bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated structure- and ligand-basedin silicoapproach to predict inhibition of cytochrome P450 2D6
Authors: Martiny Virginie Y. , Carbonell Pablo , Chevillard Florent , Moroy Gautier , Nicot Arnaud B. , Vayer Philippe , Villoutreix Bruno O. , Miteva Maria A. 
Published: August 2015

AbstractMotivation: Cytochrome P450 (CYP) is a superfamily of enzymes responsible for the metabolism of drugs, xenobiotics and endogenous compounds. CYP2D6 metabolizes about 30% of drugs and predicting potential CYP2D6 inhibition is important in early-stage drug discovery.Results: We developed an original in silico approach for the prediction of CYP2D6 inhibition combining the knowledge of the protein structure and its dynamic behavior in response to the binding of various ligands and machine learning modeling. This approach includes structural information for CYP2D6 based on the available crystal structures and molecular dynamic simulations (MD) that we performed to take into account conformational changes of the binding site. We performed modeling using three learning algorithms --support vector machine, RandomForest and NaiveBayesian --and we constructed combined models based on topological information of known CYP2D6 inhibitors and predicted binding energies computed by docking on both X-ray and MD protein conformations. In addition, we identified three MD-derived structures that are capable all together to better discriminate inhibitors and non-inhibitors compared with individual CYP2D6 conformations, thus ensuring complementary ligand profiles. Inhibition models based on classical molecular descriptors and predicted binding energies were able to predict CYP2D6 inhibition with an accuracy of 78% on the training set and 75% on the external validation set.Contact: maria.miteva@univ-paris-diderot.frSupplementary information: Supplementary data are available at Bioinformatics online.
Bayexer: an accurate and fast Bayesian demultiplexer for Illumina sequences
Authors: Yi Haisi , Li Zhe , Li Tao , Zhao Jindong 
Published: August 2015

Abstract
Summary: Demultiplexing is used after high-throughput sequencing to in silico assign reads to the samples of origin based on the sequenced reads of the indices. Existing demultiplexing tools based on the similarity between the read index and the reference index sequences may fail to provide satisfactory results on low-quality datasets. We developed Bayexer, a Bayesian demultiplexing algorithm for Illumina sequencers. Bayexer uses the information extracted directly from the contaminant sequences of the targeting reads as the training dataset for a naïve Bayes classifier to assign reads. According to our evaluation, Bayexer provides higher capability, accuracy and speed on various real datasets than other tools.
Availability and implementation : Bayexer is implemented in Perl and freely available at https://github.com/HaisiYi/Bayexer.
Contact: litao@ihb.ac.cn or lizhe@ibcas.ac.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Wedderburn and the Theory of Labour Law: Building on Kahn-Freund
Authors: Dukes Ruth 
Published: August 2015

Abstract
This paper aims to assess the nature and significance of Lord Wedderburn’s contribution to the elaboration of a theory of labour law. Noting the extent to which Wedderburn was influenced, in this respect as in others, by the work of Otto Kahn-Freund, it focuses on the question of whether Wedderburn ever developed a theory of labour law that was clearly distinguishable from Kahn-Freund’s. Were there significant differences in the two scholars’ expositions of abstentionism, or collective laissez-faire? Through a close reading of Wedderburn’s work, it is suggested that Wedderburn was a strong proponent of the principle of collective laissez-fare, in his early as well as his later writing. In the changed political context of the 1980s and 1990s, he undertook the important task of seeking to update or restate the principle as an expression of social-democratic values in the field of work and working relationships.
The Hero’s Journey: Lord Wedderburn and the ‘Political Constitution’ of Labour Law
Authors: Bogg Alan 
Published: August 2015

Abstract
For much of the twentieth century, a functionalist style of scholarship emerged as a critical and dissenting tradition in British constitutional thought. Many of its animating concerns were expressed in J. A. G. Griffith’s famous lecture, ‘The Political Constitution’. This article situates Lord Wedderburn’s work on collective labour law within the broader tradition of political constitutionalism at the London School of Economics. Lord Wedderburn’s intellectual journey in labour law was concerned with the political nature of legal discourse, and the emancipatory potential of fundamental rights discourse as a way of achieving democratic freedoms for working people. The article examines the shifts in Wedderburn’s attitude towards the human rights paradigm, in the light of his passionate commitment to the primacy of politics in the sphere of labour law. In so doing, it concludes with an affirmation of Lord Wedderburn’s remarkable intellectual legacy in framing the virtues and limitations of a ‘political constitution’ for working people.
Data integration of structured and unstructured sources for assigning clinical codes to patient stays
Authors: Scheurwegs Elyne , Luyckx Kim , Luyten Léon , Daelemans Walter , Van den Bulcke Tim 
Published: August 2015

AbstractObjective Enormous amounts of healthcare data are becoming increasingly accessible through the large-scale adoption of electronic health records. In this work, structured and unstructured (textual) data are combined to assign clinical diagnostic and procedural codes (specifically ICD-9-CM) to patient stays. We investigate whether integrating these heterogeneous data types improves prediction strength compared to using the data types in isolation.Methods Two separate data integration approaches were evaluated. Early data integration combines features of several sources within a single model, and late data integration learns a separate model per data source and combines these predictions with a meta-learner. This is evaluated on data sources and clinical codes from a broad set of medical specialties.Results When compared with the best individual prediction source, late data integration leads to improvements in predictive power (eg, overall F-measure increased from 30.6% to 38.3% for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes), while early data integration is less consistent. The predictive strength strongly differs between medical specialties, both for ICD-9-CM diagnostic and procedural codes.Discussion Structured data provides complementary information to unstructured data (and vice versa) for predicting ICD-9-CM codes. This can be captured most effectively by the proposed late data integration approach.Conclusions We demonstrated that models using multiple electronic health record data sources systematically outperform models using data sources in isolation in the task of predicting ICD-9-CM codes over a broad range of medical specialties.
Are there differences in health information exchange by health system type?
Authors: Opoku-Agyeman William , Menachemi Nir 
Published: August 2015

Background:
Despite the potential of health information exchange (HIE) to improve safety and reduce cost, hospitals have been slow to adopt HIE with only 30% of U.S. hospitals doing so in 2012.

Purpose:
The aim of this study was to explore the relationship between different health system types and how they engage in HIE.

Methods:
Data on health system types and engagement in HIE activity were combined with secondary hospital characteristics. Ordinal logistic regression analyses were used to examine the relationship between a scale measuring the level of HIE engagement and health system type controlling for hospital and market characteristics.

Results:
Data from 1552 hospitals were available for analyses. Overall, hospital in a health system of any kind exchanged more patient data elements (e.g., patient demographics, clinical summaries, laboratory results, medication history, and radiology report) compared with stand-alone hospitals (3.82 vs. 1.80, p < .001). Overall, 62.2% of hospitals were part of a health system, and among system hospitals, 125 (8.0%) were in centralized health systems, 75 (4.8%) were in centralized physician/insurance health system, 284 (18.3%) were in moderately centralized health system, 391 (25.2%) were in decentralized health system, and 91 (5.9%) were in independent health system. In regression analyses, hospitals belonging to a health system were more likely to exchange patient health data with other hospitals in the same system (OR = 3.94, p < .001) but not with hospitals outside their system (OR = 1.89, p = .445). Across health system types, there was no significant difference in the exchange of patient health data.

Practice Implications:
Hospital engagement in HIE is associated with health system membership. These findings will assist hospital leaders and managers to better understand how the structure and nature of their system may influence what their individual hospital can and cannot do in their decision to engage in HIE and other decisions that support the overall system objectives.
HER2 Gene Amplification by Fluorescence In Situ Hybridization (FISH) Compared With Immunohistochemistry (IHC) in 122 Equivocal Gastric Cancer Cases
Authors: Liu Xiaoyan , Wang Xiaoling , Wang Bo , Ren Guoping , Ding Wei 
Published: August 2015

Objective:
To determine the frequency of HER2/neu amplification and the relationship between HER2/neu expression and clinicopathologic features in gastric cancers scored immunohistochemistry (IHC) 2+.

Methods:
A total of 122 gastric cancer cases scored IHC 2+ were retrospectively analyzed for HER2 amplification by fluorescence in situ hybridization (FISH). The correlation between HER2/neu expression and clinicopathologic features was analyzed.

Results:

HER2/neu gene was amplified in 17 out of the 122 gastric cancer samples. The concordance rate between IHC and FISH was 13.9%. HER2/neu status was correlated with the age of patients (P<0.05). Polysomy of CEP17 was demonstrated in 46 cases, 11 of which (23.91%) were amplified for HER2/neu. Within the subgroups, a correlation between CEP17 polysomy and the depth of invasion was observed (P<0.05).

Conclusions:
The results highlight the necessity of FISH test for further categorization when gastric cancer cases are scored 2+ by IHC. The value of HER2/neu for a potential role as a negative prognostic factor in the equivocal gastric cancer cases is limited.
Fitness-valley crossing with generalized parent-offspring transmission
Authors: Osmond M.M. , Otto S.P. 
Published: August 2015

AbstractSimple and ubiquitous gene interactions create rugged fitness landscapes composed of coadapted gene complexes separated by “valleys” of low fitness. Crossing such fitness valleys allows a population to escape suboptimal local fitness peaks to become better adapted. This is the premise of Sewall Wright’s shifting balance process. Here we generalize the theory of fitness-valley crossing in the two-locus, bi-allelic case by allowing bias in parent-offspring transmission. This generalization extends the existing mathematical framework to genetic systems with segregation distortion and uniparental inheritance. Our results are also flexible enough to provide insight into shifts between alternate stable states in cultural systems with “transmission valleys”. Using a semi-deterministic analysis and a stochastic diffusion approximation, we focus on the limiting step in valley crossing: the first appearance of the genotype on the new fitness peak whose lineage will eventually fix. We then apply our results to specific cases of segregation distortion, uniparental inheritance, and cultural transmission. Segregation distortion favouring mutant alleles facilitates crossing most when recombination and mutation are rare, i.e., scenarios where crossing is otherwise unlikely. Interactions with more mutable genes (e.g., uniparental inherited cytoplasmic elements) substantially reduce crossing times. Despite component traits being passed on poorly in the previous cultural background, small advantages in the transmission of a new combination of cultural traits can greatly facilitate a cultural transition. While peak shifts are unlikely under many of the common assumptions of population genetic theory, relaxing some of these assumptions can promote fitness-valley crossing.
Genome wide estimates of mutation rates and spectrum inSchizosaccharomyces pombeindicate CpG sites are highly mutagenic despite the absence of DNA methylation
Authors: Behringer Megan G. , Hall David W. 
Published: August 2015

ABSTRACTWe accumulated mutations for 1952 generations in 79 initially identical, haploid lines of the fission yeastSchizosaccharomyces pombe and then performed whole-genome sequencing to determine the mutation rates and spectrum. We captured 696 spontaneous mutations across the 79 mutation accumulation lines. We compared the mutation spectrum and rate to another model ascomycetous yeast, the budding yeastSaccharomyces cerevisiae. While the two organisms are approximately 600 million years diverged from each other, they share similar life histories, genome size and genomic G/C content. We found thatSc. pombeandS. cerevisiaehave similar mutation rates, contrary to what was expected givenSc. pombe’s smaller reported effective population size.Sc. pombe’s also exhibits a strong insertion bias in comparison toS. cerevisiae,. Intriguingly, we observed an increased mutation rate at cytosine nucleotides, specifically CpG nucleotides, which is also seen inS. cerevisiae. However, the absence of methylation inSc. pombeand the pattern of mutation at these sites, primarily C→ A as opposed to C→T, strongly suggest that the increased mutation rate is not caused by deamination of methylated cytosines. This result implies that the high mutability of CpG dinucleotides in other species may be caused in part by an additional mechanism than methylation.
Experimenting with dialogic mentoring: a new model
Authors: Nahmad-Williams Lindy , Taylor Carol A 
Published: August 2015

Purpose– The purpose of this paper is to explore mentoring as a dialogic practice in relation to three themes: identity, fear of being judged and respect. It develops Bokenko and Gantt’s (2000) concept of dialogic mentoring to propose a new theorisation of mentoring as a relational, embodied, spatial, affective and ethical practice.Design/methodology/approach– The paper reports on a mentoring project that took place in a UK University which was seeking to enhance its research culture. This project used an innovative methodological approach in which mentor and mentee wrote and shared diary entries as means of building more effective and constructive mentoring experiences, and as a vehicle for reflexively analysing the mentoring process.Findings– The project outcomes were: first, a deepened appreciation and reflexive evaluation of the role played by diaries and writing in the enactment of dialogic mentoring; second, the development of a theoretical framework to enhance understanding of dialogic mentoring and third, the generation of a dialogic mentoring model encompassing multiple dimensions of the process.Practical implications– The paper provides insights to support methodological innovation in mentoring practice; it links mentoring practice with theory development to enhance mentor and mentee collaboration and reflexivity; it offers an example of good mentoring practice that could be scaled up within educational institutions wishing to enhance their research culture.Originality/value– The paper offers, first, a reflexive account of a methodologically innovative mentoring practice to enhance mentoring; and second, it proposes a new theorisation and model of dialogic mentoring practices.
The dynamics of favela justice; identity, legitimacy and legality
Authors: Bagnall David 
Published: August 2015

Purpose
– The purpose of this paper is to consider and evaluate three models of favela governance structure to appreciate the full extent of the complexity of legislature faced by favela residents and to thereby determine whether any concrete notion of justice can exist within the favela.

Design/methodology/approach
– The paper discusses the relative utilities Donna M. Goldstein’s parallel state theory, Enrique Desmond Arias’ model of state-gang mutual penetration and John Rapley’s notion of neo-medievalism through a process of setting them up in dialogue with one another.

Findings
– The paper finds that the picture of favela governance that emerges through the discussion of the varying theories is one of a delicate equilibrium that depends on a constant process of negotiation and renegotiation and that it is only within this discursive space that any meaningful notion of favela justice can emerge.

Originality/value
– The dialogic aspect of the paper creates a new space, between theories, from which a more nuanced notion of the modern favela, and the subtleties of state-gang relations therein, is able to develop.
Towards a common identity? The harmonisation of identity theft laws
Authors: Clough Jonathan 
Published: August 2015

Purpose– The purpose of this paper is to consider potential criminal law responses to the global challenge of “identity crime”. In particular, it focuses on a specific offence of “identity theft”. It begins with a discussion of the meaning of “identity” in the context of modern transactions, before defining “identity crime” and related terms. Legal responses are then considered before turning to the importance of harmonisation. The transnational nature of modern identity crimes makes it essential that law enforcement agencies not only have suitable offences at their disposal but also the frameworks to facilitate international cooperation.Design/methodology/approach– Given the increasingly transnational and organized nature of modern identity crime, this paper adopts a comparative approach. It draws upon provisions from Australia, Canada, the UK and the USA. It also looks at responses to identity crime at the regional and international level.Findings– Although there is currently no international instrument which specifically and comprehensively addresses identity theft, it is argued that there is an urgent need for further international discussion as to the desirability and form of identity theft provisions. While international agreement may not be reached, such discussions are important in assisting countries to develop appropriate legal frameworks and capacity to address the modern fraud environment.Originality/value– It is hoped that this paper will contribute to, and facilitate, important ongoing discussions as to the most effective ways in which to tackle identity crime at the national and international levels.
Association between having a CA(SA) as CEO and accruals quality
Authors: Mey Elizabeth , de Klerk Marna 
Published: August 2015

Purpose
– The purpose of this paper is to examine whether Chartered Accountants South Africa (CAs(SA)) as Chief Executive Officers (CEOs) have an association with accruals quality.

Design/methodology/approach
– The theoretical base of this paper is the link between accounting expertise and accruals quality. The sample consists of 812 observations of Johannesburg Stock Exchange (JSE)-listed firms between 2010 and 2013. The association is tested by regressing the CA(SA) as CEO interest variable and control variables on accruals quality, using three metrics of abnormal accruals.

Findings
– The overall results suggest that less accruals management and estimation error is present when the CEO is a CA(SA).

Originality/value
– This is the first study to test the association between having a CEO with a professional accounting qualification, such as CA(SA), and accruals quality. The findings will be of interest to shareholders and top executives when evaluating the appointment of a CEO.
Effectiveness of innovation protection mechanisms in Malaysian high-tech sector
Authors: Naqshbandi M.Muzamil , Kaur Sharan 
Published: August 2015

Purpose– The purpose of this paper is to empirically investigate the effectiveness of innovation protection mechanisms in four high-tech industries in Malaysia.Design/methodology/approach– A questionnaire survey is administered to 339 managers working in four Malaysian high-tech industries.Findings– The authors find that in most industries, patents are considered as the most effective innovation protection mechanism, while lead time is considered as least effective. In firms with private and foreign ownerships, patents and in firms categorized as “others” “moving quickly down the learning curve” are considered as the most effective protection mechanisms. It also emerges that “being first to market (lead time)” is considered as the least effective protection mechanism under all ownership structures. Further, young and middle-aged firms report patents, while old firms report secrecy as the most effective innovation protection mechanisms.Research limitations/implications– This paper restricted analysis to the high-tech sector in Malaysia, and thus, the findings are not generalizable to other industries. Second, this paper took into consideration only four innovation protection mechanisms. The authors suggest that future research should investigate the issue at hand in other industries and consider other innovation protection mechanisms to have a holistic view of how Malaysian firms view different innovation protection mechanisms.Practical implications– In addition to providing inputs for policy-making, the results of this paper are expected to help practitioners in deciding on the right kind of innovation protection mechanisms for their innovations based on their industry, ownership structure and firm age.Originality/value– This paper is the first of its kind conducted in the Malaysian high-tech sector and as such is expected to help policy-makers to design and implement effectively innovation protection policies.
Low-cost closed-loop control of a 3D printer gantry
Authors: Weiss Benjamin , Storti Duane W. , Ganter Mark A. 
Published: August 2015

Purpose
– The purpose of this paper is to explore the improvements in speed and precision achievable using straightforward closed-loop control for the gantry motion in additive manufacturing machines. The authors designed and built an economically viable demonstration system to quantify the performance improvement.

Design/methodology/approach
– The authors develop and evaluate a low-cost closed-loop controller for the X and Y axes of an entry-level three-dimensional (3D) printer. The system developed captures and compensates for the dynamics of the motor and the belt-driven stage and detects mechanical errors, such as skipped motor steps.

Findings
– The system produces path-following precision improvements of 40 and 75 per cent for two different sample trajectories. Correcting for skipped steps increases reliability and allows for more aggressive tuning of motion parameters; time savings of up to 25 per cent are seen by doubling acceleration rate.

Research limitations/implications
– The system presented provides an appropriate platform for further investigation into more complex, application-specific controllers and inclusion of more details of the printer dynamics that could produce still greater improvements in speed and accuracy.

Practical implications
– The performance, low cost (40 USD/axis) and applicability to the majority of sub-2000USD 3D printer designs make this work of practical significance.

Originality/value
– The CNC machining industry has for many years used similar approaches, but application to 3D printers has not been explored in the literature. This paper demonstrates the value of even a simple controller applicable to almost any 3D printer, while maintaining cost-effectiveness of the solution in a competitive market.