bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of tumor growth by a novel engineered chimeric toxin that cleaves activated mutant and wild-type RAS
Authors: Vidimar Vania , Beilhartz Greg L. , Park Minyoung , Biancucci Marco , Kieffer Matthew B. , Gius David R. , Melnyk Roman A. , Satchell Karla J. F. 
Published: December 2019

SummaryDespite nearly four decades of effort, broad inhibition of oncogenic RAS using small molecule approaches has proven to be a major challenge. Here we describe the development of a novel pan-RAS biologic inhibitor comprised of the RAS-RAP1-specific endopeptidase fused to the protein delivery machinery of diphtheria toxin. We show that this engineered chimeric toxin irreversibly cleaves and inactivates intracellular RAS at low picomolar concentrations terminating downstream signaling in receptor-bearing cells. Further, we demonstratein vivotarget engagement and reduction of tumor burden in three mouse xenograft models driven by either wild-type or mutantRAS. Intracellular delivery of a potent anti-RAS biologic through a receptor-mediated mechanism represents a promising new approach to developing RAS therapeutics against a broad array of cancers.SignificanceRAS oncoproteins have long been considered among the most elusive drug targets in cancer research. At issue is the lack of accessible drug binding sites and the extreme affinity for its GTP substrate. Covalent inhibitors against the KRAS G12C mutant have shown early clinical promise, however, targeting the other oncogenic RAS mutants across three RAS isoforms has proven challenging. Inhibition of activated wild-type RAS in the absence of canonicalRASmutations is also highly desirable in certain tumors. Here, we demonstrate delivery of an extremely potent pan-RAS and RAP1 cleaving enzyme in therapeutic quantities to specific receptor-bearing cellsin vitroandin vivo. We aim to advance this approach to engineer the first targeted pan-RAS inhibitor for cancer therapy.One Sentence SummaryEngineered chimeric toxin halts tumor growthin vivovia RAS cleavage
Neural-sliding mode approach-based adaptive estimation, isolation and tolerance of aircraft sensor fault
Authors: Taimoor Muhammad , Aijun Li 
Published: December 2019

Purpose
The purpose of this paper is to propose an adaptive neural-sliding mode-based observer for the estimation and reconstruction of unknown faults and disturbances for time-varying nonlinear systems such as aircraft, to ensure preciseness in the diagnosis of fault magnitude as well as the shape without enhancement of system complexity and cost. Fault-tolerant control (FTC) strategy based on adaptive neural-sliding mode is also proposed in the existence of faults for ensuring the stability of the faulty system.

Design/methodology/approach
In this paper, three strategies are presented: adaptive radial basis functions neural network (ARBFNN), conventional radial basis functions neural network (CRBFNN) and integral-chain differentiator. For the purpose of enhancement of fault diagnosis and isolation, a new sliding mode-based concept is introduced for the weight updating parameters of radial basis functions neural network (RBFNN).The main objective of updating the weight parameters adaptively is to enhance the effectiveness of fault diagnosis and isolation without increasing the computational complexities of the system. Results depict the effectiveness of the proposed ARBFNN approach in fault detection (FD) and approximation compared to CRBFNN, integral-chain differentiator and schemes existing in literature. In the second step, the FTC strategy is presented separately for each observer in the presence of unknown faults and failures for ensuring the stability of the system, which is validated on Boeing 747 100/200 aircraft.

Findings
The proposed adaptive neural-sliding mode approach is investigated, which depicts more effectiveness in numerous situations such as faults, disturbances and uncertainties compared to algorithms used in literature. In this paper, both the fault approximation and isolation and the fault tolerance approaches are studied.

Practical implications
For the enhancement of safety level as well as for avoiding any kind of damage, timely FD and fault tolerance have always had a significant role; therefore, the algorithms proposed in this research ensure the tolerance of faults and failures, which plays a vital role in practical life for avoiding any kind of damage.

Originality/value
In this study, a new neural-sliding mode concept is adopted for the adaptive faults approximation and reconstruction, and then the FTC algorithms are studied for each observer separately, whereas in previous studies, only the fault detection and isolation (FDI) or the fault tolerance problems were studied. Results demonstrate the effectiveness of the proposed strategy compared to the approaches given in the literature.
Energy management-based design of a Wankel hybrid-electric UAV
Authors: Donateo Teresa , Ficarella Antonio , De Pascalis Claudia Lucia 
Published: December 2019

PurposeThe purpose of this study is to investigate the optimization of design and energy management in a parallel hybrid-electric powertrain to replace the conventional engine of an existing tactical unmanned aerial vehicle (UAV) equipped with a Wankel engine with a pre-defined flight mission. The proposed powertrain can work in four different operating modes: electric, thermal, power-assist and charging.Design/methodology/approachThe power request at propeller axis of each flight segment is used as input for an in-house model that calculates the overall fuel consumption throughout the mission (Mfuel) and the maximum payload weight (Wpay) by means of an average-point analysis. These outputs depend on the energy management strategy that is expressed by the power-split ratio between engine and electric phase (Uphase) of each mission phase, according to which the components of the hybrid system are sized. The in-house model is integrated into an optimization framework to find the optimal set of Uphase and battery size that minimizes Mfuel and maximizes Wpay.FindingsIt was found a 3.24% saving of the fuel mass burned throughout the mission (or, alternative an improvement of endurance by 4.3%) with about the same maximum-payload mass (+0.2%) of the original configuration, or a smaller fuel saving with +11% more payload. The fuel saving of 3.24% corresponds to −3.25% in total emissions of CO2and a 2.34% reduction of the cost-per-mission.Practical implicationsThis study demonstrates that environmental advantages, even if limited, can be already obtained from optimal design and management of the hybrid power system with today technologies while waiting for further benefits from the introduction of advanced technologies for batteries and electric machines.Originality/valueThe main novelties are the design of the powertrain on the basis of the energy management and the application of scalability and hybridization to Wankel engines.
The impact of informal credit on rural agricultural productivity in the savannah ecological zone of Ghana
Authors: Sekyi Samuel , Domanban Paul Bata , Honya George Kwame 
Published: December 2019

PurposeThe purpose of this paper is to examine the impact of informal credit access on agricultural productivity in rural Ghana.Design/methodology/approachData sets from the Ghana Feed the Future baseline survey involving a total sample of 2,437 rural farm households were used. In order to address the problem of endogeneity and sample selectivity bias, the endogenous switching regression (ESR) model was employed to examine whether rural farm households’ with access to informal credit and those without access differ in terms of their productivity levels and whether access to informal credit affects agricultural productivity.FindingsEstimates from the ESR show that access to informal credit significantly promotes agricultural productivity. Specifically, farmers with access to informal credit were able to achieve a yield of 48.42 kg/ha more than their counterparts without informal credit access. In terms of the counterfactual, farmers without informal credit access would have increased their yield by 57.61 kg/ha if they were to have access to informal credit.Research limitations/implicationsThe study was restricted to the savannah ecological zone of Ghana. This limits the extent of generalisation of results.Originality/valueThis study provides a rigorous econometric analysis of the impacts of access to informal credit on agricultural productivity in rural Ghana. The study contributes to the current debate on the link between access to informal credit and agricultural productivity and provides valuable input for policymakers.
Pyramid ownership structure and tax avoidance among Canadian firms
Authors: Mindzak Justin , Zeng Tao 
Published: December 2019

Purpose
This paper aims to examine the relationship between pyramid ownership structure and tax avoidance.

Design/methodology/approach
This paper is an empirical work using a sample of Canadian listed firms.

Findings
Relying on several proxies for tax avoidance, the authors find that firms affiliated with pyramidal structures generally engage in more tax avoidance activities than non-affiliated firms; firms affiliated with more complex pyramids engage in more tax avoidance practices and firms located at the lower tiers of the pyramids avoid more taxes; and some pyramid-affiliated firms with larger deviation between controlling shareholders’ cash flow rights and control rights engage in more tax avoidance practices.

Social implications
A broader understanding of the relationship between pyramidal structure and tax avoidance can be pursued by including firms in other countries, where the pyramid groups (pyramid structure) are prevalent, but institutional environments differ from that of Canada.

Originality/value
This study highlights the importance of pyramid ownership in shaping tax avoidance activities among Canadian-listed firms. Canada provides an ideal setting for studying the impact of ownership structure, as it contains a diverse corporate ownership structure ranging from widely held freestanding firms to pyramidal business groups.
“Carne Fraca”
Authors: Quevedo-Silva Filipe , Freire Otavio , Spanhol-Finocchio Caroline Pauletto 
Published: December 2019

Purpose
Over the last few years, several events have reduced the consumer confidence in relation to food safety. Recently, one event that triggered discussions and concern among consumers in Brazil was the “Carne Fraca” operation which cast doubt on the quality and safety of Brazilian beef. The purpose of this paper is to analyse the impact of the news regarding a national crisis in beef production on consumers’ assessment and purchase intention of beef.

Design/methodology/approach
A quantitative study was conducted involving 417 respondents in Brazil. The procedure for the analysis consisted of the investigation of two models, incorporating mediation and moderation effects.

Findings
The results show that news on the crisis had a positive impact on risk perception. This impact was negatively moderated by consumer scepticism. Risk perception had a negative effect on the assessment of beef and purchase intention. These effects were negatively affected by risk attitude. The news directly affected consumers’ assessment of beef and indirectly affected purchase intention through mediation of perceived risk.

Originality/value
This study proposes two models, analysing the effect of the media on consumers’ assessment of beef and purchase intention, mediated by risk perception. Furthermore, the models analyse the moderating effects of scepticism and consumers’ risk attitude.
Board diversity and corporate risk: evidence from China
Authors: Bhat Kalim Ullah , Chen Yan , Jebran Khalil , Memon Zulfiqar Ali 
Published: December 2019

PurposeThe purpose of this study shows how overall board diversity influences corporate risk-taking. Board diversity is quantified into task-oriented diversity (tenure and education) and relation-oriented diversity (age and gender). Further, this study tests whether the association of board diversity and corporate risk varies across state-owned firms (SOEs) and non-state-owned firms (NSOEs).Design/methodology/approachThe authors used a sample of Chinese listed firms over the period 1999-2017. The results are estimated using the fixed-effects model. To deal with the endogeneity problem and single model bias, the authors use a dynamic model, i.e. two-step generalized method of moment’s model.FindingsThe results show that both task-oriented and relation-oriented diversity reduces corporate risk. Further, the authors document that overall board diversity reduces risk-taking across different types of firms, that is, SOEs and NSOEs. These results are consistent after controlling for endogeneity problems.Practical implicationsThe results provide implications for enhancing corporate governance practices by considering overall board diversity as an important factor influencing corporate decisions. The findings suggest that policymakers and shareholders should consider different diversity attributes important for the composition of a board, which can enhance board outcomes.Originality/valueMost of the prior studies considered only one dimension of diversity, and therefore, have overlooked the overall board diversity. Unlike prior studies, this study considers four board diversity attributes – age, gender, tenure and education, and further tests their association with corporate risk. Further, this study also examines the effect of overall diversity on corporate risk in SOEs and NSOEs.
The influence of strategic alliances on human capital development
Authors: Ferreira António , Franco Mário 
Published: December 2019

PurposeThe purpose of this paper is to analyse the influence of strategic alliances (knowledge/learning, efficiency and market motives) on the development of human capital.Design/methodology/approachTo do so, a quantitative study was chosen, with data on technology-based small and medium-sized enterprises (SMEs) in Portugal, leading to 257 valid answers.FindingsThe results obtained from a structural equation model show that motives for strategic alliances (knowledge/learning, efficiency and market) have a strong influence on the human capital of the SMEs analysed.Practical implicationsThese outcomes reveal that strategic alliances are a way for SMEs to overcome resource constraints in terms of human capital, representing an important implication for business practice. As strategic alliances influence human capital, the relations SMEs establish with other firms are increasingly important for their sustainability and development. Acting in isolation in the market can reduce this type of firm’s chances of survival.Originality/valueDespite some studies relating the formation of strategic alliances and human capital, there is a gap regarding the relationship between the role of strategic alliances and human capital in the technology-based sector. Therefore, this research represents a contribution and innovation in academic terms in this area.
Investigating international strategic brand management and export performance outcomes in the B2B context
Authors: Pyper Keith , Doherty Anne Marie , Gounaris Spiros , Wilson Alan 
Published: December 2019

Purpose
Drawing on Resource-based Theory, the purpose of this paper is to empirically examine the effect of International Strategic Brand Management (SBM) on export performance within the Business-to-Business (B2B) context. To be able to purposely assess the relationship, this paper also sets out to discover what antecedent international resources, (financial resources) and international capabilities (market information, branding and marketing planning) contribute to the ability of B2B exporters to effectively manage their brands abroad.

Design/methodology/approach
A mixed method firm-level approach was employed. First, a qualitative study of 34 in-depth interviews explored the focal inter-relationships and constructs identified within the literature. A survey of 208 successful UK exporters was then conducted and the results were analysed using structured equation modelling.

Findings
The results confirm that certain marketing capabilities (branding and marketing planning) are advantageous antecedents to the employment of effective SBM in foreign markets which, in turn, leads to increased financial and market performance internationally.

Practical implications
This paper outlines practical brand management considerations managers need to account for to achieve effective exporting. Practitioners are advised to prioritise the development of robust international branding and marketing planning capabilities which can enable them to exploit their limited financial resources for optimal benefits. Furthermore, by developing these capabilities, firms can focus on the essence of their brand and communicate their brand image through the effective strategic management of their brand to business customers, evoking positive brand associations, enhanced perceived brand value and the achievement of increased export performance.

Originality/value
This paper is the first to focus on international SBM as the deterministic factor leading to improved B2B export performance. An innovative framework is offered which positions the pivotal role of International SBM as the central focus. The construct for international branding capabilities is extended specifically for use in the B2B domain.
Creating the conditions for change: an NHS perspective
Authors: Fitzgerald Karen , Biddle Louise 
Published: December 2019

Purpose
Improving early diagnosis of cancer through system change initiatives is endemic in England’s NHS cancer services. These initiatives, however, often fail to gain traction due to the complexities of health system structures. The purpose of this paper is to explore whether using a change framework grounded in systems thinking could be of help to system leaders.

Design/methodology/approach
A portfolio of geographically independent projects, all implementing cancer service changes as part of the Accelerate, Coordinate, Evaluate Programme, was used for the study. Eight projects were purposively selected to give a varied case-mix. Two semi-structured interviews were conducted with each project. Analysis of interviews was carried out using the Framework Method.

Findings
Processes working for (growth processes) and against (limiting processes) change were evident in and common across all eight projects. Projects commonly encountered challenges of relevance, time and bounded thinking. Having a network of committed people was vital for both initiating and sustaining change. Furthermore, understanding stakeholders’ emotional responses to change helped mitigate emergent challenges.

Practical implications
Leaders should pay constant attention to the dynamics of change, taking time to anticipate and diffuse challenges whilst simultaneously working to create the conditions that help change flourish. A change framework rooted in complex systems theory can help leaders understand the contradictory and non-linear processes inherent in transformational change.

Originality/value
Few studies seek to understand change dynamics by comparing the experiences of separate change initiatives implemented contemporaneously. The findings offer leaders practical insights on how to implement transformation.
Learning disability and challenges in male prisons: programme screening evaluation
Authors: Wakeling Helen , Ramsay Laura 
Published: December 2019

Purpose
The purpose of this paper is to validate the learning screening tool (LST) and the adapted functioning checklist-revised (AFC-R) as screening tools to aid programme allocation, and to investigate whether programme decision makers were using the tools as per the guidance provided by HMPPS Interventions Services.

Design/methodology/approach
LST and AFC-R data were gathered for 555 men who had been assessed for programmes between 2015 and 2018 across eight prisons and one probation area. WAIS-IV IQ data were also gathered if completed.

Findings
The findings provide support for the use of the LST, and AFC-R in helping to make decisions about programme allocation. The LST and AFC-R correlate well with each other, and a measure of intellectual functioning (WAIS-IV). Those who were allocated to learning disability or challenges (LDC) programmes scored higher on the LST (greater problems) and lower on the AFC-R (lower functioning) compared to those allocated to mainstream programmes. The LST had adequate predictive validity. In the majority of cases, the correct procedures were followed in terms of using the tools for programme allocation.

Research limitations/implications
The sample size for examining the relationships between all three tools was limited. The research was also unable to take into consideration the clinical decision making involved in how the tools were interpreted.

Originality/value
This research contributes to the growing evidence about the effective use of LDC screening tools in forensic settings.
Mental health literacy in Pakistan: a narrative review
Authors: Begum Rubina , Choudhry Fahad Riaz , Khan Tahir Mehmood , Bakrin Faizah Safina , Al-Worafi Yaser Mohammed , Munawar Khadeeja 
Published: December 2019

PurposeThe term “Mental health literacy” is defined as knowledge and beliefs about mental disorders which aid their recognition, management or prevention. The importance of health literacy for physical health is widely studied; however, the area of mental health literacy in Pakistan has been comparatively neglected. The purpose of this paper is to address the knowledge about mental health in people living in Pakistan.Design/methodology/approachRelevant literature relating to mental health literacy was identified through various database searches. The databases searched included: PubMed, Cochrane database of Systemic Reviews, PsycINFO using the terms mental health, mental health literacy, mental health education, Pakistan.FindingsLiterature suggests that there is dearth of knowledge about mental illnesses and their treatment among public. This review also highlights the importance of mental health literacy among professionals working in the field of health care. In Pakistan, due to low literacy rate, a high percentage of poverty and dearth of trained professionals warrants an emendation in approaches established for attaining the goal of public health and psychiatric care.Practical implicationsFindings have implications for practitioners in the field of mental health care as well as designing targeted interventions for enhancing mental health literacy and help-seeking behavior in the future.Originality/valueA limited understanding and lack of improvement in mental health literacy may interfere with society’s acceptance of evidence-based mental health care which may hamper the delivery of adequate mental health services to the needy.