bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Interpretation of Genetic Variants Using Deep Learning Predicts Impact on Epigenome
Authors: Hoffman Gabriel E. , Schadt Eric E. , Roussos Panos 
Published: August 2018

ABSTRACTIdentifying causal variants underling disease risk and adoption of personalized medicine are currently limited by the challenge of interpreting the functional consequences of genetic variants. Predicting the functional effects of disease-associated protein-coding variants is increasingly routine. Yet the vast majority of risk variants are non-coding, and predicting the functional consequence and prioritizing variants for functional validation remains a major challenge. Here we develop a deep learning model to accurately predict locus-specific signals from four epigenetic assays using only DNA sequence as input. Given the predicted epigenetic signal from DNA sequence for the reference and alternative alleles at a given locus, we generate a score of the predicted epigenetic consequences for 438 million variants. These impact scores are assay-specific, are predictive of allele-specific transcription factor binding and are enriched for variants associated with gene expression and disease risk. Nucleotide-level functional consequence scores for non-coding variants can refine the mechanism of known causal variants, identify novel risk variants and prioritize downstream experiments.
Pre-acetylation in the presence of Asf1 alters Rtt019-Vps75 selectivity
Authors: Cote Joy M. , Kuo Yin-Ming , Henry Ryan A. , Scherman Hataichanok , Andrews Andrew J. 
Published: August 2018

ABSTRACTAcetylation of histones plays a critical role in maintaining the epigenetic state of the eukaryotic cell. One such acetylation site critical for DNA damage repair is H3K56ac. In Saccharomyces cerevisiae, H3K56ac is thought to be driven mainly by Rtt109, a lysine acetyltransferase (KAT) that associates with the histone chaperones Vps75 and Asf1. Both of these chaperones can increase the specificity of histone acetylation by Rtt109, but neither alter the selectivity. It has been shown that histones extracted from cells (Drosophila), presumably containing pre-acetylated histones, can incorporate higher amounts of H3K56ac relative to recombinant non-acetylated histones. We hypothesized that histone pre-acetylation and histone chaperones could function together to drive acetylation of H3K56. In the present study, we test this hypothesis using a series of singly acetylated histones to determine the impact of crosstalk on enzyme selectivity. Our data suggest that crosstalk between acetylation sites plays a major role in altering the selectivity of Rtt109-Vps75 and that the histone chaperone Asf1 mediates this crosstalk. Specifically, we show that H3K14ac/H4 functions with Asf1 to drive H3K56ac by Rtt109-Vps75. We identified an acidic patch in Asf1 that mediates this cross-talk and show that mutations to this region can alter the Asf1 mediated crosstalk that changes Rtt109-Vps75 selectivity. These data explain the genetic link between Gcn5, which acetylates H3K14 and Rtt109. More broadly these data demonstrate that acetylation sites can dictate site selectivity even in the absence of a bromodomain and helps to explain the limited complexity that has been observed of the histone post-translational modifications patterns by global proteomic studies.
Receptor Mediated Delivery of Cas9-Nanobody Induces Cisplatin Synthetic Dose Sensitivity
Authors: Roche Philip J. R , Gytz Heidi , Hussain Faiz , Liang Yingke , Laursen Nick Stub , Andersen Kasper R. , Nagar Bhushan , Akavia Uri David 
Published: August 2018

AbstractThe CRISPR/Cas9 system has shown great potential for precisely editing genomic DNA sequences by introducing site-specific DNA cuts that are subsequently repaired by the cell. However, delivery of the CRISPR ribonucleoprotein remains an understudied area and hinders realizing the full potential of the system. We prepared Cas9 ribonucleoprotein complexes chemically conjugated to the 7D12 nanobody and demonstrate receptor-mediated transfection of Cas9 into A549 non-small-cell lung cancer cells via binding to the epithelial growth factor receptor for subsequent cell internalization. We further show that transfection with a Cas9 ribonucleoprotein targeting the BRCA2 gene results in an enhanced sensitivity to the chemotherapeutic drug Cisplatin, and thereby induces a synthetic dose lethality in A549 cells.
Reinforcement corrosion research based on the linear polarization resistance method for coral aggregate seawater concrete in a marine environment
Authors: Da Bo , Yu Hongfa , Ma Haiyan , Wu Zhangyu 
Published: August 2018

Purpose
This paper aims to reduce the cost, limit the time and increase raw material source availability, coral aggregate seawater concrete (CASC) composed of coral, coral sand, seawater and cement can be widely used for the construction of ports, levees, airports and roads to achieve practical engineering values. However, the naturally porous coral structure and abundant Cl− in the seawater and coral lead to extremely severe reinforcement corrosion for CASC. It is well known that Cl− is the main cause of reinforcement corrosion in the marine environment. Therefore, it is necessary to research the reinforcement corrosion of CASC in the marine environment.

Design/methodology/approach
In this study, linear polarization resistance was adopted to test the linear polarization curves of reinforcement in CASC with different exposure times. Ecorr, Rp, Icorr and Vcorr were calculated according to the weak electrochemical polarization theory and Stern–Geary formula. The effects of concrete cover thickness, exposure time, reinforcement types and inhibitor on reinforcement corrosion in CASC were analysed. The reinforcement corrosion degradation rule was determined, which provided theoretical support for the durability improvement, security assessment, service life prediction and service quality control of CASC structures in marine islands and reef engineering.

Findings
The corrosion resistance was enhanced with increased concrete cover thickness, and the concrete cover thickness for organic new coated steel should be at least 5.5 cm to reduce the reinforcement corrosion risks in CASC structures. The corrosion resistance of different types of reinforcements followed the rule: 2205 duplex stainless steel > 316 stainless steel > organic new coated steel > zinc-chromium coated steel > common steel. In the early exposure stage, the anti-corrosion effectiveness of the calcium nitrate inhibitor (CN) was superior to that for the amino alcohol inhibitor (AA). With the extension of exposure time, the decreasing rate of anticorrosion effectiveness of CN was higher than that of AA.

Originality/value
Reinforcement corrosion of CASC in a marine environment was studied. Concrete cover thickness, exposure time, reinforcement type and inhibitor influenced the reinforcement corrosion were investigated. New technique of reinforcement anti-corrosion in marine engineering was proposed. Possible applications of CASC in marine engineering structures were suggested.
Modeling the operation of synchronized supply chains under a collaborative structure
Authors: Lopez-Campos Monica , Cannella Salvatore , Miranda Pablo A. , Stegmaier Raul 
Published: August 2018

Purpose
The purpose of this paper is to propose and model collaboration and information exchange enabler strategies, designed to accomplish significant improvements in supply chain (SC) performance. Some of these improvements to the SC include the reduction of the bullwhip effect and increased customer and SC partner benefits. The authors propose a fully collaborative replenishment model. The study details the information flow required to implement new SC collaboration strategies, clarifying a specific strategy for information sharing involving inventory levels (on hand, in process, etc.), orders and demand forecast.

Design/methodology/approach
The authors suggest the adoption of business process modelling (BPM) methodology, aimed at identifying which information should be shared by SC partners, in order to create fully collaborative strategies.

Findings
The features of BPM allow for the effortless integration of the modelled information collaboration strategies into a general network information system, creating a flexible structure that can be quickly and even automatically adapted to new conditions.

Research limitations/implications
In this paper, a serial SC has been analysed, but enterprises also commonly manage more complex kind of chains. Chains composed of more than one member in the same echelon, divergent chains, convergent chains, network chains are all different configurations that require their own algorithm. The authors use the order up to policy, but there are other policies that can be considered to extend the scope of the model.

Practical implications
BPM, specifically through Unified Modelling Language (UML) and Business Process Modelling Notation standards, represents a suitable technique to develop and implement new SC collaboration practices, serving as a communication link between managers and software developers.

Social implications
The expected results of this work imply the proposal of a reference model for collaborative supply chain (CSC) organisations, contributing to the enhancement of value creation for the whole CSC.

Originality/value
The aim of this paper is to clarify the information-sharing algorithm required to implement a collaborative structure for an SC. This algorithm is expressed using the BPM technique, specifically UML and Business Process Model and Notation standards.
Capital structure decisions: What Spanish CFOs think
Authors: de Andrés Pablo , de la Fuente Gabriel , San Martin Pablo 
Published: August 2018

Purpose
The way business practice adjusts to the models proposed by financial theory has been under moderate yet constant scrutiny from the academic world. The purpose of this paper is to contribute to this line of research by showing CFOs’ perceptions of Spanish companies with regard to their capital structure decisions.

Design/Methodology
The empirical approach is examined using information gathered through a survey answered by 140 CFOs of Spanish companies during 2011. Results are obtained from mean difference tests and ordered probit estimations.

Findings
The results of the paper show that managers attach importance to establishing and monitoring a target debt ratio and the capacity to maintain additional debt in order to provide financial flexibility. In addition, CFOs prefer internal financing to external, using debt when internal funds do not allow investments to be funded.

Originality/Value
On the whole, the results of this research show that trade-off and pecking order theories are not alternative views of the same problem, but represent complementary approaches of how companies define their capital structures.
Implementation of a strategic planning process oriented towards promoting business process management (BPM) at a clinical research centre (CRC)
Authors: Rentes Victor Cattani , de Pádua Silvia Inês Dallavalle , Coelho Eduardo Barbosa , Cintra Monica Akissue de Camargo Teixeira , Ilana Gabriela Gimenez Faustino , Rozenfeld Henrique 
Published: August 2018

Purpose
This work explores the potential benefits of aligning the strategic planning process with a BPM program in a clinical research center (CRC). The purpose of this paper is to define a process for executing strategic planning oriented towards the promotion of a BPM program.

Design/methodology/approach
The method applied is action research. This allowed the solution of a practical problem and at the same time the proposition of a new approach to promote BPM in alignment with strategy, which was synthesized in the model presented.

Findings
The analysis and structuring of the strategic planning process, with the assessment of the as-is situation, were adequate as a preparation step for the first cycle of a BPM program in the CRC. Based on lessons learned along the research project, a model was proposed for the strategic planning process oriented towards promoting BPM.

Research limitations/implications
The model was conceived from a single application at a CRC, through a cycle of action research. This is one of the limitations of this work. The model was not yet sufficiently tested in other contexts. This represents opportunities for future research.

Practical implications
The evaluation step in the action research cycle revealed that the organization in focus was satisfied with the results. New management practices in the organizations in focus were implemented as a result of this work.

Originality/value
Process improvement initiatives are a novelty in the CRC context, and this work may serve as a reference for CRC managers seeking to improve overall performance. The proposed model in this work indicates that a BPM program should start with strategic planning. An initial assessment of the as-is situation of the organization in focus was performed based on the analysis of the undesirable effects in the organization’s management practices, using a technique of the Theory of Constraints. The use of this technique facilitated the identification of solutions to the root causes identified in the assessment. The level of the assessment was deeper in comparison to results obtained with traditional tools used in strategic planning processes. The assessment supports the definition of actions oriented to solving the majority of the management dysfunctions of the organization in focus.
Translating customer needs into project decisions: identifying knowledge brokers in project networks
Authors: Waheed Zehra 
Published: August 2018

Purpose
It is essential for projects to fulfil a wide spectrum of customer expectations including social, psychological, technological, and physical ones. The purpose of this paper is to identify roles within project networks that act as transmitters and linkers of this important knowledge, thereby resulting in appropriate and timely on-ground decision-making.

Design/methodology/approach
Qualitative case analysis coupled with social network analysis (SNA) is used to map project actors and identify key knowledge brokers within a complex co-location project. The project network comprised 91 actors from a range of project partners from public and private sectors.

Findings
The research identifies key knowledge brokers where selection appears to reflect their “heavyweight” stature, high social capital, technical expertise, and personality. The research recommends early identification of brokers from within and outside the parent organization/s.

Research limitations/implications
The research covers a single, inductive, and interpretive study of a co-location project involving mature project organizations. Wider generalizability of findings to less mature organizations or those operating in vastly different sectors may be limited.

Practical implications
This study contributes to the existing body of literature on knowledge brokerage in projects and assists project managers in identifying and developing relevant brokers.

Originality/value
The study provides further evidence behind the argument that customer needs are translated into appropriate project decisions through key knowledge brokers.
Exploring the BIM and lean synergies in the Istanbul Grand Airport construction project
Authors: Koseoglu Ozan , Sakin Mehmet , Arayici Yusuf 
Published: August 2018

Purpose
The purpose of this paper is to develop a solid understanding of how integrated building information modeling (BIM) is implemented in a mega project such as the (Istanbul Grand Airport IGA) construction project, which is the main case study in the research methodology.

Design/methodology/approach
The paper examines and identifies the lean efficiency gains achieved in the IGA project and highlights the synergies between BIM and lean concepts based on the facts and figures from the case study analysis. In complex projects, there is a vital need for a comprehensive approach that would enable successful managing of design and construction information via accurate modeling, collaboration and integration throughout the project lifecycles covering various disciplines.

Findings
The research findings in the paper make a significant impact in understanding the strategic perception for BIM as a new way of working methodology for the construction industry in Turkey, since the IGA project has become not only a key learning hub for the Turkish construction industry, but also a global landmark for digital construction and project delivery. In addition it proves the mutual synergies between BIM and lean practices.

Originality/value
The IGA project is a mega-scale airport construction project with features beyond building industry challenges, and it should be designed and constructed with tight deadlines and budgets and be operated afterwards in an effective and efficient way. Can lean and BIM help for timely and on-budget completion of the project and could they support the management of the airport facility after handover? The paper also discusses the lean and BIM implementation in the project in relation to the BIM Level 3 requirements.
From feeding-back to feeding-forward: managerial feedback as a trigger of change in SMEs
Authors: Psychogios Alexandros , Blakcori Feim , Szamosi Leslie , O’Regan Nicholas 
Published: August 2018

PurposeThe purpose of this paper is to explore and theorize the process of managerial feedback in relation to change in small and medium enterprises (SMEs).Design/methodology/approachThis research embraces a qualitative methodology in the context of manufacturing SMEs. Drawing on 30 in-depth interviews, and observations conducted with various managers in six SMEs operating in three countries, it is argued that managers benefit more by using daily, ongoing, feedback as a trigger of change in their organizations.FindingsThe findings suggest that there is an overall view that managers appear to be reluctant to change existing processes using formalized feedback mechanisms, which runs counter-intuitive to the literature. In contrast, informal methods of feedback work better in enhancing organizational change. Moreover, another two features of feedback enhance this process, namely, benefits oriented and confidence oriented. As such, this study contributes to existing knowledge and practice by proposing a three-fold form of feedback through which managers expand their perspectives of feedback from feeding-back to feeding-forward thereby enhancing the opportunities of triggering change.Research limitations/implicationsFeedback should merely be considered as a dynamic and socially constructed managerial practice. A practice where actors not only exchange information and share knowledge, but also act, react and interact with each other as they constantly rethinking the change process. The proposed aspect of feedback emphasizes knowledge therapeutically and in combination with the dialogical discourse (practical illustration) that increases the odds for capturing change as a natural, rather than exceptional.Practical implicationsPractitioners, as such, may wish to consider the terminology used when it comes to studying change and its implementation in a crisis context. Using deformalized managerial feedback mechanisms to tackle a formal phenomenon like “change” could help avoid employees perceiving a negative connotation, causing resistance or confusion and feeling threatened. Therefore, the authors suggest that practitioners, during development initiatives on modernizing or altering organizational processes, consider replacing the term “change” as a formal concept.Originality/valueIt is an investigation from an exploratory perspective in studying and understanding the causes, factors and modalities that trigger managerial feedback toward organizational change in manufacturing SMEs.
Discriminatory Value of the Ascending Aorta Diameter in Suspected Acute Type A Aortic Dissection
Authors: Mark Dustin G. , Davis Justin A. , Hung Yun‐Yi , Vinson David R. 
Published: August 2018

AbstractObjectiveThe objective was to determine if ascending aorta (AscAo) diameters measured by noncontrast computed tomography (CT) allow for meaningful discrimination between patients with and without type A aortic dissection (TAAD), ideally with 100% sensitivity.MethodsThis study was a retrospective analysis of cases of TAAD, as well as controls, undergoing evaluation for TAAD with CT aortography, presenting to 21 emergency departments within an integrated health system between 2007 and 2015. AscAo diameters were determined using axial noncontrast CT images at the level of the right main pulmonary artery by two readers. AscAo diameters were additionally normalized for age, sex, and body surface area (assessed by a Z‐score, which is the number of standard deviations between the observed and expected AscAo diameters). Overall model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Comparative discrimination was assessed using both the change in AUC (∆AUC) and the continuous net reclassification index (NRI).ResultsA total of 230 cases of TAAD and 325 controls were included in the study. The median ages for cases and controls were 65 and 62 years, and the median AscAo diameters were 50 and 35 mm, respectively. The raw and normalized AscAo diameters demonstrated similarly excellent discrimination (AUCs of 0.96 vs. 0.97, respectively; ∆AUC = 0.01, p = 0.09) and an NRI of 0.30 (95% confidence interval [CI] = 0.13–0.47), both indicating small incremental improvements in classification with the use of the normalized AscAo measures. A raw AscAo diameter of 34 mm and a normalized Z‐score of 1.84 both yielded 100% sensitivity for TAAD, with respective specificities of 35% (95% CI = 29.6%–40.2%) and 67% (95% CI = 61.7%–72.2%).ConclusionsNearly all patients with TAAD appear to have enlarged AscAo diameters as measured by noncontrast CT, whereas most patients with suspected but absent TAAD have relatively normal AscAo diameters. Both raw and normalized AscAo measures provided relatively comparable discriminatory value. If validated, these data may be useful in adjudicating risk among patients with suspected TAAD in whom a criterion standard test is unavailable, nondiagnostic, or contraindicated.