Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors

Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18-76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission.

Distribution of benefits of irrigation induced technological changes and commodity markets : new evidence

A plethora of literature exists on irrigation development. However, only a few studies analyse the distributional issues associated with irrigation induced technological changes (IITC) in the context of commodity markets. Furthermore, these studies deal with only the theoretical arguments and to date no proper investigation has been conducted to examine the long-term benefits of adopting modern irrigation technology. This study investigates the long-term benefit changes of irrigation induced technological changes using data from Sri Lanka with reference to rice farming. The results show that (1) adopting modern technology on irrigation increases the overall social welfare through consumption of a larger quantity at a lower cost (2) the magnitude, sensitivity and distributional gains depend on the price elasticity of demand and supply as well as the size of the marketable surplus (3) non-farm sector gains are larger than farm sector gains (4) the distribution of the benefits among different types of producers depend on the magnitude of the expansion of the irrigated areas as well as the competition faced by traditional farmers (5) selective technological adoption and subsidies have a detrimental effect on the welfare of other producers who do not enjoy the same benefits (6) the short-term distributional effects are more severe than the long-term effects among different groups of farmers.

Determinants of health costs due to farmers’ exposure to pesticides : an empirical analysis

It is now well known that pesticide spraying by farmers has an adverse impact on their health. This is especially so in developing countries where pesticide spraying is undertaken manually. The estimated health costs are large. Studies to date have examined farmers’ exposure to pesticides, the costs of ill-health and their determinants based on information provided by farmers. Hence, some doubt has been cast on the reliability of such studies. In this study, we rectify this situation by conducting surveys among two groups of farmers. Farmers who perceive that their ill-health is due to exposure to pesticides and obtained treatment and farmers whose ill-health have been diagnosed by doctors and who have been treated in hospital for exposure to pesticides. In the paper, cost comparisons between the two groups of farmers are made. Furthermore, regression analysis of the determinants of health costs show that the quantity of pesticides used per acre per month, frequency of pesticide use and number of pesticides used per hour per day are the most important determinants of medical costs for both samples. The results have important policy implications.

Hollywood dominance : will it continue?

Hollywood has dominated the global film business since the First World War. Economic formulas used by governments to assess levels of industry dominance typically measure market share to establish the degree of industry concentration. The business literature reveals that a marketing orientation strongly correlates with superior market performance and that market leaders that possess a set of six superior marketing capabilities are able to continually outperform rival firms. This paper argues that the historical evidence shows that the Hollywood Majors have consistently outperformed rival firms and rival film industries in each of those six marketing capabilities and that unless rivals develop a similarly integrated and cohesive strategic marketing management approach to the movie business and match the Major studios’ superior capabilities, then Hollywood’s dominance will continue. This paper also proposes that in cyberspace, whilst the Internet does provide a channel that democratises film distribution, the flat landscape of the world wide web means that in order to stand out from the clutter of millions of cyber-voices seeking attention, independent film companies need to possess superior strategic marketing management capabilities and develop effective e-marketing strategies to find a niche, attract a loyal online audience and prosper. However, mirroring a recent CIA report forecasting a multi-polar world economy, this paper also argues that potentially serious longer-term rivals are emerging and will increasingly take a larger slice of an expanding global box office as India, China and other major developing economies and their respective cultural channels grow and achieve economic parity with or surpass the advanced western economies. Thus, in terms of global market share over time, Hollywood’s slice of the pie will comparatively diminish in an emerging multi-polar movie business.

Hash based disk imaging using AFF4

Forensic imaging has been facing scalability challenges for some time. As disk capacity growth continues to outpace storage IO bandwidth, the demands placed on storage and time are ever increasing. Data reduction and de-duplication technologies are now commonplace in the Enterprise space, and are potentially applicable to forensic acquisition. Using the new AFF4 forensic file format we employ a hash based compression scheme to leverage an existing corpus of images, reducing both acquisition time and storage requirements. This paper additionally describes some of the recent evolution in the AFF4 file format making the efficient implementation of hash based imaging a reality.

Organizations as intergroup contexts: Communication, discourse, and identification

wenty-eight international scholars contribute 11 chapters on the key role of communication in intergroup relations. Following an introductory essay on intergroup theory and communication processes, the text focuses on specific intergroup contexts, examining communication within and between cultural, disability, age, sex and sexuality, and language groups. The remaining chapters explore the communicating of identity across communication contexts, including small group, organizational, mass, and Internet communications. The text is designed for scholars in the fields of communication and intergroup social psychology, and is also suited for use in upper- division undergraduate and introductory graduate courses in those areas. Annotation ©2004 Book News, Inc., Portland, OR

The urban littoral frontier : land reclamation in the history of human settlements

The urban waterfront may be regarded as the littoral frontier of human settlement. Typically, over the years, it advances, sometimes retreats, where terrestrial and aquatic processes interact and frequently contest this margin of occupation. Because most towns and cities are sited beside water bodies, many of these urban centers on or close to the sea, their physical expansion is constrained by the existence of aquatic areas in one or more directions from the core. It is usually much easier for new urban development to occur along or inland from the waterfront. Where other physical constraints, such as rugged hills or mountains, make expansion difficult or expensive, building at greater densities or construction on steep slopes is a common response. This kind of development, though technically feasible, is usually more expensive than construction on level or gently sloping land, however. Moreover, there are many reasons for developing along the shore or riverfront in preference to using sites further inland. The high cost of developing existing dry land that presents serious construction difficulties is one reason for creating new land from adjacent areas that are permanently or periodically under water. Another reason is the relatively high value of artificially created land close to the urban centre when compared with the value of existing developable space at a greater distance inland. The creation of space for development is not the only motivation for urban expansion into aquatic areas. Commonly, urban places on the margins of the sea, estuaries, rivers or great lakes are, or were once, ports where shipping played an important role in the economy. The demand for deep waterfronts to allow ships to berth and for adjacent space to accommodate various port facilities has encouraged the advance of the urban land area across marginal shallows in ports around the world. The space and locational demands of port related industry and commerce, too, have contributed to this process. Often closely related to these developments is the generation of waste, including domestic refuse, unwanted industrial by-products, site formation and demolition debris and harbor dredgings. From ancient times, the foreshore has been used as a disposal area for waste from nearby settlements, a practice that continues on a huge scale today. Land formed in this way has long been used for urban development, despite problems that can arise from the nature of the dumped material and the way in which it is deposited. Disposal of waste material is a major factor in the creation of new urban land. Pollution of the foreshore and other water margin wetlands in this way encouraged the idea that the reclamation of these areas may be desirable on public health grounds. With reference to examples from various parts of the world, the historical development of the urban littoral frontier and its effects on the morphology and character of towns and cities are illustrated and discussed. The threat of rising sea levels and the heritage value of many waterfront areas are other considerations that are addressed.

Promoting student learning with online videos : a research agenda

Gen Y students are digital natives (Prensky 2001) who learn in complex and diverse ways, with a variety of learning styles apparent in any given course. This paper proposes a web 2.0 conceptual learning solution–online student videos–to respond to different learning styles that exist in the classroom.