bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple Clinical Model Composed of ECG, Shock Index, and Arterial Blood Gas Analysis for Predicting Severe Pulmonary Embolism
Authors: Bircan Ahmet , Karadeniz Nuriye , Ozden Ahmet , Cakir Munire , Varol Ercan , Oyar Orhan , Ozaydin Mehmet
Published: December 2009

Background: Objective diagnosis of severe pulmonary embolism (PE) is obligatory because of its considerable mortality. Aim: To assess the abilities of electrocardiography (ECG) score (sECG) and the newly generated scoring system composed of the scores obtained from arterial blood gas (ABG) analysis and shock index (SI) in addition to sECG in predicting severe PE. Material and Methods: The degree of pulmonary vascular obstruction (sPVO) and the right ventricular dysfunction (RVD) were determined with spiral computed tomography (CT) in 53 consequent patients with PE. Twelve-lead ECG taken within a day of PE event and ABG values were evaluated according to ECG scoring system and original Geneva system, respectively. Results: The mean age of patients was 62.6 ± 13.4 years. Right ventricular dysfunction, sPVO ≥ 50%, hypoxemia, and SI were present in 34 (64.2%), 27 (50.9%), 50 (94.3%), and 22 (41.5%) patients, respectively. The mean sECG, 5.9 ± 5.1, was correlated with sPVO, maximum diameter of right ventricle (RV), and right ventricle to left ventricle (RV/LV) ratio (r = .385, r = .415, and r = .329, respectively). The mean newly generated score was 10.9 ± 5.5 and correlated with sPVO, maximum diameter of RV, and RV/LV ratio (r = .394, r = .483, and r = .393, respectively). Receiver operator characteristic (ROC) curve analyses revealed that sECG ≥ 3.5, s (ECG + SI) ≥ 4.5, and s (ECG + SI + ABG) ≥ 9.5 predict the severe PE patients with 70.6%, 61.8%, 58.8% sensitivities and 52.6%, 63.2%, 73.7% specificities, respectively. Conclusion: Adding the scores obtained from SI and ABG to the sECG enhances the specificity of sECG in predicting RVD (+) or severe PE patients, although a lesser degree decreasing in sensitivity may occur.
An Autoethnography: Music Therapy after Laser Eye Surgery
Authors: Lee Karen V.
Published: December 2009

The following autoethnography reveals the author’s physical struggle with being confined in bed after laser eye surgery. She reflects on living simultaneously in a culture of temptation and a culture of control. The challenge causes her to shift back and forth within her personal experience while listening to music being played at her home. At a deeper level, she finds inner strength to resist using her eyes as the music therapeutically addresses her social, physical, emotional, and cognitive needs. In the end, writing the autoethnography transforms her self-experience as it sheds light on how the power of music heals her body after surgery.
Current Concepts in Ablation of Atrial Fibrillation
Authors: Chikwe Joanna , Raikhelkar Jayashree , Filsoufi Farzan , Fischer Avi
Published: December 2009

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It occurs particularly frequently in cardiac surgical patients and is associated with significant excess mortality and morbidity. Pharmacological management of AF is relatively ineffective and associated with significant side effects and complications. Clinicians have therefore pursued more definitive treatment options, both catheter based and surgical, to treat patients with AF. Surgical techniques designed to cure AF have developed in parallel with an improved understanding of the pathophysiological processes underlying this condition. This review describes the rationale behind current surgical approaches to AF and summarizes the results achieved with current techniques.
PharmAD-ventures: A Feminist Analysis of the Pharmacological Imaginary of Alzheimer’s Disease
Authors: Åsberg Cecilia , Lum Jennifer
Published: December 2009

Alzheimer’s disease (AD) may be situated within a cultural landscape produced, in part, by demographics and the marketing strategies of an aggressive biopharmaceutical industry. The simultaneously corporeal and visual domain of advertisements for anti-AD drugs generates dynamic images of gender and embodiment, and it also lends itself to feminist interventions engaging with the images and ideas circulating around aging, medicine and the body. In this article, we investigate advertisements targeting medical practitioners treating patients with AD. Working within a methodological framework we identify as ‘feminist visual studies of technoscience’, we want to propel the discussion in the direction of a broader corpus of medical media. Through this limited exercise, we hope to make a scholarly contribution to the feminist community by critiquing some of the images emerging within popular/scientific media with regard to Alzheimer’s, a disease collectively imagined within an aging Western population.
Injecting, Infection, Illness: Abjection and Hepatitis C Stigma
Authors: Harris Magdalena
Published: December 2009

While social research has documented the prevalence and ill effects of hepatitis C related stigma, there has been little analysis of the ways in which this stigma is constituted. This article addresses this gap in the literature by providing a phenomenologically informed account of the ways in which societal attitudes and regulations draw from and feed back into corporeal processes and experiences of embodiment in the creation of hepatitis C related stigma. The case is made that three components are central to hepatitis C stigma: associations with illicit drug injecting, infectiousness and societal aversion to chronic illness. The article draws upon qualitative interviews with 40 people living with chronic hepatitis C in New Zealand and Australia, as well as the researcher’s embodied experience of living with the virus. The works of Julia Kristeva and Mary Douglas are utilized to provide an analysis that moves beyond acknowledgement of societal reinforcers of stigma, such as prohibitory drug laws, to address underlying notions of boundary crossing in the production of stigma and exclusionary practices.
Habit(us), Body Techniques and Body Callusing: An Ethnography of Mixed Martial Arts
Authors: Spencer Dale C.
Published: December 2009

This article explores the carnal dimensions of existence through ethnographic research in a mixed martial arts club. Mixed martial arts (MMA) is an emergent sport where competitors in a ring or cage utilize strikes (punches, kicks, elbows and knees) as well as submission techniques to defeat opponents. Through data gathered from in-depth interviews with MMA practitioners and participant observation in an MMA club, I elucidate the social processes that are integral to the production of an MMA fighter habitus. I examine how body techniques are learned and become attached to the identity of mixed martial arts fighters. Using Crossley’s concept of reflexive body techniques, I examine how MMA fighters engage in body callusing through use of reflexive body techniques thereby allowing them to withstand the rigors of the sport.
Carotid Artery Stenting in the Nation: The Influence of Hospital and Physician Volume on Outcomes
Authors: Vogel Todd R. , Dombrovskiy Viktor Y. , Graham Alan M.
Published: December 2009

Objectives: To assess national outcomes of carotid artery stenting (CAS) with respect to hospital and practitioner volume.

Methods: The 2005 to 2006 Nationwide Inpatient Sample (NIS) was used to assess CAS with respect to hospital volume, physician volume, and associated complications. Results: Eighteen thousand five hundred ninety-nine CAS interventions were identified. The top 25% was used to define high-volume hospitals (>60 CAS/2 years) and practitioners (>30 CAS/2 years). The stroke rate after CAS was significantly different between low- and high-volume hospitals (2.35% vs 1.78%, respectively; P = .0206). The stroke rate after CAS was also significantly different between low- and high-volume practitioners (2.19% vs 1.51%, P = .0243). Hospital resource use varied significantly between low- and high-volume hospitals (length of stay [LOS]: 1.64 ± 2.10 vs 1.45 ± 11.21, P = .0006; total charges: $32 261 ± 20 562 vs $30 131 ± 19 592, P = .0047) and practitioners (LOS: 1.70 ± 2.14 vs 1.36 ± 1.36; P < .0001; total charges: $33 762 ± 21 081 vs $23 957 ± 19 713; P < .0001). Conclusions: This analysis demonstrates that hospital and physician volume are associated with outcomes and utilization after CAS. High-volume hospitals and practitioners were associated with lower procedure stroke rates and decreased hospital resource utilization.
Review: Efficient Rehabilitation Trial Designs Using Disease Progress Modeling: A Pediatric Traumatic Brain Injury Example
Authors: Forsyth Rob , Thuy Vu  , Salorio Cynthia , Christensen James , Holford Nick
Published: December 2009

Background. The identification of possible treatment effects against a background of spontaneous recovery is a major challenge to the successful completion of randomized clinical trials (RCTs) in rehabilitation research. Conventional trial outcomes such as the differences between group means of an outcome measure at a fixed time point are inefficient to an extent that is a major problem, particularly for exploratory studies seeking preliminary evidence of efficacy. Objective . To quantitate gains in study power over conventional fixed-end-point designs by using parametric end points derived from the modeling of the time course of recovery after brain injury. Methods. Nonlinear mixed effects (NLME) modeling of the recovery trajectories of 103 children rehabilitating after traumatic brain injury (TBI) as reflected in serial WeeFIM scores was performed. Pseudoreplicate data sets were generated replicating the statistical characteristics of the original data set, and these formed the basis of clinical trial simulations to derive robust estimates of study power. Results. Parametric end points derived from modeling of recovery improve study power (and reduce necessary sample size) by up to 5 times in this example. Conclusions. Parametric end points derived from models of recovery trajectories offer an efficient alternative design for exploratory clinical studies of rehabilitation interventions.
CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain–engineered monoclonal antibody
Authors: Awan Farrukh T. , Lapalombella Rosa , Trotta Rossana , Butchar Jonathan P. , Yu Bo , Benson Don M. , Roda Julie M. , Cheney Carolyn , Mo Xiaokui , Lehman Amy , Jones Jeffrey , Flynn Joseph , Jarjoura David , Desjarlais John R. , Tridandapani Susheela , Caligiuri Michael A. , Muthusamy Natarajan , Byrd John C.
Published: December 2009

CD19 is a B cell–specific antigen expressed on chronic lymphocytic leukemia (CLL) cells but to date has not been effectively targeted with therapeutic monoclonal antibodies. XmAb5574 is a novel engineered anti-CD19 monoclonal antibody with a modified constant fragment (Fc)–domain designed to enhance binding of FcγRIIIa. Herein, we demonstrate that XmAb5574 mediates potent antibody-dependent cellular cytotoxicity (ADCC), modest direct cytotoxicity, and antibody-dependent cellular phagocytosis but not complement-mediated cytotoxicity against CLL cells. Interestingly, XmAb5574 mediates significantly higher ADCC compared with both the humanized anti-CD19 nonengineered antibody it is derived from and also rituximab, a therapeutic antibody widely used in the treatment of CLL. The XmAb5574-dependent ADCC is mediated by natural killer (NK) cells through a granzyme B–dependent mechanism. The NK cell–mediated cytolytic and secretory function with XmAb5574 compared with the nonengineered antibody is associated with enhanced NK-cell activation, interferon production, extracellular signal-regulated kinase phosphorylation downstream of Fcγ receptor, and no increased NK-cell apoptosis. Notably, enhanced NK cell–mediated ADCC with XmAb5574 was enhanced further by lenalidomide. These findings provide strong support for further clinical development of XmAb5574 as both a monotherapy and in combination with lenalidomide for the therapy of CLL and related CD19+ B-cell malignancies.
The Korean Bird Information System (KBIS) through open and public participation
Authors: Paik In-Hwan , Lim Jeongheui , Chun Byung-Sun , Jin Seon-Duck , Yu Jae-Pyoung , Lee Joon-Woo , Bhak Jong , Paek Woon-Kee
Published: December 2009

Background

The importance of biodiversity conservation has been increasing steadily due to its benefits to human beings. Recently, producing and managing biodiversity databases have become much easier because of the information technology (IT) advancement. This made the general public's participation in biodiversity conservation much more practical than ever. For example, an openfree web service can be devised for a wider spectrum of people to collaborate with each other for sharing biodiversity information. Bird migration is one such area of the collaboration. Korean migratory birds are usually traceable in the important routes of the East Asian-Australia Flyway (EAAF), and they play a key role as an environmental change indicator of the Earth. Therefore, the preservation of migratory birds requires an information system which involves a broader range of voluntary and interactive knowledge network to process bird information production, circulation, and dissemination.

Results

The Korean Bird Information System (KBIS) aims to construct a cooperative partnership domestically and internationally through the acquisition, management, and sharing of Korean bird information involving both expert and non-expert groups. KBIS has six goals: data standard, system linkage, data diversity, utilization, bird knowledge network, and statistics. The key features of KBIS are to provide a simple search, gallery (photographs), and community to lead the participation of numerous non-experts, especially amateur bird watchers. The function of real-time observation data submission through the internet has been accomplished. It also provides bird banding database, statistics, and taxon network for experts. Especially, the statistics part provides the user with easy understanding of ecological trends of species based on the time and region.

Conclusion

KBIS is a tool for the conservation and management of bird diversity and ecosystem that encourages users to participate by providing the openfree data access and real-time data input web-interface. It will enhance bird knowledge networking activities locally, nationally, and internationally. In addition, it provides opportunities to enhance the public awareness for the preservation of bird diversity and species information in relevant localities through the database construction and networking activities. It can be found at http://korbird.naris.go.kr.
The implementation of e-learning tools to enhance undergraduate bioinformatics teaching and learning: a case study in the National University of Singapore
Authors: Lim Shen Jean , Khan Asif Mohammad , De Silva Mark , Lim Kuan Siong , Hu Yongli , Tan Chay Hoon , Tan Tin Wee
Published: December 2009

Background

The rapid advancement of computer and information technology in recent years has resulted in the rise of e-learning technologies to enhance and complement traditional classroom teaching in many fields, including bioinformatics. This paper records the experience of implementing e-learning technology to support problem-based learning (PBL) in the teaching of two undergraduate bioinformatics classes in the National University of Singapore.

Results

Survey results further established the efficiency and suitability of e-learning tools to supplement PBL in bioinformatics education. 63.16% of year three bioinformatics students showed a positive response regarding the usefulness of the Learning Activity Management System (LAMS) e-learning tool in guiding the learning and discussion process involved in PBL and in enhancing the learning experience by breaking down PBL activities into a sequential workflow. On the other hand, 89.81% of year two bioinformatics students indicated that their revision process was positively impacted with the use of LAMS for guiding the learning process, while 60.19% agreed that the breakdown of activities into a sequential step-by-step workflow by LAMS enhances the learning experience

Conclusion

We show that e-learning tools are useful for supplementing PBL in bioinformatics education. The results suggest that it is feasible to develop and adopt e-learning tools to supplement a variety of instructional strategies in the future.
Protein subcellular localization prediction of eukaryotes using a knowledge-based approach
Authors: Lin Hsin-Nan , Chen Ching-Tai , Sung Ting-Yi , Ho Shinn-Ying , Hsu Wen-Lian
Published: December 2009

Background

The study of protein subcellular localization (PSL) is important for elucidating protein functions involved in various cellular processes. However, determining the localization sites of a protein through wet-lab experiments can be time-consuming and labor-intensive. Thus, computational approaches become highly desirable. Most of the PSL prediction systems are established for single-localized proteins. However, a significant number of eukaryotic proteins are known to be localized into multiple subcellular organelles. Many studies have shown that proteins may simultaneously locate or move between different cellular compartments and be involved in different biological processes with different roles.

Results

In this study, we propose a knowledge based method, called KnowPredsite, to predict the localization site(s) of both single-localized and multi-localized proteins. Based on the local similarity, we can identify the "related sequences" for prediction. We construct a knowledge base to record the possible sequence variations for protein sequences. When predicting the localization annotation of a query protein, we search against the knowledge base and used a scoring mechanism to determine the predicted sites. We downloaded the dataset from ngLOC, which consisted of ten distinct subcellular organelles from 1923 species, and performed ten-fold cross validation experiments to evaluate KnowPredsite's performance. The experiment results show that KnowPredsite achieves higher prediction accuracy than ngLOC and Blast-hit method. For single-localized proteins, the overall accuracy of KnowPredsite is 91.7%. For multi-localized proteins, the overall accuracy of KnowPredsite is 72.1%, which is significantly higher than that of ngLOC by 12.4%. Notably, half of the proteins in the dataset that cannot find any Blast hit sequence above a specified threshold can still be correctly predicted by KnowPredsite.

Conclusion

KnowPredsite demonstrates the power of identifying related sequences in the knowledge base. The experiment results show that even though the sequence similarity is low, the local similarity is effective for prediction. Experiment results show that KnowPredsite is a highly accurate prediction method for both single- and multi-localized proteins. It is worth-mentioning the prediction process of KnowPredsite is transparent and biologically interpretable and it shows a set of template sequences to generate the prediction result. The KnowPredsite prediction server is available at http://bio-cluster.iis.sinica.edu.tw/kbloc/.
MapNext: a software tool for spliced and unspliced alignments and SNP detection of short sequence reads
Authors: Bao Hua , Xiong Yuanyan , Guo Hui , Zhou Renchao , Lu Xuemei , Yang Zhen , Zhong Yang , Shi Suhua
Published: December 2009

Background

Next-generation sequencing technologies provide exciting avenues for studies of transcriptomics and population genomics. There is an increasing need to conduct spliced and unspliced alignments of short transcript reads onto a reference genome and estimate minor allele frequency from sequences of population samples.

Results

We have designed and implemented MapNext, a software tool for both spliced and unspliced alignments of short sequence reads onto reference sequences, and automated SNP detection using neighbourhood quality standards. MapNext provides four main analyses: (i) unspliced alignment and clustering of reads, (ii) spliced alignment of transcript reads over intron boundaries, (iii) SNP detection and estimation of minor allele frequency from population sequences, and (iv) storage of result data in a database to make it available for more flexible queries and for further analyses. The software tool has been tested using both simulated and real data.

Conclusion

MapNext is a comprehensive and powerful tool for both spliced and unspliced alignments of short reads and automated SNP detection from population sequences. The simplicity, flexibility and efficiency of MapNext makes it a valuable tool for transcriptomic and population genomic research.
MINER: exploratory analysis of gene interaction networks by machine learning from expression data
Authors: Kadupitige Sidath Randeni , Leung Kin Chun , Sellmeier Julia , Sivieng Jane , Catchpoole Daniel R , Bain Michael E , Gaëta Bruno A
Published: December 2009

Background

The reconstruction of gene regulatory networks from high-throughput "omics" data has become a major goal in the modelling of living systems. Numerous approaches have been proposed, most of which attempt only "one-shot" reconstruction of the whole network with no intervention from the user, or offer only simple correlation analysis to infer gene dependencies.

Results

We have developed MINER (Microarray Interactive Network Exploration and Representation), an application that combines multivariate non-linear tree learning of individual gene regulatory dependencies, visualisation of these dependencies as both trees and networks, and representation of known biological relationships based on common Gene Ontology annotations. MINER allows biologists to explore the dependencies influencing the expression of individual genes in a gene expression data set in the form of decision, model or regression trees, using their domain knowledge to guide the exploration and formulate hypotheses. Multiple trees can then be summarised in the form of a gene network diagram. MINER is being adopted by several of our collaborators and has already led to the discovery of a new significant regulatory relationship with subsequent experimental validation.

Conclusion

Unlike most gene regulatory network inference methods, MINER allows the user to start from genes of interest and build the network gene-by-gene, incorporating domain expertise in the process. This approach has been used successfully with RNA microarray data but is applicable to other quantitative data produced by high-throughput technologies such as proteomics and "next generation" DNA sequencing.
PutidaNET: Interactome database service and network analysis of Pseudomonas putida KT2440
Authors: Park Seong-Jin , Choi Jong-Soon , Kim Byoung-Chul , Jho Seong-Woong , Ryu Jea-Woon , Park Daeui , Lee Kyung-A , Bhak Jong , Kim Seung Il
Published: December 2009

Background

Pseudomonas putida KT2440 (P. putida KT2440) is a highly versatile saprophytic soil bacterium. It is a certified bio-safety host for transferring foreign genes. Therefore, the bacterium is used as a model organism for genetic and physiological studies and for the development of biotechnological applications. In order to provide a more systematic application of the organism, we have constructed a protein-protein interaction (PPI) network analysis system of P. putida KT2440.

Results

PutidaNET is a comprehensive interaction database and server of P. putida KT2440 which is generated from three protein-protein interaction (PPI) methods. We used PSIMAP (Protein Structural Interactome MAP), PEIMAP (Protein Experimental Interactome MAP), and Domain-domain interactions using iPfam. PutidaNET contains 3,254 proteins, and 82,019 possible interactions consisting of 61,011 (PSIMAP), 4,293 (PEIMAP), and 30,043 (iPfam) interaction pairs except for self interaction. Also, we performed a case study by integrating a protein interaction network and experimental 1-DE/MS-MS analysis data P. putida. We found that 1) major functional modules are involved in various metabolic pathways and ribosomes, and 2) existing PPI sub-networks that are specific to succinate or benzoate metabolism are not in the center as predicted.

Conclusion

We introduce the PutidaNET which provides predicted interaction partners and functional analyses such as physicochemical properties, KEGG pathway assignment, and Gene Ontology mapping of P. putida KT2440 PutidaNET is freely available at http://sequenceome.kobic.kr/PutidaNET.
Comparative study of protein-protein interaction observed in PolyGalacturonase-Inhibiting Proteins from Phaseolus vulgaris and Glycine max and PolyGalacturonase from Fusarium moniliforme
Authors: Maulik Aditi , Ghosh Hiren , Basu Soumalee
Published: December 2009

Background

The PolyGalacturonase-Inhibiting Proteins (PGIP) of plant cell wall limit the invasion of phytopathogenic organisms by interacting with the enzyme PolyGalacturonase (PG) they secrete to degrade pectin present in the cell walls. PGIPs from different or same plant differ in their inhibitory activity towards the same PG. PGIP2 from Phaseolus vulgaris (Pv) inhibits the PG from Fusarium moniliforme (Fm) although PGIP1, another member of the multigene family from the same plant sharing 99% sequence similarity, cannot. Interestingly, PGIP3 from Glycine max (Gm) which is a homologue of PGIP2 is capable of inhibiting the same PG although the extent of similarity is lower and is 88%. It therefore appears that subtle changes in the sequence of plant PGIPs give rise to different specificity for inhibiting pathogenic PGs and there exists no direct dependence of function on the extent of sequence similarity.

Results

Structural information for any PGIP-PG complex being absent, we resorted to molecular modelling to gain insight into the mechanism of recognition and discrimination of PGs by PGIPs. We have built homology models of Pv PGIP1 and Gm PGIP3 using the crystal structure of Pv PGIP2 (1OGQ) as template. These PGIPs were then docked individually to Fm PG to elucidate the characteristics of their interactions. The mode of binding for Pv PGIP1 to Fm PG considerably differs from the mode observed for Pv PGIP2-Fm PG complex, regardless of the high sequence similarity the two PGIPs share. Both Pv PGIP2 and Gm PGIP3 despite being relatively less similar, interact with residues of Fm PG that are known from mutational studies to constitute the active site of the enzyme. Pv PGIP1 tends to interact with residues not located at the active site of Fm PG. Looking into the electrostatic potential surface for individual PGIPs, it was evident that a portion of the interacting surface for Pv PGIP1 differs from the corresponding region of Pv PGIP2 or Gm PGIP3.

Conclusion

van der Waals and eletrostatic interactions play an active role in PGIPs for proper recognition and discrimination of PGs. Docking studies reveal that Pv PGIP2 and Gm PGIP3 interact with the residues constituting the active site of Fm PG with implications that the proteins bind/block Fm PG at its active site and thereby inhibit the enzyme.
A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins
Authors: Liu Yu-Cheng , Yang Meng-Han , Lin Win-Li , Huang Chien-Kang , Oyang Yen-Jen
Published: December 2009

Background

Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors for identifying structurally flexible regions in proteins. In this respect, there are two major categories of predictors. One category of predictors attempts to identify conformationally flexible regions through analysis of protein tertiary structures. Another category of predictors works completely based on analysis of the polypeptide sequences. As the availability of protein tertiary structures is generally limited, the design of predictors that work completely based on sequence information is crucial for advances of molecular biology research.

Results

In this article, we propose a novel approach to design a sequence-based predictor for identifying conformationally ambivalent regions in proteins. The novelty in the design stems from incorporating two classifiers based on two distinctive supervised learning algorithms that provide complementary prediction powers. Experimental results show that the overall performance delivered by the hybrid predictor proposed in this article is superior to the performance delivered by the existing predictors. Furthermore, the case study presented in this article demonstrates that the proposed hybrid predictor is capable of providing the biologists with valuable clues about the functional sites in a protein chain. The proposed hybrid predictor provides the users with two optional modes, namely, the high-sensitivity mode and the high-specificity mode. The experimental results with an independent testing data set show that the proposed hybrid predictor is capable of delivering sensitivity of 0.710 and specificity of 0.608 under the high-sensitivity mode, while delivering sensitivity of 0.451 and specificity of 0.787 under the high-specificity mode.

Conclusion

Though experimental results show that the hybrid approach designed to exploit the complementary prediction powers of distinctive supervised learning algorithms works more effectively than conventional approaches, there exists a large room for further improvement with respect to the achieved performance. In this respect, it is of interest to investigate the effects of exploiting additional physiochemical properties that are related to conformational ambivalence. Furthermore, it is of interest to investigate the effects of incorporating lately-developed machine learning approaches, e.g. the random forest design and the multi-stage design. As conformational transition plays a key role in carrying out several essential types of biological functions, the design of more advanced predictors for identifying conformationally ambivalent regions in proteins deserves our continuous attention.
Identification of cell cycle-related regulatory motifs using a kernel canonical correlation analysis
Authors: Rhee Je-Keun , Joung Je-Gun , Chang Jeong-Ho , Fei Zhangjun , Zhang Byoung-Tak
Published: December 2009

Background

Gene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the expression of their target genes in specific biological processes. Despite their importance, regulators involved in diverse biological processes still remain largely unrevealed. In the present study, we propose a kernel-based approach to efficiently identify core regulatory elements involved in specific biological processes using gene expression profiles.

Results

We developed a framework that can detect correlations between gene expression profiles and the upstream sequences on the basis of the kernel canonical correlation analysis (kernel CCA). Using a yeast cell cycle dataset, we demonstrated that upstream sequence patterns were closely related to gene expression profiles based on the canonical correlation scores obtained by measuring the correlation between them. Our results showed that the cell cycle-specific regulatory motifs could be found successfully based on the motif weights derived through kernel CCA. Furthermore, we identified co-regulatory motif pairs using the same framework.

Conclusion

Given expression profiles, our method was able to identify regulatory motifs involved in specific biological processes. The method could be applied to the elucidation of the unknown regulatory mechanisms associated with complex gene regulatory processes.
Alternative paths in HIV-1 targeted human signal transduction pathways
Authors: Balakrishnan Sivaraman , Tastan Oznur , Carbonell Jaime , Klein-Seetharaman Judith
Published: December 2009

Background

Human immunodeficiency virus-1 (HIV-1) has a minimal genome of only 9 genes, which encode 15 proteins. HIV-1 thus depends on the human host for virtually every aspect of its life cycle. The universal language of communication in biological systems, including between pathogen and host, is via signal transduction pathways. The fundamental units of these pathways are protein protein interactions. Understanding the functional significance of HIV-1, human interactions requires viewing them in the context of human signal transduction pathways.

Results

Integration of HIV-1, human interactions with known signal transduction pathways indicates that the majority of known human pathways have the potential to be effected through at least one interaction with an HIV-1 protein at some point during the HIV-1 life cycle. For each pathway, we define simple paths between start points (i.e. no edges going into a node) and end points (i.e. no edges leaving a node). We then identify the paths that pass through human proteins that interact with HIV-1 proteins. We supplement the combined map with functional information, including which proteins are known drug targets and which proteins contribute significantly to HIV-1 function as revealed by recent siRNA screens. We find that there are often alternative paths starting and ending at the same proteins but circumventing the intermediate steps disrupted by HIV-1.

Conclusion

A mapping of HIV-1, human interactions to human signal transduction pathways is presented here to link interactions with functions. We proposed a new way of analyzing the virus host interactions by identifying HIV-1 targets as well as alternative paths bypassing the HIV-1 targeted steps. This approach yields numerous experimentally testable hypotheses on how HIV-1 function may be compromised and human cellular function restored by pharmacological approaches. We are making the full set of pathway analysis results available to the community.
COMUS: Clinician-Oriented locus-specific MUtation detection and deposition System
Authors: Jho Sungwoong , Kim Byoung-Chul , Ghang Ho , Kim Ji-Han , Park Daeui , Kim Hak-Min , Jung Soo-young , Yoo Ki-young , Kim Hee-Jin , Lee Sunghoon , Bhak Jong
Published: December 2009

Background

A disease-causing mutation refers to a heritable genetic change that is associated with a specific phenotype (disease). The detection of a mutation from a patient's sample is critical for the diagnosis, treatment, and prognosis of the disease. There are numerous databases and applications with which to archive mutation data. However, none of them have been implemented with any automated bioinformatics tools for mutation detection and analysis starting from raw data materials from patients. We present a Locus Specific mutation DB (LSDB) construction system that supports both mutation detection and deposition in one package.

Results

COMUS (Clinician-Oriented locus specific MUtation detection and deposition System) is a mutation detection and deposition system for developing specific LSDBs. COMUS contains 1) a DNA sequence mutation analysis method for clinicians' mutation data identification and deposition and 2) a curation system for variation detection from clinicians' input data. To embody the COMUS system and to validate its clinical utility, we have chosen the disease hemophilia as a test database. A set of data files from bench experiments and clinical information from hemophilia patients were tested on the LSDB, KoHemGene http://www.kohemgene.org, which has proven to be a clinician-friendly interface for mutation detection and deposition.

Conclusion

COMUS is a bioinformatics system for detecting and depositing new mutations from patient DNA with a clinician-friendly interface. LSDBs made using COMUS will promote the clinical utility of LSDBs. COMUS is available at http://www.comus.info.
BioBarcode: a general DNA barcoding database and server platform for Asian biodiversity resources
Authors: Lim Jeongheui , Kim Sang-Yoon , Kim Sungmin , Eo Hae-Seok , Kim Chang-Bae , Paek Woon Kee , Kim Won , Bhak Jong
Published: December 2009

Background

DNA barcoding provides a rapid, accurate, and standardized method for species-level identification using short DNA sequences. Such a standardized identification method is useful for mapping all the species on Earth, particularly when DNA sequencing technology is cheaply available. There are many nations in Asia with many biodiversity resources that need to be mapped and registered in databases.

Results

We have built a general DNA barcode data processing system, BioBarcode, with open source software - which is a general purpose database and server. It uses mySQL RDBMS 5.0, BLAST2, and Apache httpd server. An exemplary database of BioBarcode has around 11,300 specimen entries (including GenBank data) and registers the biological species to map their genetic relationships. The BioBarcode database contains a chromatogram viewer which improves the performance in DNA sequence analyses.

Conclusion

Asia has a very high degree of biodiversity and the BioBarcode database server system aims to provide an efficient bioinformatics protocol that can be freely used by Asian researchers and research organizations interested in DNA barcoding. The BioBarcode promotes the rapid acquisition of biological species DNA sequence data that meet global standards by providing specialized services, and provides useful tools that will make barcoding cheaper and faster in the biodiversity community such as standardization, depository, management, and analysis of DNA barcode data. The system can be downloaded upon request, and an exemplary server has been constructed with which to build an Asian biodiversity systemhttp://www.asianbarcode.org.
Identification of membrane-type 1 matrix metalloproteinase tyrosine phosphorylation in association with neuroblastoma progression
Authors: Nyalendo Carine , Sartelet Hervé , Barrette Stéphane , Ohta Shigeru , Gingras Denis , Béliveau Richard
Published: December 2009

Background

Neuroblastoma is a pediatric tumor of neural crest cells that is clinically characterized by its variable evolution, from spontaneous regression to malignancy. Despite many advances in neuroblastoma research, 60% of neuroblastoma, which are essentially metastatic cases, are associated with poor clinical outcome due to the lack of effectiveness of current therapeutic strategies. Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), an enzyme involved in several steps in tumor progression, has previously been shown to be associated with poor clinical outcome for neuroblastoma. Based on our recent demonstration that MT1-MMP phosphorylation is involved in the growth of fibrosarcoma tumors, we examined the potential role of phosphorylated MT1-MMP in neuroblastoma progression.

Methods

Tyrosine phosphorylated MT1-MMP was immunostained on tissue microarray samples from 55 patients with neuroblastoma detected by mass screening (known to be predominantly associated with favourable outcome), and from 234 patients with standard diagnosed neuroblastoma. In addition, the effects of a non phosphorylable version of MT1-MMP on neuroblastoma cell migration and proliferation were investigated within three-dimensional collagen matrices.

Results

Although there is no correlation between the extent of tyrosine phosphorylation of MT1-MMP (pMT1-MMP) and MYCN amplification or clinical stage, we observed greater phosphorylation of pMT1-MMP in standard neuroblastoma, while it is less evident in neuroblastoma from mass screening samples (P = 0.0006) or in neuroblastoma samples from patients younger than one year (P = 0.0002). In vitro experiments showed that overexpression of a non-phosphorylable version of MT1-MMP reduced MT1-MMP-mediated neuroblastoma cell migration and proliferation within a three-dimensional type I collagen matrix, suggesting a role for the phosphorylated enzyme in the invasive properties of neuroblastoma cells.

Conclusion

Overall, these results suggest that tyrosine phosphorylated MT1-MMP plays an important role in neuroblastoma progression and that its expression is preferentially observed in tumor specimens from neuroblastoma patients showing poor clinical outcome.
Acupuncture for dry eye: a randomised controlled trial protocol
Authors: Kim Tae-Hun , Kim Jong-In , Shin Mi-Suk , Lee Myeong Soo , Choi Jun-Yong , Jung So-Yong , Kim Ae-Ran , Seol Jae-Uk , Choi Sun-Mi
Published: December 2009

Background

Dry eye is usually managed by conventional medical interventions such as artificial tears, anti-inflammatory drugs and surgical treatment. However, since dry eye is one of the most frequent ophthalmologic disorders, safer and more effective methods for its treatment are necessary, especially for vulnerable patients. Acupuncture has been widely used to treat patients with dry eye. Our aim is to evaluate the effectiveness and safety of acupuncture for this condition.

Methods/Design

A randomised, patient-assessor blinded, sham (non-acupuncture point, shallow acupuncture) controlled study was established. Participants allocated to verum acupuncture and sham acupuncture groups will be treated three times weekly for three weeks for a total of nine sessions per participant. Seventeen points (GV23; bilateral BL2, GB4, TE23, Ex1 (Taiyang), ST1 and GB20; and left SP3, LU9, LU10 and HT8 for men, right for women) have been selected for the verum acupuncture; for the sham acupuncture, points have been selected that do not coincide with a classical acupuncture point and that are located close to the verum points, except in the case of the rim of the eye. Ocular surface disease index, tear film breakup time, the Schirmer I test, medication quantification scale and general assessment of improvement will be used as outcome variables for evaluating the effectiveness of acupuncture. Safety will also be assessed at every visit. Primary and secondary outcomes will be assessed four weeks after screening. All statistical analyses will be performed using analysis of covariance.

Discussion

The results of this trial will be used as a basis for clarifying the efficacy of acupuncture for dry eye.

Trial registration

ClinicalTrials.gov NCT00969280.
LD-Spline: Mapping SNPs on genotyping platforms to genomic regions using patterns of linkage disequilibrium
Authors: Bush William S , Chen Guanhua , Torstenson Eric S , Ritchie Marylyn D
Published: December 2009

Background

Gene-centric analysis tools for genome-wide association study data are being developed both to annotate single locus statistics and to prioritize or group single nucleotide polymorphisms (SNPs) prior to analysis. These approaches require knowledge about the relationships between SNPs on a genotyping platform and genes in the human genome. SNPs in the genome can represent broader genomic regions via linkage disequilibrium (LD), and population-specific patterns of LD can be exploited to generate a data-driven map of SNPs to genes.

Methods

In this study, we implemented LD-Spline, a database routine that defines the genomic boundaries a particular SNP represents using linkage disequilibrium statistics from the International HapMap Project. We compared the LD-Spline haplotype block partitioning approach to that of the four gamete rule and the Gabriel et al. approach using simulated data; in addition, we processed two commonly used genome-wide association study platforms.

Results

We illustrate that LD-Spline performs comparably to the four-gamete rule and the Gabriel et al. approach; however as a SNP-centric approach LD-Spline has the added benefit of systematically identifying a genomic boundary for each SNP, where the global block partitioning approaches may falter due to sampling variation in LD statistics.

Conclusion

LD-Spline is an integrated database routine that quickly and effectively defines the genomic region marked by a SNP using linkage disequilibrium, with a SNP-centric block definition algorithm.
Non-imprinted allele-specific DNA methylation on human autosomes
Authors: Zhang Yingying , Rohde Christian , Reinhardt Richard , Voelcker-Rehage Claudia , Jeltsch Albert
Published: December 2009

Background

Differential DNA methylation between alleles is well established in imprinted genes and the X chromosomes in females but has rarely been reported at non-imprinted loci on autosomes.

Results

We studied DNA methylation of cytosine-guanine dinucleotide (CpG) islands on chromosome 21 in leukocytes from several healthy individuals and observed novel cases of pronounced differential methylation of alleles. Allele-specific methylation affected complete CpG islands with methylation differences between alleles of up to 85%. The methylation differences between alleles were strongly correlated with the genotypes, excluding a connection to imprinting. We show that allele-specific methylation can lead to allelic repression of the methylated gene copy. Based on our results, allele-specific methylation is likely to affect about 10% of all human genes and to contribute to allele-specific expression and monoallelic gene silencing. Therefore, allele-specific methylation represents an epigenetic pathway of how genetic polymorphisms may lead to phenotypic variability. In most cases, we observed that some, but not all, heterozygous individuals showed allele-specific methylation, suggesting that allele-specific methylation is the outcome of an epigenetic drift, the direction of which is determined by the genetic differences between the alleles. We could show that the tendency to acquire hypermethylation in one allele was inherited.

Conclusions

We observed that larger differences in methylation levels between individuals were often coupled to allele-specific methylation and genetic polymorphisms, suggesting that the inter-individual variability of DNA methylation is strongly influenced by genetic differences. Therefore, genetic differences must be taken into account in future comparative DNA methylation studies.
Seismic imaging of complex onshore structures by 2D elastic frequency-domain full-waveform inversion
Authors: Brossier Romain , Operto Stéphane , Virieux Jean
Published: December 2009

Quantitative imaging of the elastic properties of the subsurface at depth is essential for civil engineering applications and oil- and gas-reservoir characterization. A realistic synthetic example provides for an assessment of the potential and limits of 2D elastic full-waveform inversion (FWI) of wide-aperture seismic data for recovering high-resolution P- and S-wave velocity models of complex onshore structures. FWI of land data is challenging because of the increased nonlinearity introduced by free-surface effects such as the propagation of surface waves in the heterogeneous near-surface. Moreover, the short wavelengths of the shear wavefield require an accurate S-wave velocity starting model if low frequencies are unavailable in the data. We evaluated different multiscale strategies with the aim of mitigating the nonlinearities. Massively parallel full-waveform inversion was implemented in the frequency domain. The numerical optimization relies on a limited-memory quasi-Newton algorithm thatoutperforms the more classic preconditioned conjugate-gradient algorithm. The forward problem is based upon a discontinuous Galerkin (DG) method on triangular mesh, which allows accurate modeling of free-surface effects. Sequential inversions of increasing frequencies define the most natural level of hierarchy in multiscale imaging. In the case of land data involving surface waves, the regularization introduced by hierarchical frequency inversions is not enough for adequate convergence of the inversion. A second level of hierarchy implemented with complex-valued frequencies is necessary and provides convergence of the inversion toward acceptable P- and S-wave velocity models. Among the possible strategies for sampling frequencies in the inversion, successive inversions of slightly overlapping frequency groups is the most reliable when compared to the more standard sequential inversion of single frequencies. This suggests that simultaneous inversion of multiple frequencies is critical when considering complex wave phenomena.