a predictive marker of survival in sporadic epithelial ovarian cancer.
Allogeneic MHC Gene Transfer Enhances an Effective Antitumor Immunity in the Early Period of Autologous Hematopoietic Stem Cell Transplantation
Authors: Kobayashi Akihiko , Hara Hidehiko , Ohashi Masaki , Nishimoto Takeshi , Yoshida Kimiko , Ohkohchi Nobuhiro , Yoshida Teruhiko , Aoki Kazunori 
Published: December 2007

AbstractPurpose: In autologous hematopoietic stem cell transplantation (HSCT), lymphopenia-induced homeostatic proliferation of T cells is driven by the recognition of self-antigens, and there is an opportunity to skew the T-cell repertoire during the T-cell recovery by engaging tumor-associated antigens, leading to a break of tolerance against tumors. However, the homeostatic proliferation–driven antitumor responses seem to decline rapidly in association with tumor growth. We hypothesized that a tumor-specific immune response induced by an immune gene therapy could enhance and sustain homeostatic proliferation–induced antitumor immunity.Experimental Design: The antitumor effect of allogeneic MHC (alloMHC) gene transfer was examined at the early phase of the immune reconstitution after syngeneic HSCT.Results: Syngeneic HSCT showed significant tumor growth inhibition of syngeneic colon cancer cells within a period of 30 days; however, the tumor then resumed rapid growth and the survival of the mice was not prolonged. In contrast, when the alloMHC plasmid was intratumorally injected at the early phase after syngeneic HSCT, the established tumors were markedly regressed and the survival of recipient mice was prolonged without significant toxicities, whereas no survival advantage was recognized in recipient mice injected with a control plasmid. This tumor suppression was evident even in the other tumors that were not injected with the alloMHC plasmid. The antitumor response was characterized by the development of tumor-specific T cell– and natural killer cell–mediated cytotoxicities.Conclusion: The results suggest the efficacy and safety of integrating intratumoral alloMHC gene transfer with an autologous HSCT for the treatment of solid cancers.
Differential Effects of Combined Ad5-Δ24RGD and Radiation Therapy in In vitro versus In vivo Models of Malignant Glioma
Authors: Lamfers Martine L.M. , Idema Sander , Bosscher Lisette , Heukelom Stan , Moeniralm Sharif , van der Meulen-Muileman Ida H. , Overmeer Renée M. , van der Valk Paul , van Beusechem Victor W. , Gerritsen Winald R. , Vandertop W. Peter , Dirven Clemens M.F. 
Published: December 2007

Abstract
Purpose: The integrin-targeted conditionally replicating adenovirus Ad5-Δ24RGD has been shown to possess strong oncolytic activity in experimental tumors and is currently being developed toward phase I clinical evaluation for ovarian cancer and malignant glioma. Previously, we reported that combination therapy of Ad5-Δ24RGD with irradiation led to synergistic antitumor activity in s.c. glioma xenografts. In the current study, the underlying mechanism of action to this synergy was studied and the effects of combined therapy were assessed in an orthotopic glioma model.
Experimental Design and Results: Sequencing studies in U-87 monolayers showed that delivery of irradiation before Ad5-Δ24RGD infection led to a greater oncolytic effect than simultaneous delivery or infection before irradiation. This effect was not due to enhanced virus production or release. Experiments using a luciferase-encoding vector revealed a small increase in transgene expression in irradiated cells. In tumor spheroids, combination therapy was more effective than Ad5-Δ24RGD or irradiation alone. Staining of spheroid sections showed improved penetration of virus to the core of irradiated spheroids. Mice bearing intracranial tumors received a combination of Ad5-Δ24RGD with 1 × 5 Gy total body irradiation or with 2 × 6 Gy whole brain irradiation. In contrast to the in vitro data and reported results in s.c. tumors, addition of radiotherapy did not significantly enhance the antitumor effect of Ad5-Δ24RGD.
Conclusions: Combined treatment with Ad5-Δ24RGD and irradiation shows enhanced antitumor activity in vitro and in s.c. tumors, but not in an orthotopic glioma model. These differential results underscore the significance of the selected tumor model in assessing the effects of combination therapies with oncolytic adenoviruses.
Testing for homogeneity of gametic disequilibrium across strata
Authors: Yin Xiaolin , Ma Wenqing , Tang Manlai , Guo Jianhua 
Published: December 2007

Abstract

Background
Assessing the non-random associations of alleles at different loci, or gametic disequilibrium, can provide clues about aspects of population histories and mating behavior and can be useful in locating disease genes. For gametic data which are available from several strata with different allele probabilities, it is necessary to verify that the strata are homogeneous in terms of gametic disequilibrium.

Results
Using the likelihood score theory generalized to nuisance parameters we derive a score test for homogeneity of gametic disequilibrium across several independent populations. Simulation results demonstrate that the empirical type I error rates of our score homogeneity test perform satisfactorily in the sense that they are close to the pre-chosen 0.05 nominal level. The associated power and sample size formulae are derived. We illustrate our test with a data set from a study of the cystic fibrosis transmembrane conductance regulator gene.

Conclusion
We propose a large-sample homogeneity test on gametic disequilibrium across several independent populations based on the likelihood score theory generalized to nuisance parameters. Our simulation results show that our test is more reliable than the traditional test based on the Fisher's test of homogeneity among correlation coefficients.
Denoising inferred functional association networks obtained by gene fusion analysis
Authors: Kamburov Atanas , Goldovsky Leon , Freilich Shiri , Kapazoglou Aliki , Kunin Victor , Enright Anton J , Tsaftaris Athanasios , Ouzounis Christos A 
Published: December 2007

Abstract

Background
Gene fusion detection – also known as the 'Rosetta Stone' method – involves the identification of fused composite genes in a set of reference genomes, which indicates potential interactions between its un-fused counterpart genes in query genomes. The precision of this method typically improves with an ever-increasing number of reference genomes.

Results
In order to explore the usefulness and scope of this approach for protein interaction prediction and generate a high-quality, non-redundant set of interacting pairs of proteins across a wide taxonomic range, we have exhaustively performed gene fusion analysis for 184 genomes using an efficient variant of a previously developed protocol. By analyzing interaction graphs and applying a threshold that limits the maximum number of possible interactions within the largest graph components, we show that we can reduce the number of implausible interactions due to the detection of promiscuous domains. With this generally applicable approach, we generate a robust set of over 2 million distinct and testable interactions encompassing 696,894 proteins in 184 species or strains, most of which have never been the subject of high-throughput experimental proteomics. We investigate the cumulative effect of increasing numbers of genomes on the fidelity and quantity of predictions, and show that, for large numbers of genomes, predictions do not become saturated but continue to grow linearly, for the majority of the species. We also examine the percentage of component (and composite) proteins with relation to the number of genes and further validate the functional categories that are highly represented in this robust set of detected genome-wide interactions.

Conclusion
We illustrate the phylogenetic and functional diversity of gene fusion events across genomes, and their usefulness for accurate prediction of protein interaction and function.
Rice transposable elements are characterized by various methylation environments in the genome
Authors: Takata Miwako , Kiyohara Akihiro , Takasu Atsuko , Kishima Yuji , Ohtsubo Hisako , Sano Yoshio 
Published: December 2007

Abstract

Background
Recent studies using high-throughput methods have revealed that transposable elements (TEs) are a comprehensive target for DNA methylation. However, the relationship between TEs and their genomic environment regarding methylation still remains unclear. The rice genome contains representatives of all known TE families with different characteristics of chromosomal distribution, structure, transposition, size, and copy number. Here we studied the DNA methylation state around 12 TEs in nine genomic DNAs from cultivated rice strains and their closely related wild strains.

Results
We employed a transposon display (TD) method to analyze the methylation environments in the genomes. The 12 TE families, consisting of four class I elements, seven class II elements, and one element of a different class, were differentially distributed in the rice chromosomes: some elements were concentrated in the centromeric or pericentromeric regions, but others were located in euchromatic regions. The TD analyses revealed that the TE families were embedded in flanking sequences with different methylation degrees. Each TE had flanking sequences with similar degrees of methylation among the nine rice strains. The class I elements tended to be present in highly methylated regions, while those of the class II elements showed widely varying degrees of methylation. In some TE families, the degrees of methylation were markedly lower than the average methylation state of the genome. In two families, dramatic changes of the methylation state occurred depending on the distance from the TE.

Conclusion
Our results demonstrate that the TE families in the rice genomes can be characterized by the methylation states of their surroundings. The copy number and degree of conservation of the TE family are not likely to be correlated with the degree of methylation. We discuss possible relationships between the methylation state of TEs and their surroundings. This is the first report demonstrating that TEs in the genome are associated with a particular methylation environment that is a feature of a given TE.
Bilateral cytomegalovirus (CMV) oophoritis mimicking widely metastatic carcinoma: a case report and review of the literature
Authors: Yu Jing , Solano Francis X , Seethala Raja R 
Published: December 2007

Abstract
Ovarian cytomegalovirus (CMV) infection is a rare finding reported in autopsy studies of immunocompromised patients. We report the first case of bilateral CMV oophoritis diagnosed in surgical resection specimens from a 63-year-old woman with metastatic brain lesions undergoing whole brain radiation and steroid treatment. The ovarian involvement of CMV infection was an incidental finding during the colectomy and bilateral salpingo-oophorectomy procedure for gastrointestinal bleeding and presumed ovarian metastases. In contrast to the prevailing dogma, a review of the literature found similar prevalence of pre-menopausal and post-menopausal cases. While age related vasculopathy was thought to be the prevailing mechanism for CMV oophoritis, the observation of an inflammation mediated microthrombosis in our case provides a plausible age independent mechanism suggesting that both restrictive and obstructive vascular changes can be involved in the pathogenesis of CMV oophoritis. To avoid misdiagnosis, both pathologists and clinicians should recognize ovarian involvement by CMV as a possibility in the immunocompromised patient.
Editorial—Causality, Unintended Consequences and Deducing Shared Causes
Authors: Shugan Steven M. 
Published: December 2007

Despite warnings against inferring causality from observed correlations or statistical dependence, some articles do. Observed correlation is neither necessary nor sufficient to infer causality as defined by the term's everyday usage. For example, a deterministic causal process creates pseudorandom numbers; yet, we observe no correlation between the numbers. Child height correlates with spelling ability because age causes both. Moreover, order is problematic—we hear train whistles before observing trains, yet trains cause whistles. Scientific methods specifically prohibit inferring causal theories from specific observations (i.e., effects) because, in part, many credible causes are perfectly consistent with available observations. Moreover, actions inferred from effects have more unintended consequences than actions based on sound deductive causal theories because causal theories predict multiple effects. However, an often overlooked but key feature of these theories is that we describe the cause with more variables than the effect. Consequently, inductive processes might appear deductive as the number of effects increases relative to the number of potential causes. For example, in real criminal trials, jurors judge whether sufficient evidence exists to infer guilt. In contrast, determining guilt in criminal mystery novels is deductive because the number of clues (i.e., effects) is large relative to the number of potential suspects (i.e., causes). We can make inferential tasks resemble deductive tasks by increasing the number of effects (i.e., variables) relative to the number of potential causes and seeking a shared cause for all observed effects. Moreover, under some conditions, the method of seeking shared causes might approach deductive reasoning when the number of causes is strictly limited. At least, the resulting number of possible causal theories is far less than the number generated from repeated observations of a single effect (i.e., variable).
Leadership and Decision-making in New York City and London
Authors: Savitch H. V. 
Published: December 2007

In recent years the idea of decentralisation has attained a controversial status among those concerned with the future of our cities. To its advocates, decentralisation is seen as a tool by which citizens can forge a sense of community and make their cities liveable; to others, it is a ruse which detracts from real problems, or worse, threatens the cosmopolitanism of our great cities. The debate continues across continents and by now the arguments for and against decentralisation seem to have outrun the empirical findings on the many forms it can take. This paper explores the forms and ramifications of decentralisation as it relates to the exercise of leadership in seven decentralised areas of two cities; New York and London.
Of the seven decentralised areas or sub-systems used for this study four were in New York City and three in London. The New York operations, called ‘neighbourhood districts’, include identifiable areas in various parts of the city. These are Crown Heights and Bushwickin Brooklyn, Wakefield Edenwald in the Bronx, and Washington Heights in Manhattan. The New York projects were begun in 1972, at the discretion of the Mayor, and represent the core of an experiment in administrative decentralisation.
Attapulgite as a Thixotropic Suspending Agent
Authors: Wolford John 
Published: December 2007

Abstract
Attapulgite is a hydrous magnesium aluminum silicate clay mineral with a unique structure made up of colloidal particles called spicules. Gellation takes place following dispersion when the spicules become attracted to each other, become entangled and form the matrix structure that thickens, entraps, and suspends solids. Proper dispersion and gelling is dependent on the amount of shear and length of time it is applied or the use of chemical means to facilitate dispersion. To achieve gellation chemically dispersed clay must come into contact with a chemical salt which causes spicules to associate with one another and the gel to instantly form. Attapulgite can also be used to structure organic systems with the proper use of a cationic surfactant. The basic advantages of attapulgite as a structuring agent are versatility, compatibility with a variety of liquid systems, functionality over a wide pH range, and resistance to attack by microorganisms. It is relatively economical and provides a thixotropic liquid system.
Concrete and Other Alternative Platform Designs
Authors: Fumes Olav 
Published: December 2007

ABSTRACT
The paper is chiefly devoted to the design, construction, installation and maintenance of concrete platforms. A review is given over the fixed concrete gravity platforms installed or under construction in the North Sea and elsewhere. The principles of design and construction is discussed with emphasis on –current design requirements and practice–evaluation of environmental loads foundation stability and geotechnical aspects–construction, tow-out and instal-1ation–aspects of inspection and maintenance.
The potential of applying concrete platforms for a range of water depths and soil conditions is discussed. Alternative fixed and floating concrete platforms for deep water and concepts which will not need sheltered, deep water for construction are outlined to some extent.
The experience from construction and operation of concrete platforms until now is summarized and certain design problems are looked into.
The paper concludes that prestressed and reinforced concrete, when designed and constructed in compliance with current criteria, is a well suited, durable and practically maintenance-free material for platforms exposed to the environmental conditions of the North Sea.
As for alternative platform designs other than concrete and conventional jackets, a review is given of platforms presently proposed. However brief, the review covers compliant and articulated towers, vertically moored platforms and tripod towers for deep water and hostile environment.
Sandstone Reservoirs
Authors: Weimer Robert J. , Tillman R. W. 
Published: December 2007

ABSTRACT
The origin and distribution of a sandstone reservoir for petroleum are controlled primarily by the processes by which the sand was deposited. Studies of modern environments of deposition and associated Holocene deposits provide a basis for understanding petroleum fields and predicting reservoir distribution and behavior.
The Rocky Mountain province of the United States contains structural and stratigraphic traps from which petroleum is produced from all types of sandstone reservoirs ranging in age from Cambrian to the Eocene. Three large typical stratigraphic traps, where reservoirs are of Cretaceous age, are described. The Cut Bank field, Montana produces from alluvial point bar sandstones; Patrick Draw field, Wyoming produces from marine shoreline sandstones; and, Hartzog Draw field, Wyoming produces from marine shelf sandstones.