bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting targeted therapy resistance: Integrating models to quantify environment mediated drug resistance
Authors: Picco Noemi , Sahai Erik , Maini Philip K. , Anderson Alexander R. A. 
Published: July 2017

AbstractDrug resistance is the single most important driver of cancer treatment failure for modern targeted therapies. This resistance may be due to the presence of dormant or aggressive tumor cell phenotypes or to context-driven protection. Non-malignant cells and other factors, constituting the microenvironment in which the tumor grows (the stroma), are now thought to play a crucial role in both therapeutic response and resistance. Specifically, the dialogue between the tumor and stroma has been shown to modulate the response to molecularly targeted therapies, through proliferative and survival signaling. The goal of this work is to investigate interactions between a growing tumor and its surrounding stroma in facilitating the emergence of drug resistance. We use mathematical modeling as a theoretical framework to bridge between experimental models and scales, with the aim of separating the intrinsic and extrinsic components of resistance in BRAF mutated melanoma. The model describes tumor-stroma dynamics both with and without treatment. Calibration of our model, through the integration of experimental data, revealed significant variation across animal replicates in either the intensity of stromal promotion or intrinsic tissue carrying capacity. Furthermore our study highlights the need to account for this variation in the design of treatment strategies.Major Findings.Through the integration of a simple mathematical model within vitroandin vivoexperimental growth dynamics of melanoma cell lines (both with and without drug), we were able to dissect the relative contributions of intrinsic versus environmental resistance. Our study revealed significant heterogeneityin vivo, indicating that there is a diversity of either stromal promotion or tumor carrying capacity under targeted therapy. We believe this variation may be one possible explanation for the heterogeneity observed across patients and within individual patients with multiple metastases. Therefore, quantifying this variation both withinin vivomodel systems and in individual patients could have a significant impact on the design of future treatment strategies that target both the tumor and stroma. Further, we present guidelines for building more effective and longer lasting therapeutic strategies utilizing our experimentally calibrated model. These strategies explicitly consider the protective nature of the stroma and utilize inhibitors that modulate it.PrecisQuantification of the environmental contribution to drug resistance reveals heterogeneity that significantly alters treatment dynamics that can be exploited for therapeutic gain.Financial SupportPicco and Anderson: US National Cancer Institute grant U01CA151924.Picco: UK Engineering and Physical Sciences Research Council (EPSRC grant number EP/G037280/1).Conflict of Interest DisclosureThe authors declare no potential conflicts of interest.
Repeated co-option of a conserved gene regulatory module underpins the evolution of the crustacean carapace, insect wings and other flat outgrowths
Authors: Shiga Yasuhiro , Kato Yasuhiko , Aragane-Nomura Yuko , Haraguchi Takayuki , Saridaki Theodora , Watanabe Hajime , Iguchi Taisen , Yamagata Hideo , Averof Michalis 
Published: July 2017

Summary statementThe genesvestigial, scallopedandwinglesscomprise a conserved regulatory module that was co-opted repeatedly for the evolution of flat structures, such as insect wings, and crustacean carapace, tergites and coxal plates.SummaryHow novelties arise is a key question in evolutionary developmental biology. The crustacean carapace is a novelty that evolved in the early Cambrian. In an extant crustacean,Daphnia magna, the carapace grows from the body wall as a double-layered sheet with a specialized margin. We show that the growing margin of this carapace expressesvestigial, scallopedandwingless, genes that are known to play key roles in regulating growth at the insect wing margin. RNAi-mediated knockdown ofscallopedandwinglessimpair carapace development, indicating that carapace and wing might share a common mechanism for margin outgrowth. However, carapace and wings arise in different parts of the body and their margins have different orientations, arguing that these structures have independent evolutionary origins. We show thatscallopedis also expressed at the margin of unrelated flat outgrowths (tergites and coxal plates) in the distantly related crustaceanParhyale hawaiensis. Based on these observations, we propose that thevestigial-scalloped-winglessgene module has a common role in the margin of diverse flat structures, originating before the divergence of major crustacean lineages and the emergence of insects. Repeated co-option of this module occurred independently in the carapace, wing and other flat outgrowths, underpinning the evolution of distinct novelties in different arthropod lineages.
Associations between polygenic liability for schizophrenia and level of psychosis and mood-incongruence in bipolar disorder
Authors: Allardyce Judith , Leonenko Ganna , Hamshere Marian , Pardiñas Antonio F. , Forty Liz , Knott Sarah , Smith Katherine-Gordon , Porteus David J. , Haywood Caroline , Di Florio Arianna , Jones Lisa , McIntosh Andrew M. , Owen Michael J. , Holmans Peter , Walters James T.R. , Craddock Nicholas , Jones Ian , O’Donovan Michael C. , Escott-Price Valentina 
Published: July 2017

AbstractImportanceBipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms.ObjectivesTo investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features.DesignCase-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls.Settings & Participants4399 BDcases, mean [sd] age-at-interview 46[12] years, of which 2966 were woman (67%) from the BD Research Network (BDRN) were included in the final analyses, with data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland included for comparison.ExposureStandardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform.Main outcome measureMultinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS).ResultsAcross clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.1.1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.1. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.1.1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.1. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR= 1.09, (95% C.1. 1.04, 1.15)).ConclusionWe show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms.
Robust and Bright Genetically Encoded Fluorescent Markers for Highlighting Structures and Compartments in Mammalian Cells
Authors: Chertkova Anna O. , Mastop Marieke , Postma Marten , van Bommel Nikki , van der Niet Sanne , Batenburg Kevin L. , Joosen Linda , Gadella Theodorus W.J. , Okada Yasushi , Goedhart Joachim 
Published: July 2017

AbstractTo increase our understanding of the inner working of cells, there is a need for specific markers to identify biomolecules, cellular structures and compartments. One type of markers comprises genetically encoded fluorescent probes that are linked with protein domains, peptides and/or signal sequences. These markers are encoded on a plasmid and they allow straightforward, convenient labeling of cultured mammalian cells by introducing the plasmid into the cells. Ideally, the fluorescent marker combines favorable spectroscopic properties (brightness, photostability) with specific labeling of the structure or compartment of interest. Here, we report our ongoing efforts to generate robust and bright genetically encoded fluorescent markers for highlighting structures and compartments in living cells. The plasmids are distributed by addgene:https://www.addgene.org/browse/article/28189953/Abstract Figure
Learning control of flexible manipulator with unknown dynamics
Authors: Chen Zhiguang , Yang Chenguang , Liu Xin , Wang Min 
Published: July 2017

Purpose
The purpose of this paper is to study the controller design of flexible manipulator. Flexible manipulator system is a nonlinear, strong coupling, time-varying system, which is introduced elastodynamics in the study and complicated to control. However, due to the flexible manipulator, system has a significant advantage in response speed, control accuracy and load weight ratio to attract a lot of researchers.

Design/methodology/approach
Since the order of flexible manipulator system is high, designing controller process will be complex, and have a large amount of calculation, but this paper will use the dynamic surface control method to solve this problem.

Findings
Dynamic surface control method as a controller design method which can effectively solve the problem with the system contains nonlinear and reduced design complexity.

Originality/value
The authors assume that the dynamic parameters of flexible manipulator system are unknown, and use Radial Basis Function neural network to approach the unknown system, combined with the dynamic surface control method to design the controller.
Impedance control of a cable-driven SEA with mixed H2/H∞ synthesis
Authors: Yu Ningbo , Zou Wulin 
Published: July 2017

Purpose
This paper aims to present an impedance control method with mixed H2/H∞ synthesis and relaxed passivity for a cable-driven series elastic actuator to be applied for physical human–robot interaction.

Design/methodology/approach
To shape the system’s impedance to match a desired dynamic model, the impedance control problem was reformulated into an impedance matching structure. The desired competing performance requirements as well as constraints from the physical system can be characterized with weighting functions for respective signals. Considering the frequency properties of human movements, the passivity constraint for stable human–robot interaction, which is required on the entire frequency spectrum and may bring conservative solutions, has been relaxed in such a way that it only restrains the low frequency band. Thus, impedance control became a mixed H2/H∞ synthesis problem, and a dynamic output feedback controller can be obtained.

Findings
The proposed impedance control strategy has been tested for various desired impedance with both simulation and experiments on the cable-driven series elastic actuator platform. The actual interaction torque tracked well the desired torque within the desired norm bounds, and the control input was regulated below the motor velocity limit. The closed loop system can guarantee relaxed passivity at low frequency. Both simulation and experimental results have validated the feasibility and efficacy of the proposed method.

Originality/value
This impedance control strategy with mixed H2/H∞ synthesis and relaxed passivity provides a novel, effective and less conservative method for physical human–robot interaction control.
Deep Spatial-Temporal Model for rehabilitation gait: optimal trajectory generation for knee joint of lower-limb exoskeleton
Authors: Liu Du-Xin , Wu Xinyu , Du Wenbin , Wang Can , Chen Chunjie , Xu Tiantian 
Published: July 2017

PurposeThe purpose of this paper is to model and predict suitable gait trajectories of lower-limb exoskeleton for wearer during rehabilitation walking. Lower-limb exoskeleton is widely used for assisting walk in rehabilitation field. One key problem for exoskeleton control is to model and predict suitable gait trajectories for wearer.Design/methodology/approachIn this paper, the authors propose a Deep Spatial-Temporal Model (DSTM) for generating knee joint trajectory of lower-limb exoskeleton, which first leverages Long-Short Term Memory framework to learn the inherent spatial-temporal correlations of gait features.FindingsWith DSTM, the pathological knee joint trajectories can be predicted based on subject’s other joints. The energy expenditure is adopted for verifying the effectiveness of new recovery gait pattern by monitoring dynamic heart rate. The experimental results demonstrate that the subjects have less energy expenditure in new recovery gait pattern than in others’ normal gait patterns, which also means the new recovery gait is more suitable for subject.Originality/valueLong-Short Term Memory framework is first used for modeling rehabilitation gait, and the deep spatial–temporal relationships between joints of gait data can obtained successfully.
Compliant training control of ankle joint by exoskeleton with human EMG-torque interface
Authors: Li Zhan , Cheng Hong , Guo Hongliang , Sun Xiaohong 
Published: July 2017

Purpose
The purpose of this paper is to make compliant training control of exoskeleton for ankle joint with electromyograph (EMG)-torque interface.

Design/methodology/approach
A virtual compliant mapping which is modeled by mass-spring-damper system is incorporated into the whole system at the reference input. The EMG-torque interface contains both data acquisition and torque estimator/predictor, and extreme learning machine is utilized for joint torque estimation/prediction from multiple channels of EMG signals.

Findings
The reference ankle joint angle to follow is produced from the compliance mapping whose input is the measured/predicted torque on healthy subjects. The control system works well with the desired angle to track. In the actuation level, the input torque to drive the ankle exoskeleton is less than the actual torque of the subject(s). This may have positive influence on diminishing overshoot of input torque from motors and protect the actuators. The torque prediction and final tracking control performance demonstrate the efficiency of the presented architecture.

Originality/value
This work can be beneficial to compliant training of ankle exoskeleton system for pilots and enhance current training control module in rehabilitation.
Genetic algorithm-based compliant robot path planning: an improved Bi-RRT-based initialization method
Authors: Lin Du , Shen Bo , Liu Yurong , Alsaadi Fuad E. , Alsaedi Ahmed 
Published: July 2017

Purpose
The purpose of this paper is to improve the performance of the genetic algorithm-based compliant robot path planning (GACRPP) in complex dynamic environment by proposing an improved bidirectional rapidly exploring random tree (Bi-RRT)-based population initialization method.

Design/methodology/approach
To achieve GACRPP in complex dynamic environment with high performance, an improved Bi-RRT-based population initialization method is proposed. First, the grid model is adopted to preprocess the working space of mobile robot. Second, an improved Bi-RRT is proposed to create multi-cluster connections between the starting point and the goal point. Third, the backtracking method is used to generate the initial population based on the multi-cluster connections generated by the improved Bi-RRT. Subsequently, some comparative experiments are implemented where the performances of the improved Bi-RRT-based population initialization method are compared with other population initialization methods, and the comparison results of the improved genetic algorithm (IGA) combining with the different population initialization methods are shown. Finally, the optimal path is further smoothed with the help of the technique of quadratic B-spline curves.

Findings
It is shown in the experiment results that the improved Bi-RRT-based population initialization method is capable of deriving a more diversified initial population with less execution time and the IGA combining with the proposed population initialization method outperforms the one with other population initialization methods in terms of the length of optimal path and the execution time.

Originality/value
In this paper, the Bi-RRT is introduced as a population initialization method into the GACRPP problem. An improved Bi-RRT is proposed for the purpose of increasing the diversity of initial population. To characterize the diversity of initial population, a new notion of breadth is defined in terms of Hausdorff distance between different paths.
Public-sector reforms and balanced scorecard adoption: an Ethiopian case study
Authors: Bobe Belete Jember , Mihret Dessalegn Getie , Obo Degefe Duressa 
Published: July 2017

Purpose
The purpose of this paper is to examine adoption of the balanced scorecard (BSC) by a large public-sector health organisation in an African country, Ethiopia as part of a programme to implement a unified sector-wide strategic planning and performance monitoring system. The study explains how this trans-organisational role of the BSC is constituted, and explores how it operates in practice at the sector-and organisation-levels.

Design/methodology/approach
The study employs the case-study method. Semi-structured interview data and documentary evidence are analysed by drawing on the concept of translation from actor-network theory.

Findings
The case-study organisation adopted the BSC as a part of broader public-sector reforms driven by political ideology. Through a centralised government decision, the BSC was framed as a sector-wide system aimed at: aligning the health sector’s strategic policy goals with strategic priorities and operational objectives of organisations in the sector; and unifying performance-monitoring of the sector’s organisations by enabling aggregation of performance information to a sector level in a timely manner to facilitate health sector policy implementation. While the political ideology facilitated BSC adoption for trans-organisational use, it provided little organisational discretion to integrate financial administration and human resource management practices to the BSC framework. Further, inadequate piloting of information system use for the anticipated BSC model, originating from the top-down approach followed in the BSC implementation, inhibited implementation of the BSC with a balanced emphasis between the planning and performance monitoring roles of the BSC. As a result, the BSC underwent a pragmatic shift in emphasis and was reconceptualised as a system of enhancing strategic alignment through integrated planning, compared to the balanced emphasis between the planning and performance monitoring roles initially anticipated.

Originality/value
The study provides a theory-based explanation of how politico-ideological contexts might facilitate the framing of novel roles for the BSC and how the roles translate into practice.
The accounting profession and education
Authors: Verhoef Grietjie , Samkin Grant 
Published: July 2017

Purpose
The purpose of this paper is to examine how the actions of the accounting profession, the state, universities, and academics have inhibited the development of South African accounting research.

Design/methodology/approach
A multiple history approach using traditional archival material and oral history is used.

Findings
Since the late nineteenth-century, a network of human and non-human actors has ensured that accounting education in South Africa retained a technical focus. By prescribing and detailing the accounting syllabuses required for university accreditation, the South African Institute of Chartered Accountants (SAICA) and its predecessors exercise direct control over accounting education. As a result, little appetite exists for a discipline based on academic enquiry or engagement with international scholars. While the SAICA claims to support accounting research, this support is conditional on its meeting the professional body’s particular view of scholarship.

Research limitations/implications
The limitations associated with this research are that it focusses on one particular professional body in one jurisdiction. The South African situation provides a cautionary tale of how universities, particularly those in developing countries, should take care not to abdicate their responsibilities for the setting of syllabi or course content to professional bodies. Accounting academics, particularly those in a developing country currently experiencing major social, political, and economic problems, are in a prime position to engage in research that will benefit society as a whole.

Originality/value
Although actor network theory has been used in accounting research and in particular to explain accounting knowledge creation, the use of this particular theoretical lens to examine the construction of professional knowledge is limited. This study draws on Callon’s (1986) four moments to explain how various human actors including the accounting profession, the state, universities, and accounting academics, along with non-human actors such as accreditation, regulation, and transformation, have brought about South African academic disengagement with the discipline.
The anatomy of business failure
Authors: Dias Artur , Teixeira Aurora A.C. 
Published: July 2017

Purpose
The purpose of this paper is to analyze the aftermath of business failure (BF) by addressing: how the individual progressed and developed new ventures, how individuals changed business behaviors and practices in light of a failure, and what was the effect of previous failure on the individual’s decisions to embark on subsequent ventures.

Design/methodology/approach
The authors resort to qualitative methods to understand the aftermath of BF from a retrospective point of a successful entrepreneur. Specifically, the authors undertook semi-structured interviews to six entrepreneurs, three from the north of Europe and three from the south and use interpretative phenomenological analysis.

Findings
The authors found that previous failure impacted individuals strongly, being shaped by the individual’s experience and age, and their perception of blame for the failure. An array of moderator costs was identified, ranging from antecedents to institutions that were present in the individual’s lives. The outcomes are directly relatable to the failed experience by the individual. The authors also found that the failure had a significant effect on the individual’s career path.

Originality/value
While predicting the failure of healthy firms or the discovery of the main determinants that lead to such an event have received increasingly more attention in the last two decades, the focus on the consequences of BF is still lagging behind. The present study fills this gap by analyzing the aftermath of BF.