bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of SHP2 phosphatase inhibition in cancers with nucleotide-cycling oncogenic RAS, RAS-GTP dependent oncogenic BRAF and NF1 loss
Authors: Nichols Robert J. , Haderk Franziska , Stahlhut Carlos , Schulze Christopher J. , Hemmati Golzar , Wildes David , Tzitzilonis Christos , Mordec Kasia , Marquez Abby , Romero Jason , Hsieh Daphne , Kiss Gert , Koltun Elena S. , Gill Adrian L. , Singh Mallika , Goldsmith Mark A. , Smith Jacqueline A. M. , Bivona Trever G. 
Published: September 2017

AbstractOncogenic alterations in the RAS-RAF-MEK-ERK pathway, including mutant forms of KRAS, BRAF, and loss of the tumor suppressor and RAS GTPase-activating protein (GAP) NF1, drive the growth of a wide spectrum of human cancers. While BRAF and MEK inhibitors are effective in many patients with oncogenic BRAF V600E, there are no effective targeted therapies for individuals with cancers driven by other pathway alterations, including oncogenic KRAS, non-V600E BRAF, and NF1 loss. Here, we show that targeting the PTPN11/SHP2 phosphatase with a novel small molecule allosteric inhibitor is effective against cancers bearing nucleotide-cycling oncogenic RAS (e.g. KRAS G12C), RAS-GTP dependent oncogenic BRAF (e.g. class 3 BRAF mutants), or NF1 loss in multiple preclinical models in vitro and in vivo. SHP2 inhibition suppressed the levels of RAS-GTP and phosphorylated ERK in these models and induced growth inhibition. Expression of a constitutively active mutant of the RAS guanine nucleotide exchange factor (GEF) SOS1 rescued cells from the effects of SHP2 inhibition, suggesting that SHP2 blockade decreases oncogenic RAS-RAF-MEK-ERK signaling by disrupting SOS1-mediated RAS-GTP loading. Our findings illuminate a critical function for SHP2 in promoting oncogenic RAS activation and downstream signaling in cancers with nucleotide-cycling oncogenic RAS, RAS-GTP dependent oncogenic BRAF, and NF1 loss. SHP2 inhibition thus represents a rational, biomarker-driven therapeutic strategy to be tested in patients with cancers of diverse origins bearing these oncogenic drivers and for which current treatments are largely ineffective.
Data quality of Whole Genome Bisulfite Sequencing on Illumina platforms
Authors: Raine Amanda , Liljedahl Ulrika , Nordlund Jessica 
Published: September 2017

AbstractThe powerful HiSeq X sequencers with their patterned flowcell technology and fast turnaround times are instrumental for many large-scale genomic and epigenomic studies. However, assessment of DNA methylation by sodium bisulfite treatment results in sequencing libraries of low diversity, which may impact data quality and yield. In this report we assess the quality of WGBS data generated on the HiSeq X system in comparison with data generated on the HiSeq 2500 system and the newly released NovaSeq system. We report a systematic issue with low basecall quality scores assigned to guanines in the second read of WGBS when using certain Real Time Analysis (RTA) software versions on the HiSeq X sequencer, reminiscent of an issue that was previously reported with certain HiSeq 2500 software versions. However, with the HD.3.4.0/RTA 2.7.7 software upgrade for the HiSeq X system, we observed an overall improved quality and yield of the WGBS data generated, which in turn empowers cost-effective and high quality DNA methylation studies.
Organisation of feed-forward loop motifs reveals architectural principles in natural and engineered networks
Authors: Gorochowski Thomas E. , Grierson Claire S. , di Bernardo Mario 
Published: September 2017

AbstractNetwork motifs are significantly expressed sub-graphs that have been proposed as building blocks for natural and engineered networks. Detailed functional analysis has been performed for many types of motif in isolation, but less is known about how motifs work together to perform complex tasks. To address this issue we measure the aggregation of network motifs via methods that extract precisely how these structures are connected. Applying this approach to a broad spectrum of networked systems and focusing on the widespread feed-forward loop motif, we uncover striking differences in motif organisation. The types of connection are often highly constrained, differ between domains, and clearly capture architectural principles. We show how this information can be used to effectively predict functionally important nodes in the metabolic network ofEscherichia coli. Our findings have implications for understanding how networked systems are constructed from motif parts and elucidates constraints that guide their evolution.
Trait Evolution with Jumps: Illusionary Normality
Authors: Bartoszek Krzysztof 
Published: September 2017

ABSTRACTPhylogenetic comparative methods for real-valued traits usually make use of stochastic process whose trajectories are continuous. This is despite biological intuition that evolution is rather punctuated than gradual. On the other hand, there has been a number of recent proposals of evolutionary models with jump components. However, as we are only beginning to understand the behaviour of branching Ornstein–Uhlenbeck (OU) processes the asymptotics of branching OU processes with jumps is an even greater unknown. In this work we build up on a previous study concerning OU with jumps evolution on a pure birth tree. We introduce an extinction component and explore via simulations, its effects on the weak convergence of such a process. We furthermore, also use this work to illustrate the simulation and graphic generation possibilities of the mvSLOUCH package.
Systematic mapping of the free energy landscapes of a growing immunoglobulin domain identifies a kinetic intermediate associated with co-translational proline isomerization
Authors: Waudby Christopher A. , Karyadi Maria-Evangelia , Wlodarski Tomasz , Cassaignau Anaïs M. E. , Chan Sammy , Schmidt-Engler Julian M. , Wentink Anne S. , Camilloni Carlo , Vendruscolo Michele , Cabrita Lisa D. , Christodoulou John 
Published: September 2017

AbstractCo-translational folding is a fundamental molecular process that ensures efficient protein biosynthesis and minimizes the wasteful or hazardous formation of misfolded states. However, the complexity of this process makes it extremely challenging to obtain structural characterizations of co-translational folding pathways. Here we contrast observations in translationally-arrested nascent chains with those of a systematic C-terminal truncation strategy. We create a detailed description of chain length-dependent free energy landscapes associated with folding of the FLN5 filamin domain, in isolation and on the ribosome. By using this approach we identify and characterize two folding intermediates, including a partially folded intermediate associated with the isomerization of a conserved proline residue, which, together with measurements of folding kinetics, raises the prospect that neighboring unfolded domains might accumulate during biosynthesis. We develop a simple model to quantify the risk of misfolding in this situation, and show that catalysis of folding by peptidyl-prolyl isomerases is essential to eliminate this hazard.
Numerical algorithms for solving shallow water hydro-sediment-morphodynamic equations
Authors: Xia Chunchen , Cao Zhixian , Pender Gareth , Borthwick Alistair 
Published: September 2017

PurposeThe purpose of this paper is to present a fully conservative numerical algorithm for solving the coupled shallow water hydro-sediment-morphodynamic equations governing fluvial processes, and also to clarify the performance of a conventional algorithm, which redistributes the variable water-sediment mixture density to the source terms of the governing equations and accordingly the hyperbolic operator is rendered similar to that of the conventional shallow water equations for clear water flows.Design/methodology/approachThe coupled shallow water hydro-sediment-morphodynamic equations governing fluvial processes are arranged in full conservation form, and solved by a well-balanced weighted surface depth-gradient method along with a slope-limited centred scheme. The present algorithm is verified for a spectrum of test cases, which involve complex flows with shock waves and sediment transport processes with contact discontinuities over irregular topographies. The computational results of the conventional algorithm are compared with those of the present algorithm and evaluated by available referenced data.FindingsThe fully conservative numerical algorithm performs satisfactorily over the spectrum of test cases, and the conventional algorithm is confirmed to work similarly well.Originality/valueA fully conservative numerical algorithm, without redistributing the water-sediment mixture density, is proposed for solving the coupled shallow water hydro-sediment-morphodynamic equations. It is clarified that the conventional algorithm, involving redistribution of the water-sediment mixture density, performs similarly well. Both algorithms are equally applicable to problems encountered in computational river modelling.
A novel design for microfluidic chamber based on reverse flow optimization
Authors: Chen Xueye , Li Tiechuan 
Published: September 2017

Purpose
This paper aims presents topology optimization of microfluidic channels with reverse flow.

Design/methodology/approach
A circular chamber with an inlet and an outlet are chosen as an initial design domain. The energy dissipation is chosen as an objective function. The incompressible Navier–Stokes equation is applied for simulating the fluidic motion in channels. An artificial friction force which is proportional to the flow velocity is substituted into the Navier–Stokes equation for controlling the design variable.

Findings
The effect of a bifurcation angle between the inlet and the outlet on a topological structure is analyzed. The flow velocity, pressure and design variable for every bifurcation angle are obtained.

Originality/value
This work is instructive to the design of a microfluidic system.
Fuzzy inference system application for failure analyzing in automobile industry
Authors: Geramian Arash , Mehregan Mohammad Reza , Garousi Mokhtarzadeh Nima , Hemmati Mohammadreza 
Published: September 2017

Purpose
Nowadays, quality is one of the most important key success factors in the automobile industry. Improving the quality is based on optimizing the most important quality characteristics and usually launched by highly applied techniques such as failure mode and effect analysis (FMEA). According to the literature, however, traditional FMEA suffers from some limitations. Reviewing the literature, on one hand, shows that the fuzzy rule-base system, under the artificial intelligence category, is the most frequently applied method for solving the FMEA problems. On the other hand, the automobile industry, which highly takes advantages of traditional FMEA, has been deprived of benefits of fuzzy rule-based FMEA (fuzzy FMEA). Thus, the purpose of this paper is to apply fuzzy FMEA for quality improvement in the automobile industry.

Design/methodology/approach
Firstly, traditional FMEA has been implemented. Then by consulting with a six-member quality assurance team, fuzzy membership functions have been obtained for risk factors, i.e., occurrence (O), severity (S), and detection (D). The experts have also been consulted about constructing the fuzzy rule base. These evaluations have been performed to prioritize the most critical failure modes occurring during production of doors of a compact car, manufactured by a part-producing company in Iran.

Findings
Findings indicate that fuzzy FMEA not only solves problems of traditional FMEA, but also is highly in accordance with it, in terms of some priorities. According to results of fuzzy FMEA, failure modes E, pertaining to the sash of the rear right door, and H, related to the sash of the front the left door, have been ranked as the most and the least critical situations, respectively. The prioritized failures could be considered to facilitate future quality optimization.

Practical implications
This research provides quality engineers of the studied company with the chance of ranking their failure modes based on a fuzzy expert system.

Originality/value
This study utilizes the fuzzy logic approach to solve some major limitations of FMEA, an extensively applied method in the automobile industry.
Analyzing the causes of delay in development projects by fuzzy analysis
Authors: Ghiasi Vahed , Kaivan Ebrahim , Arzjani Nima , Arzjani Danial 
Published: September 2017

Purpose
The purpose of this paper is to identify and prioritize the causes of delay in development projects and present strategies to reduce the delay.

Design/methodology/approach
The discussion includes the failure mode and effects analysis (FMEA) method for converting survey data, fuzzy risk priority number (FRPN) for prioritizing the delay factors, and the proposed solutions to reduce the delay of projects.

Findings
The research provided prioritized delay factors to show the importance of each delay factor in the projects by analyzing the survey data. Results show that lack of proper contract price to win the tender has the most impact on the delay of development project between delay factors.

Originality/value
This study offered some guidelines for people who are involved with contracts and development projects, so that they can use these suggestions to prevent possible factors that may cause delay in projects. This paper also demonstrated a process of analyzing the data which was provided by FMEA and FRPN methods.
Interpretive structural modeling for integrating quality management in manufacturing and service counterparts
Authors: Goyal Gaurav , Samalia Harsh Vardhan , Verma Piyush 
Published: September 2017

Purpose
The purpose of this paper is to identify and rank the contextual relationship among the quality management (QM) constructs for manufacturing and its related service organizations providing integrated value bundles, which has got limited research attention.

Design/methodology/approach
The QM constructs of manufacturing and services are selected by performing the citation analysis. Studies related to manufacturing and service are selected by reviewing their citations index in the three major research databases namely ProQuest, Scopus and Google Scholar. The subjective responses from both industry and academia are taken in order to gain better understanding of the contextual relationship among the QM constructs. Finally, an integrated model is proposed using Micmac analysis and Interpretive Structural Modeling (ISM).

Findings
The citation analysis lead to identification of 12 QM constructs: top management commitment, supplier relationship management, human resource management, strategic focus, customer focus, quality of information sharing, process management, servicescape, employee involvement, service quality, supply chain flexibility and customer satisfaction. The expert opinions of executives in the automotive industry and academia resulted in the development of contextual relationships among the identified QM constructs for the development of an ISM model, which is a major contribution of this study.

Originality/value
The unique focus of this study is on analyzing the contextual relationship among QM aspects in manufacturing and services as clubbed offering. The researchers in the existing literature have so far differentiated between manufacturing and services but this study integrates the QM constructs for manufacturing and its associated services through expert feedback and proposes an ISM model.
International perspectives on homeownership and home equity extraction by senior households
Authors: Haurin Donald , Moulton Stephanie 
Published: September 2017

PurposeThis paper links the literatures on the life-cycle hypothesis, homeownership, home equity and pensions. Empirically, the focus is on the EU and USA. The paper aims to explore the extent that seniors extract their home equity and discuss the financial instruments available for equity extraction.Design/methodology/approachThe study uses data from the EU and USA to determine homeownership rates, house values and mortgage debt. With these values, the amount of seniors’ home equity is measured for each country. The usage of home equity extraction methods is reported and factors limiting their use are identified.FindingsSeniors’ home equity is a substantial share of their total wealth. Estimates for 2013 are that their home equity equals about €5tn in the USA and over €8tn in large EU countries. The authors find that only a small share of seniors extracts their home equity. While there are supply side constraints in many countries, the evidence suggests that the cause of low extraction rates is the lack of demand. Various reasons for the lack of demand are discussed.Practical implicationsThe increasing share of seniors in most countries’ population suggests that there will be increasing pressure on public pension systems. One among many options to address this issue is to impose a wealth test for eligibility, where wealth includes home equity. This study suggests that although home equity is substantial for many seniors, they are reluctant to access the funds.Originality/valueThe paper highlights the importance of home equity in the EU and USA and the factors that affect the primary methods of extraction.
Technological leverage in higher education: an evolving pedagogy
Authors: Pillai K. Rajasekharan , Prakash Ashish Viswanath 
Published: September 2017

PurposeThe purpose of the study is to analyse the perception of students toward a computer-based exam on a custom-made digital device and their willingness to adopt the same for high-stake summative assessment.Design/methodology/approachThis study followed an analytical methodology using survey design. A modified version of students’ perception of e-assessment questionnaire (SPEAQ) was used to elicit information from the subjects, who were drawn from a first-year post-graduate course in management and commerce, soliciting voluntary participation in the survey. SmartPLS 2.0 was the major analytical tool used to understand the theoretical robustness of observed and latent variables through structural equation modelling. The final model was retained based on the structural significance of the path coefficients.FindingsThe results of the study offer ample evidence to establish the proposed theoretical relationship. It was found that the subjects of the study maintained a positive attitude toward e-assessment. Hence, the introduction of e-exams for high-stake assessment is suitable to current generation students.Research limitations/implicationsFindings of the study may be irrelevant to students who are not subject to e-learning processes, as an e-assessment can only be effective when students have ample exposure to working on computers.Practical/implicationsA major practical implication of the study is that e-exams will positively influence the outcome of education and effectiveness of the teaching–learning process. Technology, as an eclectic paradigm, can amplify the educational outcome by boosting the competency of students to meet challenges of any emerging situations.Originality/valueThe idea of an e-exam, using a custom-made device, is unprecedented. This paper offers a convincing empirical evidence to academic administrators to integrate e-assessment with e-learning programs.
Internet based learning (IBL) in higher education: a literature review
Authors: Yadav Rajan , Tiruwa Anurag , Suri Pradeep Kumar 
Published: September 2017

PurposeThe growing use of internet-based learning (IBL) platforms in institutions of higher education is producing profound changes in the traditional teaching learning process worldwide. This paper aims to identify and understand the ways in which higher education institutions draw benefits by the use of such means, synthesizing the literature research.Design/methodology/approachThe study synthesized the literature research by using a mixed method approach in which both Web of Science (WoS) and bibliographic techniques were used to retrieve the relevant data base.FindingsThe comprehensive review of the literature suggests that communication technology (CT), massive open online courseware (MOOCs), social networking sites (SNSs), blogs, real simple syndication (RSS) and YouTube are creating new possibilities and avenues of collaborative learning by transforming the traditional class and teacher-centric system.Research limitations/implicationsMultiplicity of the IBL platforms and rapid technological obsolesce are some of the limitations of this paper.Originality/valueThe findings of this study are highly useful in developing a strategic framework to accelerate the integration of IBL platforms to make teaching learning process more interactive and informative.
Fundamental solution for a two-dimensional problem in transversely isotropic micropolar thermoelastic media
Authors: Chawla Vijay , Ahuja Sanjeev , Rani Varsha 
Published: September 2017

Purpose
The purpose of this paper is to study the fundamental solution in transversely isotropic micropolar thermoelastic media. With this objective, the two-dimensional general solution in transversely isotropic thermoelastic media is derived.

Design/methodology/approach
On the basis of the general solution, the fundamental solution for a steady point heat source on the surface of a semi-infinite transversely isotropic micropolar thermoelastic material is constructed by six newly introduced harmonic functions.

Findings
The components of displacement, stress, temperature distribution and couple stress are expressed in terms of elementary functions. From the present investigation, a special case of interest is also deduced and compared with the previous results obtained.

Practical implications
Fundamental solutions can be used to construct many analytical solutions of practical problems when boundary conditions are imposed. They are essential in the boundary element method as well as the study of cracks, defects and inclusions.

Originality/value
Fundamental solutions for a steady point heat source acting on the surface of a micropolar thermoelastic material is obtained by seven newly introduced harmonic functions. From the present investigation, some special cases of interest are also deduced.