bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and SNP-tolerant detection of complex variants and splicing in short reads
Authors: Wu Thomas D. , Nacu Serban 
Published: February 2010

Abstract
Motivation: Next-generation sequencing captures sequence differences in reads relative to a reference genome or transcriptome, including splicing events and complex variants involving multiple mismatches and long indels. We present computational methods for fast detection of complex variants and splicing in short reads, based on a successively constrained search process of merging and filtering position lists from a genomic index. Our methods are implemented in GSNAP (Genomic Short-read Nucleotide Alignment Program), which can align both single- and paired-end reads as short as 14 nt and of arbitrarily long length. It can detect short- and long-distance splicing, including interchromosomal splicing, in individual reads, using probabilistic models or a database of known splice sites. Our program also permits SNP-tolerant alignment to a reference space of all possible combinations of major and minor alleles, and can align reads from bisulfite-treated DNA for the study of methylation state.
Results: In comparison testing, GSNAP has speeds comparable to existing programs, especially in reads of ≥70 nt and is fastest in detecting complex variants with four or more mismatches or insertions of 1–9 nt and deletions of 1–30 nt. Although SNP tolerance does not increase alignment yield substantially, it affects alignment results in 7–8% of transcriptional reads, typically by revealing alternate genomic mappings for a read. Simulations of bisulfite-converted DNA show a decrease in identifying genomic positions uniquely in 6% of 36 nt reads and 3% of 70 nt reads.
Availability: Source code in C and utility programs in Perl are freely available for download as part of the GMAP package at http://share.gene.com/gmap.
Contact: twu@gene.com
Direct inter-subdomain interactions switch between the closed and open forms of the Hsp70 nucleotide-binding domain in the nucleotide-free state
Authors: Shida Meiri , Arakawa Akihiko , Ishii Ryohei , Kishishita Seiichiro , Takagi Tetsuo , Kukimoto-Niino Mutsuko , Sugano Sumio , Tanaka Akiko , Shirouzu Mikako , Yokoyama Shigeyuki 
Published: February 2010

The 70 kDa heat-shock proteins (Hsp70s) are highly conserved chaperones that are involved in several cellular processes, such as protein folding, disaggregation and translocation. In this study, the crystal structures of the human Hsp70 nucleotide-binding domain (NBD) fragment were determined in the nucleotide-free state and in complex with adenosine 5′-(β,γ-imido)triphosphate (AMPPNP). The structure of the nucleotide-free NBD fragment is similar to that of the AMPPNP-bound NBD fragment and is designated as the `closed form'. In the nucleotide-free NBD fragment the closed form is intrinsically supported through interactions between Tyr15, Lys56 and Glu268 which connect subdomains IA, IB and IIB at the centre of the protein. Interaction with the substrate-binding domain (SBD) of Hsp70 or the BAG domain of BAG1 impairs this subdomain connection and triggers the rotation of subdomain IIA around a hydrophobic helix from subdomain IA. The subdomain rotation is limited by Asp199 and Asp206 from subdomain IIA and clearly defines the open form of the NBD. The open form is further stabilized by a new interaction between Gly230 from subdomain IIB and Ser340 from subdomain IIA. The structure of the NBD in the nucleotide-free state is determined by switching of the inter-subdomain interactions.
Structure of the unbound form of HIV-1 subtype A protease: comparison with unbound forms of proteases from other HIV subtypes
Authors: Robbins Arthur H. , Coman Roxana M. , Bracho-Sanchez Edith , Fernandez Marty A. , Gilliland C. Taylor , Li Mi , Agbandje-McKenna Mavis , Wlodawer Alexander , Dunn Ben M. , McKenna Robert 
Published: February 2010

The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7 Å resolution and refined as a homodimer in the hexagonal space groupP61to anRcrystof 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations.
Rapid chain tracing of polypeptide backbones in electron-density maps
Authors: Terwilliger Thomas C. 
Published: February 2010

A method for the rapid tracing of polypeptide backbones has been developed. The method creates an approximate chain tracing that is useful for visual evaluation of whether a structure has been solved and for use in scoring the quality of electron-density maps. The essence of the method is to (i) sample candidate Cαpositions at spacings of approximately 0.6 Å along ridgelines of high electron density, (ii) list all possible nonapeptides that satisfy simple geometric and density criteria using these candidate Cαpositions, (iii) score the nonapeptides and choose the highest scoring ones, and (iv) find the longest chains that can be made by connecting nonamers. An indexing and storage scheme that allows a single calculation of most distances and density values is used to speed up the process. The method was applied to 42 density-modified electron-density maps at resolutions from 1.5 to 3.8 Å. A total of 21 428 residues in these maps were traced in 24 CPU min with an overall r.m.s.d. of 1.61 Å for Cαatoms compared with the known refined structures. The method appears to be suitable for rapid evaluation of electron-density map quality.
Structural insights into the assembly of the human and archaeal signal recognition particles
Authors: Wild Klemens , Bange Gert , Bozkurt Gunes , Segnitz Bernd , Hendricks Astrid , Sinning Irmgard 
Published: February 2010

The signal recognition particle (SRP) is a conserved ribonucleoprotein (RNP) complex that co-translationally targets membrane and secretory proteins to membranes. The assembly of the particle depends on the proper folding of the SRP RNA, which in mammalia and archaea involves an induced-fit mechanism within helices 6 and 8 in the S domain of SRP. The two helices are juxtaposed and clamped together upon binding of the SRP19 protein to their apices. In the current assembly paradigm, archaeal SRP19 causes the asymmetric loop of helix 8 to bulge out and expose the binding platform for the key player SRP54. Based on a heterologous archaeal SRP19–human SRP RNA structure, mammalian SRP19 was thought not to be able to induce this change, thus explaining the different requirements of SRP19 for SRP54 recruitment. In contrast, the crystal structures of a crenarchaeal and the all-human SRP19–SRP RNA binary complexes presented here show that the asymmetric loop is bulged out in both binary complexes. Differences in SRP assembly between mammalia and archaea are therefore independent of SRP19 and are based on differences in SRP RNA itself. A new SRP-assembly scheme is presented.
ScotlandsPlaces XML: bespoke XML or XML mapping?
Authors: Beamer Ashley , Gillick Mark 
Published: February 2010

PurposeThe purpose of this paper is to investigate web services (in the form of parameterised URLs), specifically in the context of the ScotlandsPlaces project. This involves cross‐domain querying, data retrieval and display via the development of a bespoke XML standard rather than existing XML formats and mapping between them.Design/methodology/approachIn looking at the different heritage domain datasets as well as the metadata formats used for storage and data exchange, the ScotlandsPlaces XML format is revealed as the most appropriate for this type of project. The nature of the project itself and the need for dynamic web services are in turn explored.FindingsIt was found that, due to the nature of the project, the combination of a bespoke ScotlandsPlaces XML format and a set of matching web services was the best choice in terms of the retrieval of different domain datasets, as well as the desired extensible nature of the project.Research limitations/implicationsIt may have proven useful to investigate the datasets of more ScotlandsPlaces partners, but as yet only a limited number of first phase partners' datasets could be studied, as the second phase of the project has yet to begin.Originality/valueRather than an information portal, the ScotlandsPlaces web site aggregates disparate types of record, whether site records, archival or otherwise, into a single web site and makes these records discoverable via geographical searching. Aggregated data are accessed through web service queries (using a bespoke XML format developed specifically for the project for data return) and allow partner organisations to add their datasets regardless of the organisational domain. The service also allows spatially referenced records to be plotted on to a geo‐browser via a KML file, which in turn lets users evaluate the results based on geographical location.
Developing a web tool for searching and viewing collections of high‐quality cultural images
Authors: Lazarinis Fotis 
Published: February 2010

PurposeSearching for information and viewing visual representations of products in e‐organisations is a common activity of the e‐visitors to these organisations. For example, in e‐museums, users are shown images or other visual information of the existing objects. The aim of this paper is to present a tool which supports the effective searching for images in e‐organisations. The tool also supports the effective presentation of high‐quality images with zooming facilities. The tool is used in searching for and viewing high‐resolution cultural images in order to test its usefulness.Design/methodology/approachInitially, the problems of finding and effectively viewing high‐quality images in e‐organisations are discussed. Then, a review of the literature on zoomable browsers, which discuss effective ways of depicting large quantities of visual data on small screens or in a fast mode, through the web, is presented. Concept‐based image retrieval and the image‐browsing modules of the proposed tool are described. Finally, the system is evaluated with the aid of real users in viewing high‐quality cultural images downloaded from the web. The opinions of the users are presented, along with other statistics, and future research plans are discussed.FindingsThe emphasis of the evaluation was on the zoomable image viewer of the presented web tool. The evaluation showed that the zooming viewer is easy to use and reduces significantly the data that need to be downloaded for viewing high‐quality images.Originality/valueThe integrated searching and viewing application could be used in e‐organisations for searching for and viewing detailed images of their products and exhibits. Further, the zoomable image browser could be used for viewing libraries of high‐quality image collections in a time‐ and network‐efficient mode.
The Bookshelf: digitisation and access to copyright items in Norway
Authors: Moe Skarstein Vigdis 
Published: February 2010

PurposeThe purpose of this paper is to provide an overview of the challenges faced in digitising copyright‐protected books and other materials within the National Library of Norway.Design/methodology/approachFollowing a description of Bokhylla, or The Bookshelf, the paper outlines the strategies adopted within the National Library of Norway for digitising a range of materials, including books.FindingsThe National Library of Norway has negotiated a contract with Kopinor, an organisation that represents rights‐holders from about 30 different organisations, and this will enable users to access some 50,000 copyright‐protected books within the next three years.Originality/valueCopyright presents challenges in any digitisation project. Norway has adopted a unique solution for enabling its citizens to gain digital access to materials deposited within the National Library.
Peer reference redefined: new uses for undergraduate students
Authors: Faix Allison I. , Bates Margaret H. , Hartman Lisa A. , Hughes Jennifer H. , Schacher Casey N. , Elliot Brooke J. , Woods Alexander D. 
Published: February 2010

PurposeThis paper aims to redefine the peer reference model – using student assistants to staff the reference desk – by expanding it to include upper‐level undergraduate students from various disciplines providing full reference service with minimal supervision as well as performing paraprofessional‐level duties.Design/methodology/approachSet within a backdrop of budget cuts, severe time and staffing limitations, and increasing demands for library services, the paper assesses the processes and results of implementing this new model of peer reference at a medium‐sized academic library.FindingsThe findings suggest that undergraduate students are not only capable but perhaps optimal at providing high‐quality reference service to their peers.Originality/valueThis paper redefines the peer reference model, using a case study carried out in a US university library.
Critically divided?
Authors: Tregear Angela , Dobson Suzanne , Brennan Mary , Kuznesof Sharron 
Published: February 2010

Purpose“Theory versus practice” and “rigour versus relevance” debates have long been a feature of the discipline of marketing, not least within the sub‐field of marketing education, where authors have increasingly called for the adoption of more critical approaches as a means to enhance undergraduate degrees. To date, however, little is actually known about how undergraduate programmes are perceived by those who deliver them. The aim of this research is to investigate educators' views of the primary purpose of undergraduate degrees, and their perceptions and experiences of critical approaches.Design/methodology/approachA series of 23 exploratory interviews was conducted, followed by a national survey of UK marketing educators. For the main phase of data analysis, multivariate techniques were employed.FindingsRespondents generally agreed that intellectual rigour is a priority in marketing education. However, significant differences in opinion were identified on the extent to which degrees actually provide this, the extent to which students should be treated as customers, and whether curricula should be driven by industry. In terms of critical approaches, the majority of staff rated such approaches as important to undergraduate programmes, and most had introduced at least one type in their own teaching. There were no significant differences in ratings and experiences of critical approaches between those respondents who emphasised industry relevance in marketing education and the rest.Originality/valueThe divergence of views revealed by the research raises important questions about how marketing is currently positioned to different stakeholders, and how the discipline may evolve in future.
High Court considers whether FSA disclosures are exempt from freedom of information requests
Authors: Gray Joanna 
Published: February 2010

PurposeThe purpose of this paper is to report and comment on the High Court ruling on whether Financial Services Authority (FSA) disclosures are exempt from freedom of information requests.Design/methodology/approachThe paper outlines the facts surrounding the case and comments on the decision.FindingsThe High Court allowed the FSA's appeal in respect of the Owen appeal and the second part of the Lewis appeal (that the names of the seven firms investigated by the FSA as a result of the mystery shopping should not be disclosed) but agreed with the Tribunal on the first part of the Lewis appeal, that the names of the firms subject to the mystery shopping exercise could be disclosed.Originality/valueThis appeal shows how two very differently motivated, yet equally well‐intentioned, regulatory regimes can come into conflict.
Portfolio optimisation and bootstrapping
Authors: Srivatsa Rahul , Smith Andrew , Lekander Jon 
Published: February 2010

PurposeThe purpose of this paper is to develop a more robust methodology for asset allocation for the property investment market which takes into account inherent valuation and data issues.Design/methodology/approachThe methodology applied is that of a bootstrap, borrowed from Carlstein, and is applied to an investment universe consisting of UK equities, gilts and property. The bootstrap selectively re‐samples the return time series by maintaining the economic cycle. The resulting return series is then used in the standard mean‐variance optimisation (MVO) on an unconstrained basis. Finally, a “sanity” test is applied on the correlation matrix to ensure that spurious instances do not skew the results.FindingsThe bootstrapped optimisation provides a range within which the portfolio weights can be manoeuvred instead of a static point under the standard MVO. It provides a more robust methodology for asset allocation and without giving any undue significance to one year of extreme result.Research limitations/implicationsThe current analysis is based on unconstrained portfolio optimisation, with a very limited investment universe. Additionally, by conforming with the MVO methodology, normality of asset returns is implicitly assumed, which is clearly not the case in the data used. Future work will also focus on an all‐property portfolio.Practical implicationsThe proposed methodology will prove to be useful for making asset allocation decisions, particularly in turbulent financial markets.Originality/valueThe paper focuses solely on bootstrapping with the IPD UK annual index and is particularly significant after one year of extremely poor performance of UK property. The results will be of use to fund managers and portfolio analysts.
Inhibition of ErbB2 by Herceptin reduces survivin expression via the ErbB2–β‐catenin/TCF4‐survivin pathway in ErbB2‐overexpressed breast cancer cells
Authors: Zhu Hongxia , Zhang Guo , Wang Yan , Xu Ninghong , He Shun , Zhang Wei , Chen Meigui , Liu Mei , Quan Lanping , Bai Jingfeng , Xu Ningzhi 
Published: February 2010

Overexpression of ErbB2 is associated with poor prognosis in breast cancer. Targeting of ErbB2 is a very common therapeutic strategy in ErbB2‐overexpressed breast cancer. Herceptin is the first approved and most widely used agent for ErbB2‐targeting therapy in breast cancer. Even though the clinical application has been performed for more than 10 years, the exact mechanism underlying how Herceptin exhibits its effects has not been fully elucidated. In this study, we found that Herceptin could inhibit the expression of survivin in ErbB2‐overexpressed cell lines. Overexpression of survivin could abrogate the inhibition of cell growth induced by Herceptin. Herceptin could reduce survivin expression at the transcriptional level. The β‐catenin/T‐cell factor (TCF) pathway played a very crucial role in this cascade. We found that Herceptin could reduce tyrosine phosphorylation levels of ErbB2 and β‐catenin. Herceptin treatment induced degradation of β‐catenin protein, resulting in reduced binding affinity of β‐catenin/TCF4 to the promoter region of survivin. When we cross‐mutated the TCF4 binding sites in the promoter region of survivin, the reduction of survivin promoter activity almost diminished. Taken together, we showed that Herceptin could inhibit survivin expression through the ErbB2–β‐catenin/TCF4‐survivin pathway in ErbB2‐overexpressed breast cancer cells. This indicates that there may be a new cascade axis from ErbB2 to survivin.(Cancer Sci 2010; 101: 1156–1162)
Overexpression of Necl‐5 correlates with unfavorable prognosis in patients with lung adenocarcinoma
Authors: Nakai Reiko , Maniwa Yoshimasa , Tanaka Yugo , Nishio Wataru , Yoshimura Masahiro , Okita Yutaka , Ohbayashi Chiho , Satoh Naoyuki , Ogita Hisakazu , Takai Yoshimi , Hayashi Yoshitake 
Published: February 2010

Nectin‐like molecule‐5 (Necl‐5) is an immunoglobulin (Ig)‐like molecule that is up‐regulated in many types of cancer cells. It was shown experimentally that Necl‐5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl‐5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl‐5. The relationship between expression of Necl‐5 and clinicopathological features was analyzed, and the influence of Necl‐5 expression on outcomes in these patients was assessed. A strong expression of Necl‐5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl‐5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease‐free survival rate in patients with positive Necl‐5 overexpression was significantly lower than that in patients with negative Necl‐5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl‐5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease‐free survival rate of the Necl‐5‐positive group was significantly lower than that of the Necl‐5‐negative group (P = 0.0192). These results indicate that Necl‐5 plays a role in mediating tumor cell invasion and that the overexpression of Necl‐5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma.(Cancer Sci 2010; 101: 1326–1330)
The effects of mild induced hypothermia on the myocardium: a systematic review
Authors: Kelly F. E. , Nolan J. P. 
Published: February 2010

SummaryMild induced hypothermia improves neurological outcome and reduces mortality among initially comatose survivors of out‐of‐hospital cardiac arrest. Similar pathological processes occur in the heart and the brain, namely ischaemia followed by reperfusion injury. Animal data indicate that mild induced hypothermia results in improved myocardial salvage, reduced infarct size, reduced left ventricular remodelling and better long‐term left ventricular function. Several small human studies suggest that infarct size may be reduced by mild induced hypothermia, although this has not reached significance in any human study to date. There are variable reports of harm to the myocardium caused by mild induced hypothermia, including reduced myocardial contractility and cardiac output, electrocardiographic changes and arrhythmias, especially bradycardia. These harmful effects are reversible with rewarming.