Reprint of “Safe places for pedestrians: Using cognitive work analysis to consider the relationships between the engineering and urban design of footpaths”

Footpaths provide an integral component of our urban environments and have the potential to act as safe places for people and the focus for community life. Despite this, the approach to designing footpaths that are safe while providing this sense of place often occurs in silos. There is often very little consideration given to how designing for sense of place impacts safety and vice versa. The aim of this study was to use a systems analysis and design framework to develop a design template for an ‘ideal’ footpath system that embodies both safety and sense of place. This was achieved through using the first phase of the Cognitive Work Analysis framework, Work Domain Analysis, to specify a model of footpaths as safe places for pedestrians. This model was subsequently used to assess two existing footpath environments to determine the extent to which they meet the design requirements specified. The findings show instances where the existing footpaths both meet and fail to meet the design requirements specified. Through utilising a systems approach for footpaths, this paper has provided a novel design template that can inform new footpath design efforts or be used to evaluate the extent to which existing footpaths achieve their safety and sense of place requirements.     

Regulation Theory,Global Competition Among Cities And Capital Embeddedness

This paper reviews the contribution of regulation theory to our understanding of urban development and its regulation by the state. The theory provides a useful instrument for convergence of politics, economics and geography in which the crucial questions of territoriality of local states and the embeddedness of capital can be considered. But there remains much to be explored both in the mode of development of the global economy over time, and in the relationship between global economic structures and local political institutions. The further development of regulation theory demands a reconceptualisation of power and the absorption of ecological/environmental and feminist discourses into the debates.     

Housing and Economic Development in Indian Country: Challenge and Opportunity

Global Warming: Climate Change: The IPCC Scientific Assessment J. T. Houghton, G. J. Jenkins, and J. J. Ephraums, editors. Cambridge University Press, Cambridge, UK, 1990. 305 pp. $34.95 (paperback).

Global Warming: Leaving Eden to Protect and Manage the Earth E. G. Nisbet. Cambridge University Press, Cambridge, UK, 1991. 358 pp. $14.95 (paperback).

Global Warming: Global Environmental Issues: A Climatological Approach David D. Kemp. Routledge, Chapman and Hall, London, 1990. 220 pp. $15.95 (paperback).

Global Warming: Global Climate Change and Life on Earth Richard L. Wyman, editor. Rout-ledge, Chapman and Hall, London, 1991. 282 pp. $24.95 (paperback).

Global Warming: Global Climate Change and California Joseph B. Knox and Ann Foley Scheuring, editors. University of California Press, Berkeley, 1992. 184 pp. $12.95 (paperback).

The Environment: Race and the Incidence of Environmental Hazards: A Time for Discourse Bunyan Bryant and Paul Mohai, editors. Westview Press, San Francisco, 1992. 251 pp. $32.00 (paperback).

The Environment: Sustaining the Earth John Young. Harvard University Press, Cambridge, MA, 1990. 202 pp. $10.95 (paperback).

The Environment: Rural Environmental Planning for Sustainable Communities Frederick O. Sargent, Paul Lusk, Jose A. Rivera, and Maria Varela. Island Press, Washington, DC, 1991. 254 pp. $24.95 (paperback).

The Environment: Environmental Politics: Public Costs, Private Rewards Michael S. Greve and Fred L. Smith, Jr., editors. Praeger, New York, 1992. 212 pp. $19.95 (paperback).

Planning and Its Subfields: Customer Service in Local Government: Challenges for Planners and Managers Bruce W. McClendon. Planners Press, American Planning Association, Chicago, 1992. 194 pp. $45.95, $34.95 (paperback).

Planning and Its Subfields: Reviving the American Dream: The Economy, the States and the Federal Government Alice M. Rivlin. Brookings Institution, Washington, DC, 1992. 196 pp. $15.95.

Planning and Its Subfields: Left Coast City: Progressive Politics in San Francisco, 1975-1991 Richard Edward DeLeon. University Press of Kansas, Lawrence, 1992. 239 pp. $35.00, $14.95 (paperback).

Planning and Its Subfields: The New Frontier for Land Policy: Planning and Growth Management in the States John M. DeGrove, with Deborah Miness. Lincoln Institute of Land Policy, Cambridge, MA, 1992. 176 pp. $18.95 (paperback).

Planning and Its Subfields: Magic Lands: Western Cityscapes and American Culture After 1940 John M. Findlay. University of California Press, Berkeley, 1992. 394 pp. $35.00.

Planning and Its Subfields: The Power of Maps Denis Wood. Guilford Press, New York, 1992. 248 pp. $35.00, $15.95 (paperback).

Planning and Its Subfields: Put up or Give Way: States, Economic Competitiveness, and Poverty John Sidor. Council of State Community Development Agencies, Washington, DC, 1991.243 pp. $20.00 (paperback).

Planning and Its Subfields: North American Free Trade: Assessing the Impact Nora Lustig, Barry P. Bosworth, and Robert Z. Lawrence, editors. Brookings Institution, Washington, DC, 1992. 274 pp. $28.95, $10.95 (paperback).

Briefly Noted: Electronic Byways: State Policies for Rural Development Through Telecommunications Edwin B. Parker and Heather Hudson, with Don A. Dillman, Sharon Strover, and Frederick Williams. Westview, Boulder, CO, 1992. 306 pp. $57.50, $18.85 (paperback).

Briefly Noted: Credit Where It's Due: Development Banking for Communities Julia Ann Parzen and Michael Hall Kieschnick. Temple University Press, Philadelphia, PA, 1992. 275 pp. $29.95.

Briefly Noted: Reclaiming the Past Landmarks of Women's History Page Putnam Miller, editor. Indiana University Press, Bloomington, 1992. 232 pp. $35.00.

Briefly Noted: Renewing Cities Ross J. Gittell. Princeton University Press, Princeton, NJ, 1992. 232 pp., $39.50.

Briefly Noted: Regions Reconsidered: Economic Networks, Innovation, and Local Development in Industrialized Countries Edward Bergman, Gunther Maier, and Franz Todtling, editors. Mansell, London, 1991. 312 pp. $80.00.

Briefly Noted: Defense, Welfare and Growth: Perspective and Evidence Steve Chan and Alex Mintz, editors. Routledge, Chapman and Hall, New York, 1992. 248 pp. $59.95.

Briefly Noted: The Changing Image of the City: Planning for Downtown Omaha, 1945-1973 Janet R. Daly-Bednarek. University of Nebraska Press, Lincoln, 1992. 292 pp. $37.50.     

Acute β-Hydroxy-β-Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes

Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine‐derived metabolite β‐hydroxy‐β‐methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB‐treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator‐activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP‐activated protein kinase. As a result, HMB‐treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.     

Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP

The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post‐translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C‐terminal “follower” sequence, rather than the canonical N‐terminal “leader” sequence. We report herein the structural and biochemical characterization of BotP, a leucyl‐aminopeptidase‐like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N‐terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn²⁺ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro‐ mycin.     

Protein Kinases and Parkinson’s Disease

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.     

Silk proteins for biomedical applications: Bioengineering perspectives

Biomaterials of either natural or synthetic origin are used to fabricate implantable devices, as carriers for bioactive molecules or as substrates to facilitate tissue regeneration. For the design of medical devices it is fundamental to use materials characterized by non-immunogenicity, biocompatibility, slow and/or controllable biodegradability, non-toxicity, and structural integrity. The success of biomaterial-derived biodevices tends to be based on the biomimetic architecture of the materials. Recently, proteins from natural precursors that are essentially structural and functional polymers, have gained popularity as biomaterials. The silks produced by silkworms or spiders are of particular interest as versatile protein polymers. These form the basis for diverse biomedical applications that exploit their unique biochemical nature, biocompatibility and high mechanical strength. This review discusses and summarizes the latest advances in the engineering of silk-based biomaterials, focusing specifically on the fabrication of diverse bio-mimetic structures such as films, hydrogels, scaffolds, nanofibers and nanoparticles; their functionalization and potential for biomedical applications.