bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategic responses to shocks: Comparative adjustment costs, transaction costs, and opportunity costs
Authors: Argyres Nicholas , Mahoney Joseph T. , Nickerson Jackson 
Published: November 2018

Research SummaryShocks, whether they derive from shifts in demand, supply, regulation, or innovation, can create the need for competitive repositioning by industry participants when they disrupt established sources of competitive advantage. Such situations can therefore create a canonical strategic problem: whether, where, and how to (re‐)position following an industry shock. In this paper, we explore the role of comparative adjustment costs in determining competitive advantage in dynamic environments. In so doing, we synthesize contributions from Penrose, Porter, and Williamson to conceptualize the relationship between adjustment costs and related concepts such as resources/capabilities, dynamic capabilities, transaction costs, and opportunity costs.Managerial SummaryWhether, where, and how should leaders reposition their firms in response to industry shocks? This paper develops a framework to guide leaders charged with making these decisions. The framework emphasizes that firms facing an industry shock must: (a) assess their firm's cost and time to move to each new position, and compare that cost and time to rivals' costs and time to move to those same positions; (b) compare the cost of delaying repositioning (such as forfeiting first mover advantage) to the profits from remaining in its original position, and (c) consider that, in order to speed repositioning, the efficient choice may be to temporarily accept certain hazards from outsourcing, and later integrate to eliminate those hazards. We illustrate the framework using an example from the smartphone industry.
Template‐Synthesized Vertical Needle Array as Injection Platform for Microalgae
Authors: Mukaibo Hitomi 
Published: November 2018

AbstractIncreasing numbers of studies in the past few decades have demonstrated vertically‐oriented nanoneedles arrays (NNAs) as innovative tools to interrogate and manipulate biological cells, where the needles are inserted into the cells as functional probes for high‐throughput detection and biomolecule delivery. However, majority of these studies use mammalian cells: leaving NNA application to plant cells still in its infancy and largely unexplored. This paper highlights our contributions in exploring the utility of NNAs to microalgae – a diverse group of aquatic, photosynthetic organisms studied intensively as bio‐factories for producing high‐value‐added products such as fuels and pharmaceuticals. Microalgal strain development processes have long suffered from the hard cell wall that surrounds the cell and inhibits delivery of foreign materials into the cell. Conically‐shaped, metallic NNAs were developed with template synthesis that successfully penetrate through the cell wall barrier and achieve material injection – using the widely studied model microalga, Chlamydomonas reinhardtii. Earlier works from mammalian cells are introduced and discussed to clarify the framework established in this field, while recent studies of both mammalian and microalgal cells are also referenced to examine the trends, challenges, and future perspectives of NNA application to microalgae.
LncRNA‐Jak3:Jak3 coexpressed pattern regulates monosodium urate crystal‐induced osteoclast differentiation through Nfatc1/Ctsk expression
Authors: Lee Chi‐Pin , Huang Yu‐Nan , Nithiyanantham Srinivasan , Huang Chung‐Ming , Ko Ying‐Chin 
Published: November 2018

AbstractLncRNA transcripts have been emerged as gene regulators through transcriptional and posttranscriptional regulation. Monosodium urate monohydrate (MSU) elicits inflammatory response and a critical regulator of bone erosion in gout. The aim of this study is to clarify the pro‐osteogenic role of LncRNA in MSU‐induced osteoclast differentiation. We performed microarray analysis to identify stage specific expressions of LncRNA and mRNA during osteoclast differentiation in RAW264.7 cells. Among the 314 pairs of LncRNA‐mRNA coexpressed patterns in the osteoclast lineage, 22 pairs revealed to have inflammatory function. Importantly, LncRNA‐Jak3 and Jak3 co‐expression patterns were significantly upregulated in the osteoclasts. In specific, Jak3 contributes to MSU‐induced osteoclasts differentiation by positively regulating expression of the osteoclast factor, nuclear factor of activated T‐cells 1 (Nfatc1). Mechanistically, LncRNA‐Jak3‐mediated Nfatc1 activation upregulated cathepsin K (Ctsk) expressions. LncRNA‐Jak3 knockdown abolished formation of MSU‐induced mature osteoclasts. In addition, we found that gout patients showed increased levels of LncRNA‐Jak3 in the mononuclear cells. Our data demonstrate that the critical functional role of LncRNA‐Jak3 in osteoclast differentiation via Jak3/Nfatc1/Ctsk axis. Finally, characterization of these regulatory networks is likely to reveal novel drug targets and opportunities for therapeutic intervention in bone erosion.
Entrepreneurial engagement in a depleted small town: Legitimacy and embeddedness
Authors: Bensemann Jo , Warren Lorraine , Anderson Alistair 
Published: November 2018

AbstractOur study of entrepreneurial engagement within a depleted New Zealand community contributes to understanding the role of place and legitimacy in entrepreneurial practice. General decline characterised Stanton until a newcomer entrepreneur started several businesses that rejuvenated the town. She became a local economic hero to many stakeholders; but others deployed social narratives of place that drew on different values. Our analysis of interactions shows how perceptions of place legitimise or vilify and we demonstrate how place intercedes upon economically generated legitimacy of entrepreneurial practice. Social constructions of place and notions of embeddedness influenced this entrepreneurial enactment. Conceptually, we challenge ideas about universal legitimacy ensuing from economic entrepreneurial benefits. Our theoretical contribution offers socio-spatial propositions for understanding entrepreneurial legitimacy through place.
Arterial spin labelling and diffusion-weighted magnetic resonance imaging in differentiation of recurrent head and neck cancer from post-radiation changes
Authors: Abdel Razek A A K 
Published: November 2018

AbstractObjectiveTo assess arterial spin labelling and diffusion-weighted imaging in the differentiation of recurrent head and neck cancer from post-radiation changes.MethodsA retrospective study was conducted of 47 patients with head and neck cancer, treated with radiotherapy, who underwent magnetic resonance arterial spin labelling and diffusion-weighted magnetic resonance imaging. Tumour blood flow and apparent diffusion co-efficient of the lesion were calculated.ResultsThere was significant difference (p= 0.001) in tumour blood flow between patients with recurrent head and neck cancer (n= 31) (47.37 ± 16.3 ml/100 g/minute) and those with post-radiation changes (n= 16) (18.80 ± 2.9 ml/100 g/minute). The thresholds of tumour blood flow and apparent diffusion co-efficient used for differentiating recurrence from post-radiation changes were more than 24.0 ml/100 g/minute and 1.21 × 10−3mm2/second or less, with area under the curve values of 0.94 and 0.90, and accuracy rates of 88.2 per cent and 88.2 per cent, respectively. The combined tumour blood flow and apparent diffusion co-efficient values used for differentiating recurrence from post-radiation changes had an area under the curve of 0.96 and an accuracy of 90.2 per cent.ConclusionCombined tumour blood flow and apparent diffusion co-efficient can differentiate recurrence from post-radiation changes.
THE WOMAN TO THE PLOW; AND THE MAN TO THE HEN-ROOST: WIVES, HUSBANDS AND BEST-SELLING BALLADS IN SEVENTEENTH-CENTURY ENGLAND
Authors: Marsh Christopher 
Published: November 2018

ABSTRACTThis paper investigates the representation of marital relations in some of the most successful broadside ballads published in seventeenth-century England. It explains the manner in which these have been selected as part of a funded research project, and it proceeds to question an existing historiographical emphasis on ballads in which marriages were portrayed as under threat due to a combination of wifely failings (scolding, adultery, violence) and husbandly shortcomings (sexual inadequacy, jealousy, weakness). Best-selling ballads were much more sympathetic to married women in particular than we might have expected, and the implications of this for our understanding of the ballad market and early modern culture more generally may be significant. These ballads, it is argued, were often aimed particularly at women, and they grew out of an interesting negotiation between male didacticism and female taste. Throughout the paper, an attempt is made to understand ballads as songs and visual artefacts, rather than merely as texts.
‘WHO THE HELL ARE ORDINARY PEOPLE?’ ORDINARINESS AS A CATEGORY OF HISTORICAL ANALYSIS
Authors: Langhamer Claire 
Published: November 2018

ABSTRACTOrdinariness was a frequently deployed category in the political debates of 2016. According to one political leader, the vote for Brexit was ‘a victory for ordinary, decent people who've taken on the establishment and won’. In making this claim, Nigel Farage sought to link a dramatic political moment with a powerful, yet conveniently nebulous, construction of the ordinary person. In this paper, I want to historicise recent use of the category by returning to another moment when ordinariness held deep political significance: the years immediately following the Second World War. I will explore the range of values, styles and specific behaviours that gave meaning to the claim to be ordinary; consider the relationship between ordinariness, everyday experience and knowledge; and map the political work ordinariness was called upon to perform. I argue that the immediate post-war period was a critical moment in the formation of ordinariness as a social category, an affective category, a moral category, a consumerist category and, above all, a political category. Crucially, ordinariness itself became a form of expertise, a finding that complicates our understanding of the ‘meritocratic moment’.
ANTI-SOCIALISM, LIBERALISM AND INDIVIDUALISM: RETHINKING THE REALIGNMENT OF SCOTTISH POLITICS, 1945–1970
Authors: Petrie Malcolm 
Published: November 2018

ABSTRACTThis paper presents an alternative interpretation of Scottish politics between 1945 and 1970, a period that witnessed the decline of a once-powerful Unionist tradition, the revival of Liberalism and the rise of the Scottish National party (SNP). While existing accounts have focused principally upon social and economic factors, this study foregrounds the role of ideology and rhetoric. During the 1940s and early 1950s, Scottish Unionists were, like their Conservative colleagues elsewhere in Britain, able to construct a popular, but essentially negative, anti-socialist coalition that prioritised the defence of individual liberty. This electoral alliance, defined by opposition to Labour's programme of nationalisation and expressed via an individualist idiom, was able to attract broad support; it was, however, always provisional, and proved increasingly difficult to sustain after the Conservative party returned to office in 1951. It was, this paper suggests, the fragmenting of this anti-socialist coalition in the late 1950s and early 1960s that created the opportunity for both the Liberals and the SNP to present alternative renderings of this individualist appeal, and to emerge as credible political alternatives. Crucially, by the 1960s, individual liberty was beginning to be understood in constitutional rather than economic terms.
Clapham revisited: the decline of the Norwich worsted industry (c. 1700–1820)
Authors: Sugden Keith 
Published: November 2018

AbstractThis study utilises several sources of male occupational data to track the decline of the Norwich worsted industry, c. 1700–1820. The data show that the industry began to fall away during the second half of the eighteenth century, if not sooner, and earlier than has been previously realised. The transfer of the industry to the north of England began before the introduction of steam-powered spinning or weaving. Market competition, notably from Lancashire printed fustians and cottons, and the loss of export trade through war, were the likely causal factors.
Suppressive effect of syndecan ectodomains and N-desulfated heparins on osteoclastogenesis via direct binding to macrophage-colony stimulating factor
Authors: Kim Jin-Man , Lee Kyunghee , Kim Mi Yeong , Shin Hong-In , Jeong Daewon 
Published: November 2018

AbstractSyndecans, a family of cell surface heparan sulfate proteoglycans, regulate cell differentiation via binding of their heparan sulfate chains to growth factors and cytokines and play a role in tumor growth and progression, wound repair, and intestinal mucosal damage. However, the functional and mechanistic roles of syndecans in osteoclast differentiation and bone metabolism are yet unclear. Here, we demonstrated that post-translationally glycosylated ectodomains of syndecan-1 to 4 obtained from mammalian cells efficiently suppressed osteoclast differentiation compared to those obtained from Escherichia coli with no systems for glycosylation. A concomitant decrease in the expression of osteoclast markers such as nuclear factor of activated T cells 1 (NFATc1), c-Fos, and ATP6V0D2 was observed. In addition, heparan sulfate and selectively N-desulfated heparin derivatives with 2-O- and 6-O-sulfate groups and no anticoagulant activity in blood inhibited osteoclast differentiation. The inhibitory effects of syndecan ectodomains, heparan sulfate, and N-desulfated heparin derivatives on osteoclast differentiation were attributed to their direct binding to the macrophage-colony stimulating factor (M-CSF), resulting in the blocking of M-CSF-mediated downstream signals such as extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), p38, and Akt. Furthermore, mice injected with syndecan ectodomains, heparan sulfate, and N-desulfated heparin derivatives into periosteal regions of calvaria showed reduction in the formation of tartrate-resistant acid phosphatase (TRAP)-positive mature osteoclasts on the calvarial bone surface, thereby exhibiting decreased bone resorption. Together, these results revealed a novel role of heparan sulfate chains of syndecan ectodomains in the regulation of osteoclast differentiation.
Asxl1 exerts an antiproliferative effect on mouse lung maturation via epigenetic repression of the E2f1-Nmyc axis
Authors: Moon Seungtae , Im Sun-Kyoung , Kim Nackhyoung , Youn Hyesook , Park Ui-Hyun , Kim Joo-Yeon , Kim A.-Reum , An So-Jung , Kim Ji-Hoon , Sun Woong , Hwang Jin-Taek , Kim Eun-Joo , Um Soo-Jong 
Published: November 2018

AbstractAlthough additional sex combs-like 1 (ASXL1) has been extensively described in hematologic malignancies, little is known about the molecular role of ASXL1 in organ development. Here, we show that Asxl1 ablation in mice results in postnatal lethality due to cyanosis, a respiratory failure. This lung defect is likely caused by higher proliferative potential and reduced expression of surfactant proteins, leading to reduced air space and defective lung maturation. By microarray analysis, we identified E2F1-responsive genes, including Nmyc, as targets repressed by Asxl1. Nmyc and Asxl1 are reciprocally expressed during the fetal development of normal mouse lungs, whereas Nmyc downregulation is impaired in Asxl1-deficient lungs. Together with E2F1 and ASXL1, host cell factor 1 (HCF-1), purified as an Asxl1-bound protein, is recruited to the E2F1-binding site of the Nmyc promoter. The interaction occurs between the C-terminal region of Asxl1 and the N-terminal Kelch domain of HCF-1. Trimethylation (me3) of histone H3 lysine 27 (H3K27) is enriched in the Nmyc promoter upon Asxl1 overexpression, whereas it is downregulated in Asxl1-deleted lung and -depleted A549 cells, similar to H3K9me3, another repressive histone marker. Overall, these findings suggest that Asxl1 modulates proliferation of lung epithelial cells via the epigenetic repression of Nmyc expression, deficiency of which may cause hyperplasia, leading to dyspnea.
Extracellular and ER-stored Ca2+ contribute to BIRD-2-induced cell death in diffuse large B-cell lymphoma cells
Authors: Bittremieux Mart , La Rovere Rita M. , Schuermans Marleen , Luyten Tomas , Mikoshiba Katsuhiko , Vangheluwe Peter , Parys Jan B. , Bultynck Geert 
Published: November 2018

AbstractThe anti-apoptotic protein Bcl-2 is upregulated in several cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). In a subset of these cancer cells, Bcl-2 blocks Ca2+-mediated apoptosis by suppressing the function of inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) located at the endoplasmic reticulum (ER). A peptide tool, called Bcl-2/IP3 receptor disruptor-2 (BIRD-2), was developed to disrupt Bcl-2/IP3R complexes, triggering pro-apoptotic Ca2+ signals and killing Bcl-2-dependent cancer cells. In DLBCL cells, BIRD-2 sensitivity depended on the expression level of IP3R2 channels and constitutive IP3 signaling downstream of the B-cell receptor. However, other cellular pathways probably also contribute to BIRD-2-provoked cell death. Here, we examined whether BIRD-2-induced apoptosis depended on extracellular Ca2+ and more particularly on store-operated Ca2+ entry (SOCE), a Ca2+-influx pathway activated upon ER-store depletion. Excitingly, DPB162-AE, a SOCE inhibitor, suppressed BIRD-2-induced cell death in DLBCL cells. However, DPB162-AE not only inhibits SOCE but also depletes the ER Ca2+ store. Treatment of the cells with YM-58483 and GSK-7975A, two selective SOCE inhibitors, did not protect against BIRD-2-induced apoptosis. Similar data were obtained by knocking down STIM1 using small interfering RNA. Yet, extracellular Ca2+ contributed to BIRD-2 sensitivity in DLBCL, since the extracellular Ca2+ buffer ethylene glycol tetraacetic acid (EGTA) blunted BIRD-2-triggered apoptosis. The protective effects observed with DPB162-AE are likely due to ER Ca2+-store depletion, since a similar protective effect could be obtained using the sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin. Thus, both the ER Ca2+-store content and extracellular Ca2+, but not SOCE, are critical factors underlying BIRD-2-provoked cell death.
Structural basis for the second step of group II intron splicing
Authors: Chan Russell T. , Peters Jessica K. , Robart Aaron R. , Wiryaman Timothy , Rajashankar Kanagalaghatta R. , Toor Navtej 
Published: November 2018

AbstractThe group II intron and the spliceosome share a common active site architecture and are thought to be evolutionarily related. Here we report the 3.7 Å crystal structure of a eukaryotic group II intron in the lariat-3′ exon form, immediately preceding the second step of splicing, analogous to the spliceosomal P complex. This structure reveals the location of the intact 3′ splice site within the catalytic core of the group II intron. The 3′-OH of the 5′ exon is positioned in close proximity to the 3′ splice site for nucleophilic attack and exon ligation. The active site undergoes conformational rearrangements with the catalytic triplex having different configurations before and after the second step of splicing. We describe a complete model for the second step of group II intron splicing that incorporates a dynamic catalytic triplex being responsible for creating the binding pocket for 3′ splice site capture.
Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2
Authors: Liu Zuqiang , Ge Yan , Wang Haiyan , Ma Congrong , Feist Mathilde , Ju Songguang , Guo Z. Sheng , Bartlett David L. 
Published: November 2018

AbstractThe complex immune tumour microenvironment requires an equally complex immunotherapy approach, especially when the cancer-immune set point is non-inflamed. Oncolytic viruses expressing immune activating cytokines might optimally modify the immune microenvironment and improve the antitumour effects. In this study, we have explored a variety of IL-2 constructs expressed by a tumour-selective oncolytic vaccinia virus, designed to maintain IL-2 in the tumour microenvironment to reduce systemic toxicity. An IL-2 construct combining a glycosylphosphatidylinositol (GPI) anchor with a rigid peptide linker leads to functional IL-2 expression on the tumour cell surface and in the tumour microenvironment. This virus construct effectively modifies the cancer-immune set point and treats a variety of murine tumour models with no toxic side effects. In combination with PD-1/PD-L1 blockade this virus cures most of the mice with a high tumour burden. This combination represents a treatment for cancers which are to date unresponsive to immunotherapy.
Bi-directional signaling by membrane-bound KitL induces proliferation and coordinates thymic endothelial cell and thymocyte expansion
Authors: Buono Mario , Thézénas Marie-Laëtitia , Ceroni Alessandro , Fischer Roman , Nerlov Claus 
Published: November 2018

AbstractThe ligand for the c-Kit receptor, KitL, exists as a membrane-associated (mKitL) and a soluble form (sKitL). KitL functions outside c-Kit activation have not been identified. We show that co-culture of c-Kit– and mKitL–expressing NIH3T3 cells results in signaling through mKitL: c-Kit–bound mKitL recruits calcium-modulating cyclophilin ligand (CAML) to selectively activate Akt, leading to CREB phosphorylation, mTOR pathway activation, and increased cell proliferation. Activation of mKitL in thymic vascular endothelial cells (VECs) induces mKitL- and Akt-dependent proliferation, and genetic ablation of mKitL in thymic VECs blocks their c-Kit responsiveness and proliferation during neonatal thymic expansion. Therefore, mKitL–c-Kit form a bi-directional signaling complex that acts in the developing thymus to coordinate thymic VEC and early thymic progenitor (ETP) expansion by simultaneously promoting ETP survival and VEC proliferation. This mechanism may be relevant to both normal tissues and malignant tumors that depend on KitL–c-Kit signaling for their proliferation.
Membrane association and remodeling by intraflagellar transport protein IFT172
Authors: Wang Qianmin , Taschner Michael , Ganzinger Kristina A. , Kelley Charlotte , Villasenor Alethia , Heymann Michael , Schwille Petra , Lorentzen Esben , Mizuno Naoko 
Published: November 2018

AbstractThe cilium is an organelle used for motility and cellular signaling. Intraflagellar transport (IFT) is a process to move ciliary building blocks and signaling components into the cilium. How IFT controls the movement of ciliary components is currently poorly understood. IFT172 is the largest IFT subunit essential for ciliogenesis. Due to its large size, the characterization of IFT172 has been challenging. Using giant unilamellar vesicles (GUVs), we show that IFT172 is a membrane-interacting protein with the ability to remodel large membranes into small vesicles. Purified IFT172 has an architecture of two globular domains with a long rod-like protrusion, resembling the domain organization of coatomer proteins such as COPI-II or clathrin. IFT172 adopts two different conformations that can be manipulated by lipids or detergents: 1) an extended elongated conformation and 2) a globular closed architecture. Interestingly, the association of IFT172 with membranes is mutually exclusive with IFT57, implicating multiple functions for IFT172 within IFT.