ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis

Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family are known to influence development, angiogenesis, coagulation and progression of arthritis. As proteinases their substrates include the von Willebrand factor precursor and extracellular matrix components such as procollagen, hyalectans (hyaluronan-binding proteoglycans including aggrecan), decorin, fibromodulin and cartilage oligomeric matrix protein. ADAMTS levels and activities are regulated at multiple levels through the control of gene expression, mRNA splicing, protein processing and inhibition by TIMP (tissue inhibitor of metalloproteinases). A recent screen of human cartilage has shown that multiple members of the ADAMTS family may be important in connective tissue homeostasis and pathology

Multi-threaded Output in CMS using ROOT

CMS has worked aggressively to make use of multi-core architectures, routinely running 4- to 8-core production jobs in 2017. The primary impediment to efficiently scaling beyond 8 cores has been our ROOT-based output module, which has been necessarily single threaded. In this paper we explore the changes made to the CMS framework and our ROOT output module to overcome the previous scaling limits, using two new ROOT features: the \texttt{TBufferMerger} asynchronous file merger, and Implicit Multi-Threading. We examine the architecture of the new parallel output module, the specific accommodations and modifications that were made to ensure compatibility with the CMS framework scheduler, and the performance characteristics of the new output module.Comment: Submitted to CHEP 2018 - 23rd International Conference on Computing in High Energy and Nuclear Physics; 6 pages, 4 figures, uses webofc clas

The role of proteases in pathologies of the synovial joint

Synovial (diarthrodial) joints are employed within the body to provide skeletal mobility and have a characteristic structure adapted to provide a smooth almost frictionless surface for articulation. Pathologies of the synovial joint are an important cause of patient morbidity and can affect each of the constituent tissues. A common feature of these pathologies is degenerative changes in the structure of the tissue which is mediated, at least in part, by proteolytic activity. Most tissues of the synovial joint are composed primarily of extracellular matrix and key pathological roles in the degeneration of this matrix are performed by metalloproteinases such as matrix metallproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). However, other proteases such as cathepsin K are likely to play an important role, especially in bone turnover. In addition to the cleavage of structural proteins, proteolytic activities are employed to regulate the activity of other proteases, growth factors, cytokines and other inflammatory mediators. Proteases combine to form complex regulatory networks, the correct functioning of which is required for tissue homeostasis and the imbalance of which may be a feature of pathology. A precise understanding of the proteases involved in these networks is required for a true understanding of the associated pathology

UA1B2/1 Clearance Jeanette Interview

Paper describing research process and preparation for oral history interview with Clearance Jeanette

Cyclic loading of tendon fascicles using a novel fatigue loading system increases interleukin-6 expression by tenocytes

Repetitive strain or ‘overuse’ is thought to be a major factor contributing to the development of tendinopathy. The aims of our study were to develop a novel cyclic loading system, and use it to investigate the effect of defined loading conditions on the mechanical properties and gene expression of isolated tendon fascicles. Tendon fascicles were dissected from bovine-foot extensors and subjected to cyclic tensile strain (1 Hz) at 30% or 60% of the strain at failure, for 0 h (control), 15 min, 30 min, 1 h, or 5 h. Post loading, a quasi-static test to failure assessed damage. Gene expression at a selected loading regime (1 h at 30% failure strain) was analyzed 6 h post loading by quantitative real-time polymerase chain reaction. Compared with unloaded controls, loading at 30% failure strain took 5 h to lead to a significant decrease in failure stress, whereas loading to 60% led to a significant reduction after 15 min. Loading for 1 h at 30% failure strain did not create significant structural damage, but increased Collagen-1-alpha-chain-1 and interleukin-6 (IL6) expression, suggesting a role of IL6 in tendon adaptation to exercise. Correlating failure properties with fatigue damage provides a method by which changes in gene expression can be associated with different degrees of fatigue damage

Cascadian cross border cooperation challenged: the case of the Shared Waters Alliance

The process of globalization is resulting in a proliferation of political, economic, ecological, and cultural ties that extend across the borders of nation-states. Compounded with the fact that central governments are less interested or capable of addressing every cross border issue, subnational actors are more likely to engage in cross border diplomacy. The border region within Cascadia, a region at the western edge of the US-Canadian border, is not unique in this respect and has been experiencing a rise in subnational cross border interactions. However, cross border actors Cascadia are not fully empowered to engage institutionally or formally. Obstacles such as differing government structures, Canadian sovereignty concerns, and a US emphasis on border security inhibit formalized engagement by local border actors. As a result, ad hoc, cooperative measures are one of a few viable options for cross border stakeholders concerned with a localized but transboundary environmental problem. Cooperation can be induced by strong social capital, that is the existence of social linkages, shared norms of behavior, shared expectations, and shared beliefs and understandings. The Shared Waters Alliance (SWA) is a transboundary working group in Cascadia. An informal and voluntary group, the SWA is limited in focus to environmental issues in the Boundary Bay Basin. Despite its informal nature the group has none-the-less operated continuously for over a decade. At a cursory glance, it would seem the SWA is a successful model of cooperative transboundary environmental governance within Cascadia. The work of this thesis seeks to establish if indeed the SWA longevity speaks to the construction of cross border social capital. In order to examine whether this is true, several separate lines of inquiry where pursued: how much social capital, along structural and cognitive dimensions has actually been established by the group, and what are the main challenges that exist or threaten to inhibit the group\u27s success? A third line of inquiry sought to determine tangible suggestions that could help the SWA rise above or mitigate some of the obstacles it faces. The SWA was not necessarily chosen because it was assumed to be a model of perfection. Rather given the group\u27s durability, it seems worthwhile to investigate it operates. While it may or may not be a model for other environmental managers to follow, determining the successes and failings of the SWA can still provide a road map for other transboundary efforts to follow, or avoid. Conducting a case study of this group was done by pairing two differing yet complementary methods. Inductive, qualitative interviews were conducted with a small handful of SWA participants. The goal of these interviews was to draw out major themes in regards to the social atmosphere within the group, the challenges that were perceived to exist, and what actions each individual interviewee would like to see the SWA undertake in the future. The themes teased out of interview analysis were then used to create a survey that was administered to the group as a whole. The combination of two differing research methods sought to not only allow for the results from the first method to inform development of the second, but to also combine the richness and depth of qualitative inquiry with the statistical generalizations from quantitative surveys. The findings revealed a complex social dynamic. The SWA has largely been successful at establishing and growing connections across the border and creating a friendly, trustworthy forum for communication and networking. However, it also appears that the SWA has not been able to expand beyond passive activities to make substantive efforts to improve environmental conditions, somewhat to the chagrin of stakeholders. While the SWA faces a plethora of challenges, it does not appear that effects stemming from border security practices are among them. Largely, the biggest issues for the group come from external forces they can\u27t easily change, such as lack of empowerment or lack of resources and funding. Largely, there are few instances of differing perceptions between sub-groups of stakeholders. In general Canadians have the same opinions as Americans, Government as non-government, and local government as regional/federal government. However, several critical differing perceptions exist between the opinions of those in government and non-government, and on occasion, between levels of government. As a whole, the SWA is valued by involved stakeholders, although there is a wide enthusiasm at the suggestion of making changes. While the suggestions given were quite general, it appears that most stakeholders hope the group could become more goal-oriented and more organized and systematic. What stakeholders do not seem interested in doing is burdening themselves with more volunteer activities

Respected Pillars of the Community: A values-based profile of the British Market Maven

Market Mavens are consumers who are active purveyors of word of mouth (WOM) communication in society. In contrast to opinion leaders, mavens provide information that cuts across product categories, and advise on old and new products. Consequently, mavens can impact a wider number of social networks with WOM, and are therefore a valuable target for marketers. Despite much empirical work, a socio-demographic profile of the market maven remains elusive, and recently work has focused on those intrinsic characteristics that may distinguish mavens from others. However, no previous work has considered the possibility that personal values may be a distinguishing maven factor. Using the original market maven scale, the full Rokeach value survey and the List of Values (LOV), this research (n = 158) found mavens to place significantly more importance on several values than do non-mavens. Results suggest that mavenism has an external social dimension to sharing marketplace information that is not motivated out of self-interest, but by altruism and a genuine concern for others. Contrary to some previous research, this study shows that market mavens can be identified in a useful way to marketing practitioners. In addition to the obvious need for marketing communications to supply the maven with plenty of information about products and services, communications strategies need to focus on positioning brands around the values which reflect altruism, respect, helpfulness, and responsibility. In this way, the usefulness of market mavens and WOM communications can be harnessed successfully

An Atlas of Land Entry Ports on the Canada-US Border

In a departure from the norm, this article provides no policy analysis, but instead serves simply as a reference document. The following maps identify the names and locations of all legal land portsof-entry along the Canada – U.S. border. Each port shown here is one at which a person can directly travel by personal vehicle (or on foot) from Canadian to U.S. soil