bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 transcription factor for the NEDD9/HEF1/Cas-L gene: potential targets in Non-Small Cell Lung Cancer treatment
Authors: ROUSSEAU Bénédicte , JACQUOT Catherine , LE PALABE Julie , MALLETER Marine , TOMASONI Christophe , BOUTARD Tifenn , SAKANYAN Vehary , ROUSSAKIS Christos 
Published: May 2015

AbstractLung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents. Considering the high proportion of mutant proteins in tumor cells and the high rate of mutation of the TP53 gene in all cancers and in NSCLC in particular, this gene is a perfect target. Certain new molecules have been shown to restore the activity of mutated p53 protein, for example PRIMA-1, which reactivates the His273 mutant p53. In a previous study, we presented triazine A190, a molecule with a cytostatic activity that blocks cells in the G1 phase and induces apoptosis. Here, we show that A190 not only restores mutant p53 activity, but also induces an overexpression of the NEDD9 gene, leading to apoptotic death. These findings might offer hope for the development of new targeted therapies, specific to tumor cells, which spare healthy cells.
Post-transcriptional regulation of gene expression by Unr
Authors: Ray Swagat , Catnaigh Pól Ó , Anderson Emma C. 
Published: May 2015

Unr (upstream of N-ras) is a eukaryotic RNA-binding protein that has a number of roles in the post-transcriptional regulation of gene expression. Originally identified as an activator of internal initiation of picornavirus translation, it has since been shown to act as an activator and inhibitor of cellular translation and as a positive and negative regulator of mRNA stability, regulating cellular processes such as mitosis and apoptosis. The different post-transcriptional functions of Unr depend on the identity of its mRNA and protein partners and can vary with cell type and changing cellular conditions. Recent high-throughput analyses of RNA–protein interactions indicate that Unr binds to a large subset of cellular mRNAs, suggesting that Unr may play a wider role in translational responses to cellular signals than previously thought.
Novel signalling mechanism and clinical applications of sperm-specific PLCζ
Authors: Nomikos Michail 
Published: May 2015

Egg activation is the first step of embryonic development and in mammals is triggered by a series of cytoplasmic calcium (Ca2+) oscillations. Sperm–egg fusion initiates these Ca2+ oscillations by introducing a sperm-specific protein factor into the egg cytoplasm. Substantial evidence indicates that this protein is a sperm-specific phospholipase C (PLC), termed PLC-zeta (PLCζ). PLCζ stimulates cytoplasmic Ca2+ oscillations matching those at fertilization triggering early embryonic development in several mammalian species. Structurally, PLCζ is comprised of four EF-hands, a C2 domain, and X and Y catalytic domains. PLCζ is an unusual PLC since it lacks a pleckstrin homology (PH) domain. It is also distinctive in that its X–Y linker is not involved in auto-inhibition of catalytic activity, but instead binds to phosphatidylinositol 4,5-bisphosphate (PIP2). Moreover, relative to other PLC isoforms, PLCζ possesses unique potency in stimulating Ca2+ oscillations in eggs, although it does not appear to bind to plasma membrane PIP2. In contrast, PLCζ appears to interact with intracellular vesicles in eggs that contain PIP2. I discuss the recent advances in our knowledge of the intriguing biochemical and physiological properties of sperm PLCζ and postulate potential roles for PLCζ in terms of clinical diagnosis and therapy for certain forms of male infertility.
Determining the geometry of oligomers of the human epidermal growth factor family on cells with &lt;10 nm resolution
Authors: Needham Sarah R. , Zanetti-Domingues Laura C. , Scherer Kathrin M. , Hirsch Michael , Rolfe Daniel J. , Roberts Selene K. , Martin-Fernandez Marisa L. , Clarke David T. , Tynan Christopher J. 
Published: May 2015

There is a limited range of methods available to characterize macromolecular organization in cells on length scales from 5–50 nm. We review methods currently available and show the latest results from a new single-molecule localization-based method, fluorophore localization imaging with photobleaching (FLImP), using the epidermal growth factor (EGF) receptor (EGFR) as an example system. Our measurements show that FLImP is capable of achieving spatial resolution in the order of 6 nm.
Regulation of Pannexin-1 channel activity
Authors: Taylor Kirk A. , Wright Joy R. , Mahaut-Smith Martyn P. 
Published: May 2015

Pannexin-1 (Panx1) forms anion-selective channels with a permeability up to 1 kDa and represents a pathway for the release of cytosolic ATP. Several structurally similar connexin (Cx) proteins have been identified in platelets and shown to play roles in haemostasis and thrombosis. More recently, functional Panx1 channels have been demonstrated on the surface of human platelets [Taylor et al. (2014) J. Thromb. Haemost. 12, 987–998]. Since their identification in the year 2000, several mechanisms have been reported to activate Panx1 channels, including mechanical stimulation, oxygen-glucose deprivation, a rise of [Ca2+]i, caspase cleavage and phosphorylation. Within this review, the regulation of Panx1 channels is discussed, with a focus on how they may contribute to platelet function.
CMOS phase shifter with low phase‐variation VGA for V‐band application and Ku‐band scaled design
Authors: Lee Dongho 
Published: May 2015

A 90° fine tuning phase shifter design with low insertion phase‐variation a VGA for V‐band phased array systems is presented. The vector‐sum phase shifters require low phase‐variation VGAs with a gain control range of about 10 dB for good digital control performance. The measured data for discrete devices have found that a cascode has 20° better phase variation performance than a common source in the required gain control range at 50 GHz. To demonstrate the design, the Ku‐band scaled phase shifter has been fabricated in 0.13 µm standard CMOS process. It consists of 90°/0° hybrids with lumped elements and two cascode VGAs. The 91° continuous phases with the gain of 2.7 ± 0.9 dB are obtained at 13 GHz.
The Traditions of Grammar Writing in Karl Philipp Moritz’s (1756–1793) Grammars of English (1784) and Italian (1791)
Authors: Tintemann Ute 
Published: May 2015

SummaryUntil the late 18th century, authors of vernacular grammars often adopted the categories of Latin grammar to describe these languages. However, by adapting the Latin system to English, German or Italian, grammarians could succeed only in part, because these languages work in different ways. In the present paper, the author discusses the solutions that Karl Philipp Moritz (1756–1793) proposes in hisEnglischeandItaliänische Sprachlehre für die Deutschen, textbooks for German learners. The author analyses to what extent Moritz’s grammar descriptions were influenced by the Latin model as well as by the traditions of English and Italian grammar writing that he encountered in his sources. It will be demonstrated that he translated extensively from the works of other authors: For his English textbook (Moritz 1784), he mainly used James Greenwood’s (1683?–1737)The Royal English Grammar(1737), and for Italian (Moritz 1791), he profited especially from Benedetto Rogacci’s (1646–1719)Pratica, e compendiosa istruzione circa l’uso emendato, ed elegante della Lingua Italiana(1711).
Iconicity in Saussure’s Linguistic Work
Authors: Joseph John E. 
Published: May 2015

SummaryFerdinand de Saussure (1857–1913) is routinely criticized for denying the possibility of iconicity in language through his principle of the arbitrariness of linguistic signs. Yet two of his articles, one from the beginning (1877) and the other from the end (1912) of his career, propose analyses of the development of certain Latin verbs and adjectives in which iconicity plays a key role. Saussure did not dismiss iconicity, but limited its sphere of application to the relationship between signs and their referents, which falls outside linguistics as he defined it. Hence iconicity does not contradict arbitrariness, which applies to the relationship between signifier and signified within the linguistic sign.
European identities and the revival of nationalism in the European Union
Authors: Wodak Ruth , Boukala Salomi 
Published: May 2015

To date, the concept of ‘European identity’ remains quite vague and obscure. Who is European and who is not? What values do Europeans share, and who is included in or excluded from the European community? This paper deals with the renegotiation of European identity/ies and the simultaneous increase of discourses about national security and nationalism in Europe, especially during the financial crisis since 2008. We first discuss a range of theoretical approaches to European identity from an interdisciplinary perspective. In a second step, after summarising theDiscourse-Historical Approach(DHA) to Critical Discourse Studies (CDS) and especially the concept oftopos, we illustrate the link between discursive constructions of European identities and cultural ‘Others’ via some recent examples of European and national debates on migration and economic issues. More specifically, we first analyse a speech by Geert Wilders on immigration and multiculturalism after the clashes in Tunisia in 2011 and the subsequent arrival of many refugees in Italy; secondly, we focus on a speech about British relations to the European Union in the 21st century by the British Prime Minister, David Cameron. It becomes apparent that debates about European identities – especially since the financial crisis of 2008 – have increasingly been accompanied by debates about both more traditional racialised cultural concerns and more recently, about economic security, leading to new distinctions between ‘Us’, the ‘real Europeans’, and ‘Them’, the ‘Others’. In this way, the socio-political unification of Europe is challenged – once again.
Where will the axe fall?
Authors: Amankwah-Amoah Joseph 
Published: May 2015

Purpose– This study aims to examine the types of attributions after a business failure. Although business failure has garnered a plethora of scholarly attention, there remains an ambiguity and a lack of clarity about the process and types of attribution after a business failure.Design/methodology/approach– The paper is based on a synthesis of the multiple streams of research on the subject. This led to the development of an integrated framework of attributions after business failure.Findings– The paper integrates the business failure literature and attribution theory to develop a 2 × 2 conceptual framework which accounts for not only the effect on pace (time) but alsolocusof causality in the attribution process. Crossing the two main causes of business failure with two types of attribution produces the 2 × 2 matrix of types of attribution after a business failure which includes early internal attribution, late internal attribution, early external attribution and late external attribution.Research limitations/implications– The theorisation of the literature offers a number of implications for theory and practice.Originality/value– The study also explains the underlying processes inherent in learning from others’ failures and consequences of business failure. The framework removes some of the ambiguity in the existing literature and outlines a number of fruitful avenues for future research.
LSS, a problem solving skill for graduates and SMEs
Authors: Shokri Alireza , Nabhani Farhad 
Published: May 2015

Purpose– This paper aims to investigate the feasibility of a systematic Lean Six Sigma (LSS) education through the curriculum of business schools to respond to the existing gap between the graduate’s expectation of employability and skill requirements by the small and medium-sized enterprises (SMEs).Design/methodology/approach– A UK business school has been used as a case study to conduct extensive module and programme review followed by a semi-structured interview with potentially suitable core and programme-specific module tutors and comparative analysis.Findings– The result revealed a high potential of the existing modules in the business schools equivalent to the private sector training providers to increase the level of LSS problem-solving knowledge and skill for all graduates and improve their employability and productivity for the SMEs.Originality/value– The result of this study highlights the role of LSS to reduce the knowledge and skill gap between the business schools as the source of the explicit knowledge, graduates as the knowledge and skill bearer and SMEs as the knowledge and skill users.
Violent work environments
Authors: Tutenges Sébastien , Søgaard Thomas Friis , Krøll Lea Trier , Bloomfield Kim , Hesse Morten 
Published: May 2015

Purpose– Over the last decade a substantial pool of research has emerged on bouncers and their influence on the safety conditions in nightlife environments. Comparatively little, however, has been written on bouncers themselves and their working conditions. The purpose of this paper is to identify the perceived risks, stress and other work-related problems among bouncers working in Danish nightlife.Design/methodology/approach– A survey was conducted. In total, 238 bouncers were contacted and 159 of them completed a questionnaire.Findings– In total, 40 percent reported having been threatened with a weapon and 58 percent reported that they had been physically assaulted at work. Moreover, 16 percent reported feeling stressed and 50 percent reported weekly sleeping difficulties.Originality/value– These findings highlight some of the costs of working in the night-time economy. They may be used to improve the working conditions of bouncers and, by implication, help improve the general safety conditions in nightlife environments.
Evaluation of torque as a means of in-process sensing of tool wear in friction stir welding of metal matrix composites
Authors: Prater Tracie , Gibson Brian , Cox Chase , Cook George E. , Strauss Al , Longhurst William 
Published: May 2015

Purpose
The purpose of this paper is to evaluate the tool experiences using torque during welding as a means of in-process sensing for tool wear. Metal matrix composites (MMCs) are materials with immense potential for aerospace structural applications. The major barrier to implementation of these materials is manufacturability, specifically joining MMCs to themselves or other materials using fusion welding. Friction stir welding (FSW) is an excellent candidate process for joining MMCs, as it occurs below the melting point of the material, thus precluding the formation of degradative intermetallics’ phases present in fusion welded joints. The limiting factor for use of FSW in this application is wear of the tool. The abrasive particles which give MMCs their enhanced properties progressively erode the tool features that facilitate vertical mixing and consolidation of material during welding, resulting in joints with porosity. While wear can be mitigated by careful selection of process parameters and/or the use of harder tool materials, these approaches have significant complexities and limitations.

Design/methodology/approach
This study evaluates using the torque the tool experiences during welding as a means of in-process sensing for tool wear. Process signals were collected during linear FSW of Al 359/SiC/20p and correlated with wear of the tool probe. The results of these experiments demonstrate that there is a correlation between torque and wear, and the torque process signal can potentially be exploited to monitor and control tool wear during welding.

Findings
Radial deterioration of the probe during joining of MMCs by FSW corresponds to a decrease in the torque experienced by the tool. Experimentally observed relationship between torque and wear opens the door to the development of in-process sensing, as the decay in the torque signal can be correlated to the amount of volume lost by the probe. The decay function for tool wear in FSW of a particular MMC can be determined experimentally using the methodology presented here. The decay of the torque signal as the tool loses volume presents a potential method for control of the wear process.

Originality/value
This work has near-term commercial applications, as a means of monitoring and controlling wear in process could serve to grow commercial use of MMCs and expand the design space for these materials beyond net or near-net-shape parts.
Ecological connectivity research in urban areas
Authors: LaPoint Scott , Balkenhol Niko , Hale James , Sadler Jonathan , van der Ree Rodney 
Published: May 2015

SummaryThe successful movement of individuals is fundamental to life. Facilitating these movements by promoting ecological connectivity has become a central theme in ecology and conservation. Urban areas contain more than half of the world's human population, and their potential to support biodiversity and to connect their citizens to nature is increasingly recognized. Promoting ecological connectivity within these areas is essential to reaching this potential. However, our current understanding of ecological connectivity within urban areas appears limited.We reviewed the published scientific literature to assess the state‐of‐the‐art of ecological connectivity research in urban areas, summarized trends in study attributes and highlighted knowledge gaps.We found 174 papers that investigated ecological connectivity within urban areas. These papers addressed either structural (48) or functional connectivity (111), and some addressed both (15), but contained substantial geographic and taxonomic biases. These papers rarely defined the aspect of connectivity they were investigating and objective descriptions of the local urban context were uncommon. Formulated hypotheses ora prioripredictions were typically unstated and many papers used suboptimal study designs and methods.We suggest future studies explicitly consider and quantify the landscape within their analyses and make greater use of available and rapidly developing tools and methods for measuring functional connectivity (e.g. biotelemetry or landscape genetics). We also highlight the need for studies to clearly define how the terms ‘urban’ and ‘connectivity’ have been applied.Knowledge gaps in ecological connectivity in urban areas remain, partly because the field is still in its infancy and partly because we must better capitalize on the state‐of‐the‐art technological and analytical techniques that are increasingly available. Well‐designed studies that employed high‐resolution data and powerful analytical techniques highlight our abilities to quantify ecological connectivity in urban areas. These studies are exemplary, setting the standards for future research to facilitate data‐driven and evidence‐based biodiversity‐friendly infrastructure planning in urban areas.
Efficacy and safety of chemotherapy for newly diagnosed advanced non‐small cell lung cancer with venous thromboembolism
Authors: Zhang Xueli , Li Huiqiao , Chen Wenhui , Yang Yuanhua , Wang Chen , Zhang Yuhui 
Published: May 2015

AbstractBackgroundVenous thromboembolism (VTE) is a serious complication in patients with lung cancer. The benefit of chemotherapy for lung cancer patients with VTE remains unknown. This study was conducted to elucidate the efficacy and safety of chemotherapy for advanced non‐small cell lung cancer (NSCLC) in patients with VTE.MethodsNewly diagnosed patients with advanced (i.e. stage IIIB and IV) NSCLC with VTE who received systemic chemotherapy were studied. Response rates, progression‐free survival (PFS), overall survival (OS), and toxicity were retrospectively analyzed.ResultsIn this study, 21 patients who received chemotherapy plus anticoagulation therapy between December 2009 and February 2011 were included. The objective response and disease control rates within the first regimen were 14.29% (3/21) and 76.19 %(16/21), respectively. The median PFS, one‐year survival rate, and median OS were 5.50 months, 33.30%, and 8.70 months, respectively. The main grade 3/4 toxicities observed included neutropenia (28.57%), nausea 4 (19.05%), and anemia 2 (9.52%). Major bleeding was not observed.ConclusionChemotherapy for newly diagnosed patients with advanced NSCLC and VTE was feasible and had acceptable toxicity; however, the survival of these patients remained inferior to that of patients without VTE.
Diagnostic criteria in 72 women with erosive vulvovaginal lichen planus
Authors: Kennedy Harriet , Oakley Amanda , Rowan Darion , Lamont Duncan 
Published: May 2015

AbstractBackgroundErosive vulvovaginal lichen planus (EVLP) is a chronic, painful dermatosis affecting mucocutaneous sites. Clinicopathological diagnostic criteria have been described on the basis of expert consensus. The aim of this study was to review the presentation of EVLP, particularly assessing the frequency of suggested diagnostic criteria.MethodsClinical signs, symptoms and histological features of women with a clinical diagnosis of EVLP were identified from clinical records and photographs.ResultsIn all, 72 women with an average age of 67 years were included. Pain or burning were documented in 66/72 cases (92%) and itch in 36 (50%). Clinical images showed well‐demarcated red shiny areas or erosions at the vaginal introitus (96%), scarring with loss of normal architecture (88%) and hyperkeratotic border and Wickham striae (46%). A total of 27 women had mucosal disease at another site (38%) and 24 had vaginal involvement (33%). Vulval histology was available for 45/72 cases (63%). The most prevalent histological finding was a band of inflammation with predominant lymphocytes (35/72, 49%). Overall, 97% of cases had at least three of nine suggested diagnostic criteria.ConclusionsThe most frequent findings in women with EVLP were symptoms of pain or burning, well‐demarcated red shiny areas or erosions at the introitus and scarring with loss of architecture. Our findings support the recently described diagnostic criteria for EVLP.
Use of developmental temperature and gastrointestinal tract location to isolate pure Trichostrongylus vitrinus from mixed, naturally acquired trichostrongylid infections in sheep
Authors: Blackburn PJ , Carmichael IH , Walkden‐Brown SW , Greenslade S 
Published: May 2015

ObjectiveTo isolate Trichostrongylus vitrinus from naturally‐acquired mixed trichostrongylid infections (predominantly Trichostrongylus spp. and Teladorsagia circumcincta) in sheep using differential larval development temperatures and the anatomical location of adults.MethodsFaeces were collected from ewes with mixed, naturally acquired trichostrongylid infection, and incubated at low temperatures (4°C or 8°C) for 20–68 days depending on temperature. Harvested infective larvae were passaged through worm‐free lambs, from which the first 5 m of small intestine was collected and adult worms recovered. Purity of infection with T. vitrinus was assessed by examination of spicules on 100 adult male worms. Eggs of recovered adult female worms were cultured at 25°C and harvested larvae were re‐passaged through worm‐free lambs.ResultsLow temperature incubation (≤8°C) successfully exploited variation in the developmental temperature required by pre‐parasitic stages of small intestinal nematodes, allowing T. vitrinus to develop while others did not. Differential organ harvest from infected sheep allowed isolation of T. vitrinus from other gastrointestinal nematodes, with amplification of pure T. vitrinus achieved by passage through a further generation of lambs.ConclusionA successful method for the isolation of pure T. vitrinus from mixed infections is described. The resulting pure strain of T. vitrinus has been amplified and is held by two institutions for use in research (CSIRO reference SARDI 2011 strain).