bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive response to BET inhibition induces therapeutic vulnerability to MCL1 inhibitors in breast cancer
Authors: Yan Gonghong , Wang Heping , Luna Augustin , Bozorgui Behnaz , Li Xubin , Sanchez Maga , Dereli Zeynep , Kahraman Nermin , Kara Goknur , Chen Xiaohua , Lu Yiling , Babur Ozgun , Cokol Murat , Ozpolat Bulent , Sander Chris , Mills Gordon B. , Korkut Anil 
Published: July 2019

AbstractThe development of effective targeted therapies for the treatment of basal-like breast cancers remains challenging. Here, we demonstrate that BET inhibition induces a multi-faceted adaptive response program leading to MCL1 protein-driven evasion of apoptosis in breast cancers. Consequently, co-targeting MCL1 and BET is highly synergistic inin vitroandin vivobreast cancer models. Drug response and genomics analyses revealed that MCL1 copy number alterations, including low-level gains, are selectively enriched in basal-like breast cancers and associated with effective BET and MCL1 co-targeting. The mechanism of adaptive response to BET inhibition involves upregulation of critical lipid metabolism enzymes including the rate-limiting enzyme stearoyl-CoA desaturase (SCD). Changes in the lipid metabolism are associated with increases in cell motility and membrane fluidity as well as transitions in cell morphology and adhesion. The structural changes in the cell membrane leads to re-localization and activation of HER2/EGFR which can be interdicted by inhibiting SCD activity. Active HER2/EGFR, in turn, induces accumulation of MCL1 protein and therapeutic vulnerability to MCL1 inhibitors. The BET protein, lipid metabolism and receptor tyrosine kinase activation cascade is observed in patient cohorts of basal-like and HER2-amplified breast cancers. The high frequency of MCL1 chromosomal amplifications (>30%) and gains (>50%) in basal-like breast cancers suggests that BET and MCL1 co-inhibition may have therapeutic utility in this aggressive subtype.
Characterization of Rose rosette virus and development of reverse genetic system for studying virus accumulation and movement in whole plants
Authors: Verchot Jeanmarie , Herath Venura , Urrutia Cesar D. , Gayral Mathieu , Lyle Kelsey , Shires Madalyn K. , Ong Kevin , Byrne David 
Published: July 2019

ABSTRACTRose rosette virus (RRV) is an Emaravirus, a negative-sense RNA virus with a 7-segmented genome that is enclosed by a double membrane. While the genome sequences of many emaraviruses are reported, there is negligible information concerning virus replication and movement in host plants. Computational methods determined that RNA1 encoded the RNA dependent RNA polymerase (RdRp), RNA2 encoded glycoprotein precursor, and the RNA3 encoded the nucleocapsid (N), all share significant homologies with similar proteins of the Orthobunyavirus family. The RRV terminal UTR sequences are complementary and share significant identity with the UTR sequences of Bunyamwera virus. We report a minireplicon system and a full length infectious clone of RRV, which are the first for any emaravirus species. The photoreversible fluorescent iLOV protein was used to replace the RNA5 open reading frame (R5-iLOV). We demonstrate that agro-infiltration of Nicotiana benthamiana leaves to deliver RNA1, RNA3, and R5-iLOV cDNAs led to iLOV expression. A mutation was introduced into the RdRp active site and iLOV expression was eliminated. Delivery of four segments or seven segments of the RRV infectious clone produced systemic infection in N. benthamiana and rose plants. iLOV was also fused to the glycoprotein precursor (R2-iLOV). Using confocal microscopy, the R2-iLOV was seen in spherical bodies along membrane strands inside N. benthamiana epidermal cells. This new technology will enable future research to functionally characterize the RRV proteins, to study the virus-host interactions governing local and systemic infection, and examine the subcellular functions of the Gc.IMPORTANCERRV has emerged as a severe threat to cultivated roses, causing millions of dollars in losses to commercial producers. The majority of the viral gene products have not been researched or characterized until now. We constructed a minireplicon system and an infectious clone of the seven-segmented RRV genome that is contained in a binary vector and delivered by Agrobacterium. This technology has been slow to develop for viruses with negative-strand RNA genomes. It has been especially tricky for plant viruses with multicomponent negative-strand RNA genomes. We report the first reverse genetic system for a member of the genus Emaravirus, Rose rosette virus (RRV). We introduced the iLOV fluorescent protein as a fusion to the Gc protein and as a replacement for the open reading frame in genome segment 5. This game-changing reverse genetic system creates new opportunities for studying negative-strand RNA viruses in plants.
Disentangling causal relationships between inflammatory markers and depression: a bidirectional Mendelian randomization analysis
Authors: Dardani Christina , Yarmolinsky James , Robinson Jamie , Zheng Jie , Smith George Davey , Lewis Sarah J , Sinclair Lindsey I 
Published: July 2019

AbstractBackgroundThe inflammatory markers C-reactive protein (CRP), interleukin-1 receptor antagonist (IL1-Ra), and interleukin-6 (IL-6) have been associated with depression risk in observational studies. The causal nature of these associations is unclear as conventional observational designs are susceptible to reverse causation and residual confounding. Bidirectional Mendelian randomization (MR) analysis uses genetic variants to proxy for risk factors to help elucidate the presence, magnitude, and direction of causal relationships between traits.MethodsWe performed bidirectional two-sample MR to examine causal associations between circulating CRP, IL1-Ra, and IL-6 and major depressive disorder (MDD) in 135,458 cases and 344,901 controls in the Psychiatric Genetics Consortium. Genetic instruments to proxy inflammatory markers and liability to MDD were constructed by obtaining single-nucleotide polymorphisms (SNPs) associated with these phenotypes in genome-wide association study meta-analyses. Wald ratios and inverse-variance weighted random-effects models were employed to generate causal effect estimates and various sensitivity analyses were performed to examine violations of MR assumptions.ResultsThere was evidence supporting a causal effect of circulating IL-6 on risk of MDD (per natural-log increase: OR 0.85, 95% CI: 0.75-0.96, P=0.007). Higher circulating levels of IL-6 as influenced by variants in the IL6R gene region represent lower cellular binding of IL-6 to its receptor and therefore the present results suggest that IL-6 increases the risk of MDD. We found limited evidence supporting a causal effect of CRP (1.06, 95% CI 0.93-1.22; P=0.36) or IL1-Ra (OR 0.95, 95% CI: 0.87-1.03, P=0.20) on risk of MDD. Reverse direction MR analyses suggested limited evidence for a causal effect of genetic liability to MDD on any of the inflammatory markers examined.ConclusionsThese findings support a causal role of IL-6-related pathways in development of major depressive disorder and suggest the possible efficacy of interleukin-6 inhibition as a therapeutic target for depression.
DMENet: Diabetic Macular Edema Diagnosis using Hierarchical Ensemble of CNN’s
Authors: Singh Rajeev Kumar , Gorantla Rohan 
Published: July 2019

AbstractDiabetic Macular Edema (DME) is an advanced stage of Diabetic Retinopathy (DR) and can lead to permanent vision loss. Currently, it affects 26.7 million people globally and on account of such huge number of DME cases and limited number of ophthalmologists, it is desirable to automate the diagnosis process. Computer-assisted, deep learning based diagnosis will help in early detection, following which appropriate medication can help to mitigate the vision loss. Method: In order to automate the screening of DME, we propose a novel DMENet Algorithm which is built on the pillars of Convolutional Neural Networks (CNN’s). DMENet analyses the preprocessed color fundus images and passes it through a two-stage pipeline. The first stage detects the presence or absence of DME whereas the second stage takes the positive cases and grades the images based on severity. In both the stages, we use a novel Hierarchical Ensemble of CNN’s (HE-CNN). This paper uses two of the popular publicly available datasets IDRiD and MESSIDOR for classification. Preprocessing on the images is performed using morphological opening, Gaussian kernel and the dataset is augmented to solve the class imbalance problem. Results: The proposed methodology achieved an Accuracy of 96.12%, Sensitivity of 96.32%, Specificity of 95.84%, and F–1 score of 0.9609. Conclusion: These excellent results establishes the validity of the proposed methodology for use in DME screening and solidifies the applicability of HE-CNN classification technique in the domain of bio-medical imaging.
Drug target discovery via network modeling: a mathematical model of theE. colifolate network response to trimethoprim
Authors: Jalli Inderpreet , Lunt Sophia , Xu Wenjia , Lopez Carmen , Contreras Andreas , Wilmot Cari-Sue , Shih Timothy , Nijhout Frederik 
Published: July 2019

AbstractThe antibiotic trimethoprim targets the bacterial dihydrofolate reductase enzyme and subsequently affects the entire folate network. We present an expanded mathematical model of trimethoprim’s action on theEscherichia colifolate network that greatly improves upon Kwonet al.(2008). The improvement upon the Kwon Model lends greater insight into the effects of trimethoprim at higher resolution and accuracy. More importantly, the presented mathematical model enables drug target discovery in a way the earlier model could not. Using the improved mathematical model as a scaffold, we use parameter optimization to search for new drug targets that replicate the effect of trimethoprim. We present the model and model-scaffold strategy as an efficient route for drug target discovery.
ADCK4 deficiency destabilizes the coenzyme Q complex, which is rescued by 2,4-dihydroxybenzoic acid treatment
Authors: Widmeier Eugen , Yu Seyoung , Nag Anish , Chung Youn Wook , Nakayama Makiko , Hugo Hannah , Buerger Florian , Schapiro David , Choi Won-Il , Kim Jae-woo , Ryu Ji-Hwan , Lee Min Goo , Clarke Catherine F. , Hildebrandt Friedhelm , Gee Heon Yung 
Published: July 2019

AbstractADCK4mutations usually manifest as steroid-resistant nephrotic syndrome, and cause coenzyme Q10(CoQ10) deficiency. However, the function of ADCK4 remains obscure. We investigated ADCK4 function using mouse and cell models. Podocyte-specificAdck4deletion in mice significantly reduced survival and caused severe focal segmental glomerular sclerosis with extensive interstitial fibrosis and tubular atrophy, which were prevented by treatment with 2,4-dihydroxybenzoic acid (2,4-diHB), an analog of CoQ10precursor molecule. ADCK4 knockout podocytes exhibited significantly decreased CoQ10level, respiratory chain activity, mitochondrial potential, and dysmorphic mitochondria with loss of cristae formation, which were rescued by 2,4-diHB treatment, thus attributing these phenotypes to decreased CoQ10levels. ADCK4 interacted with mitochondrial proteins including COQ5, and also cytoplasmic proteins including myosin and heat shock proteins. ADCK4 knockout decreased COQ complex levels, and the COQ5 level was rescued by ADCK4 overexpression in ADCK4 knockout podocytes. Overall, ADCK4 is required for CoQ10biosynthesis and mitochondrial function in podocytes.
A longitudinal study of the textual characteristics in the chairman’s statements of Guinness
Authors: Moreno Alonso , Jones Michael John , Quinn Martin 
Published: July 2019

Purpose
The purpose of this paper is to longitudinally analyse the evolution of multiple narrative textual characteristics in the chairman’s statements of Guinness from 1948 to 1996, with the aim of studying impression management influences. It attempts to contribute insights on impression management over time.

Design/methodology/approach
The paper attempts to contribute to external accounting communication literature, by building on the socio-psychological tradition within the functionalist-behavioural transmission perspective. The paper analyses multiple textual characteristics (positive, negative, tentative, future and external references, length, numeric references and first person pronouns) over 49 years and their potential relationship to profitability. Other possible disclosure drivers are also controlled.

Findings
The findings show that Guinness consistently used qualitative textual characteristics with a self-serving bias, but did not use those with a more quantitative character. Continual profits achieved by the company, and the high corporate/personal reputation of the company/chairpersons, inter alia, may well explain limited evidence of impression management associated with quantitative textual characteristics. The context appears related to the evolution of the broad communication pattern.

Practical implications
Impression management is likely to be present in some form in corporate disclosures of most companies, not only those companies with losses. If successful, financial reporting quality may be undermined and capital misallocations may result. Companies with a high public exposure such as those with a high reputation or profitability may use impression management in a different way.

Originality/value
Studies analysing multiple textual characteristics in corporate narratives tend to focus on different companies in a single year, or in two consecutive years. This study analyses multiple textual characteristics over many consecutive years. It also gives an original historical perspective, by studying how impression management relates to its context, as demonstrated by a unique data set. In addition, by using the same company, the possibility that different corporate characteristics between companies will affect results is removed. Moreover, Guinness, a well-known international company, was somewhat unique as it achieved continual profits.
Journey or toolbox? Integrated reporting and processes of organisational change
Authors: Higgins Colin , Stubbs Wendy , Tweedie Dale , McCallum Gregory 
Published: July 2019

PurposeMotivated by Morgan’s (1997) analysis of the “paradoxical” role of metaphors in understanding and managing organisations, the purpose of this paper is to assess in what respects organisations using integrated reporting (IR) are on a “journey” of organisational change.Design/methodology/approachThe paper analyses IR practitioner literature to interpret the IR journey metaphor more precisely. The authors then use in-depth interviews to assess the extent to which this metaphor captures how six early adopter organisations in Australia implement IR, and what changes result, over four years.FindingsThe journey metaphor implies substantive and holistic organisational change. By contrast, the authors find organisations use IR in contextual, instrumental and piecemeal ways. The authors propose a “toolbox” metaphor to help (re)present how organisations adapt their reporting to fit decisions already made, and challenges presented, through ordinary and ongoing strategic management.Research limitations/implicationsMorgan (1997) stresses metaphors are invariably used to both describe and manage organisations. The authors’ analysis identifies specific ways the IR journey metaphor is descriptively misleading. The authors’ “toolbox” metaphor suggests different ways organisations are, or could, manage IR to create value.Originality/valueThis is the first paper to provide a systematic analysis of the IR journey metaphors, and to assess in what respects this metaphor captures actual organisational practice. The findings also challenge the broader notion in academic research that reporting frameworks can lead organisational change.
Simulation of active cancellation system based on N-order SSC algorithm
Authors: Wu Yacong , Huang Jun , Yi Mingxu , Zhang Chaopu 
Published: July 2019

Purpose
The purpose of this paper is to introduce the theoretical basis of N-order spectral spreading-compressing (SSC) frequency shift interference algorithm and expand it to active cancellation. An active cancellation simulation and verification system based on N-order SSC algorithm is established and carried out; simultaneously, the absorbing material coating stealth simulation of two kinds of thickness is carried out to compare the stealth effect with active cancellation system.

Design/methodology/approach
The active cancellation method based on N-order SSC algorithm is proposed based on theoretical formula derivation; the active cancellation simulation and verification system is established in MATLAB/Simulink. The full-size model is built by CATIA and meshed by hypermesh. The omnidirectional radar cross section (RCS) is calculated in cadFEKO, and the results are analyzed in postFEKO.

Findings
The simulations are implemented on a stealth fighter, and results show that after active cancellation, the peak of spectrum analyzer has reduced in all azimuths, the omnidirectional RCS has also decreased and the detection probability of almost all azimuths has dropped under 50 per cent. The absorbing material coating stealth simulations of two kinds of thickness are carried out, and results show that the stealth effect of active cancellation is much better than absorbing material coating.

Practical implications
An active cancellation system based on SSC algorithm is proposed in this paper, and the effect of active cancellation is verified and compared with that of absorbing materials. A new method for the current active stealth is provided in this paper.

Originality/value
Active cancellation simulation and verification system is established. RCS calculation module, signal-to-noise-ratio (SNR) calculation module and detection probability module are built to verify the effect of active cancellation system. Simultaneously, the absorbing material coating stealth simulation is carried out, and the stealth effect of absorbing material coating and active cancellation are compared and analyzed.
Linking employees’ affective commitment and knowledge sharing for an increased customer orientation
Authors: Lombardi Sara , Sassetti Sara , Cavaliere Vincenzo 
Published: July 2019

Purpose
Building on the attitude–behavior relationship model, this study aims to contribute to customer orientation literature by suggesting that service employees’ commitment (i.e. personal attitude) affects their customer orientation via the effect of their participation in knowledge sharing with colleagues (i.e. employees’ behavior).

Design/methodology/approach
The empirical analysis has been developed around survey data, collected from 165 service workers of Italian museums. The hypotheses are tested through the SPSS PROCESS macro plugin.

Findings
Drawing on the importance of human capital to tourism organizations, this study illustrates that affective commitment has a positive and significant influence on employees’ customer orientation, and that this relationship is fully mediated by knowledge-sharing behaviors.

Practical implications
As attitudes are more stable than behaviors, the findings suggest that managers of tourism organizations implement appropriate selection and recruitment techniques, together with adequate involvement and empowerment activities, to identify and support individuals whose attitudes fit the organizational goals.

Originality/value
Acknowledging the contribution that workers can give to service organizations’ success, this paper enriches the understanding of the mechanisms that underlie the relationship between employees’ attitudes and their orientation toward the customer. Building on the cognitive dissonance theory, it adds to extant research on the individual antecedents of employees’ customer orientation by shedding light on the attitude–behavior relationship in tourism organizations.
Employees’ evaluative repertoires of tourism and hospitality jobs
Authors: Schneider Anna , Treisch Corinna 
Published: July 2019

Purpose
This paper aims to examine employees’ evaluative repertoires of tourism and hospitality jobs and segments them based on a set of job attribute preferences. Understanding the social–cultural underpinnings of employees’ job preferences is vital if employers are to overcome the challenging task of finding and retaining talented employees in the tourism and hospitality industry.

Design/methodology/approach
A discrete-choice experiment with waiters, barkeepers, cooks and front-desk employees working in the Tyrolean tourism industry was conducted. Employees were categorized into distinct segments using a hierarchical Bayesian analysis and a cluster analysis.

Findings
Results show that flexible working hours and the ability to balance professional and private aspirations are the most important job attributes for employees. Overall, the evaluative repertoires of the “green” and “domestic (family)” conventions are most prevalent.

Research limitations/implications
This study contributes to literature on talent management by providing insights into employees’ evaluations of jobs and their evaluative repertoires embedded in the broader social–cultural context.

Practical implications
Industry representatives and employers can adapt their recruiting and retention strategies based on employees’ job preferences.

Social implications
Adapting job attributes according to employees’ evaluative repertoires helps to ensure the long-term sustainability of the industry workforce.

Originality/value
Applying the Economics of Convention (EC) perspective, combining organizational job attributes and socially embedded evaluative repertoires provides a new approach to analysing and understanding employees’ job preferences.
Mobile nodes for improving security and lifetime efficiency in wireless sensor networks
Authors: Salah Mohammed Saïd , Abderrahim Maizate , Mohamed Ouzzif , Mohamed Toumi 
Published: July 2019

Purpose
This paper aims to provide an acceptable level of security while taking into account limited capabilities of the sensors. This paper proposes a mobile approach to securing data exchanged by structured nodes in a cluster.

Design/methodology/approach
The approach is based on mobile nodes with significant calculation and energy resources that allow cryptographic key management and periodic rekeying. However, mobility in wireless sensor networks aims to increase the security and lifetime of the entire network. The technical methods used in this paper are based on cryptography elliptic curves and key management through a balanced binary tree.

Findings
To maintain the effectiveness of critical applications based on wireless sensor networks, a good level of nodes security must be ensured, taking into account their limited energy and computing. Collaboration between powerful mobile nodes provides better coverage and a good key management. Owing to the significant capabilities of the mobile nodes, they can be used to secure critical applications at the same time if needed in applications requiring difficult operations.

Originality/value
To compare the performance of the proposed approach with other mobile algorithms, the following metrics are focused on: the energy consumed by normal sensors and cluster heads, the number of packets exchanged during key installation, time to generate and distribute cryptographic keys and the memory used by the different sensors to store keys.