bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arctic architectures
Authors: Hemmersam Peter 
Published: January 2016

ABSTRACTIn 1968, the British/Swedish architect Ralph Erskine published an article ‘Architecture and town planning in the north’ in this journal, in which he called for a particular Arctic approach to the design of buildings and cities that is distinct from mainstream architecture due to conditions such as harsh climate, resident indigenous or sparse population and remoteness. One hundred years after his birth (in 1914), Erskine is still considered the authoritative ‘Arctic architect’, and his approach is paradigmatic among many architects dealing with the built environment in the Arctic, sub-Arctic and northern regions.However, a study of the literature on architectural practice and the built environment in the north reveals a number of varying conceptions of Arctic architecture. These different perspectives are social in nature and construct the architectural technologies, the natural environment and society in different configurations. This article finds that architectural discourses and readings of the Arctic change under the influence of social, cultural, political and architectural paradigms. The perspectives identified in the article are seen to be critical supplements to Erskine's utopian approach to developing new sustainable forms of urbanism and architecture in the Arctic. They also reveal that new conceptions do not necessarily replace previous ones but often overlap and place earlier ideas into fresh concepts and that certain conceptions appear to perpetuate over the decades, such as the Arctic as an ‘empty space’. The thinking on Arctic futures is, in many ways, trapped in certain modernist and utopian modes, and this article contributes to widening the range of possible relationships between people and the Arctic environment, using architecture as an aperture.
Physical Activity Perceptions and Influences among Older Adults in Rural Nova Scotia
Authors: Witcher Chad S. G. , Holt Nicholas L. , Young Wendy , Blanchard Chris , Murnaghan Donna , Spence John C. 
Published: January 2016

RÉSUMÉCette étude a identifié les facteurs qui influencent la participation à l’activité physique (AP) chez les adultes âgés de milieu rural en Nouvelle-Écosse, et a étudié comment le contexte rural peut influer sur la participation et la promotion de l’AP. Les données ont été recueillies au moyen d’entrevues semi-structurées individuelles avec 20 adultes plus âgés (Âgem = 77,5 ans) des régions rurales du Cap-Breton, Nouvelle-Écosse, et soumis à des procédures d’analyse thématique (Braun & Clarke, 2006). Quatre thèmes représentant facteurs qui influent sur la priorisation des AP ont été identifiés: (1) Le contexte historique de l’activité, le travail et la productivité; (2) déjà s’etant occupé avec les activités au jour le jour; (3) étant / restant sur la route; et (4) une approche prudente. Ces résultats suggèrent que la promotion de l’AP devrait être contextuellement saillant, et ils soulignent la nécessité d’une compréhension commune entre les personnes âgées en milieu rural et les promoteurs de l’AP sur ce qui constitue être «physiquement actif.” La promotion effective de l’AP chez les adultes ruraux âgés peut nécessitent le déplacement de méthodes contemporaines de cette promotion.
Qualitative Research in theCJA/RCV:An 18-Year Analysis (1995–2012)
Authors: Humble Áine M. , Green Maureen 
Published: January 2016

RÉSUMÉDes chercheurs ont suggérés que la recherche qualitative augmente dans le domaine de la gérontologie, mais peu d'analyses systématiques ont testés cette assertion. En utilisantLa Revue canadienne du vieillissement/Canadian Journal on Agingcomme étude de cas, des articles représentant des projets de recherche originaux de 1995 à 2012 ont été analysés. Un sur quatre articles représentait des recherches qualitatives, et les résultats en intervals de trois ans ont montrés une augmentation évidente des résultats venants des études qualitatives durant cette période de 18 ans: (a) 1995–1997: 10%; (b) 199 –2000: 19%; (c) 200 –2003: 25%; (d) 2004–2006: 25%; (e) 2007–2009: 29%; et (f) 2010–2012: 43%. Dans chaque intervalle de temps (à l'exception de 2004–2006), les articles en langue française utilisaient d’avantage de méthodologie qualitative que les articles en anglais. Les articles françaises utilisaient une conception de la recherche qualitative plus souvent que les articles en anglais. Les sujets de recherche, les méthodologies, et la stratégie de recueil des données sont aussi examinés.
Exploring practical approaches to maximising data quality in electronic healthcare records in the primary care setting and associated benefits. Report of panel-led discussion held at SAPC in July 2014
Authors: Dungey Sheena , Glew Simon , Heyes Barbara , Macleod John , Tate A. Rosemary 
Published: January 2016

BackgroundElectronic healthcare records provide information about patient care over time which not only affords the opportunity to improve patient care directly through effective monitoring and identification of care requirements but also offers a unique platform for both clinical and service-model research essential to the longer-term development of the health service. The quality of the recorded data can, however, be variable and can compromise the validity of data use both for primary and secondary purposes.ObjectivesIn order to explore the challenges and benefits of and approaches to recording high quality primary care electronic records, a Clinical Practice Research Datalink (CPRD) sponsored workshop was held at the Society of Academic Primary Care (SAPC) conference in 2014 with the aim of engaging GPs and other data users.MethodsThe workshop was held as a structured discussion, led by an expert panel and focused around three questions: (1) What are the data quality priorities for clinicians and researchers? How do these priorities differ or overlap? (2) What challenges might GPs face in provision of good data quality both for treating their patients and for research? Do these aims conflict? (3) What tools (such as data metrics and visualisations or software components) could assist the GP in improving data quality and patient management and could this tie in with analytical processes occurring at the research stage?ResultsThe discussion highlighted both overlap and differences in the perceived data quality priorities and challenges for different user groups. Five key areas of focus were agreed upon and recommendations determined for moving forward in improving quality.ConclusionsThe importance of good high quality electronic healthcare records has been set forth along with the need for a practical user-considered and collaborative approach to its improvement.
HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death
Authors: Jacobsen A V , Lowes K N , Tanzer M C , Lucet I S , Hildebrand J M , Petrie E J , van Delft M F , Liu Z , Conos S A , Zhang J-G , Huang D C S , Silke J , Lessene G , Murphy J M 
Published: January 2016

AbstractNecroptosis is a caspase-independent form of regulated cell death that has been implicated in the development of a range of inflammatory, autoimmune and neurodegenerative diseases. The pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL), is the most terminal known obligatory effector in the necroptosis pathway, and is activated following phosphorylation by Receptor Interacting Protein Kinase-3 (RIPK3). Activated MLKL translocates to membranes, leading to membrane destabilisation and subsequent cell death. However, the molecular interactions governing the processes downstream of RIPK3 activation remain poorly defined. Using a phenotypic screen, we identified seven heat-shock protein 90 (HSP90) inhibitors that inhibited necroptosis in both wild-type fibroblasts and fibroblasts expressing an activated mutant of MLKL. We observed a modest reduction in MLKL protein levels in human and murine cells following HSP90 inhibition, which was only apparent after 15 h of treatment. The delayed reduction in MLKL protein abundance was unlikely to completely account for defective necroptosis, and, consistent with this, we also found inhibition of HSP90 blocked membrane translocation of activated MLKL. Together, these findings implicate HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90’s previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3.
Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway
Authors: Cherepkova M Y , Sineva G S , Pospelov V A 
Published: January 2016

AbstractLeukemia inhibitory factor (LIF) is indispensable to maintain the pluripotent state of mouse embryonic stem cells (ESCs), but the mechanisms underlying the role of LIF/STAT3 pathway are yet poorly understood. Here we first showed that the LIF/STAT3-regulated signaling pathway contributes to the maintenance of self-renewal and pluripotency of mouse ESCs by suppressing mTOR (mammalian target of rapamycin), which is necessary for early differentiation. When LIF is withdrawn from culture medium, the mTOR activity rapidly increases as detected by phosphorylation of its targets – ribosomal protein S6 and translation factor 4EBP1. In turn, suppression of STAT3 phosphorylation on Tyr-705 by a specific small molecule WP1066 also activates phosphorylation of the mTOR target S6 ribosomal protein. LIF removal strongly activates ERK activity indicating that ERK can be involved in either direct phosphorylation of mTOR or phosphorylation of an upstream negative regulator of mTOR – TSC1/TSC2 proteins. According to western blotting data, LIF withdrawal leads to phosphorylation of TSC2 protein thereby relieving its negative effect on mTOR activity. mTOR activation is accompanied by a decrease of pluripotent gene expression Oct-4, Nanog, Sox2 and by an augmentation of fgf5 gene expression – a marker of post-implantation epiblast. Together, these data indicate that LIF-depleted mouse ESCs undergo a transition from the LIF/STAT3-supported pluripotent state to the FGFR/ERK-committed primed-like state with expression of early differentiation markers mediated through activation of mTOR signaling.
Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak
Authors: Megyesi J , Tarcsafalvi A , Seng NSHL , Hodeify R , Price PM 
Published: January 2016

AbstractApoptosis is a regulated form of cell death that proceeds by defined biochemical pathways. Most apoptosis is controlled by interactions between pro-survival and pro-apoptotic Bcl-2 family proteins in which death is often the consequence of permeabilization of the mitochondrial outer membrane. Many drugs affect this equilibrium to favor apoptosis but this process is not completely understood. We show that the chemotherapeutic drug cisplatin initiates an apoptotic pathway by phosphorylation of a pro-survival Bcl-2 family member, Bcl-xL, by cyclin-dependent kinase 2. The phosphorylation occurred at a previously unreported site and its biologic significance was demonstrated by a phosphomimetic modification of Bcl-xL that was able to induce apoptosis without addition of cisplatin. The mechanism of cell death induction was similar to that initiated by pro-apoptotic Bcl-2 family proteins, that is, phosphorylated Bcl-xL translocated to the mitochondrial membrane, and formed pores in the membrane. This initiated cytochrome c release and caspase activation that resulted in cell death.
Termination layer compensated tunnelling magnetoresistance in ferrimagnetic Heusler compounds with high perpendicular magnetic anisotropy
Authors: Jeong Jaewoo , Ferrante Yari , Faleev Sergey V. , Samant Mahesh G. , Felser Claudia , Parkin Stuart S. P. 
Published: January 2016

AbstractAlthough high-tunnelling spin polarization has been observed in soft, ferromagnetic, and predicted for hard, ferrimagnetic Heusler materials, there has been no experimental observation to date of high-tunnelling magnetoresistance in the latter. Here we report the preparation of highly textured, polycrystalline Mn3Ge films on amorphous substrates, with very high magnetic anisotropy fields exceeding 7 T, making them technologically relevant. However, the small and negative tunnelling magnetoresistance that we find is attributed to predominant tunnelling from the lower moment Mn–Ge termination layers that are oppositely magnetized to the higher moment Mn–Mn layers. The net spin polarization of the current reflects the different proportions of the two distinct termination layers and their associated tunnelling matrix elements that result from inevitable atomic scale roughness. We show that by engineering the spin polarization of the two termination layers to be of the same sign, even though these layers are oppositely magnetized, high-tunnelling magnetoresistance is possible.
Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness
Authors: Avgustinova Alexandra , Iravani Marjan , Robertson David , Fearns Antony , Gao Qiong , Klingbeil Pamela , Hanby Andrew M. , Speirs Valerie , Sahai Erik , Calvo Fernando , Isacke Clare M. 
Published: January 2016

AbstractStromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis. Mechanistically, Wnt7a-mediated fibroblast activation is not dependent on classical Wnt signalling. Instead, we demonstrate that Wnt7a potentiates TGFβ receptor signalling both in 3D in vitro and in vivo models, thus highlighting the interaction between two of the key signalling pathways in development and disease. Importantly, in clinical breast cancer cohorts, tumour cell Wnt7a expression correlates with a desmoplastic, poor-prognosis stroma and poor patient outcome.
Ancient balancing selection at tan underlies female colour dimorphism in Drosophila erecta
Authors: Yassin Amir , Bastide Héloïse , Chung Henry , Veuille Michel , David Jean R. , Pool John E. 
Published: January 2016

AbstractDimorphic traits are ubiquitous in nature, but the evolutionary factors leading to dimorphism are largely unclear. We investigate a potential case of sexual mimicry in Drosophila erecta, in which females show contrasting resemblance to males. We map the genetic basis of this sex-limited colour dimorphism to a region containing the gene tan. We find a striking signal of ancient balancing selection at the ‘male-specific enhancer’ of tan, with exceptionally high sequence divergence between light and dark alleles, suggesting that this dimorphism has been adaptively maintained for millions of years. Using transgenic reporter assays, we confirm that these enhancer alleles encode expression differences that are predicted to generate this pigmentation dimorphism. These results are compatible with the theoretical prediction that divergent phenotypes maintained by selection can evolve simple genetic architectures.
Energy disruptors: rising stars in anticancer therapy?
Authors: Bost F , Decoux-Poullot A-G , Tanti J F , Clavel S 
Published: January 2016

AbstractThe metabolic features of tumor cells diverge from those of normal cells. Otto Warburg was the first to observe that cancer cells dramatically increase their glucose consumption to generate ATP. He also claimed that cancer cells do not have functional mitochondria or oxidative phosphorylation (OXPHOS) but simply rely on glycolysis to provide ATP to the cell, even in the presence of oxygen (aerobic glycolysis). Several studies have revisited this observation and demonstrated that most cancer cells contain metabolically efficient mitochondria. Indeed, to sustain high proliferation rates, cancer cells require functional mitochondria to provide ATP and intermediate metabolites, such as citrate and cofactors, for anabolic reactions. This difference in metabolism between normal and tumors cells causes the latter to be more sensitive to agents that can disrupt energy homeostasis. In this review, we focus on energy disruptors, such as biguanides, 2-deoxyglucose and 5-aminoimidazole-4-carboxamide ribonucleotide, that interfere with the main metabolic pathways of the cells, OXPHOS, glycolysis and glutamine metabolism. We discuss the preclinical data and the mechanisms of action of these disruptors at the cellular and molecular levels. Finally, we consider whether these drugs can reasonably contribute to the antitumoral therapeutic arsenal in the future.
Mucin 1-mediated chemo-resistance in lung cancer cells
Authors: Ham S Y , Kwon T , Bak Y , Yu J-H , Hong J , Lee S K , Yu D-Y , Yoon D-Y 
Published: January 2016

AbstractPaclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial–mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and β-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and β-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers.
Bone alterations are associated with ankle osteoarthritis joint pain
Authors: Nakamura Yukio , Uchiyama Shigeharu , Kamimura Mikio , Komatsu Masatoshi , Ikegami Shota , Kato Hiroyuki 
Published: January 2016

AbstractThe etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain.
Graphene/GaSe-Nanosheet Hybrid: Towards High Gain and Fast Photoresponse
Authors: Lu Rongtao , Liu Jianwei , Luo Hongfu , Chikan Viktor , Wu Judy Z. 
Published: January 2016

AbstractWhile high photoconductive gain has been recently achieved in graphene-based hybrid phototransistors using semiconductor two-dimensional transition/post-transition metal dichalcogenides or quantum dots sensitizers, obtaining fast photoresponse simutaneously remains a challenge that must be addressed for practical applications. In this paper we report a graphene/GaSe nanosheets hybrid photodetector, in which GaSe nanosheets provide a favorable geometric link to graphene conductive layer through van Der Waals force. After a vacuum annealing process, a high gain in exceeding 107 has been obtained simitaneously with a dynamic response time of around 10 ms for both light on and off. We attribute the high performance to the elimination of possible deep charge traps, most probably at the graphene/GaSe nanosheets interface. This result demonstrates high photoconductive gain and fast photoresponse can be achieved simultaneously and a clean interface is the key to the high performance of these hybrid devices.
Surface–Atmosphere Moisture Interactions in the Frozen Ground Regions of Eurasia
Authors: Ford Trent W. , Frauenfeld Oliver W. 
Published: January 2016

AbstractClimate models simulate an intensifying Arctic hydrologic cycle in response to climatic warming, however the role of surface-atmosphere interactions from degrading frozen ground is unclear in these projections. Using Modern-Era Retrospective Analysis for Research and Applications (MERRA) data in high-latitude Eurasia, we examine long-term variability in surface-atmosphere coupling as represented by the statistical relationship between surface evaporative fraction (EF) and afternoon precipitation. Changes in EF, precipitation and their statistical association are then related to underlying permafrost type and snow cover. Results indicate significant positive trends in July EF in the Central Siberian Plateau, corresponding to significant increases in afternoon precipitation. The positive trends are only significant over continuous permafrost, with non-significant or negative EF and precipitation trends over isolated, sporadic and discontinuous permafrost areas. Concurrently, increasing EF and subsequent precipitation are found to coincide with significant trends in May and June snowmelt, which potentially provides the moisture source for the observed enhanced latent heating and moisture recycling in the region. As climate change causes continuous permafrost to transition to discontinuous, discontinuous to sporadic, sporadic to isolated and isolated permafrost disappears, this will also alter patterns of atmospheric convection, moisture recycling and hence the hydrologic cycle in high-latitude land areas.
X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study
Authors: Park Hanwook , Yeom Eunseop , Lee Sang Joon 
Published: January 2016

AbstractX-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measurein vivoblood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conductingin vivoX-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.