Innovation processes and industrial districts

In this survey, we examine the operations of innovation processes within industrial districts by exploring the ways in which differentiation, specialization, and integration affect the generation, diffusion, and use of new knowledge in such districts. We begin with an analysis of the importance of the division of labour and then investigate the effects of social embeddedness on innovation. We also consider the effect of forms of organization within industrial districts at various stages of product and process life, and we examine the negative aspects of embeddedness for innovation. We conclude with a discussion of the possible consequences of new information and communications technologies on innovation in industrial districts

Transaction Costs, Trust, and the Structuring of Markets

This paper examines the institutional arrangements that develop when the risks of opportunism and other contributors to transaction costs are high but transactions are nevertheless necessary for economic efficiency. Williamson's argument that high levels of transaction costs lead firms to choose vertical integration (hierarchical organisation) in preference to using markets is well known. But this is far from the whole story because markets are not uniform. In fact, modern "market economies" embrace a wide range of institutions for exchanging ownership of goods and services. The types of transactions undertaken are not only varied, but some important markets are themselves hierarchies that are structured in ways that are analogous to firms precisely in order to reduce their costs of operation, including the transaction costs that arise from using them. In this paper, I look at the evolution of a select but important group of markets that have been consciously constructed over long periods and with frequent modifications because of environmental change and learning by participants. These are markets in which the use of up-to-date information is especially important because conditions may alter quickly, and in which risk, uncertainty, and the potential for opportunistic behaviour are factors that affect their operations in significant ways. When transaction and agency costs arise in such markets, responses have concentrated on finding mechanisms for reducing them to tolerable levels rather than on abandoning transactions altogether through the internalisation of activities. The logic of constructed markets is illustrated by an examination of the evolution of membership regulations by the London and New York Stock Exchanges in the nineteenth and early twentieth centuries

Printed Word Warfare in the Backcountry: Publishing for the State of Franklin

This paper engages in an historical, print culture analysis of the political material, both governmental and partisan, generated by the late 18th century struggle to establish the State of Franklin. The State of Franklin was an attempt by frontier Euro-American settlements in an area roughly encompassed by present day eastern Tennessee to formally secede from North Carolina and thereafter gain admittance to the new United States union as the 14th state. Although the establishment of Franklin was vehemently opposed by the North Carolina legislature and anti-secession settlers in the region, a rudimentary government apparatus was cobbled together by the Franklin separatists and persisted from 1784-1790. Near constant tension, occassionally violent, between pro-Franklin and anti-Franklin forces often handicapped even the most basic of government operations and printing was, consequently, a lesser concern in the attempt to form the first trans-Appalachian state. Nonetheless, like other 18th century political movements that encompassed literate populations, the State of Franklin made recourse to the printing press to circulate arguments justifying its existence. While no evidence suggests that printing operations ever set up shop within the short-lived borders of Franklin, would-be Franklin partisans and their North Carolina-loyalist opponents utilized the established printers of eastern North Carolina to wage a backcountry war of the written word

The Mountains at the End of the World: Subcultural Appropriations of Appalachia and the Hillbilly Image, 1990-2010

There is an aversion within the field of Appalachian Studies to addressing the cultural formulations of the Appalachian/hillbilly/mountaineer as an icon of aggressive resistance. The aversion is understandable, as for far too long images of the irrationally and savagely violent mountaineer were integral to the most gross popular culture stereotypes of Appalachia. Media consumers often take pleasure or comfort in these images, which usually occur in a reactionary context with the hillbilly as either a type of nationally necessary savage OR as an unregenerate barbarian against whom a national civilization will triumph and benefit by the struggle. I bookend my study with two artifacts of Appalachian representation, linked in specific subject matter, but separated by twenty years. The 1991 West Virginia Public Television-produced documentary film The Dancing Outlaw quickly became an underground cult classic—an object of both absurdist delight and cultural identification within the punk subculture, particularly among those with both a punk sensibility and personal connections to the Appalachian region (birth, upbringing, residency, ancestry). In 2009, MTV and the resources of its wildly popular Jackass franchise revisited the locale and family featured in this earlier documentary and produced the sophisticated and polished film The Wild, Wonderful Whites of West Virginia. The core purpose of this project, however, is to examine why Appalachia and/or the hillbilly, as constructed within and across these subcultures, possessed such appeal during this historical moment. My hypothesis is that such appeal lies primarily (but not exclusively) in the negative characteristics of the region and its inhabitants that are represented throughout a variety of subcultural texts: documentary film, art house cinema, niche regional literature, and independent zine publishing and early blogging. For both those identifying themselves as Appalachians/hillbillies (or some related variation thereof) and those “playing” as Appalachians/hillbillies, these images become statements of resistance and survival to challenge the national mass culture and the political ideologies supporting it

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery

Demographic, Psychological, and School Environment Correlates of Bullying Victimization and School Hassles in Rural Youth

Little is known about bullying in rural areas. The participants in this study included 3,610 racially diverse youth (average age = 12.8) from 28 rural schools who completed the School Success Profile-Plus. Binary logistic regression models were created to predict bullying victimization in the past 12 months, and ordered logistic regression was used to predict school hassles in the past 12 months. Overall, 22.71% of the sample experienced bullying victimization and school victimization rates ranged from 11% to 38%. Risk factors for bullying victimization included younger students and students experiencing depression and anxiety. Being female, Hispanic/Latino or African American, was associated with lower bullying victimization. Thirty-nine percent of the sample reported a high level of school hassles. Younger students and students with higher levels of anxiety and depression were at increased risk for school hassles. Students from larger schools reported high levels of school hassles, while students from schools with more teachers with advanced degrees reported fewer school hassles

SiViT

The Signalling Visualisation Toolkit (SiViT), is a cancer cell signalling network visualisation tool that provides an intuitive games-based real-time interactive interface to models of cancer cell dynamics. SiViT provides a games-technology approach to unlocking the complexities of cancer cells to anti-cancer drugs. SiViT can load a wide range of biological models in the form of SBML, but the work focuses on the Abertay Cancer cell model. SiViT allows clinicians and biologists to directly interact with the cancer cell model, introducing drugs or mutations. SiViT animates the effects of these introductions on the internal elements of the cell pathways and nodes. Showing how the cell network responds to these introductions such as increased or decreased activity, or re-rerouting to bypass the effected region of the network. Indicating the effectiveness of drugs, drug resistance and suggesting area for further experimentation.Offering bi-directional interaction and explorations. With drug inserts updating the model in real-time. Timings of drug introduction or mutations is crucial and SiViT allows for changes to occur at specific timings and model the result. This is critical in the exploration of combination therapees. SiViT follows the visual guidelines from existing literature on cell networking and dynamics, with ongoing HCI work being conducted to ensure information is visualised accessibly. SiViT was part of the UKRI Main Exhibition Stand at the American Association for the Advancement of Science 2019 conference. SiViT was the catalyst for a new 4-year project led by Macmillan Cancer Support on optimising health and social care service provision through interactive network visualisation.<br/

Scaling Up a Multifaceted Violence Prevention Package: County-Level Impact of the North Carolina Youth Violence Prevention Center

OBJECTIVE: Multifaceted approaches to youth-violence prevention package evidence-based programs into initiatives that yield large-scale impact. This study assessed the impact of a package of evidence-based violence prevention programs, implemented as part of the North Carolina Youth Violence Prevention Center, on county-level violence indicators. METHOD: Using growth-curve modeling, the target county was compared to all other counties in North Carolina and a comparison county. RESULTS: Results reveal downward trends on several county-level indicators (i.e., undisciplined/delinquent complaints, total delinquent complaints, juvenile arrests–aggravated assaults, and short-term suspensions) throughout the intervention period. However, statistical tests were unable to confirm that intervention-period scores on youth-violence indicators were significantly different than expected scores given the relationship between pretest and intervention-period scores in other North Carolina counties. CONCLUSIONS: Although additional administrative data points are needed to support the hypotheses, this study provides preliminary evidence of the effectiveness of North Carolina Youth Violence Prevention Center interventions

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): evaluation using an endogenous HCC model

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.The present study was supported in part by grants from The James S. McDonnell Foundation, National Cancer Institute Grant R01 CA138540-01A1 (DS), National Institutes of Health Grant R01 CA134721 (PBF), the Samuel Waxman Cancer Research Foundation (SWCRF) (DS and PBF), National Institutes of Health Grants R01 GM078240 and P50 GM67041 (SES), the Johnson and Johnson Clinical Innovation Award (UH), and the Boston University Ignition Award (UH). JLSW was supported by Alnylam Pharmaceuticals, Inc. DS is the Harrison Endowed Scholar in Cancer Research and Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research. The authors acknowledge Dr. Lauren E. Brown (Dept. Chemistry, Boston University) for the synthesis of FQI1 and FQI2, and Lucy Flynn (Dept. Biology, Boston University) for initially identifying G2/M effects caused by FQI1. (James S. McDonnell Foundation; R01 CA138540-01A1 - National Cancer Institute; R01 CA134721 - National Institutes of Health; R01 GM078240 - National Institutes of Health; P50 GM67041 - National Institutes of Health; Samuel Waxman Cancer Research Foundation (SWCRF); Johnson and Johnson Clinical Innovation Award; Boston University Ignition Award; Alnylam Pharmaceuticals, Inc.)Published versio