bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the Athena SWAN award scheme for gender equality as a complex social intervention in a complex system: analysis of Silver award action plans in a comparative European perspective
Authors: Schmidt Evanthia Kalpazidou , Ovseiko Pavel V. , Henderson Lorna R , Kiparoglou Vasiliki 
Published: February 2019

AbstractBackgroundGiven that the complex mix of structural, cultural, and institutional factors has produced barriers for women in science, an equally complex intervention is required to understand and address them. The Athena SWAN award scheme for gender equality has become a widespread means to address barriers for women’s advancement and leadership in the United Kingdom, Ireland, Australia, the United States of America, and Canada, while he European Commission is exploring the introduction of a similar award scheme across Europe.MethodsThis study analyses the design and implementation of 16 departmental Athena SWAN Silver action plans in Medical Sciences at one of the world’s leading universities in Oxford, United Kingdom. Data pertaining to the design and implementation of gender equality interventions were extracted from the action plans, analysed thematically, coded using categories from the 2015 Athena SWAN Charter Awards Handbook, and synthesised against a typology of gender equality interventions in the European Research Area. The results were further analysed against the complexity research literature framework, where research organisations are perceived as dynamic systems that adapt, interact and co-evolve with other systems.ResultsAthena SWAN is a complex contextually-embedded system of action planning within the context of universities. It depends on a multitude of contextual variables that relate in complex, non-linear ways, and dynamically adapt to constantly moving targets and new emergent conditions. Athena SWAN Silver action plans conform to the key considerations of complexity: 1) multiple actions and areas of intervention with a focus on the complex system embedded in and the local dynamics, 2) the non-linearity of interventions and the constantly emerging conditions, 3) impact in terms of contribution to change, improved conditions to foster change, and the increased probability that change can occur.ConclusionsTo enact effective sustainable gender equality structural and cultural change, it is necessary to acknowledge and operationalize complexity as a frame of reference. Athena SWAN is the single most comprehensive and systemic gender equality scheme in Europe and can be strengthened further by promoting the integration of sex and gender analysis in research and education. Gender equality policies in the wider European Research Area can benefit from exploring Athena SWAN’s contextually-embedded systemic approach to dynamic action planning and inclusive focus on all genders and categories of staff and students.
LUXendins reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics
Authors: Ast Julia , Arvaniti Anastasia , Fine Nicholas H.F. , Nasteska Daniela , Ashford Fiona B. , Stamataki Zania , Koszegi Zsombor , Bacon Andrea , Trapp Stefan , Jones Ben J. , Hastoy Benoit , Tomas Alejandra , Reissaus Christopher A. , Linnemann Amelia K. , D’Este Elisa , Calebiro Davide , Johnsson Kai , Podewin Tom , Broichhagen Johannes , Hodson David J. 
Published: February 2019

ABSTRACTThe glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label. LUXendin645 produces intense and specific membrane labeling throughout live and fixed tissue. GLP1R signaling can additionally be evoked when the receptor is allosterically modulated in the presence of LUXendin645. Using LUXendin645 and STED-compatible LUXendin651 we describe islet GLP1R expression patterns, reveal higher-order GLP1R organization including the existence of membrane nanodomains, and track single receptor subpopulations. We furthermore show that different fluorophores can confer agonistic behavior on the LUXendin backbone, with implications for the design of stabilized incretin-mimetics. Thus, our labeling probes possess divergent activation modes, allow visualization of endogenous GLP1R, and provide new insight into class B GPCR distribution and dynamics.
A re-interpretation of the experimental data of Shinder and Taube “Three-dimensional Tuning of Head Direction Cells in Rats”, Journal of Neurophysiology 121(1), 2019
Authors: Laurens Jean , Angelaki Dora E. 
Published: February 2019

AbstractIn a recent study, Shinder and Taube (2019) concluded that head direction cells in the anterior thalamus of rats are tuned to one-dimensional (1D, yaw-only) motion exclusively, in contrast to recent findings in bats (Finkelstein et al. 2015), mice (Angelaki et al. 2016; Cham et al. 2017; Laurens et al. 2017), and rats (Page et al. 2017). Here we re-interpret the author’s experimental results using model comparison and demonstrate that, contrary to their conclusions, their data actually supports the dual-axis rule (Page et al. 2017) and tilted azimuth model (Laurens and Angelaki 2018), where head direction cells use gravity to integrate 3D rotation signals about all cardinal axes of the head. We further show that this study is inconclusive regarding the presence of vertical orientation tuning; i.e. whether head direction cells encode 3D orientation in the horizontal and vertical planes conjunctively. Using model simulations, we demonstrate that, even if 3D tuning existed, the experimental protocol and data analyses used by Shinder and Taube (2019) would not have revealed it. We conclude that the actual experimental data of Shinder and Taube (2019) are compatible with the 3D properties of head direction cells discovered by other groups, yet incorrect conclusions were reached because of incomplete and qualitative analyses.
Endothelial specific PER2 at the crossroads of light elicited circadian amplitude enhancement as novel cardioprotective strategy and transcriptional regulation of HIF1A-dependent metabolic adaptation to myocardial ischemia
Authors: Oyama Yoshimasa , Bartman Colleen M. , Bonney Stephanie , Lee J. Scott , Walker Lori A. , Han Jun , Borchers Christoph H. , Buttrick Peter M. , Clendenen Nathan , Colgan Sean P. , Eckle Tobias 
Published: February 2019

ABSTRACTConsistent daylight oscillations and abundant oxygen availability are fundamental to human health. While both are connected from an evolutionary and cellular perspective, only oxygen is an established therapy in cardiovascular medicine. Here, we probe the mechanistic intersection between light-(Period 2, PER2) and oxygen-(hypoxia inducible factor, HIF1A) sensing pathways in cellular adaptation to low oxygen conditions with respect to myocardial ischemia.Using a whole genome array from daylight exposed wildtype orPer2−/−mice, an affinity purification-mass spectrometry-based proteomics screen for PER2 targets in hypoxic human endothelial cells, and targeted metabolomics from human healthy volunteers after daylight therapy, we investigated the intersection of light and hypoxia elicited pathways. Housing mice under daylight conditions prior to myocardial ischemia and reperfusion (IR)-injury, uncovered circadian PER2 amplitude enhancement as novel cardioprotective strategy, mimicking HIF1A metabolic adaptation to myocardial ischemia in a PER2 regulated manner. Whole genome array analysis from daylight exposed wildtype andPer2−/−mice or myocardial IR-injury in endothelial specific PER2 deficient mice (Per2loxP/loxP-VE-Cadherin -Cre) revealed a critical role for light elicited PER2 in maintaining the endothelial barrier function during myocardial ischemia. Mechanistic studies in human endothelia pointed towards a master transcriptional regulatory role for endothelial PER2 in metabolic reprograming to hypoxia via HIF1A, which was mimicked during normoxic PER2 stabilization. Translational investigation of light elicited pathways in human healthy volunteers found similar increases of PER2 or mimicking of HIF1A dependent metabolism. These studies identify light elicited circadian amplitude enhancement of endothelial PER2 as a novel cardioprotective strategy. Furthermore, these studies identify PER2 as critical control point of endothelial metabolic reprograming to maintain vascular integrity during myocardial IR-injury and implicate the use of daylight therapy to increase endothelial PER2 signaling as a strategy for the treatment of coronary artery disease.
Src-dependent DBL family members drive resistance to vemurafenib in human melanoma
Authors: Feddersen Charlotte R. , Schillo Jacob L. , Varzavand Afshin , Vaughn Hayley R. , Wadsworth Lexy S. , Voigt Andrew P. , Zhu Eliot Y. , Jennings Brooke M. , Mullen Sarah A. , Bobera Jeremy , Riordan Jesse D. , Stipp Christopher S. , Dupuy Adam J. 
Published: February 2019

ABSTRACTThe use of selective BRAF inhibitors (BRAFi) has produced remarkable outcomes for patients with advanced cutaneous melanoma harboring a BRAFV600E mutation. Unfortunately, the majority of patients eventually develop drug-resistant disease. We employed a genetic screening approach to identify gain-of-function mechanisms of BRAFi resistance in two independent melanoma cell lines. Our screens identified both known and unappreciated drivers of BRAFi resistance, including multiple members of the DBL family. Mechanistic studies identified a DBL/Rac1/Pak signaling axis capable of driving resistance to both current and next-generation BRAF inhibitors. However, we show that the Src inhibitor, saracatinib, can block the DBL-driven resistance. Our work highlights the utility of our straightforward genetic screening method in identifying new drug combinations to combat acquired BRAFi resistance.
RumimiR: a detailed microRNA database focused on ruminant species
Authors: Céline Bourdon , Philippe Bardou , Etienne Aujean , Sandrine Le Guillou , Gwenola Tosser-Klopp , Fabienne Le Provost 
Published: February 2019

ABSTRACTIn recent years, the increasing use of Next Generation Sequencing technologies to explore the genome has generated large quantities of data. For microRNAs, more and more publications have described several thousand sequences, all species included. In order to obtain a detailed description of microRNAs from the literature for three ruminant species (bovine, caprine and ovine), a new database has been created: RumimiR. To date, 2,887, 2,733 and 5,095 unique microRNAs of bovine, caprine and ovine species, respectively, have been included. In addition to the most recent reference genomic position and sequence of each microRNA, this database contains details on the animals, tissue origins and experimental conditions available from the publications. Identity with human or mouse microRNA is mentioned. The RumimiR database enables data filtering, the selection of microRNAs being based on defined criteria such as animal status or tissue origin. For ruminant studies, RumimiR supplements the widely used miRBase database by browsing and filtering using complementary criteria, and the integration of all published sequences described as novel. The principal goal of this database is to provide easy access to all ruminant microRNAs described in the literature.
The pseudogene SURFIN 4.1 is vital for merozoite formation in blood stage P. falciparum
Authors: Macedo-Silva Tatiane , Araujo Rosana Beatriz Duque , Wunderlich Gerhard 
Published: February 2019

AbstractThe surf gene family of the human malaria parasite Plasmodium falciparum encodes for antigens with largely unknown functions. Three of the ten surf genes found in the P. falciparum 3D7 genome are annotated as pseudogenes, and one of these – surf4.1 (PF3D7_0402200) - was continuously transcribed in P. falciparum 3D7 blood stage forms. GFP-tagging revealed that despite several stop codons a full-length protein was expressed, which localized to developing merozoites. Analysis of cDNAs showed that no specific editing occurred pointing to readthrough of stop codons during translation. Intriguingly, attempts to generate parasite lines containing an additional artificial stop codon failed. Transcript knockdown revealed that surf4.1 is essential for merozoite formation in late trophozoite/schizont stages while DNA replication seemed not to be influenced. SURFIN4.1 is the first example of a plasmodial multigene family member of which a knockout is deleterious and may pose as a novel target for anti-malarial therapy.
Structural disconnections explain brain network dysfunction after stroke
Authors: Griffis Joseph C. , Metcalf Nicholas V. , Corbetta Maurizio , Shulman Gordon L. 
Published: February 2019

SummaryFunctional connectivity (FC) studies have identified physiological signatures of stroke that correlate with behavior. Using structural and functional MRI data from 114 stroke patients, 24 matched controls, and the Human Connectome Project, we tested the hypothesis that structural disconnection, not damage to critical regions, underlies FC disruptions. Disconnection severity outperformed damage to putative FC connector nodes for explaining reductions in system modularity, and multivariate models based on disconnection outperformed damage models for explaining FC disruptions within and between systems. Across patients, disconnection and FC patterns exhibited a low-dimensional covariance dominated by a single axis linking interhemispheric disconnections to reductions in FC measures of interhemispheric system integration, ipsilesional system segregation, and system modularity, and that correlated with multiple behavioral deficits. These findings clarify the structural basis of FC disruptions in stroke patients and demonstrate a low-dimensional link between perturbations of the structural connectome, disruptions of the functional connectome, and behavioral deficits.
Enzyme kinetics of tobacco Rubisco expressed in Escherichia coli varies depending on the small subunit composition
Authors: Lin Myat T. , Stone William D. , Chaudhari Vishal , Hanson Maureen R. 
Published: February 2019

AbstractRubisco catalyzes the first step in carbon fixation and has been a strategic target to improve photosynthetic efficiency. In plants, Rubisco is a complex made up of eight large subunits encoded by a chloroplast gene, rbcL, and eight small subunits expressed from a nuclear gene family and targeted to chloroplast stroma. Biogenesis of Rubisco in plants requires a chaperonin system composed of Cpn60α, Cpn60β and Cpn20, which helps fold the large subunit, and multiple chaperones including RbcX, Raf1, Raf2 and BSD2, which help the dimerization of the folded large subunits and subsequent assembly with the small subunits into L8S8 holoenzymes. A recent study successfully assembled functional Arabidopsis Rubisco in Escherichia coli by co-expressing the two subunits with Arabidopsis chaperonins and chaperones (Aigner et al., 2017). In this study, we modified the expression vectors used in that study and adapted them to express tobacco Rubisco by replacing the Arabidopsis genes with tobacco ones. Next, we surveyed the small subunits present in tobacco, co-expressed each with the large subunit and successfully produced active tobacco enzymes composed of different small subunits in E. coli. These enzymes produced in E. coli have carboxylation kinetics very similar to that of the native tobacco Rubisco. We also produced tobacco Rubisco with a recently discovered trichome small subunit in E. coli and found that it has a higher catalytic rate and a lower CO2 affinity compared to the enzymes with other small subunits. Our improvements in the E. coli Rubisco expression system will allow us to probe features of both the chloroplast and nuclear-encoded subunits of Rubisco that affect its catalytic rate and CO2 specificity.
Efficient mesoscale phenotypic screening in cultured primary neuron culture
Authors: Nedrud David , He Yungui , Schmidt Daniel 
Published: February 2019

AbstractA longstanding question in neuroscience is how the activity of ion channels shapes neuronal activity and, as a result, computation in circuits and networks. Optogenetic reagents are tools to answer this question by enabling precise and dynamic perturbation of cellular states. However, development of these reagents can be hampered by low-throughput assays in non-physiological contexts. Here, we develop an all optical phenotypic screen in cultured primary hippocampal neurons that enables the functional assessment of large libraries of genetically encoded optogenetic actuators. Combining real-time analysis and data reduction methods allows for continuous observation of several thousand neurons for several days without onerous data storage overhead. This screening system may be useful in a diversity of research questions that can be coupled to optical perturbation and sensing.
Cyber threats confronting the digital built environment
Authors: Parn Erika A. , Edwards David 
Published: February 2019

Purpose
Smart cities provide fully integrated and networked connectivity between virtual/digital assets and physical building/infrastructure assets to form digital economies. However, industrial espionage, cyber-crime and deplorable politically driven cyber-interventions threaten to disrupt and/or physically damage the critical infrastructure that supports national wealth generation and preserves the health, safety and welfare of the populous. The purpose of this paper is to present a comprehensive review of cyber-threats confronting critical infrastructure asset management reliant upon a common data environment to augment building information modelling (BIM) implementation.

Design/methodology/approach
An interpretivist, methodological approach to reviewing pertinent literature (that contained elements of positivism) was adopted. The ensuing mixed methods analysis: reports upon case studies of cyber-physical attacks; reveals distinct categories of hackers; identifies and reports upon the various motivations for the perpetrators/actors; and explains the varied reconnaissance techniques adopted.

Findings
The paper concludes with direction for future research work and a recommendation to utilize innovative block chain technology as a potential risk mitigation measure for digital built environment vulnerabilities.

Originality/value
While cyber security and digitization of the built environment have been widely covered within the extant literature in isolation, scant research has hitherto conducted an holistic review of the perceived threats, deterrence applications and future developments in a digitized Architecture, Engineering, Construction and Operations (AECO) sector. This review presents concise and lucid reference guidance that will intellectually challenge, and better inform, both practitioners and researchers in the AECO field of enquiry.
Marie Unna hereditary hypotrichosis accompanied by multiple familial trichoepithelioma in a Chinese family
Authors: Huang Ye , Cai Chuan , Ren Li , Cui Caijuan , Zhang Xue , Liu Wei 
Published: February 2019

AbstractMarie Unna hereditary hypotrichosis (MUHH) and multiple familial trichoepithelioma (MFT) are both autosomal dominant disorders. Recently, certain genes (HR and EPS8L3) have been found to be responsible for MUHH, while CYLD has been demonstrated to be the main pathogenic gene in MFT patients. However, there exist a number of CYLD mutation‐negative MFT cases, for which the causative gene has been unknown. Here, we identified a large, five‐generation Han Chinese family with several patients presenting with MUHH and MFT. Sanger sequencing of three genes in 13 family members was performed. We found that the c.1A>G mutation in an inhibitory upstream open‐reading frame of HR (U2HR) was present in all MUHH patients, while no pathogenic variants were found in the 3ʹ‐ or 5ʹ‐untranslated regions, exons or flanking intronic sequences of EPS8L3 or CYLD in any family members. Subsequently, whole‐genome sequencing was performed for five affected and one unaffected family member. We found no CYLD variants but identified an FABP12 variant (rs536105592 G>A) in the patients with both MUHH and MFT. These results suggest that the U2HR mutation was responsible for MUHH and the FABP12 variant may be coincidental in the accompanying MFT in this unique pedigree. This report deepens our understanding of the genetic basis of hair follicle diseases.
In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab
Authors: Kiyohara Takahiro , Shijimaya Takako , Miyamoto Mari , Nagano Naoko , Nakamaru Sei , Makimura Kaoru , Tanimura Hirotsugu 
Published: February 2019

AbstractA 65‐year‐old Japanese man presented with a dome‐shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin–eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier‐like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in‐transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in‐transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in‐transit recurrence of Merkel cell carcinoma.
Seismic receiver coupling to the seafloor
Authors: Landschulze Marcus 
Published: February 2019

ABSTRACTThe presence of geophysical receivers on the seafloor changes the local wave field due to the receiver seafloor interaction. The resulting PP‐ and PS‐wave distortion of the wave field is often referred to as receiver coupling to the seafloor and can make data processing challenging and sometimes impossible. This paper provides an overview of the mathematical approaches to describe receiver coupling, how to estimate receiver coupling and what the difficulties and possible solutions are. The first section shows how the mathematical approach developed from a simple model considering only the vertical receiver component to include all three receiver components and their interactions with the seafloor. In the second section, I show how receiver coupling can be measured and how it can be improved using mathematical and data‐driven approaches.