Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions ; (2) to elucidate the molecular basis of their biological effects ; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation

Correspondence between Zebulon Weaver, Arno B. Cammerer, and David C. Chapman, 1935-36

Zebulon Weaver (1872-1948) was a lawyer and U.S. Representative from western North Carolina. He was a member of the North Carolina Park Commission and was involved in the land acquisition process that went towards establishment of the Great Smoky Mountain National Park and development of the Blue Ridge Parkway. This correspondence between David C. Chapman, President of the Great Smoky Mountains Conservation Association, Arno Cammerer, , Director of the National Park Service, and Zebulon Weaver-a set of 10 letters-revolves around issues in land acquisition for the park. Zebulon Weaver to David C. Chapman, December 20, 1935 In this letter Weaver refers to disagreeing with Mr. Cammerer’s view regarding land acquisition by the Park and also states he would be going to Washington soon to deal with the issue. David C. Chapman to Zebulon Weaver, December 14, 1935 In this letter David Chapman refers to an enclosed letter from Mr. Cammerer stating that 445,000 acres were needed to complete the park instead of 400,000. Chapman feels it would be helpful if Weaver went to Washington to sort this matter out with the Attorney General. Arno B. Cammerer to David C. Chapman, December 7, 1935 In this letter Cammerer states he was not comfortable to acquire 400,000 acres to establish Smokies as a completed park. He also advises Chapman’s conservation group to await the efforts of the Park to secure more money for securing what he considered sufficient acreage needed for completion of the park. David C. Chapman to Arno B. Cammerer, December 14, 1935 In this letter Chapman states he was confident of securing a ruling from the Attorney General that once 400,000 acreas were acquired the Smokies would be considered a completed park. Delaying this further for more acreage would create a lot of disappointment and bad feelings about the delays in completing this venture. David C. Chapman to Zebulon Weaver, December 24, 1935 In this letter Chapman mentions that Representative from the Subcommittee of the Appropriations Committee were of the same opinion as with Weaver and saw no reasons for delay in the completion of the Park. David C. Chapman to Zebulon Weaver, January 3, 1936 In this letter Chapman states that he agrees with Cam that declaring the Smokies a completed park might prevent them from getting the balance of the money needed for the park. He also requests Weaver to follow up on this matter with Secretary Ickes or the President in Washington. Zebulon Weaver to David C. Chapman, January 6, 1936 In this letter Weaver mentions he feels that acquiring 400,000 acres would allow the Smokies to be established as a completed park and that he was confident it would be open within the year. He also mentions following up on the matters with Daniels, Cam, and if possible Secretary Ickes. David C. Chapman to Zebulon Weaver, January 11, 1936 In this letter Chapman states that Cam thought they had enough acreage for the Smokies to be declared a completed park but that Cam wanted to wait till they got the allotment. David C. Chapman to Zebulon Weaver, January 24, 1936 In this letter Champan mentions while some allotment had come through, it was important for the matter to be pursued to get the remaining money. He also mentions Senator McKeller being unhappy with Cam since the latter did not spend any of the allotted money in Tennessee. Zebulon Weaver to David C. Chapman, January 27, 1936 In this letter Weaver discusses the source of the allotted funds. He also states he was sorry that Cam’s role was being misunderstood by McKeller while people in North Carolina thought he was spending money on Tennessee

Correspondence: Arno B. Cammerer to Zebulon Weaver, September 14, 1934

Zebulon Weaver (1872-1948) was a lawyer and U.S. Representative from western North Carolina. He was a member of the North Carolina Park Commission and was involved in the land acquisition process that went towards establishment of the Great Smoky Mountain National Park and development of the Blue Ridge Parkway. In this letter addressed to Weaver, Cammerer, Director of the National Park Service, lets Weaver know in response to the latter’s enquiry that while it was not possible to identify the allotments made to North Carolina and Tennessee separately, or about developments in the park, the Park Service would like to see the development of the North Carolina side of the park boundary extended to Little Tennessee River and establishing park headquarters in both North Carolina and Tennessee

Correspondence: "Cam" [Arno B. Cammerer] to Zebulon Weaver, August 8, 1932

Zebulon Weaver (1872-1948) was a lawyer and U.S. Representative from western North Carolina. He was a member of the North Carolina Park Commission and was involved in the land acquisition process that went towards establishment of the Great Smoky Mountain National Park and development of the Blue Ridge Parkway. In this two page letter, Cam furnishes Weaver with a memo regarding the possibilities of acquiring a loan from the Reconstruction Finance Commission to purchase lands for the Great Smoky Mountain National Park

Quinuclidine Derivatives as Potential Antiparasitics▿

There is an urgent need for the development of new drugs for the treatment of tropical parasitic diseases such as Chagas' disease and leishmaniasis. One potential drug target in the organisms that cause these diseases is sterol biosynthesis. This paper describes the design and synthesis of quinuclidine derivatives as potential inhibitors of a key enzyme in sterol biosynthesis, squalene synthase (SQS). A number of compounds that were inhibitors of the recombinant Leishmania major SQS at submicromolar concentrations were discovered. Some of these compounds were also selective for the parasite enzyme rather than the homologous human enzyme. The compounds inhibited the growth of and sterol biosynthesis in Leishmania parasites. In addition, we identified other quinuclidine derivatives that inhibit the growth of Trypanosoma brucei (the causative organism of human African trypanosomiasis) and Plasmodium falciparum (a causative agent of malaria), but through an unknown mode(s) of action

Urban Development as a Continuum: A Multinomial Logistic Regression Approach

peer reviewedUrban development is a complex process influenced by a number of driving forces, including spatial planning, topography and urban economics. Identifying these drivers is crucial for the regulation of urban development and the calibration of predictive models. Existing land-use models generally consider urban development as a binary process, through the identification of built versus non-built areas. This study considers urban development as a continuum, characterized by different level of densities, which can be related to different driving forces. A multinomial logistic regression model was employed to investigate the effects of drivers on different urban densities during the past decade in Wallonia, Belgium. Sixteen drivers were selected from sets of driving forces including accessibility, geophysical features, policies and socioeconomic factors. It appears that urban development in Wallonia is remarkably influenced by land-use policies and accessibility. Most importantly, our results highlight that the impact of different drivers varies along with urban density.ARC - Floodlan