bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Dissection of the Conjugative Coupling Protein TrwB
Authors: de Paz Héctor D. , Larrea Delfina , Zunzunegui Sandra , Dehio Christoph , de la Cruz Fernando , Llosa Matxalen 
Published: April 2010

ABSTRACT

The conjugative coupling protein TrwB is responsible for connecting the relaxosome to the type IV secretion system during conjugative DNA transfer of plasmid R388. It is directly involved in transport of the relaxase TrwC, and it displays an ATPase activity probably involved in DNA pumping. We designed a conjugation assay in which the frequency of DNA transfer is directly proportional to the amount of TrwB. A collection of point mutants was constructed in the TrwB cytoplasmic domain on the basis of the crystal structure of TrwBΔN70, targeting the nucleotide triphosphate (NTP)-binding region, the cytoplasmic surface, or the internal channel in the hexamer. An additional set of transfer-deficient mutants was obtained by random mutagenesis. Most mutants were impaired in both DNA and protein transport. We found that the integrity of the nucleotide binding domain is absolutely required for TrwB function, which is also involved in monomer-monomer interactions. Polar residues surrounding the entrance and inside the internal channel were important for TrwB function and may be involved in interactions with the relaxosomal components. Finally, the N-terminal transmembrane domain of TrwB was subjected to random mutagenesis followed by a two-hybrid screen for mutants showing enhanced protein-protein interactions with the related TrwE protein of
Bartonella tribocorum
. Several point mutants were obtained with mutations in the transmembranal helices: specifically, one proline from each protein may be the key residue involved in the interaction of the coupling protein with the type IV secretion apparatus.
Clinical tests in shoulder examination: how to perform them
Authors: Moen Maarten Hendrik , de Vos Robert-Jan , Ellenbecker Todd S , Weir Adam 
Published: April 2010

BackgroundThis article describes the best clinical tests of shoulder function and injury as identified in a recent systematic review published in theBritish Journal of Sports Medicine.DiscussionA description of the different tests is given, with photographs of the exact test procedure.
Mechanical characterization of matrix coarse-grained soils with a large-sized triaxial device
Authors: Seif El Dine Bassel , Dupla Jean Claude , Frank Roger , Canou Jean , Kazan Youssam 
Published: April 2010

This paper presents an experimental program that characterizes the mechanical behavior of heterogeneous soils using a large-sized triaxial apparatus (300 mm diameter and 600 mm height). A particular class of heterogeneous soil called matrix coarse-grained soil, composed of a mixture of a sandy matrix (Fontainebleau sand) and inclusions (gravels), was studied. The experimental procedure to rebuild samples is presented first with a description of a typical test setup. A synthesis of the experimental results obtained is then presented. A particular focus is placed on studying the influence of basic soil parameters: the properties of the inclusions (volumetric fraction, particle size, grading parameter) and the initial state of stress in the soil. The two classical methods used to study the mechanical properties of matrix coarse-grained soils in the laboratory (clipping and clipping-substitution) are evaluated.
A domain decomposition algorithm for constraint satisfaction
Authors: Naanaa Wady 
Published: April 2010

This article presents a domain decomposition algorithm for solving constraint satisfactions problems (CSPs). The proposed algorithm relies on a weak form of neighborhood substitutability referred to as directional substitutability. The main idea is that although two values may not be neighborhood substitutable if we consider the whole neighborhood of a given variable, they could be substitutable if we only focus on a part of the neighborhood induced by an orientation of the constraint graph. Directional substitutability provides a mean to decompose value domains into chains of directionally substitutable values that can be attempted simultaneously during search.
We report experiments carried out on several binary CSPs which clearly indicate that variations of classical algorithms which exploit directional substitutability often outperform the original algorithms.
Ranking tournaments
Authors: Coleman Tom , Wirth Anthony 
Published: April 2010

Ranking is a fundamental activity for organizing and, later, understanding data. Advice of the form “
a
should be ranked before
b
” is given. If this advice is consistent, and complete, then there is a total ordering on the data and the ranking problem is essentially a sorting problem. If the advice is consistent, but incomplete, then the problem becomes topological sorting. If the advice is inconsistent, then we have the feedback arc set (FAS) problem: The aim is then to rank a set of items to satisfy as much of the advice as possible. An instance in which there is advice about every pair of items is known as a tournament. This ranking task is equivalent to ordering the nodes of a given directed graph from left to right, while minimizing the number of arcs pointing left.

In the past, much work focused on finding good, effective heuristics for solving the problem. Recently, a proof of the NP-completeness of the problem (even when restricted to tournaments) has accompanied new algorithms with approximation guarantees, culminating in the development of a PTAS (polynomial time approximation scheme) for solving FAS on tournaments.
In this article, we reexamine many existing algorithms and develop some new techniques for solving FAS. The algorithms are tested on both synthetic and nonsynthetic datasets. We find that, in practice, local-search algorithms are very powerful, even though we prove that they do not have approximation guarantees. Our new algorithm is based on reversing arcs whose nodes have large indegree differences, eventually leading to a total ordering. Combining this with a powerful local-search technique yields an algorithm that is as strong, or stronger than, existing techniques on a variety of data sets.
Optimizing MEMS-based storage devices for mobile battery-powered systems
Authors: Khatib Mohammed G. , Hartel Pieter H. 
Published: April 2010

An emerging storage technology, called MEMS-based storage, promises nonvolatile storage devices with ultrahigh density, high rigidity, a small form factor, and low cost. For these reasons, MEMS-based storage devices are suitable for battery-powered mobile systems such as PDAs. For deployment in such systems, MEMS-based storage devices must consume little energy. This work mainly targets reducing the energy consumption of this class of devices.
We derive the operation modes of a MEMS-based storage device and systemically devise a policy in each mode for energy saving. Three types of policies are presented: power management, shutdown, and data-layout policy. Combined, these policies reduce the total energy consumed by a MEMS-based storage device. A MEMS-based storage device that enforces these policies comes close to Flash with respect to energy consumption and response time. However, enhancement on the device level is still needed; we present some suggestions to resolve this issue.
Predicting and preventing inconsistencies in deployed distributed systems
Authors: Yabandeh Maysam , Knežević Nikola , Kostić Dejan , Kuncak Viktor 
Published: April 2010

We propose a new approach for developing and deploying distributed systems, in which nodes predict distributed consequences of their actions and use this information to detect and avoid errors. Each node continuously runs a state exploration algorithm on a recent consistent snapshot of its neighborhood and predicts possible future violations of specified safety properties. We describe a new state exploration algorithm, consequence prediction, which explores causally related chains of events that lead to property violation.
This article describes the design and implementation of this approach, termed CrystalBall. We evaluate CrystalBall on RandTree, BulletPrime, Paxos, and Chord distributed system implementations. We identified new bugs in mature Mace implementations of three systems. Furthermore, we show that if the bug is not corrected during system development, CrystalBall is effective in steering the execution away from inconsistent states at runtime.
Attitudes of sixth form female students toward the IT field
Authors: Leiviskä Katja , Siponen Mikko 
Published: April 2010

It is well known that girls are not interested in computer science, information systems (IS), and software engineering studies. While the underlying reasons for this phenomenon have been studied in the US, Canada, and Australia, only a few studies have been carried out in Europe and in Scandinavia. To fill this gap in the research, we have analyzed the qualitative responses of 64 female sixth form students concerning their attitudes towards studying information technology (IT), including computer science, information systems, and software engineering disciplines, and their views about IT as a profession.
The results suggest that the IT field is seen in quite a positive light by the girls. Although many of the respondents do not consider IT to be their profession, they nevertheless have positive attitudes towards the field. According to the respondents, the field is growing and developing; it is respected, and seen as the field of the future. Girls who want to become IT professionals see that the profession entails good employment possibilities and benefits and is respected. Some girls have negative views towards the field. These views illustrate the underlying reasons why these girls do not want to study IT. The girls did not perceive the field to be human-related (the work is only computer-related, according to the respondents). The need for skills in mathematics and physics are also listed as key reasons why some girls do not want to become IT students.
The results of the study suggest that there is a need to clarify among sixth form students the fact that IT jobs can be divided into computer science, information systems, and software engineering, all of which require different competences.
A survey of buffer management policies for packet switches
Authors: Goldwasser Michael H. 
Published: April 2010

Over the past decade, there has been great interest in the study of buffer management policies in the context of packet transmission for network switches. In a typical model, a switch receives packets on one or more input ports, with each packet having a designated output port through which it should be transmitted. An online policy must consider bandwidth limits on the rate of transmission, memory constraints impacting the buffering of packets within a switch, and variations in packet properties used to differentiate quality of service. With so many constraints, a switch may not be able to deliver all packets, in which case some will be dropped
In the online algorithms community, researchers have used competitive analysis to evaluate the quality of an online policy in maximizing the value of those packets it is able to transmit. In this article, we provide a detailed survey of the field, describing various models of the problem that have been studied, and summarizing the known results.
Expression of p21 Protein Predicts Clinical Outcome in DLBCL Patients Older than 60 Years Treated with R-CHOP but not CHOP: A Prospective ECOG and Southwest Oncology Group Correlative Study on E4494
Authors: Winter Jane N. , Li Shuli , Aurora Vikas , Variakojis Daina , Nelson Beverly , Krajewska Maryla , Zhang Lijun , Habermann Thomas M. , Fisher Richard I. , Macon William R. , Chhanabhai Mukesh , Felgar Raymond E. , Hsi Eric D. , Medeiros L. Jeffrey , Weick James K. , Weller Edie A. , Melnick Ari , Reed John C. , Horning Sandra J. , Gascoyne Randy D. 
Published: April 2010

Abstract
Purpose: To prospectively investigate the prognostic significance of p21 and p53 expression in diffuse large B-cell lymphoma in the context of the U.S. Intergroup trial comparing conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to rituximab-CHOP (R-CHOP) induction, with or without maintenance rituximab.
Experimental Design: Immunohistochemical staining of 197 paraffin-embedded biopsy specimens was scored by an independent panel of experts.
Results: The cyclin-dependent kinase inhibitor, p21, was expressed in 55% of cases examined. In a multivariable analysis adjusting for International Prognostic Index score and BCL2 status, p21 expression was a significant, independent, favorable predictive factor for failure-free survival (relative risk, 0.3; P = 0.001) and overall survival (relative risk, 0.3; P = 0.003) for patients treated with R-CHOP. Expression of p21 was not predictive of outcome for CHOP-treated patients.
Only p21-positive cases benefited from the addition of rituximab to CHOP. Among p21-positive patients, treatment with R-CHOP was associated with a higher failure-free survival rate at 5 years compared with CHOP (61% versus 24%; P = 0.01). In contrast, no significant differences were detected in failure-free survival according to treatment arm for p21-negative patients. Expression of p53, alone or in combination with p21, did not predict for outcome in univariable or multivariable analyses.
Conclusions: In this study, p21 protein expression emerged as an important independent predictor of a favorable clinical outcome when rituximab was added to CHOP therapy. These data suggest that rituximab-related effects on lymphoma survival pathways may be functionally linked to p21 activity. Clin Cancer Res; 16(8); 2435–42. ©2010 AACR.
A Novel Prognostic Model for Malignant Mesothelioma Incorporating Quantitative FDG-PET Imaging with Clinical Parameters
Authors: Nowak Anna K. , Francis Roslyn J. , Phillips Michael J. , Millward Michael J. , van der Schaaf Agatha A. , Boucek Jan , Musk Arthur W. , McCoy Melanie J. , Segal Amanda , Robins Peter , Byrne Michael J. 
Published: April 2010

Abstract
Purpose: Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease.
Experimental Design: Patients with malignant pleural mesothelioma underwent helical thoracoabdominal computed tomography and FDG-PET scans at baseline. Patients were treated as clinically indicated and followed for survival. FDG-PET variables derived included total glycolytic volume, a composite of tumor volume and glycolytic activity.
Results: Ninety-three patients were accrued from 2003 to 2006. Of 89 eligible assessable patients, 28 had undergone pleurodesis before enrolment. Seventeen patients remained alive at analysis; median survival is 15.4 months. On univariate analysis, significant prognostic factors were: total glycolytic volume on FDG-PET (P = 0.003), sarcomatoid histology (P &lt; 0.0005), weight loss (P = 0.031), computed tomography stage (P = 0.015), and European Organization for Research and Treatment of Cancer good prognostic score (P = 0.049). In patients with epithelioid or biphasic histology, baseline total glycolytic volume remained predictive of survival in patients with (P = 0.01) or without (P = 0.018) previous pleurodesis. In multivariate analysis, no variable other than histology contributed to the model in patients with sarcomatoid histology; total glycolytic volume and weight loss contributed to the models in patients with nonsarcomatoid histology. computed tomography–assessed tumor-node-metastasis stage did not contribute to the model. A nomogram, which incorporates quantitative PET parameters and pleurodesis into prognostic information, is presented.
Conclusions: Sarcomatoid histology remains the strongest prognostic factor. In patients with non sarcomatoid disease, volumetric FDG-PET parameters are more predictive of survival than tumor-node-metastasis staging, suggesting that tumor volume and glycolytic activity may be more important determinants of prognosis in malignant pleural mesothelioma than anatomic extent of disease. Clin Cancer Res; 16(8); 2409–17. ©2010 AACR.
Selective Cytotoxicity to HER2-Positive Tumor Cells by a Recombinant e23sFv-TD-tBID Protein Containing a Furin Cleavage Sequence
Authors: Wang Fang , Ren Jing , Qiu Xiu-Chun , Wang Li-Feng , Zhu Qing , Zhang Ying-Qi , Huan Yi , Meng Yan-Ling , Yao Li-Bo , Chen Si-Yi , Xu Yan-Ming , Yang An-Gang 
Published: April 2010

Abstract
Purpose: The HER2 antigen is a recognized target on breast cancer cells for immunotherapy. To overcome the immunogenicity and systemic toxicity of traditional immunotoxins, a novel human immunoproapoptotic molecule was developed and its antitumor activity was investigated.
Experimental Design: Recombinant e23sFv-TD-tBID, consisting of a single-chain anti-HER2 antibody fragment linked to a human active truncated Bid by a 10–amino acid residue furin cleavage sequence, was bacterially expressed. Purified e23sFv-TD-tBID was tested for binding, internalization, and cytotoxic activity in cell and for tumor localization and antitumor activity in athymic nude mice bearing established human tumor xenografts.
Results: e23sFv-TD-tBID selectively binds to HER2-positive cells and induces apoptotic cell death in vitro and in vivo. An investigation of its mechanism of action has revealed that e23sFv-TD-tBID was internalized on binding to the surface of HER2-positive tumor cells, proteolytically cleaved and transported directly to cytosol. The antitumor activity of e23sFv-TD-tBID was shown in a dose-dependent manner when injected i.p. into immunodeficient mice bearing human breast carcinomas. Moreover, this immunoproapoptotic protein, either given as a single dose or in combination with chemotherapy agents, significantly inhibited tumor growth without any observed toxic side effects on mice. Magnetic resonance imaging further showed the specific targeting and good penetration of tumors by e23sFv-TD-tBID in vivo. The therapeutic value of e23sFv-TD-tBID to human was shown by its cytotoxic effects on primary patient-derived breast tumor cells but not on endothelial cells.
Conclusion: These data suggest that recombinant e23sFv-TD-tBID has therapeutic potential for HER2-positive tumors and warrant further testing for clinical applications. Clin Cancer Res; 16(8); 2284–94. ©2010 AACR.
ERBB2 and TOP2A in Breast Cancer: A Comprehensive Analysis of Gene Amplification, RNA Levels, and Protein Expression and Their Influence on Prognosis and Prediction
Authors: Brase Jan C. , Schmidt Marcus , Fischbach Thomas , Sültmann Holger , Bojar Hans , Koelbl Heinz , Hellwig Birte , Rahnenführer Jörg , Hengstler Jan G. , Gehrmann Mathias C. 
Published: April 2010

AbstractPurpose: The prognostic and predictive relevance of epidermal growth factor receptor 2 (ERBB2) and topoisomerase II α (TOP2A) have long been a matter of debate. However, the correlation of DNA amplification, RNA levels, and protein expression and their prognostic role and association with anthracycline responses in node-negative breast cancer have not yet been evaluated.Experimental Design: We first analyzed TOP2A and ERBB2 at the levels of gene amplification, and RNA and protein expression, and studied their correlations. Additionally, TOP2A and ERBB2 were analyzed in 782 node-negative breast carcinomas in patients who did not receive systemic therapy and in 80 patients treated with epirubicin and cyclophosphamide (EC) prior to surgery.Results: TOP2A gene amplification did not correlate with protein expression (P = 0.283) and showed an association with gene expression with only borderline significance (P = 0.047). By contrast, TOP2A RNA levels correlated with protein expression (P &lt; 0.001). TOP2A gene expression was significantly associated with the metastasis-free interval (MFI; P &lt; 0.001) and was associated with complete remission in patients treated with EC (P = 0.002). In contrast to TOP2A, ERBB2 gene amplification correlated with RNA level (P &lt; 0.001) and protein expression (P &lt; 0.001). ERBB2 gene expression was associated with the MFI only in estrogen receptor–positive carcinomas, whereas ERBB2 protein expression (P = 0.032) was associated with MFI in the entire cohort.Conclusions: Overall, our study indicates that the TOP2A RNA level is a good prognostic marker and is also associated with a favorable response to anthracyclin-based therapy. By contrast, ESR1 was associated with poorer responses to anthracyclin-based therapy, whereas the association with ERBB2 RNA was not significant. Clin Cancer Res; 16(8); 2391–401. ©2010 AACR.
Development of a Functional Assay for Homologous Recombination Status in Primary Cultures of Epithelial Ovarian Tumor and Correlation with Sensitivity to Poly(ADP-Ribose) Polymerase Inhibitors
Authors: Mukhopadhyay Asima , Elattar Ahmed , Cerbinskaite Aiste , Wilkinson Sarah J. , Drew Yvette , Kyle Suzanne , Los Gerrit , Hostomsky Zdenek , Edmondson Richard J. , Curtin Nicola J. 
Published: April 2010

Abstract
Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors selectively target homologous recombination (HR)–defective cells and show good clinical activity in hereditary breast and ovarian cancer associated with BRCA1 or BRCA2 mutations. A high proportion (up to 50%) of sporadic epithelial ovarian cancers (EOC) could be deficient in HR due to genetic or epigenetic inactivation of BRCA1/BRCA2 or other HR genes. Therefore, there is a potential for extending the use of PARP inhibitors to these patients if HR status can be identified. We developed a functional assay of HR status in primary cultures of EOCs based on Rad51 focus formation that correlates well with sensitivity to the potent PARP inhibitor AG014699.
Experimental Design: Primary cultures were derived from ascitic fluid from patients with EOCs. HR status was investigated by γH2AX and Rad51 focus formation by immunofluorescence. Cytotoxicity to PARP inhibitors was tested by sulforhodamine B and survival assay.
Results: Twenty-five cultures were evaluated for HR status and cytotoxicity to PARP inhibitor. Following exposure to AG014699, there was an increase in Rad51 foci (HR competent) in 9 of 24 (36%) but no increase (HR deficient) in 16 of 24 (64%) cultures. Cytotoxicity was observed in 15 of 16 (93%) HR-deficient samples but not in 9 of 9 HR-competent samples following 24-hour exposure to 10 μmol/L AG014699.
Conclusion: HR status can be determined in primary cancer samples by Rad51 focus formation, and this correlates with in vitro response to PARP inhibition. Use of this assay as a biomarker now needs testing in the setting of a clinical trial. Clin Cancer Res; 16(8); 2344–51. ©2010 AACR.