bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topology of gene expression networks as revealed by data mining and modeling
Authors: Lukashin Alexander V. , Lukashev Matvey E. , Fuchs Rainer 
Published: October 2003

Abstract
Motivation: Interpretation of high-throughput gene expression profiling requires a knowledge of the design principles underlying the networks that sustain cellular machinery. Recently a novel approach based on the study of network topologies has been proposed. This methodology has proven to be useful for the analysis of a variety of biological systems, including metabolic networks, networks of protein–protein interactions, and gene networks that can be derived from gene expression data. In the present paper, we focus on several important issues related to the topology of gene expression networks that have not yet been fully studied.
Results: The networks derived from gene expression profiles for both time series experiments in yeast and perturbation experiments in cell lines are studied. We demonstrate that independent from the experimental organism (yeast versus cell lines) and the type of experiment (time courses versus perturbations) the extracted networks have similar topological characteristics suggesting together with the results of other common principles of the structural organization of biological networks. A novel computational model of network growth that reproduces the basic design principles of the observed networks is presented. Advantage of the model is that it provides a general mechanism to generate networks with different types of topology by a variation of a few parameters. We investigate the robustness of the network structure to random damages and to deliberate removal of the most important parts of the system and show a surprising tolerance of gene expression networks to both kinds of disturbance.
A fast layout algorithm for protein interaction networks
Authors: Han Kyungsook , Ju Byong-Hyon 
Published: October 2003

Abstract
Motivation: Graph drawing algorithms are often used for visualizing relational information, but a naive implementation of a graph drawing algorithm encounters real difficulties when drawing large-scale graphs such as protein interaction networks.
Results: We have developed a new, extremely fast layout algorithm for visualizing large-scale protein interaction networks in the three-dimensional space. The algorithm (1) first finds a layout of connected components of an entire network, (2) finds a global layout of nodes with respect to pivot nodes within a connected component and (3) refines the local layout of each connected component by first relocating midnodes with respect to their cutvertices and direct neighbors of the cutvertices and then by relocating all nodes with respect to their neighbors within distance 2. Advantages of this algorithm over classical graph drawing methods include: (1) it is an order of magnitude faster, (2) it can directly visualize data from protein interaction databases and (3) it provides several abstraction and comparison operations for effectively analyzing large-scale protein interaction networks.
Availability: http://wilab.inha.ac.kr/interviewer/
Learning to predict protein–protein interactions from protein sequences
Authors: Gomez Shawn M. , Noble William Stafford , Rzhetsky Andrey 
Published: October 2003

Abstract
In order to understand the molecular machinery of the cell, we need to know about the multitude of protein–protein interactions that allow the cell to function. High-throughput technologies provide some data about these interactions, but so far that data is fairly noisy. Therefore, computational techniques for predicting protein–protein interactions could be of significant value. One approach to predicting interactions in silico is to produce from first principles a detailed model of a candidate interaction. We take an alternative approach, employing a relatively simple model that learns dynamically from a large collection of data. In this work, we describe an attraction–repulsion model, in which the interaction between a pair of proteins is represented as the sum of attractive and repulsive forces associated with small, domain- or motif-sized features along the length of each protein. The model is discriminative, learning simultaneously from known interactions and from pairs of proteins that are known (or suspected) not to interact. The model is efficient to compute and scales well to very large collections of data. In a cross-validated comparison using known yeast interactions, the attraction–repulsion method performs better than several competing techniques.
Automatic discovery and classification of bioinformatics Web sources
Authors: Rocco Daniel , Critchlow Terence 
Published: October 2003

Abstract
Motivation: The World Wide Web provides an incredible resource to genomics researchers in the form of query access to distributed data sources—e.g. BLAST sequence homology search interfaces. The number of these autonomous sources and their rate of change outpaces the speed at which they can be manually classified, meaning that the available data is not being utilized to its full potential. Manually maintaining a wrapper library will not scale to accommodate the growth of genomics data sources on the Web, challenging us to produce an automated system that can find, classify and wrap new sources without constant human intervention. Previous research has not addressed the problem of automatically locating, classifying and integrating classes of bioinformatics data sources.
Results: This paper presents an overview of a system for finding classes of bioinformatics data sources and integrating them behind a unified interface. We describe our approach for automatic classification of new Web sources into relevance categories that eliminates the human effort required to maintain a current repository of sources. Our approach is based on a meta-data description of classes of interesting sources that describes the important features of an entire class of services without tying that description to any particular Web source. We examine the features of this format in the context of BLAST sources to show how it relates to Web sources that are being described. We then show how a description can be used to determine if an arbitrary Web source is an instance of the described service. To validate the effectiveness of this approach, we have constructed a prototype that correctly classifies approximately two-thirds of the BLAST sources we tested. We conclude with a discussion of these results, the factors that affect correct automatic classification and areas for future study.
Greedily building protein networks with confidence
Authors: Bader Joel S. 
Published: October 2003

Abstract
Motivation: With genome sequences complete for human and model organisms, it is essential to understand how individual genes and proteins are organized into biological networks. Much of the organization is revealed by proteomics experiments that now generate torrents of data. Extracting relevant complexes and pathways from high-throughput proteomics data sets has posed a challenge, however, and new methods to identify and extract networks are essential. We focus on the problem of building pathways starting from known proteins of interest.
Results: We have developed an efficient, greedy algorithm, SEEDY, that extracts biologically relevant biological networks from protein–protein interaction data, building out from selected seed proteins. The algorithm relies on our previous study establishing statistical confidence levels for interactions generated by two-hybrid screens and inferred from mass spectrometric identification of protein complexes. We demonstrate the ability to extract known yeast complexes from high-throughput protein interaction data with a tunable parameter that governs the trade-off between sensitivity and selectivity. DNA damage repair pathways are presented as a detailed example. We highlight the ability to join heterogeneous data sets, in this case protein–protein interactions and genetic interactions, and the appearance of cross-talk between pathways caused by re-use of shared components.
Significance and comparison: The significance of the SEEDY algorithm is that it is fast, running time O[(E + V) log V] for V proteins and E interactions, a single adjustable parameter controls the size of the pathways that are generated, and an associated P-value indicates the statistical confidence that the pathways are enriched for proteins with a coherent function. Previous approaches have focused on extracting sub-networks by identifying motifs enriched in known biological networks. SEEDY provides the complementary ability to perform a directed search based on proteins of interest.
Availability: SEEDY software (Perl source), data tables and confidence score models (R source) are freely available from the author.
Developmental influences on auditory perception in female zebra finches - is there a sensitive phase for song preference learning?
Authors: Riebel Katharina 
Published: October 2003

AbstractSong plays an important role in mate choice in oscine songbirds. Male advertising song is culturally transmitted resulting in individual- or population-specific song variants. Evidence is accumulating that female song preferences are influenced by those song variants they experienced when young, but the nature and timing of the acquisition process itself is still poorly understood. Song acquisition (as well as sexual imprinting) has been studied in more detail in zebra finches (Taeniopygia guttata) than in any other songbird species, making it timely to review the consequences of early exposure on female song perception in this species. The current literature provides substantial evidence not only for preference learning but also for exposure-dependent perceptual fine-tuning. Sensitivity for song preference learning changes over the course of development. Preference learning does not seem to occur earlier than 25 days of age (hence paralleling the time course for song acquisition in males), but a potential endpoint is currently less obvious. However, studies so far have focussed on the outcome rather than the process of learning, and thus have not aimed at delineating a sensitive phase. Early acquired song preferences seem highly stable regardless of additional experience, which suggests a self-terminating process as previously found for sexual imprinting. There are still obvious gaps in our understanding of the mechanisms underlying the process of song preference learning, but these seem worthwhile addressing, as the consequences for mate choice might differ dramatically depending on when and from whom learning takes place.
Adverse Prognostic Effect of Methylation in Colorectal Cancer Is Reversed by Microsatellite Instability
Authors: Ward Robyn Lynne , Cheong Kay , Ku Su-Lyn , Meagher Alan , O’Connor Terence , Hawkins Nicholas John 
Published: October 2003

Purpose: DNA methylation is an important biologic event in colorectal cancer and in some cases is associated with the development of microsatellite instability (MSI). In this study, we sought to determine the prognostic significance of DNA methylation, both in univariate analysis and in concert with other clinicopathologic factors known to influence outcome. Patients and Methods: Fresh tissue (625 cancers) was obtained from 605 individuals (age range, 29 to 99 years) undergoing curative surgery for colorectal cancer at one institution during a period of 8 years. Clinicopathologic details were recorded for all tumors, including stage, grade, type, vascular space invasion, and clinical follow-up to 5 years. Microsatellite status was assessed using standard markers. Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at methylated-in-tumor loci (MINT)1, MINT2, MINT12, and MINT31 loci were assessed by bisulfite-PCR. Results: Patients with microsatellite unstable tumors (12%) had better disease-specific survival than those with microsatellite stable (MSS) tumors (univariate analysis: hazard ratio [HR], 0.53; 95% CI, 0.27 to 1.0). Overall survival of individuals with MSS tumors was influenced by three independently significant factors: tumor stage (HR, 7.3; 95% CI, 5.1 to 10.4), heavy tumor methylation (HR, 2.1; 95% CI, 1.1 to 4.0), and vascular space invasion (HR, 1.9; 95% CI, 1.3 to 2.9). In MSS tumors, methylation at any single site was not independently predictive of survival. Neither methylation nor microsatellite status predicted a favorable response to chemotherapy. Conclusion: DNA methylation is associated with a worse outcome in colorectal cancer, but this adverse prognostic influence is lost in those methylated tumors showing MSI. The mechanisms of these events warrant additional investigation.
Randomized Trial of Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy Versus Systemic Chemotherapy and Palliative Surgery in Patients With Peritoneal Carcinomatosis of Colorectal Cancer
Authors: Verwaal Vic J. , van Ruth Serge , de Bree Eelco , van Slooten Gooike W. , van Tinteren Harm , Boot Henk , Zoetmulder Frans A.N. 
Published: October 2003

Purpose: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin.Patients and Methods: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival.Results: After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P = .032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P < .0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P < .0001).Conclusion: Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.
Dissemination of Information on Potentially Fatal Adverse Drug Reactions for Cancer Drugs From 2000 to 2002: First Results From the Research on Adverse Drug Events and Reports Project
Authors: Ladewski Lisa A. , Belknap Steven M. , Nebeker Jonathan R. , Sartor Oliver , Lyons E. Allison , Kuzel Timothy C. , Tallman Martin S. , Raisch Dennis W. , Auerbach Amy R. , Schumock Glen T. , Kwaan Hau C. , Bennett Charles L. 
Published: October 2003

Purpose: To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug–associated adverse drug reactions (ADRs) reported in the postmarketing setting. Methods: ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed. Results: Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period. Conclusion: Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.
Randomized Phase III Trial of Standard Timed Doxorubicin Plus Cisplatin Versus Circadian Timed Doxorubicin Plus Cisplatin in Stage III and IV or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study
Authors: Gallion Holly H. , Brunetto Virginia L. , Cibull Michael , Lentz Samuel S. , Reid Gary , Soper John T. , Burger Robert A. , Andersen Willie 
Published: October 2003

Purpose: To determine if circadian timed (CT) chemotherapy results in improved response, progression-free survival (PFS), overall survival (OS), and lower toxicity, when compared with standard timed (ST) chemotherapy. Materials and Methods: Eligibility criteria were stage III, IV, or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery; measurable disease; and no prior chemotherapy. Therapy was randomized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2, or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm. Cycles were repeated every 3 weeks to a maximum of eight cycles. Results: The ST arm included 169 patients, and the CT arm included 173 patients. The objective response rate (complete responses plus partial responses) was 46% in the ST group compared with 49% in the CT group (P = .26, one tail). Median PFS and OS were 6.5 and 11.2 months, respectively, in the ST group; and 5.9 and 13.2 months, respectively, in the CT group (PFS: P = .31; OS: P = .21, one tail). Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group, versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group. Grade 3 or 4 leukopenia occurred in 73% of patients in the ST arm and in 63% of patients in the CT arm. There were eight treatment-related deaths. Conclusion: In this trial, no significant benefit in terms of response rate, PFS or OS, or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma.
Early Molecular Response of Marrow Disease to Biologic Therapy Is Highly Prognostic in Neuroblastoma
Authors: Cheung Irene Y. , Lo Piccolo M. Serena , Kushner Brian H. , Cheung Nai-Kong V. 
Published: October 2003

Purpose: A promising treatment strategy for stage 4 neuroblastoma patients is the repeated application of anti-GD2 immunotherapy after activating myeloid effectors with granulocyte-macrophage colony-stimulating factor (GM-CSF). To use early marrow response as a prognostic marker is particularly relevant for patients not likely to benefit from this therapy. Patients and Methods: Eighty-six stage 4 neuroblastoma patients older than 1 year at diagnosis were classified in four clinical groups on protocol entry: complete remission or very good partial remission (n = 33), primary refractory (n = 33), secondary refractory (n = 10), and progressive disease (n = 10). Bone marrow samples collected before and following treatment were assayed for GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction. Response and survival analyses were performed on posttreatment samples before the third cycle at 1.8 months from protocol entry. Results: GD2 synthase mRNA was evident in pretreatment marrow samples of the four clinical groups (42%, 52%, 60%, and 80% of samples, respectively), with median transcript level of 10.0, 16.6, 26.5, and 87.2, respectively. This marker became negative following antibody plus GM-CSF in 77% of complete remission or very good partial remission, 45% of primary refractory, 25% of secondary refractory, and 0% of progressive disease group. Progression-free survival was statistically different between responder and nonresponder groups (P < .0001). Among patients with minimal residual disease, molecular responders had a significantly lower risk of disease progression at a median follow-up of 29.8 months (P = .0001). Conclusion: GD2 synthase mRNA is a sensitive response marker of neuroblastoma in the bone marrow. It is particularly useful for minimal residual disease evaluation and may potentially be useful as an early predictor of resistance to antibody plus GM-CSF immunotherapy.
Effects of loading and size on maximum power output and gait characteristics in geckos
Authors: Irschick Duncan J. , Vanhooydonck Bieke , Herrel Anthony , Andronescu Anemone 
Published: October 2003

SUMMARYStride length, stride frequency and power output are all factors influencing locomotor performance. Here, we first test whether mass-specific power output limits climbing performance in two species of geckos(Hemidactylus garnoti and Gekko gecko) by adding external loads to their bodies. We then test whether body size has a negative effect on mass-specific power output. Finally, we test whether loading affects kinematics in both gecko species. Lizards were induced to run vertically on a smooth wooden surface with loads of 0-200% of body mass (BM) in H. garnoti and 0-100% BM in G. gecko. For each stride, we calculated angular and linear kinematics (e.g. trunk angle, stride length),performance (maximum speed) and mean mass-specific power output per stride. The addition of increasingly large loads caused an initial increase in maximum mass-specific power output in both species, but for H. garnoti,mass-specific power output remained constant at higher loads (150% and 200%BM), even though maximum velocity declined. This result, in combination with the fact that stride frequency showed no evidence of leveling off as speed increased in either species, suggests that power limits maximum speed. In addition, the large gecko (G. gecko) produced significantly less power than the smaller H. garnoti, despite the fact that both species ran at similar speeds. This difference disappeared, however, when we recalculated power output based on higher maximum speeds for unloaded G. gecko moving vertically obtained by other researchers. Finally, the addition of external loads did not affect speed modulation in either species:both G. gecko and H. garnoti increase speed primarily by increasing stride frequency, regardless of loading condition. For a given speed, both species take shorter but more strides with heavier loads, but for a given load, G. gecko attains similar speeds to H. garnotiby taking longer but fewer strides.