WorldWideScience

Sample records for advanced synfuel production

  1. Oil sand synfuel production using nuclear energy

    International Nuclear Information System (INIS)

    Barnert, H.

    1984-10-01

    The importance of oil sand as a primary energy carrier is illustrated. The oil sand mining project 'synfuel' in Fort McMurray, Alberta, Canada, is described. On the basis of a layout of an In-situ-process different possibilities of introducing nuclear energy to the process are described. This leads to an increase of the product yield, leading finally to a doubling of the energy output compared to the reference layout. The introduction of nuclear energy contributes to the reduction of emissions, in particular to the emission of carbon dioxide in the conversion process. (orig.)

  2. Acid gas removal in synfuels production

    Energy Technology Data Exchange (ETDEWEB)

    Eickmeyer, A.G.; Gangriwala, H.A.

    1981-12-01

    The CO/sub 2/, H/sub 2/S and COS contents of gas streams of some synfuel processes and the costs for removal of these gases are tabulated. Four different types of acid gas removal processes discussed are chemisorption, physical adsorption, hybrid or combination of the first two, and sulfur conversion processes. Results of an economic study of H/sub 2/S and CO/sub 2/ removal at pressures of 1379, 2758, and 4137 kPa for 13.8 million normal m/sup 3//day of gas containing 1% H/sub 2/S and 22% CO/sub 2/. The processes considered were selective removal of H/sub 2/S with a solvent process (CATASOL 3) followed by removal of CO/sub 2/ by either the CATASOL 4A physical solvent or the CATACARB process (catalyzed hot potassium). The main feature influencing the selection of acid gas removal process are the gas composition and pressure and availability of low-level waste heat. Capital investment, utilities, and chemical costs were considered for various processes. Since the cost of commercial size synfuel process plants runs into billions of dollars, the added cost of acid gas removal must be carefully considered. (BLM)

  3. Assessment of synfuel spill cleanup options

    Energy Technology Data Exchange (ETDEWEB)

    Petty, S.E.; Wakamiya, W.; English, C.J.; Strand, J.A.; Mahlum, D.D.

    1982-04-01

    Existing petroleum-spill cleanup technologies are reviewed and their limitations, should they be used to mitigate the effects of synfuels spills, are discussed. The six subsections of this report address the following program goals: synfuels production estimates to the year 2000; possible sources of synfuel spills and volumes of spilled fuel to the year 2000; hazards of synfuels spills; assessment of existing spill cleanup technologies for oil spills; assessment of cleanup technologies for synfuel spills; and disposal of residue from synfuel spill cleanup operations. The first goal of the program was to obtain the most current estimates on synfuel production. These estimates were then used to determine the amount of synfuels and synfuel products likely to be spilled, by location and by method of transportation. A review of existing toxicological studies and existing spill mitigation technologies was then completed to determine the potential impacts of synthetic fuel spills on the environment. Data are presented in the four appendixes on the following subjects: synfuel production estimates; acute toxicity of synfuel; acute toxicity of alcohols.

  4. Mirror Advanced Reactor Study (MARS). Final report. Volume 2. Commercial fusion synfuels plant

    International Nuclear Information System (INIS)

    Donohue, M.L.; Price, M.E.

    1984-07-01

    Volume 2 contains the following chapters: (1) synfuels; (2) physics base and parameters for TMR; (3) high-temperature two-temperature-zone blanket system for synfuel application; (4) thermochemical hydrogen processes; (5) interfacing the sulfur-iodine cycle; (6) interfacing the reactor with the thermochemical process; (7) tritium control in the blanket system; (8) the sulfur trioxide fluidized-bed composer; (9) preliminary cost estimates; and (10) fuels beyond hydrogen

  5. Labor productivity in heavy construction: impact on synfuels program employment

    Energy Technology Data Exchange (ETDEWEB)

    Kusterer, K.C.

    1980-06-01

    This study focuses on variations in labor productivity in the heavy construction industry. Productivity is one of a number of factors likely to affect the speed and cost of constructing a synthetic fuels plant. The findings of this study are presented with reference to synthetic fuels plants, but they are relevant to other large energy facilities as well. The data were gathered through a detailed literature search and extensive in-depth interviews with consultants in heavy industrial construction, union officials, and management. In this manner the most important determinants of labor productivity were identified and ranked in terms of relative significance. The type of project under construction is the most important factor affecting the productivity of heavy construction labor. Projects characterized by the utility work syndrome are large, complex, relatively unique, highly regulated, and have cost-plus contracts and tight deadlines. Such projects generally have lower-than-average levels of labor productivity. Labor productivity is also lowered by worker and management morale problems, due to delays and design changes, and by high levels of unemployment among construction workers. Finally, boom town conditions, caused by workers moving to live near large projects located in rural areas, also are likely to result in below-average labor productivity.Synthetic fuels plants are likely to have a number of these identified characteristics. Consequently, the findings suggest that labor productivity may well be a problem for the timely development of an economically competitive synthetic fuels industry.

  6. Review of fusion synfuels

    International Nuclear Information System (INIS)

    Fillo, J.A.

    1980-01-01

    Thermonuclear fusion offers an inexhaustible source of energy for the production of hydrogen from water. Depending on design, electric generation efficiencies of approx. 40 to 60% and hydrogen production efficiencies by high-temperature electrolysis of approx. 50 to 65% are projected for fusion reactors using high-temperatures blankets. Fusion/coal symbiotic systems appear economically promising for the first generation of commercial fusion synfuels plants. Coal production requirements and the environmental effects of large-scale coal usage would be greatly reduced by a fusion/coal system. In the long term, there could be a gradual transition to an inexhaustible energy system based solely on fusion

  7. Proceedings of Brookhaven National Laboratory's fusion/synfuel workshop

    International Nuclear Information System (INIS)

    Fillo, J.A.; Powell, J.R.

    1979-01-01

    The fusion synfuels workshop held at Brookhaven National Laboratory (BNL) on August 27-29, 1979 examined the current status of candidate synfuel processes and the R and D required to develop the capability for fusion synfuel production. Participants divided into five working groups, covering the following areas: (1) economics and applications; (2) high-temperature electrolysis; (3) thermochemical processes (including hybrid thermo-electrochemical); (4) blanket and materials; and (5) high-efficiency power cycles. Each working group presented a summary of their conclusions and recommendations to all participants during the third day of the Workshop. These summaries are given

  8. Thermal and structural design aspects of high-temperature blankets for fusion synfuel production

    International Nuclear Information System (INIS)

    Powell, J.R.; Fillo, J.A.; Reich, M.

    1981-01-01

    The most promising process, high temperature electrolysis (HTE) of steam at temperatures of greater than or equal to 1000 0 C is examined. In HTE, a large fraction (up to approx. 50%) of the energy input to split water to hydrogen and oxygen comes from thermal energy. For the projected operating conditions achieved by high temperature fusion blankets, overall efficiencies for hydrogen production should be on the order of 60%. The design, thermal-hydraulics, and materials for such blankets are discussed

  9. Coal-based synfuel continues to grow

    Energy Technology Data Exchange (ETDEWEB)

    Morey, M.

    2002-11-01

    This paper summarises a recent study by Platts Research and Consulting/RDI. The results show that synfuel production has the potential to reach 80 million tons per year, a sharp jump from total production of less than 4 million tons in 1999. Growth is being spurred by the number of developments, including redevelopment of machines to more advantageous locations, greater regulatory certainty in the claiming of section 29 tax credits, ownership of plants by companies that can make full use of the tax credit, and a wider and more sanguine acceptance among consumers using the products. 1 fig., 1 tab.

  10. Tax credit synfuels influence coal markets

    Energy Technology Data Exchange (ETDEWEB)

    Morey, M.; Leshock, C. [Resource Data International, Boulder, CO (USA)

    2000-05-01

    The recent introduction of synthetic coal products has upset the balance between supply and demand in the US coal market. The imbalance is being driven by the operation of more than 40 facilities that were rapidly pushed into commercial service to meet a 1 July 1998 deadline to qualify for a tax credit. A study by Resource Data International found that synthetic coal will increase in importance and become a critical issue for both coal producers and consumers until 31 December 2007 when the credit expires. The tax credit is granted to qualifying fuels that have undergone a chemical change. However, many plants tout their use of waste coal, pond fines and other mining wastes. The credit amount is based on calorific value. RDI found that 44 synfuel plants were operating to some degree during 1999 with 10 being a West Virginia, 8 in Kentucky and 7 in Pennsylvania. 2 figs.

  11. Procedure for matching synfuel users with potential suppliers. Appendix B. Proposed and ongoing synthetic fuel production projects

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-08-07

    To assist the Department of Energy, Office of Fuels Conversion (OFC), in implementing the synthetic fuel exemption under the Powerplant and Industrial Fuel Use Act (FUA) of 1978, Resource Consulting Group, Inc. (RCG), has developed a procedure for matching prospective users and producers of synthetic fuel. The matching procedure, which involves a hierarchical screening process, is designed to assist OFC in: locating a supplier for a firm that wishes to obtain a synthetic fuel exemption; determining whether the fuel supplier proposed by a petitioner is technically and economically capable of meeting the petitioner's needs; and assisting the Synthetic Fuels Corporation or a synthetic fuel supplier in evaluating potential markets for synthetic fuel production. A data base is provided in this appendix on proposed and ongoing synthetic fuel production projects to be used in applying the screening procedure. The data base encompasses a total of 212 projects in the seven production technologies.

  12. Synfuel bandwagon. [Administration succumbed to pressure to do something - anything

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, B.

    1979-12-24

    Paul R. Ignatius and Eugene Zuckert decided in late March 1979 that the US needed a synthetic fuels program on the space-program scale, according to Mr. Bartlett. He says that along with lawyer Lloyd Cutler, they drafted a memorandum outlining their idea and submitted it to the White House and key congressional leaders on April 22, 1979. It called for a $200 billion crash synfuels program and the idea caught on with legislators. In June the House of Representatives increased the goal of the program from 500,000 barrels per day to 2 million barrels per day. It then approved the program as an attachment to the Defense Production Act reauthorization. The press began talking about a synfuels bandwagon. On July 15, President Carter announced a new energy program that included, among other things, plans to produce synfuel at the rate of 2.5 million bbl/day oil equivalent by 1990. Mr. Bartlett reviews the economics of the program, its environmental aspects, and its proposed production schedule, citing the views of various critics and experts. He concludes that, In the end the pressure to do something - anything - about the energy crisis...proved overwhelming. We will be paying the price for a long time to come.

  13. Literature survey of properties of synfuels derived from coal

    Science.gov (United States)

    Reynolds, T. W.; Niedzwiecki, R. W.; Clark, J. S.

    1980-02-01

    A literature survey of the properties of synfuels for ground-based gas turbine applications is presented. Four major concepts for converting coal into liquid fuels are described: solvent extraction, catalytic liquefaction, pyrolysis, and indirect liquefaction. Data on full range syncrudes, various distillate cuts, and upgraded products are presented for fuels derived from various processes, including H-coal, synthoil, solvent-refined coal, donor solvent, zinc chloride hydrocracking, co-steam, and flash pyrolysis. Some typical ranges of data for coal-derived low Btu gases are also presented.

  14. Literature survey of properties of synfuels derived from coal

    Science.gov (United States)

    Reynolds, T. W.; Niedzwiecki, R. W.; Clark, J. S.

    1980-01-01

    A literature survey of the properties of synfuels for ground-based gas turbine applications is presented. Four major concepts for converting coal into liquid fuels are described: solvent extraction, catalytic liquefaction, pyrolysis, and indirect liquefaction. Data on full range syncrudes, various distillate cuts, and upgraded products are presented for fuels derived from various processes, including H-coal, synthoil, solvent-refined coal, donor solvent, zinc chloride hydrocracking, co-steam, and flash pyrolysis. Some typical ranges of data for coal-derived low Btu gases are also presented.

  15. Screening of synfuel processes for HTGR application

    International Nuclear Information System (INIS)

    1981-02-01

    The aim of this study is to select for further study, the several synfuel processes which are the most attractive for application of HTGR heat and energy. In pursuing this objective, the Working Group identified 34 candidate synfuel processes, cut the number of processes to 16 in an initial screening, established 11 prime criteria with weighting factors for use in screening the remaining processes, developed a screening methodology and assumptions, collected process energy requirement information, and performed a comparative rating of the processes. As a result of this, three oil shale retorting processes, two coal liquefaction processes and one coal gasification process were selected as those of most interest for further study at this time

  16. Determination of total solutes in synfuel wastewaters

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, J.R.; Bonomo, F.S.

    1984-03-01

    Efforts to investigate both lyophilization and the measurement of colligative properties as an indication of total solute content are described. The objective of the work described is to develop a method for measuring total dissolved material in retort wastewaters which is simple and rugged enough to be performed in a field laboratory in support of pollution control tests. The analysis should also be rapid enough to provide timely and pertinent data to the pollution control plant operator. To be of most value, the technique developed also should be applicable to other synfuel wastewaters, most of which contain similar major components as oil shale retort waters. 4 references, 1 table.

  17. Animal Production Research Advances

    African Journals Online (AJOL)

    Animal Production Research Advances is a peer-review journal established expressly to promote the production of all animal species utilized as food. The journal has an international scope and is intended for professionals in animal production and related sciences. We solicit contributions from animal production and ...

  18. Proceedings of the opportunities in the synfuels industry

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-31

    World interest in coal-based synthetic fuels technology is like a roller coaster ride. Interest soars when energy prices are high or world oil supplies are threatened. When energy is inexpensive and oil is plentiful, interest plummets. However, some people remain undaunted by the ups and downs of the synfuels industry. They cling tenaciously to the idea that coal-based synthetic fuels are the world`s energy future. They are the select group attending the SynOps `92 symposium in Bismarck, North Dakota. SynOps `92 participants represent an extraordinary combination of visionaries and practical thinkers. They believe the ``coal refinery`` concept will eventually provide the most efficient and productive use of our coal resources. They know that coal is a valuable resource which can be used to produce a huge variety of valuable nonfuel products. They also recognize that until technology can make alternative fuels economically feasible, the world will continue to rely heavily on fossil fuels--especially coal, the world`s most abundant energy resource. Individual papers have been entered.

  19. Proceedings of the opportunities in the synfuels industry

    International Nuclear Information System (INIS)

    1992-01-01

    World interest in coal-based synthetic fuels technology is like a roller coaster ride. Interest soars when energy prices are high or world oil supplies are threatened. When energy is inexpensive and oil is plentiful, interest plummets. However, some people remain undaunted by the ups and downs of the synfuels industry. They cling tenaciously to the idea that coal-based synthetic fuels are the world's energy future. They are the select group attending the SynOps '92 symposium in Bismarck, North Dakota. SynOps '92 participants represent an extraordinary combination of visionaries and practical thinkers. They believe the ''coal refinery'' concept will eventually provide the most efficient and productive use of our coal resources. They know that coal is a valuable resource which can be used to produce a huge variety of valuable nonfuel products. They also recognize that until technology can make alternative fuels economically feasible, the world will continue to rely heavily on fossil fuels--especially coal, the world's most abundant energy resource. Individual papers have been entered

  20. Advanced Production Planning Models

    Energy Technology Data Exchange (ETDEWEB)

    JONES,DEAN A.; LAWTON,CRAIG R.; KJELDGAARD,EDWIN A.; WRIGHT,STEPHEN TROY; TURNQUIST,MARK A.; NOZICK,LINDA K.; LIST,GEORGE F.

    2000-12-01

    >This report describes the innovative modeling approach developed as a result of a 3-year Laboratory Directed Research and Development project. The overall goal of this project was to provide an effective suite of solvers for advanced production planning at facilities in the nuclear weapons complex (NWC). We focused our development activities on problems related to operations at the DOE's Pantex Plant. These types of scheduling problems appear in many contexts other than Pantex--both within the NWC (e.g., Neutron Generators) and in other commercial manufacturing settings. We successfully developed an innovative and effective solution strategy for these types of problems. We have tested this approach on actual data from Pantex, and from Org. 14000 (Neutron Generator production). This report focuses on the mathematical representation of the modeling approach and presents three representative studies using Pantex data. Results associated with the Neutron Generator facility will be published in a subsequent SAND report. The approach to task-based scheduling described here represents a significant addition to the literature for large-scale, realistic scheduling problems in a variety of production settings.

  1. Marketing technologically advanced products

    OpenAIRE

    Bender, Horst

    1989-01-01

    This paper calls for a merger of technology and marketing under a customer value perspective; for an enhancement of the traditional technological innovation orientation of the technology-based firm with a market thrust. It establishes technology-based products as product-service offerings that are derived from technological innovation. The aim in marketing technology-based products is an improved understanding of how an organization can combine a technology orientation with a customer value t...

  2. Marketing technologically advanced products

    NARCIS (Netherlands)

    Bender, Horst

    1989-01-01

    This paper calls for a merger of technology and marketing under a customer value perspective; for an enhancement of the traditional technological innovation orientation of the technology-based firm with a market thrust. It establishes technology-based products as product-service offerings that are

  3. Animal Production Research Advances: Submissions

    African Journals Online (AJOL)

    Where this is not possible, authors should submit two copies of original article not yet published anywhere and accompanied with a 3.5” diskette containing the article labeled appropriately in MS Word version to: Editor–in–Chief, Animal Production Research Advances Tropical Animal Health and Production Research Lab

  4. Animal Production Research Advances: Journal Sponsorship

    African Journals Online (AJOL)

    Animal Production Research Advances: Journal Sponsorship. Journal Home > About the Journal > Animal Production Research Advances: Journal Sponsorship. Log in or Register to get access to full text downloads.

  5. Advanced uncooled sensor product development

    Science.gov (United States)

    Kennedy, A.; Masini, P.; Lamb, M.; Hamers, J.; Kocian, T.; Gordon, E.; Parrish, W.; Williams, R.; LeBeau, T.

    2015-06-01

    The partnership between RVS, Seek Thermal and Freescale Semiconductor continues on the path to bring the latest technology and innovation to both military and commercial customers. The partnership has matured the 17μm pixel for volume production on the Thermal Weapon Sight (TWS) program in efforts to bring advanced production capability to produce a low cost, high performance product. The partnership has developed the 12μm pixel and has demonstrated performance across a family of detector sizes ranging from formats as small as 206 x 156 to full high definition formats. Detector pixel sensitivities have been achieved using the RVS double level advanced pixel structure. Transition of the packaging of microbolometers from a traditional die level package to a wafer level package (WLP) in a high volume commercial environment is complete. Innovations in wafer fabrication techniques have been incorporated into this product line to assist in the high yield required for volume production. The WLP seal yield is currently > 95%. Simulated package vacuum lives >> 20 years have been demonstrated through accelerated life testing where the package has been shown to have no degradation after 2,500 hours at 150°C. Additionally the rugged assembly has shown no degradation after mechanical shock and vibration and thermal shock testing. The transition to production effort was successfully completed in 2014 and the WLP design has been integrated into multiple new production products including the TWS and the innovative Seek Thermal commercial product that interfaces directly to an iPhone or android device.

  6. Preparation of environmental analyses for synfuel and unconventional gas technologies

    Energy Technology Data Exchange (ETDEWEB)

    Reed, R.M. (ed.)

    1982-09-01

    Government agencies that offer financial incentives to stimulate the commercialization of synfuel and unconventional gas technologies usually require an analysis of environmental impacts resulting from proposed projects. This report reviews potentially significant environmental issues associated with a selection of these technologies and presents guidance for developing information and preparing analyses to address these issues. The technologies considered are western oil shale, tar sand, coal liquefaction and gasification, peat, unconventional gas (western tight gas sands, eastern Devonian gas shales, methane from coal seams, and methane from geopressured aquifers), and fuel ethanol. Potentially significant issues are discussed under the general categories of land use, air quality, water use, water quality, biota, solid waste disposal, socioeconomics, and health and safety. The guidance provided in this report can be applied to preparation and/or review of proposals, environmental reports, environmental assessments, environmental impact statements, and other types of environmental analyses. The amount of detail required for any issue discussed must, by necessity, be determined on a case-by-case basis.

  7. Synfuel program analysis. Volume I. Procedures-capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Muddiman, J. B.; Whelan, J. W.

    1980-07-01

    This is the first of the two volumes describing the analytic procedures and resulting capabilities developed by Resource Applications (RA) for examining the economic viability, public costs, and national benefits of alternative synfuel projects and integrated programs. This volume is intended for Department of Energy (DOE) and Synthetic Fuel Corporation (SFC) program management personnel and includes a general description of the costing, venture, and portfolio models with enough detail for the reader to be able to specifiy cases and interpret outputs. It also contains an explicit description (with examples) of the types of results which can be obtained when applied to: the analysis of individual projects; the analysis of input uncertainty, i.e., risk; and the analysis of portfolios of such projects, including varying technology mixes and buildup schedules. In all cases, the objective is to obtain, on the one hand, comparative measures of private investment requirements and expected returns (under differing public policies) as they affect the private decision to proceed, and, on the other, public costs and national benefits as they affect public decisions to participate (in what form, in what areas, and to what extent).

  8. Synthetic biology advances for pharmaceutical production

    Science.gov (United States)

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  9. Animal Production Research Advances: Editorial Policies

    African Journals Online (AJOL)

    Focus and Scope. Animal production research advances is a peer-review journal established expressly to promote the production of all animal species utilized as food. The journal has an international scope and is intended for professionals in animal production and related sciences. We solicit contributions from animal ...

  10. Synfuels from fusion: using the tandem mirror reactor and a thermochemical cycle to produce hydrogen

    International Nuclear Information System (INIS)

    Werner, R.W.

    1982-01-01

    This study is concerned with the following area: (1) the tandem mirror reactor and its physics; (2) energy balance; (3) the lithium oxide canister blanket system; (4) high-temperature blanket; (5) energy transport system-reactor to process; (6) thermochemical hydrogen processes; (7) interfacing the GA cycle; (8) matching power and temperature demands; (9) preliminary cost estimates; (10) synfuels beyond hydrogen; and (11) thermodynamics of the H 2 SO 4 -H 2 O system

  11. Synfuels from fusion: using the tandem mirror reactor and a thermochemical cycle to produce hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Werner, R.W. (ed.)

    1982-11-01

    This study is concerned with the following area: (1) the tandem mirror reactor and its physics; (2) energy balance; (3) the lithium oxide canister blanket system; (4) high-temperature blanket; (5) energy transport system-reactor to process; (6) thermochemical hydrogen processes; (7) interfacing the GA cycle; (8) matching power and temperature demands; (9) preliminary cost estimates; (10) synfuels beyond hydrogen; and (11) thermodynamics of the H/sub 2/SO/sub 4/-H/sub 2/O system. (MOW)

  12. [Advances of alkaline amylase production and applications].

    Science.gov (United States)

    Yang, Haiquan; Liu, Long; Li, Jianghua; Du, Guocheng; Chen, Jian

    2012-04-01

    Alkaline amylase is one of alkaline enzymes with optimum pH in the alkaline range, and it could keep stability and efficiently hydrolyze starch under alkaline conditions. Alkaline amylase finds wide applications in textile, detergent, pharmaceutical, food and other fields. Alkaline amylases could be produced by alkaliphilic microorganisms. In this work, the advances of alkaline amylase production and applications were reviewed.

  13. Advances in product family and product platform design methods & applications

    CERN Document Server

    Jiao, Jianxin; Siddique, Zahed; Hölttä-Otto, Katja

    2014-01-01

    Advances in Product Family and Product Platform Design: Methods & Applications highlights recent advances that have been made to support product family and product platform design and successful applications in industry. This book provides not only motivation for product family and product platform design—the “why” and “when” of platforming—but also methods and tools to support the design and development of families of products based on shared platforms—the “what”, “how”, and “where” of platforming. It begins with an overview of recent product family design research to introduce readers to the breadth of the topic and progresses to more detailed topics and design theory to help designers, engineers, and project managers plan, architect, and implement platform-based product development strategies in their companies. This book also: Presents state-of-the-art methods and tools for product family and product platform design Adopts an integrated, systems view on product family and pro...

  14. Advanced verb form production in story retelling.

    Science.gov (United States)

    Sutter, J C; Johnson, C J

    1995-10-01

    This study investigated the rate at which 60 elementary school children produced three advanced verb forms--past progressive, past perfect progressive, and past perfect--when asked to retell literate narratives, a discourse genre that originates from written prose and frequently contains these advanced verb forms. The three verb forms were embedded in nine story episodes and told to the children. The children were then asked to retell the stories. Verb form production by the children was scored as either "borrowed" or substituted spontaneous production. During their story-retelling episodes, the 6-, 7-, and 8-year-old children borrowed all verb forms under investigation from the stimuli stories. They significantly preferred to borrow the past progressive over the past perfect progressive and past perfect forms. Rate of verb form production by 8-year-old children was significantly higher than for the younger age groups. These data suggest that advanced verb form production is influenced by the children's sensitivity to the type of narrative register (i.e., 1st or 3rd person perspective), the propositional ability associated with narrative development, and the progressive meaning of the -ing suffix.

  15. Gas reactor international cooperative program. HTR-synfuel application assessment

    International Nuclear Information System (INIS)

    1979-09-01

    This study assesses the technical, environmental and economic factors affecting the application of the High Temperature Gas-Cooled Thermal Reactor (HTR) to: synthetic fuel production; and displacement of fossil fuels in other industrial and chemical processes. Synthetic fuel application considered include coal gasification, direct coal liquefaction, oil shale processing, and the upgrading of syncrude to motor fuel. A wide range of other industrial heat applications was also considered, with emphasis on the use of the closed-loop thermochemical energy pipeline to supply heat to dispersed industrial users. In this application syngas (H 2 +CO 2 ) is produced at the central station HTR by steam reforming and the gas is piped to individual methanators where typically 1000 0 F steam is generated at the industrial user sites. The products of methanation (CH 4 + H 2 O) are piped back to the reformer at the central station HTR

  16. Gas reactor international cooperative program. HTR-synfuel application assessment

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    This study assesses the technical, environmental and economic factors affecting the application of the High Temperature Gas-Cooled Thermal Reactor (HTR) to: synthetic fuel production; and displacement of fossil fuels in other industrial and chemical processes. Synthetic fuel application considered include coal gasification, direct coal liquefaction, oil shale processing, and the upgrading of syncrude to motor fuel. A wide range of other industrial heat applications was also considered, with emphasis on the use of the closed-loop thermochemical energy pipeline to supply heat to dispersed industrial users. In this application syngas (H/sub 2/ +CO/sub 2/) is produced at the central station HTR by steam reforming and the gas is piped to individual methanators where typically 1000/sup 0/F steam is generated at the industrial user sites. The products of methanation (CH/sub 4/ + H/sub 2/O) are piped back to the reformer at the central station HTR.

  17. Dietary advanced glycation end products and aging.

    Science.gov (United States)

    Luevano-Contreras, Claudia; Chapman-Novakofski, Karen

    2010-12-01

    Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer's disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.

  18. Dietary Advanced Glycation End Products and Aging

    Directory of Open Access Journals (Sweden)

    Karen Chapman-Novakofski

    2010-12-01

    Full Text Available Advanced glycation end products (AGEs are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food and endogenously (in humans with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.

  19. Advanced Cloud Forecasting for Solar Energy Production

    Science.gov (United States)

    Werth, D. W.; Parker, M. J.

    2017-12-01

    A power utility must decide days in advance how it will allocate projected loads among its various generating sources. If the latter includes solar plants, the utility must predict how much energy the plants will produce - any shortfall will have to be compensated for by purchasing power as it is needed, when it is more expensive. To avoid this, utilities often err on the side of caution and assume that a relatively small amount of solar energy will be available, and allocate correspondingly more load to coal-fired plants. If solar irradiance can be predicted more accurately, utilities can be more confident that the predicted solar energy will indeed be available when needed, and assign solar plants a larger share of the future load. Solar power production is increasing in the Southeast, but is often hampered by irregular cloud fields, especially during high-pressure periods when rapid afternoon thunderstorm development can occur during what was predicted to be a clear day. We are currently developing an analog forecasting system to predict solar irradiance at the surface at the Savannah River Site in South Carolina, with the goal of improving predictions of available solar energy. Analog forecasting is based on the assumption that similar initial conditions will lead to similar outcomes, and involves the use of an algorithm to look through the weather patterns of the past to identify previous conditions (the analogs) similar to those of today. For our application, we select three predictor variables - sea-level pressure, 700mb geopotential, and 700mb humidity. These fields for the current day are compared to those from past days, and a weighted combination of the differences (defined by a cost function) is used to select the five best analog days. The observed solar irradiance values subsequent to the dates of those analogs are then combined to represent the forecast for the next day. We will explain how we apply the analog process, and compare it to existing

  20. Non-electrical uses of thermal energy generated in the production of fissile fuel in fusion--fission reactors: a comparative economic parametric analysis for a hybrid with or without synthetic fuel production

    International Nuclear Information System (INIS)

    Tai, A.S.; Krakowski, R.A.

    1979-01-01

    A parametric analysis has been carried out for testing the sensitivity of the synfuel production cost in relation to crucial economic and technologic quantities (investment costs of hybrid and synfuel plant, energy multiplication of the fission blanket, recirculating power fraction of the fusion driver, etc.). In addition, a minimum synfuel selling price has been evaluated, from which the fission--fusion--synfuel complex brings about a higher economic benefit than does the fusion--fission hybrid entirely devoted to fissile-fuel and electricity generation. Assuming an electricity cost of 2.7 cents/kWh, an annual investment cost per power unit of 4.2 to 6 $/GJ (132 to 189 k$/MWty) for the fission--fusion complex and 1.5 to 3 $/GJ (47 to 95 k$/MWty) for the synfuel plant, the synfuel production net cost (i.e., revenue = cost) varies between 6.5 and 8.6 $/GJ. These costs can compete with those obtained by other processes (natural gas reforming, resid partial oxidation, coal gasification, nuclear fission, solar electrolysis, etc.). This study points out a potential use of the fusion--fission hybrid other than fissile-fuel and electricity generation

  1. Advanced Gasification By-Product Utilization

    Energy Technology Data Exchange (ETDEWEB)

    Rodney Andrews; Aurora Rubel; Jack Groppo; Brock Marrs; Ari Geertsema; Frank Huggins; M. Mercedes Maroto-Valer; Brandie M. Markley; Zhe Lu; Harold Schobert

    2006-08-31

    With the passing of legislation designed to permanently cap and reduce mercury emissions from coal-fired utilities, it is more important than ever to develop and improve upon methods of controlling mercury emissions. One promising technique is carbon sorbent injection into the flue gas of the coal-fired power plant. Currently, this technology is very expensive as costly commercially activated carbons are used as sorbents. There is also a significant lack of understanding of the interaction between mercury vapor and the carbon sorbent, which adds to the difficulty of predicting the amount of sorbent needed for specific plant configurations. Due to its inherent porosity and adsorption properties as well as on-site availability, carbons derived from gasifiers are potential mercury sorbent candidates. Furthermore, because of the increasing restricted use of landfilling, the coal industry is very interested in finding uses for these materials as an alternative to the current disposal practice. The results of laboratory investigations and supporting technical assessments conducted under DOE Subcontract No. DE-FG26-03NT41795 are reported. This contract was with the University of Kentucky Research Foundation, which supports work with the University of Kentucky Center for Applied Energy Research and The Pennsylvania State University Energy Institute. The worked described was part of a project entitled ''Advanced Gasification By-Product Utilization''. This work involved the development of technologies for the separation and characterization of coal gasification slags from operating gasification units, activation of these materials to increase mercury and nitrogen oxide capture efficiency, assessment of these materials as sorbents for mercury and nitrogen oxides, assessment of the potential for leaching of Hg captured by the carbons, analysis of the slags for cement applications, and characterization of these materials for use as polymer fillers. The

  2. Advanced monitoring and control in biopharmaceutical production

    NARCIS (Netherlands)

    Soons, Z.I.T.A.

    2008-01-01

    Bioprocesses are characterised by natural variability in raw materials, initial conditions, human intervention, and varying properties of the micro-organism. In traditional biopharmaceutical production quality of the product is currently tested at the end of the production process only. Recently the

  3. Advanced glycation end product ligands for the receptor for advanced glycation end products: Biochemical characterization and formation kinetics

    NARCIS (Netherlands)

    Valencia, J.V.; Weldon, S.C.; Quinn, D.; Kiers, G.H.; Groot, J. de; TeKoppele, J.M.; Hughes, T.E.

    2004-01-01

    Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown.

  4. Advancing Student Productivity: An Introduction to Evernote

    Science.gov (United States)

    Korzaan, Melinda; Lawrence, Cameron

    2016-01-01

    This lab exercise exposes students to Evernote, which is a powerful productivity application that has gained significant purchase in professional work environments. In many academic settings the introductory computer applications course has a specific focus on standard productivity applications such as MS Word and MS Excel. While ensuring fluency…

  5. Advancing Consumer Product Composition and Chemical ...

    Science.gov (United States)

    This presentation describes EPA efforts to collect, model, and measure publically available consumer product data for use in exposure assessment. The development of the ORD Chemicals and Products database will be described, as will machine-learning based models for predicting chemical function. Finally, the talk describes new mass spectrometry-based methods for measuring chemicals in formulation and articles. This presentation is an invited talk to the ICCA-LRI workshop "Fit-For-Purpose Exposure Assessments For Risk-Based Decision Making". The talk will share EPA efforts to characterize the components of consumer products for use in exposure assessment with the international exposure science community.

  6. Tri-State Synfuels Project Review: Volume 12. Fluor project status. [Proposed Henderson, Kentucky coal to gasoline plant; engineering

    Energy Technology Data Exchange (ETDEWEB)

    1982-06-01

    The purpose of this report is to document and summarize activities associated with Fluor's efforts on the Tri-State Synfuels Project. The proposed facility was to be coal-to-transport fuels facility located in Henderson, Kentucky. Tri-State Synfuels Company was participating in the project as a partner of the US Department of Energy per terms of a Cooperative Agreement resulting from DOE's synfuel's program solicitation. Fluor's initial work plan called for preliminary engineering and procurement services to the point of commitment for construction for a Sasol Fischer-Tropsch plant. Work proceeded as planned until October 1981 when results of alternative coal-to-methanol studies revealed the economic disadvantage of the Synthol design for US markets. A number of alternative process studies followed to determine the best process configuration. In January 1982 Tri-State officially announced a change from Synthol to a Methanol to Gasoline (MTG) design basis. Further evaluation and cost estimates for the MTG facility eventually led to the conclusion that, given the depressed economic outlook for alternative fuels development, the project should be terminated. Official announcement of cancellation was made on April 13, 1982. At the time of project cancellation, Fluor had completed significant portions of the preliminary engineering effort. Included in this report are descriptions and summaries of Fluor's work during this project. In addition location of key project data and materials is identified and status reports for each operation are presented.

  7. Technological Advance for Alginate Production in Mexico

    Directory of Open Access Journals (Sweden)

    Hernández-Carmona G.

    2012-04-01

    Full Text Available Alginates are polysaccharides extracted from brown seaweeds. They are used in food industry, pharmaceutical, textile, among other, because of their properties to give high viscous solution and gel forming. This review describes the optimized process at pilot plant level for alginate production. The process includes washing the algae with HCl at pH 4, extraction of the alginate in Na2CO3 solution at pH 10 and heating to 80oC, dilution of the paste and filtrate with a vacuum rotary filter. Alginate precipitation is carried out by adding CaCl2 filtration. The fibers obtained are treated with HCl to obtain alginic acid. The product is neutralized with Na2CO3 to obtain sodium alginate. The product is dried with hot air, milled, and screened at different mesh sizes. We described the different products obtained and their physical and chemical properties. Finally, costs and barriers found that limit the alginate production at commercial level in Mexico are discussed, including the lack of the industrial design, the international cost of the alginates, the policy to give the seaweeds beds concessions, and the role of the investors.

  8. Recent advances in Phytosterol Oxidation Products.

    Science.gov (United States)

    O'Callaghan, Yvonne; McCarthy, Florence O; O'Brien, Nora M

    2014-04-11

    Phytosterols and their oxidation products have become increasingly investigated in recent years with respect to their roles in diet and nutrition. We present a comprehensive review of recent literature on Phytosterol Oxidation Products (POP) identifying critical areas for future investigation. It is evident that POP are formed on food storage/preparation; are absorbed and found in human serum; do not directly affect cholesterol absorption; have evidence of atherogenicity and inflammation; have distinct levels of cytotoxicity; are implicated with high levels of oxidative stress, glutathione depletion, mitochondrial dysfunction and elevated caspase activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Systems-Level Synthetic Biology for Advanced Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Ruffing, Anne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jensen, Travis J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Strickland, Lucas Marshall [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Meserole, Stephen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tallant, David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    Cyanobacteria have been shown to be capable of producing a variety of advanced biofuels; however, product yields remain well below those necessary for large scale production. New genetic tools and high throughput metabolic engineering techniques are needed to optimize cyanobacterial metabolisms for enhanced biofuel production. Towards this goal, this project advances the development of a multiple promoter replacement technique for systems-level optimization of gene expression in a model cyanobacterial host: Synechococcus sp. PCC 7002. To realize this multiple-target approach, key capabilities were developed, including a high throughput detection method for advanced biofuels, enhanced transformation efficiency, and genetic tools for Synechococcus sp. PCC 7002. Moreover, several additional obstacles were identified for realization of this multiple promoter replacement technique. The techniques and tools developed in this project will help to enable future efforts in the advancement of cyanobacterial biofuels.

  10. Recent advances in fuel product and manufacturing process development

    International Nuclear Information System (INIS)

    Slember, R.J.; Doshi, P.K.

    1987-01-01

    This paper discusses advancements in commercial nuclear fuel products and manufacturing made by the Westinghouse Electric Corporation in response to the commercial nuclear fuel industry's demand for high reliability, increased plant availability and improved operating flexibility. The features and benefits of Westinghouse's most advanced fuel products--VANTAGE 5 for PWR plants and QUAD+ for BWR plants--are described, as well as 'high performance' fuel concepts now under development for delivery in the late 1980s. The paper also disusses the importance of in-process quality control throughout manufacturing towards reducing product variability and improving fuel reliability. (author)

  11. Advanced Turbine Systems (ATS) program conceptual design and product development

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-08-31

    Achieving the Advanced Turbine Systems (ATS) goals of 60% efficiency, single-digit NO{sub x}, and 10% electric power cost reduction imposes competing characteristics on the gas turbine system. Two basic technical issues arise from this. The turbine inlet temperature of the gas turbine must increase to achieve both efficiency and cost goals. However, higher temperatures move in the direction of increased NO{sub x} emission. Improved coatings and materials technologies along with creative combustor design can result in solutions to achieve the ultimate goal. GE`s view of the market, in conjunction with the industrial and utility objectives, requires the development of Advanced Gas Turbine Systems which encompass two potential products: a new aeroderivative combined-cycle system for the industrial market, and a combined-cycle system for the utility sector that is based on an advanced frame machine. The GE Advanced Gas Turbine Development program is focused on two specific products: (1) a 70 MW class industrial gas turbine based on the GE90 core technology utilizing an innovative air cooling methodology; (2) a 200 MW class utility gas turbine based on an advanced Ge heavy-duty machine utilizing advanced cooling and enhancement in component efficiency. Both of these activities required the identification and resolution of technical issues critical to achieving ATS goals. The emphasis for the industrial ATS was placed upon innovative cycle design and low emission combustion. The emphasis for the utility ATS was placed on developing a technology base for advanced turbine cooling, while utilizing demonstrated and planned improvements in low emission combustion. Significant overlap in the development programs will allow common technologies to be applied to both products. GE Power Systems is solely responsible for offering GE products for the industrial and utility markets.

  12. 78 FR 25268 - Proposed Guidance on Deposit Advance Products

    Science.gov (United States)

    2013-04-30

    ... guidance on payday loans and subprime lending.\\1\\ Although the FDIC encourages banks to respond to... less stringent loan underwriting requirements. Loans exhibiting subprime credit characteristics are.... Description of Guidance A deposit advance product is a small-dollar, short-term loan that a depository...

  13. Inhibition of protein glycation and advanced glycation end products ...

    African Journals Online (AJOL)

    Advanced glycation end products (AGEs) formation is increased in diabetes mellitus, leading to microvascular and macrovascular complications. Recently, much attention has been focused on natural and synthetic inhibitors to delay the onset or progression of diabetes and its comorbidities. Ascorbic acid (AA) can react with ...

  14. 75 FR 44015 - Certain Semiconductor Products Made by Advanced Lithography Techniques and Products Containing...

    Science.gov (United States)

    2010-07-27

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-729] Certain Semiconductor Products Made by... the sale within the United States after importation of certain semiconductor products made by advanced... importation, or the sale within the United States after importation of certain semiconductor products made by...

  15. Microbial engineering for the production of advanced biofuels.

    Science.gov (United States)

    Peralta-Yahya, Pamela P; Zhang, Fuzhong; del Cardayre, Stephen B; Keasling, Jay D

    2012-08-16

    Advanced biofuels produced by microorganisms have similar properties to petroleum-based fuels, and can 'drop in' to the existing transportation infrastructure. However, producing these biofuels in yields high enough to be useful requires the engineering of the microorganism's metabolism. Such engineering is not based on just one specific feedstock or host organism. Data-driven and synthetic-biology approaches can be used to optimize both the host and pathways to maximize fuel production. Despite some success, challenges still need to be met to move advanced biofuels towards commercialization, and to compete with more conventional fuels.

  16. ESO Advanced Data Products for the Virtual Observatory

    Science.gov (United States)

    Retzlaff, J.; Delmotte, N.; Rite, C.; Rosati, P.; Slijkhuis, R.; Vandame, B.

    2006-07-01

    Advanced Data Products, that is, completely reduced, fully characterized science-ready data sets, play a crucial role for the success of the Virtual Observatory as a whole. We report on on-going work at ESO towards the creation and publication of Advanced Data Products in compliance with present VO standards on resource metadata. The new deep NIR multi-color mosaic of the GOODS/CDF-S region is used to showcase different aspects of the entire process: data reduction employing our MVM-based reduction pipeline, calibration and data characterization procedures, standardization of metadata content, and, finally, a prospect of the scientific potential illustrated by new results on deep galaxy number counts.

  17. Selection and development of advanced nuclear fuel products

    International Nuclear Information System (INIS)

    Stucker, David L.; Miller, Richard S.; Arnsberger, Peter L.

    2004-01-01

    The highly competitive international marketplace requires a continuing product development commitment, short development cycle times and timely, on-target product development to assure customer satisfaction and continuing business. Westinghouse has maintained its leadership position within the nuclear fuel industry with continuous developments and improvements to fuel assembly materials and design. This paper presents a discussion of the processes used by Westinghouse in the selection and refinement of advanced concepts for deployment in the highly competitive US and international nuclear fuel fabrication marketplace. (author)

  18. Natural product-based nanomedicine: recent advances and issues.

    Science.gov (United States)

    Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

    2015-01-01

    Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds' low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications.

  19. Natural product-based nanomedicine: recent advances and issues

    Science.gov (United States)

    Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

    2015-01-01

    Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111

  20. European regulatory tools for advanced therapy medicinal products.

    Science.gov (United States)

    Flory, Egbert; Reinhardt, Jens

    2013-12-01

    Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of biopharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.

  1. Advances in utilization of renewable substrates for biosurfactant production

    Science.gov (United States)

    2011-01-01

    Biosurfactants are amphiphilic molecules that have both hydrophilic and hydrophobic moieties which partition preferentially at the interfaces such as liquid/liquid, gas/liquid or solid/liquid interfaces. Such characteristics enable emulsifying, foaming, detergency and dispersing properties. Their low toxicity and environmental friendly nature and the wide range of potential industrial applications in bioremediation, health care, oil and food processing industries makes them a highly sought after group of chemical compounds. Interest in them has also been encouraged because of the potential advantages they offer over their synthetic counterparts in many fields spanning environmental, food, biomedical, petrochemical and other industrial applications. Their large scale production and application however are currently restricted by the high cost of production and by the limited understanding of their interactions with cells and with the abiotic environment. In this paper, we review the current knowledge and latest advances in the search for cost effective renewable agro industrial alternative substrates for their production. PMID:21906330

  2. Natural product-based nanomedicine: recent advances and issues

    Directory of Open Access Journals (Sweden)

    Watkins R

    2015-09-01

    Full Text Available Rebekah Watkins,1,2,* Ling Wu,1,* Chenming Zhang,3–5 Richey M Davis,3,5,6 Bin Xu1,3 1Department of Biochemistry, 2Program in Nanoscience, 3Center for Drug Discovery, 4Department of Biological Systems Engineering, 5Institute for Critical Technology and Applied Science, 6Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA *These authors contributed equally to this work Abstract: Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. Keywords: natural products, nanomedicine, drug delivery, bioavailability, targeting, controlled release

  3. Hydrogen production from water: Recent advances in photosynthesis research

    Energy Technology Data Exchange (ETDEWEB)

    Greenbaum, E.; Lee, J.W. [Oak Ridge National Lab., TN (United States). Chemical Technology Div.

    1997-12-31

    The great potential of hydrogen production by microalgal water splitting is predicated on quantitative measurement of the algae`s hydrogen-producing capability, which is based on the following: (1) the photosynthetic unit size of hydrogen production; (2) the turnover time of photosynthetic hydrogen production; (3) thermodynamic efficiencies of conversion of light energy into the Gibbs free energy of molecular hydrogen; (4) photosynthetic hydrogen production from sea water using marine algae; (5) the potential for research advances using modern methods of molecular biology and genetic engineering to maximize hydrogen production. ORNL has shown that sustained simultaneous photoevolution of molecular hydrogen and oxygen can be performed with mutants of the green alga Chlamydomonas reinhardtii that lack a detectable level of the Photosystem I light reaction. This result is surprising in view of the standard two-light reaction model of photosynthesis and has interesting scientific and technological implications. This ORNL discovery also has potentially important implications for maximum thermodynamic conversion efficiency of light energy into chemical energy by green plant photosynthesis. Hydrogen production performed by a single light reaction, as opposed to two, implies a doubling of the theoretically maximum thermodynamic conversion efficiency from {approx}10% to {approx}20%.

  4. Role of advanced glycation end products in cellular signaling

    Directory of Open Access Journals (Sweden)

    Christiane Ott

    2014-01-01

    Full Text Available Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs. Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes.

  5. Accumulation of advanced glycation end products in canine atherosclerosis.

    Science.gov (United States)

    Chiers, K; Vandenberge, V; Ducatelle, R

    2010-07-01

    Atherosclerosis is an uncommon lesion in animals and particularly in dogs. Prominent atherosclerotic lesions of the coronary arteries are described in three dogs. These comprised an expansion of the tunica media by the accumulation of foam cells and/or cholesterol crystals, with subsequent narrowing of the vascular lumen. Immunohistochemical analysis revealed the accumulation of advanced glycation end products (AGEs) in foam cells, macrophages and lymphocytes. As in man, these findings suggest a possible role of AGEs in the development of canine atherosclerosis. (c) 2009 Elsevier Ltd. All rights reserved.

  6. Knowledge Management Platform in Advanced Product Quality Planning

    Science.gov (United States)

    Chiliban, Bogdan; Baral, Lal Mohan; Kifor, Claudiu

    2014-12-01

    Knowledge is an essential part of organizational competitiveness. This vital resource must be managed correctly within organizations in order to achieve desired performance levels within all undertakings. The process of managing knowledge is a very difficult one due to the illusive nature of the resource itself. Knowledge is stored within every aspect of an organization starting from people and ending with documents and processes. The Knowledge Management Platform is designed as a facilitator for managers and employees in all endeavours knowledge related within the Advanced Product Quality Planning Procedure

  7. Environmental benefits of advanced oil and gas exploration and production technology

    Energy Technology Data Exchange (ETDEWEB)

    None

    1999-10-01

    THROUGHOUT THE OIL AND GAS LIFE CYCLE, THE INDUSTRY HAS APPLIED AN ARRAY OF ADVANCED TECHNOLOGIES TO IMPROVE EFFICIENCY, PRODUCTIVITY, AND ENVIRONMENTAL PERFORMANCE. THIS REPORT FOCUSES SPECIFICALLY ON ADVANCES IN EXPLORATION AND PRODUCTION (E&P) OPERATIONS.

  8. Recent Advances in Second Generation Ethanol Production by Thermophilic Bacteria

    Directory of Open Access Journals (Sweden)

    Sean Michael Scully

    2014-12-01

    Full Text Available There is an increased interest in using thermophilic bacteria for the production of bioethanol from complex lignocellulosic biomass due to their higher operating temperatures and broad substrate range. This review focuses upon the main genera of thermophilic anaerobes known to produce ethanol, their physiology, and the relevance of various environmental factors on ethanol yields including the partial pressure of hydrogen, ethanol tolerance, pH and substrate inhibition. Additionally, recent development in evolutionary adaptation and genetic engineering of thermophilic bacteria is highlighted. Recent developments in advanced process techniques used for ethanol production are reviewed with an emphasis on the advantages of using thermophilic bacteria in process strategies including separate saccharification and fermentation, simultaneous saccharification and fermentation (SSF, and consolidated bioprocessing (CBP.

  9. Major advances in fresh milk and milk products: fluid milk products and frozen desserts.

    Science.gov (United States)

    Goff, H D; Griffiths, M W

    2006-04-01

    Major technological advances in the fluid milk processing industry in the last 25 yr include significant improvements in all the unit operations of separation, standardization, pasteurization, homogenization, and packaging. Many advancements have been directed toward production capacity, automation, and hygienic operation. Extended shelf-life milks are produced by high heat treatment, sometimes coupled with microfiltration or centrifugation. Other nonthermal methods have also been investigated. Flavored milk beverages have increased in popularity, as have milk beverages packaged in single-service, closeable plastic containers. Likewise, the frozen dairy processing industry has seen the development of large-capacity, automated processing equipment for a wide range of products designed to gain market share. Significant advancements in product quality have been made, many of these arising from improved knowledge of the functional properties of ingredients and their impact on structure and texture. Incidents of foodborne disease associated with dairy products continue to occur, necessitating even greater diligence in the control of pathogen transmission. Analytical techniques for the rapid detection of specific types of microorganisms have been developed and greatly improved during this time. Despite tremendous technological advancements for processors and a greater diversity of products for consumers, per capita consumption of fluid milk has declined and consumption of frozen dairy desserts has been steady during this 25-yr period.

  10. Advances in the production of freeform optical surfaces

    Science.gov (United States)

    Tohme, Yazid E.; Luniya, Suneet S.

    2007-05-01

    Recent market demands for free-form optics have challenged the industry to find new methods and techniques to manufacture free-form optical surfaces with a high level of accuracy and reliability. Production techniques are becoming a mix of multi-axis single point diamond machining centers or deterministic ultra precision grinding centers coupled with capable measurement systems to accomplish the task. It has been determined that a complex software tool is required to seamlessly integrate all aspects of the manufacturing process chain. Advances in computational power and improved performance of computer controlled precision machinery have driven the use of such software programs to measure, visualize, analyze, produce and re-validate the 3D free-form design thus making the process of manufacturing such complex surfaces a viable task. Consolidation of the entire production cycle in a comprehensive software tool that can interact with all systems in design, production and measurement phase will enable manufacturers to solve these complex challenges providing improved product quality, simplified processes, and enhanced performance. The work being presented describes the latest advancements in developing such software package for the entire fabrication process chain for aspheric and free-form shapes. It applies a rational B-spline based kernel to transform an optical design in the form of parametrical definition (optical equation), standard CAD format, or a cloud of points to a central format that drives the simulation. This software tool creates a closed loop for the fabrication process chain. It integrates surface analysis and compensation, tool path generation, and measurement analysis in one package.

  11. Advanced glycation end products regulate interleukin-1? production in human placenta

    OpenAIRE

    SENO, Kotomi; SASE, Saoko; OZEKI, Ayae; TAKAHASHI, Hironori; OHKUCHI, Akihide; SUZUKI, Hirotada; MATSUBARA, Shigeki; IWATA, Hisataka; KUWAYAMA, Takehito; SHIRASUNA, Koumei

    2017-01-01

    Maternal obesity is a major risk factor for pregnancy complications, causing inflammatory cytokine release in the placenta, including interleukin-1? (IL-1?), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic and placental inflammation with elevated circulating advanced glycation end products (AGEs). IL-1? is a pivotal inflammatory cytokine associated with obesity and pregnancy complications, and its production is regulated by NLR family pyrin domain-containing 3 (NLRP3)...

  12. New Advances in Infant Feeding: New Products and Novel Technologies.

    Science.gov (United States)

    Pina-Pérez, Maria C; Martínez, Antonio; Rodrigo, Dolores

    2017-01-01

    Breastfeeding is the best way to provide ideal food for infants. However, there are many situations in which breastfeeding is unviable (maternal illness, hygiene problems, intravenous feeding requirement, storage). Safe, efficient, and nutritious products should be offered by the industry to mothers and healthcare professionals as an alternative. The present review aims to update the state of the art regarding the most innovative developments in infant feeding formulation and, the promising novel technologies that are being investigated to achieve a balance between the microbiological stability, organoleptic and nutritional value of baby food. The research lines included in the present systematic review are focused on both, the most innovative ingredients and emergent technologies applied increasing the offer of tailor-made nutritional profiled products with improved quality and safety. According to the reviewed research and recently published patents the current emergence of a new generation of infant products is remarkable, with specific product lines aimed at infants at different stages of development and affected by several disorders (low-weight babies, premature neonates, allergenic patients), with special emphasis on the application of novel technologies (e.g. High Hydrostatic Pressure (HHP) and microencapsulation) as potential techniques to ensure the microbiological safety of developed products, and the improvement of their nutritional value, complementary to the addition of functional ingredients, such as omega 3 and 6 fatty acids, amino acids, prebiotics and probiotics, and medicinal herb supplementation (e.g. lemon balm, royal jelly). The present research work provides a general view of recent advances in infant products processing and formulation focusing on the technological effects and quality/safety developments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products.

    Science.gov (United States)

    Maeda, Sayaka; Matsui, Takanori; Ojima, Ayako; Takeuchi, Masayoshi; Yamagishi, Sho-Ichi

    2014-09-01

    Advanced glycation end products (AGEs) not only inhibit DNA synthesis but also play a role in diabetic retinopathy by evoking apoptosis and inflammation in retinal pericytes via interaction with a receptor for AGE (RAGE). Similarly, sulforaphane, which is a naturally occurring isothiocyanate that is found in widely consumed cruciferous vegetables, protects against oxidative stress-induced tissue damage. Therefore, we hypothesized that sulforaphane could inhibit AGE-induced pericytes injury through its antioxidative properties. Advanced glycation end product stimulated superoxide generation as well as RAGE gene and protein expression in bovine-cultured retinal pericytes, and these effects were prevented by the treatment with sulforaphane. Antibodies directed against RAGE also blocked AGE-evoked reactive oxygen species generation in pericytes. Sulforaphane and antibodies directed against RAGE significantly inhibited the AGE-induced decrease in DNA synthesis, apoptotic cell death, and up-regulation of monocyte chemoattractant protein 1 messenger RNA levels in pericytes. For the first time, the present study demonstrates that sulforaphane could inhibit DNA synthesis, apoptotic cell death, and inflammatory reactions in AGE-exposed pericytes, partly by suppressing RAGE expression via its antioxidative properties. Blockade of the AGE-RAGE axis in pericytes by sulforaphane might be a novel therapeutic target for the treatment of diabetic retinopathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Advanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics.

    Science.gov (United States)

    Valencia, Jessica V; Weldon, Stephen C; Quinn, Douglas; Kiers, Geesje H; DeGroot, Jeroen; TeKoppele, Johan M; Hughes, Thomas E

    2004-01-01

    Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown. Using standardized procedures and a variety of AGE measures, the present study aimed to characterize the AGEs that bind to RAGE and their formation kinetics in vitro. To produce AGEs with varying RAGE binding affinity, bovine serum albumin (BSA) AGEs were prepared with 0.5M glucose, fructose, or ribose at times of incubation from 0 to 12 weeks or for up to 3 days with glycolaldehyde or glyoxylic acid. The AGE-BSAs were characterized for RAGE binding affinity, fluorescence, absorbance, carbonyl content, reactive free amine content, molecular weight, pentosidine content, and N-epsilon-carboxymethyl lysine content. Ribose-AGEs bound RAGE with high affinity within 1 week of incubation in contrast to glucose- and fructose-AGE, which required 12 and 6 weeks, respectively, to generate equivalent RAGE ligands (IC50=0.66, 0.93, and 1.7 microM, respectively). Over time, all of the measured AGE characteristics increased. However, only free amine content robustly correlated with RAGE binding affinity. In addition, detailed protocols for the generation of AGEs that reproducibly bind RAGE with high affinity were developed, which will allow for further study of the RAGE-AGE interaction.

  15. Performance modelling for product development of advanced window systems

    DEFF Research Database (Denmark)

    Appelfeld, David

    The research presented in this doctoral thesis shows how the product development (PD) of Complex Fenestration Systems (CFSs) can be facilitated by computer-based analysis to improve the energy efficiency of fenestration systems as well as to improve the indoor environment. The first chapter defines...... and methods,which can address interrelated performance parameters of CFS, are sought. It is possible to evaluate such systems by measurements, however the high cost and complexity of the measurements are limiting factors. The studies in this thesis confirmed that the results from the performance measurements...... of CFSs can be interpreted by simulations and hence simulations can be used for the performance analysis of new CFSs. An advanced simulation model must be often developed and needs to be validated by measurements before the model can be reused. The validation of simulations against the measurements proved...

  16. Advanced therapy medicinal products: current and future perspectives.

    Science.gov (United States)

    Hanna, Eve; Rémuzat, Cécile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Advanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget. The aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access. Clinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area. The database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers' expectations. ATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest that ATMPs may reach the market earlier than

  17. Statins stimulate the production of a soluble form of the receptor for advanced glycation end products

    OpenAIRE

    Quade-Lyssy, Patricia; Kanarek, Anna Maria; Baiersdörfer, Markus; Postina, Rolf; Kojro, Elzbieta

    2013-01-01

    The beneficial effects of statin therapy in the reduction of cardiovascular pathogenesis, atherosclerosis, and diabetic complications are well known. The receptor for advanced glycation end products (RAGE) plays an important role in the progression of these diseases. In contrast, soluble forms of RAGE act as decoys for RAGE ligands and may prevent the development of RAGE-mediated disorders. Soluble forms of RAGE are either produced by alternative splicing [endogenous secretory RAGE (esRAGE)] ...

  18. Hydroponic food production: a definitive guidebook for the advanced home gardener and the commercial hydroponic grower

    National Research Council Canada - National Science Library

    Resh, Howard M

    2013-01-01

    Hydroponic Food Production: A Definitive Guidebook for the Advanced Home Gardener and the Commercial Hydroponic Grower details advances that have taken place in this field since the publication of the previous edition in 2001...

  19. Aging ovary and the role for advanced glycation end products.

    Science.gov (United States)

    Pertynska-Marczewska, Magdalena; Diamanti-Kandarakis, Evanthia

    2017-03-01

    The hypothalamic gonadotropin-releasing hormone pulse generator, the pituitary gonadotropes, the ovaries, and the uterus play a crucial role in female fertility. A decline in reproductive performance represents a complex interplay of actions at all levels of the hypothalamic-pituitary-ovarian axis. Recently, in the field of female reproductive aging attention is drawn to the carbonyl stress theory. Advanced glycation end products (AGEs) contribute directly to protein damage, induce a chain of oxidative stress (OS) reactions, and increase inflammatory reactions. Here, we highlight some of the mechanisms underlying glycation damage in the ovary. Searches of electronic databases were performed. Articles relevant to possible role of OS, AGEs, and receptor for AGE (RAGE) in aging ovary were summarized in this interpretive literature review. Follicular microenvironment undergoes an increase in OS with aging. Data support the role of OS in ovulatory dysfunction because AGEs are well-recognized mediators of increased OS. RAGE and AGE-modified proteins with activated nuclear factor-kappa B are expressed in human ovarian tissue. It was suggested that accumulation of AGEs products at the level of the ovarian follicle might trigger early ovarian aging or could be responsible for reduced glucose uptake by granulosa cells, potentially altering follicular growth. Moreover, impaired methylglyoxal detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive aging. Further investigation of the role for the AGE-RAGE axis in the ovarian follicular environment is needed, and results could relate to assisted reproduction technology outcomes and new measures of ovarian reserve.

  20. Hydrogen energy for tomorrow: Advanced hydrogen production technologies

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-08-01

    The future vision for hydrogen is that it will be cost-effectively produced from renewable energy sources and made available for widespread use as an energy carrier and a fuel. Hydrogen can be produced from water and when burned as a fuel, or converted to electricity, joins with oxygen to again form water. It is a clean, sustainable resource with many potential applications, including generating electricity, heating homes and offices, and fueling surface and air transportation. To achieve this vision, researchers must develop advanced technologies to produce hydrogen at costs competitive with fossil fuels, using sustainable sources. Hydrogen is now produced primarily by steam reforming of natural gas. For applications requiring extremely pure hydrogen, production is done by electrolysis. This is a relatively expensive process that uses electric current to dissociate, or split, water into its hydrogen and oxygen components. Technologies with the best potential for producing hydrogen to meet future demand fall into three general process categories: photobiological, photoelectrochemical, and thermochemical. Photobiological and photoelectrochemical processes generally use sunlight to split water into hydrogen and oxygen. Thermochemical processes, including gasification and pyrolysis systems, use heat to produce hydrogen from sources such as biomass and solid waste.

  1. Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS.

    Science.gov (United States)

    Garg, Deepika; Merhi, Zaher

    2016-10-21

    Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and proteins. Additionally, AGEs accumulate in the ovaries of women with PCOS potentially contributing to the well-documented abnormal steroidogenesis and folliculogenesis. A systematic review of articles and abstracts available in PubMed was conducted and presented in a systemic manner. This article reports changes in steroidogenic enzyme activity in granulosa and theca cells in PCOS and PCOS-models. It also described the changes in AGEs and their receptors in the ovaries of women with PCOS and presents the underlying mechanism(s) whereby AGEs could be responsible for the PCOS-related changes in granulosa and theca cell function thus adversely impacting steroidogenesis and follicular development. AGEs are associated with hyperandrogenism in PCOS possibly by altering the activity of various enzymes such as cholesterol side-chain cleavage enzyme cytochrome P450, steroidogenic acute regulatory protein, 17α-hydroxylase, and 3β-hydroxysteroid dehydrogenase. AGEs also affect luteinizing hormone receptor and anti-Mullerian hormone receptor expression as well as their signaling pathways in granulosa cells. A better understanding of how AGEs alter granulosa and theca cell function is likely to contribute meaningfully to a conceptual framework whereby new interventions to prevent and/or treat ovarian dysfunction in PCOS can ultimately be developed.

  2. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials.

    Science.gov (United States)

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. No failure risk rate per development phase is available for ATMPs. The discontinuation rate may prove helpful when assessing the

  3. Effect of dietary advanced glycation end products on mouse liver.

    Directory of Open Access Journals (Sweden)

    Raza Patel

    Full Text Available UNLABELLED: The exact pathophysiology of non-alcoholic steatohepatitis (NASH is not known. Previous studies suggest that dietary advanced glycation end products (AGEs can cause oxidative stress in liver. We aim to study the effects of dietary AGEs on liver health and their possible role in the pathogenesis of NASH. METHODS: Two groups of mice were fed the same diet except the AGE content varied. One group was fed a high AGE diet and the second group was fed a regular AGE diet. Liver histology, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, insulin resistance and glucose tolerance were assessed. RESULTS: Histology revealed that neutrophil infiltration occurred in the livers of the high AGE group at week 26; steatosis did not accompany liver inflammation. At week 39 livers from both groups exhibited macro- or micro-steatosis, yet no inflammation was detected. Higher insulin levels were detected in the regular AGE group at week 26 (P = 0.034, compared to the high AGE group. At week 39, the regular AGE group showed higher levels of alanine aminotransferase (P<0.01 and aspartate aminotransferase (P = 0.02 than those of the high AGE group. CONCLUSIONS: We demonstrate that a high AGE diet can cause liver inflammation in the absence of steatosis. Our results show that dietary AGEs could play a role in initiating liver inflammation contributing to the disease progression of NASH. Our observation that the inflammation caused by high AGE alone did not persist suggests interesting future directions to investigate how AGEs contribute to pro-oxidative and anti-oxidative pathways in the liver.

  4. Advanced glycation end products and their relevance in female reproduction.

    Science.gov (United States)

    Merhi, Z

    2014-01-01

    Do advanced glycation end products (AGEs) and their receptors play a role in female reproduction? AGEs might contribute to the etiology of polycystic ovary syndrome (PCOS) and infertility. The endogenous AGEs are produced in the body by chemical reactions. Exogenous sources of AGEs are diet and smoking. AGEs have been proposed to be among the main intermediaries involved in several diseases, such as metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease, ovarian aging, inflammation, neurodegenerative disorders and PCOS. A systematic review was performed for all available basic science and clinical peer-reviewed articles published in PubMed from 1987 to date. Abstracts of annual meetings of the Endocrine Society and American Society for Reproductive Medicine were also reviewed. A total of 275 publications and scientific abstracts were identified from the initial search. Sixty-two papers and four published scientific abstracts were selected for full review. The main outcomes were the regulatory effects of AGEs on: (i) granulosa cells, adipocyte physiology, obesity and insulin resistance in women with PCOS and in polycystic ovary animal models and (ii) infertility and measures of ovarian reserve. There is an intricate relationship between the AGE-RAGE (receptor for AGEs) system and some aspects of PCOS, such as granulosa cell dysfunction, adipocyte pathophysiology, obesity and insulin resistance. Additionally, irregular ovarian AGE signaling might in part explain the abnormal ovarian histology observed in women with PCOS. The ovarian dysfunction due to AGEs in women without PCOS suggests a role for the AGE-RAGE system in the ovarian follicular environment, and might relate to assisted reproduction technology outcome and measures of ovarian reserve. The body of literature currently available limits these findings. The results obtained from granulosa cell lines and animal models may not fully extrapolate to humans. This review underscores a critical need

  5. Recent Advances and Challenges towards Sustainable Polyhydroxyalkanoate (PHA) Production

    DEFF Research Database (Denmark)

    Kourmentza, Constantina; Plácido, Jersson; Venetsaneas, Nikolaos

    2017-01-01

    Sustainable biofuels, biomaterials, and fine chemicals production is a critical matter that research teams around the globe are focusing on nowadays. Polyhydroxyalkanoates represent one of the biomaterials of the future due to their physicochemical properties, biodegradability, and biocompatibility...... polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing....

  6. Advancing in software product management: An incremental method engineering approach

    NARCIS (Netherlands)

    van de Weerd, I.

    2009-01-01

    Hardly any figures exist on the success of product software companies. What we do know is that a good Software Product Management (SPM) practice pays off. However, not many IT-professionals know how to implement SPM practices in their organization, which causes many companies to not have the proper

  7. Recent advances in membrane technologies for biorefining and bioenergy production.

    Science.gov (United States)

    He, Yi; Bagley, David M; Leung, Kam Tin; Liss, Steven N; Liao, Bao-Qiang

    2012-01-01

    The bioeconomy, and in particular, biorefining and bioenergy production, have received considerable attention in recent years as a shift to renewable bioresources to produce similar energy and chemicals derived from fossil energy sources, represents a more sustainable path. Membrane technologies have been shown to play a key role in process intensification and products recovery and purification in biorefining and bioenergy production processes. Among the various separation technologies used, membrane technologies provide excellent fractionation and separation capabilities, low chemical consumption, and reduced energy requirements. This article presents a state-of-the-art review on membrane technologies related to various processes of biorefining and bioenergy production, including: (i) separation and purification of individual molecules from biomass, (ii) removal of fermentation inhibitors, (iii) enzyme recovery from hydrolysis processes, (iv) membrane bioreactors for bioenergy and chemical production, such as bioethanol, biogas and acetic acid, (v) bioethanol dehydration, (vi) bio-oil and biodiesel production, and (vii) algae harvesting. The advantages and limitations of membrane technologies for these applications are discussed and new membrane-based integrated processes are proposed. Finally, challenges and opportunities of membrane technologies for biorefining and bioenergy production in the coming years are addressed. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Recent Advances and Challenges towards Sustainable Polyhydroxyalkanoate (PHA) Production

    Science.gov (United States)

    Kourmentza, Constantina; Plácido, Jersson; Venetsaneas, Nikolaos; Burniol-Figols, Anna; Varrone, Cristiano; Gavala, Hariklia N.; Reis, Maria A. M.

    2017-01-01

    Sustainable biofuels, biomaterials, and fine chemicals production is a critical matter that research teams around the globe are focusing on nowadays. Polyhydroxyalkanoates represent one of the biomaterials of the future due to their physicochemical properties, biodegradability, and biocompatibility. Designing efficient and economic bioprocesses, combined with the respective social and environmental benefits, has brought together scientists from different backgrounds highlighting the multidisciplinary character of such a venture. In the current review, challenges and opportunities regarding polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing. PMID:28952534

  9. Recent Advances and Challenges towards Sustainable Polyhydroxyalkanoate (PHA) Production.

    Science.gov (United States)

    Kourmentza, Constantina; Plácido, Jersson; Venetsaneas, Nikolaos; Burniol-Figols, Anna; Varrone, Cristiano; Gavala, Hariklia N; Reis, Maria A M

    2017-06-11

    Sustainable biofuels, biomaterials, and fine chemicals production is a critical matter that research teams around the globe are focusing on nowadays. Polyhydroxyalkanoates represent one of the biomaterials of the future due to their physicochemical properties, biodegradability, and biocompatibility. Designing efficient and economic bioprocesses, combined with the respective social and environmental benefits, has brought together scientists from different backgrounds highlighting the multidisciplinary character of such a venture. In the current review, challenges and opportunities regarding polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing.

  10. Production process for advanced space satellite system cables/interconnects.

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza, Luis A.

    2007-12-01

    This production process was generated for the satellite system program cables/interconnects group, which in essences had no well defined production process. The driver for the development of a formalized process was based on the set backs, problem areas, challenges, and need improvements faced from within the program at Sandia National Laboratories. In addition, the formal production process was developed from the Master's program of Engineering Management for New Mexico Institute of Mining and Technology in Socorro New Mexico and submitted as a thesis to meet the institute's graduating requirements.

  11. Advance Planning of Form Properties in the Written Production of Single and Multiple Words

    Science.gov (United States)

    Damian, Markus F.; Stadthagen-Gonzalez, Hans

    2009-01-01

    Three experiments investigated the scope of advance planning in written production. Experiment 1 manipulated phonological factors in single word written production, and Experiments 2 and 3 did the same in the production of adjective-noun utterances. In all three experiments, effects on latencies were found which mirrored those previously…

  12. Understanding the NPD - Production interface : Advanced industrialisation and growth in the composite industry

    NARCIS (Netherlands)

    Chatzimichali, A.P.; Potter, K.D.; Smulders, F.E.H.M.

    2013-01-01

    This paper provides an initial attempt to theoretically describe and understand how the composite product supply chain could reach advanced levels of industrialisation. At the heart of this work rest the interface between NPD (New Product Development) and Production as the central point where

  13. Production of biopharmaceutical proteins by yeast: Advances through metabolic engineering

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2013-01-01

    Production of recombinant proteins for use as pharmaceuticals, so-called biopharmaceuticals, is a multi-billion dollar industry. Many different cell factories are used for the production of biopharmaceuticals, but the yeast Saccharomyces cerevisiae is an important cell factory as it is used for p...... production. The involvement of directed metabolic engineering through the integration of tools from genetic engineering, systems biology and mathematical modeling, is also discussed....... by yeast are human serum albumin, hepatitis vaccines and virus like particles used for vaccination against human papillomavirus. Here is given a brief overview of biopharmaceutical production by yeast and it is discussed how the secretory pathway can be engineered to ensure more efficient protein...

  14. Hydrogen production from algal biomass - Advances, challenges and prospects.

    Science.gov (United States)

    Show, Kuan-Yeow; Yan, Yuegen; Ling, Ming; Ye, Guoxiang; Li, Ting; Lee, Duu-Jong

    2018-06-01

    Extensive effort is being made to explore renewable energy in replacing fossil fuels. Biohydrogen is a promising future fuel because of its clean and high energy content. A challenging issue in establishing hydrogen economy is sustainability. Biohydrogen has the potential for renewable biofuel, and could replace current hydrogen production through fossil fuel thermo-chemical processes. A promising source of biohydrogen is conversion from algal biomass, which is abundant, clean and renewable. Unlike other well-developed biofuels such as bioethanol and biodiesel, production of hydrogen from algal biomass is still in the early stage of development. There are a variety of technologies for algal hydrogen production, and some laboratory- and pilot-scale systems have demonstrated a good potential for full-scale implementation. This work presents an elucidation on development in biohydrogen encompassing biological pathways, bioreactor designs and operation and techno-economic evaluation. Challenges and prospects of biohydrogen production are also outlined. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Advances in Metabolic Engineering of Cyanobacteria for Photosynthetic Biochemical Production

    OpenAIRE

    Lai, Martin C.; Lan, Ethan I.

    2015-01-01

    Engineering cyanobacteria into photosynthetic microbial cell factories for the production of biochemicals and biofuels is a promising approach toward sustainability. Cyanobacteria naturally grow on light and carbon dioxide, bypassing the need of fermentable plant biomass and arable land. By tapping into the central metabolism and rerouting carbon flux towards desirable compound production, cyanobacteria are engineered to directly convert CO2 into various chemicals. This review discusses the d...

  16. Advancement in Productivity of Arabic into English Machine Translation Systems from 2008 to 2013

    Science.gov (United States)

    Abu-Al-Sha'r, Awatif M.; AbuSeileek, Ali F.

    2013-01-01

    This paper attempts to compare between the advancements in the productivity of Arabic into English Machine Translation Systems between two years, 2008 and 2013. It also aims to evaluate the progress achieved by various systems of Arabic into English electronic translation between the two years. For tracing such advancement, a comparative analysis…

  17. Multivariate data analysis as a tool in advanced quality monitoring in the food production chain

    DEFF Research Database (Denmark)

    Bro, R.; van den Berg, F.; Thybo, A.

    2002-01-01

    This paper summarizes some recent advances in mathematical modeling of relevance in advanced quality monitoring in the food production chain. Using chemometrics-multivariate data analysis - it is illustrated how to tackle problems in food science more efficiently and, moreover, solve problems...

  18. The receptor for advanced glycation end products in ventilator-induced lung injury

    NARCIS (Netherlands)

    Kuipers, Maria T.; Aslami, Hamid; Tuinman, Pieter Roel; Tuip-de Boer, Anita M.; Jongsma, Geartsje; van der Sluijs, Koenraad F.; Choi, Goda; Wolthuis, Esther K.; Roelofs, Joris J. T. H.; Bresser, Paul; Schultz, Marcus J.; van der Poll, Tom; Wieland, Catharina W.

    2014-01-01

    Mechanical ventilation (MV) can cause ventilator-induced lung injury (VILI). The innate immune response mediates this iatrogenic inflammatory condition. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that can amplify immune and inflammatory responses. We

  19. Receptor for advanced glycation end products is protective during murine tuberculosis

    NARCIS (Netherlands)

    van Zoelen, Marieke A. D.; Wieland, Catharina W.; van der Windt, Gerritje J. W.; Florquin, Sandrine; Nawroth, Peter P.; Bierhaus, Angelika; van der Poll, Tom

    2012-01-01

    The development of active tuberculosis after infection with Mycobacterium tuberculosis is almost invariably associated with a persistent or transient state of relative immunodeficiency. The receptor for advanced glycation end products (RAGE) is a promiscuous receptor that is involved in pulmonary

  20. Receptor for advanced glycation end products is protective during murine tuberculosis.

    NARCIS (Netherlands)

    Zoelen, M.A. van; Wieland, C.W.; Windt, G.J. van der; Florquin, S.; Nawroth, P.P.; Bierhaus, A.; Poll, T. van der

    2012-01-01

    The development of active tuberculosis after infection with Mycobacterium tuberculosis is almost invariably associated with a persistent or transient state of relative immunodeficiency. The receptor for advanced glycation end products (RAGE) is a promiscuous receptor that is involved in pulmonary

  1. The receptor for advanced glycation end products in ventilator-induced lung injury

    NARCIS (Netherlands)

    Kuipers, Maria T; Aslami, Hamid; Tuinman, Pieter Roel; Tuip-de Boer, Anita M; Jongsma, Geartsje; van der Sluijs, Koenraad F; Choi, Goda; Wolthuis, Esther K; Roelofs, Joris Jth; Bresser, Paul; Schultz, Marcus J; van der Poll, Tom; Wieland, Catharina W

    2014-01-01

    BACKGROUND: Mechanical ventilation (MV) can cause ventilator-induced lung injury (VILI). The innate immune response mediates this iatrogenic inflammatory condition. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that can amplify immune and inflammatory responses.

  2. Advanced glycation end products in the skin are enhanced in COPD

    NARCIS (Netherlands)

    Hoonhorst, Susan J. M.; Loi, Adele T. Lo Tam; Hartman, Jorine E.; Telenga, Eef D.; van den Berge, Maarten; Koenderman, Leo; Lammers, Jan Willem J.; Boezen, H. Marike; Postma, Dirkje S.; ten Hacken, Nick H. T.

    Background. Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) inducing oxidative stress and local tissue injury, resulting in pulmonary inflammation. Advanced glycation end products (AGEs) are produced by glycation and oxidation processes and their formation is

  3. Advanced Product Water Removal and Management (APWR) Fuel Cell System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a passive, self-regulating, gravity-independent Advanced Product Water Removal and management (APWR) system for incorporation into Polymer...

  4. Advanced Product Water Removal and Management (APWR) Fuel Cell System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a passive, self-regulating, gravity-independent Advanced Product Water Removal (APWR) system for Polymer Electrolyte Membrane (PEM)...

  5. Hydrothermal Carbonization of Seaweed For Advanced Biochar Production

    Directory of Open Access Journals (Sweden)

    Prakoso Tirto

    2018-01-01

    Full Text Available Seaweed such as Eucheuma Cottonii is a potential source of biomaterialIts high moisture content makes it suitable for hydrothermal conversion process since it doesn’t need to utilize dry feedstock. The aim of this study is to convert the biomass of red seaweed Eucheuma Cottonii into alternative fuels and high value biomaterials using hydrothermal process. The hydrothermal process seaweed Eucheuma Cottonii produce two types of products, liquid product and char (solid. This research focus on the char product. The char from hydrothermal process was then activated using the tubular furnace. The yield for activated char is 7.5 % and results of SEM analysis of activated char showed the formation of allotropes carbon include carbon micro spheres, carbon micro fibres and graphene. These structures have encountered application in a wide range of technological fields, such as adsorption, catalysis, hydrogen storage or electronics.

  6. Molecular Breeding of Advanced Microorganisms for Biofuel Production

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakuragi

    2011-01-01

    Full Text Available Large amounts of fossil fuels are consumed every day in spite of increasing environmental problems. To preserve the environment and construct a sustainable society, the use of biofuels derived from different kinds of biomass is being practiced worldwide. Although bioethanol has been largely produced, it commonly requires food crops such as corn and sugar cane as substrates. To develop a sustainable energy supply, cellulosic biomass should be used for bioethanol production instead of grain biomass. For this purpose, cell surface engineering technology is a very promising method. In biobutanol and biodiesel production, engineered host fermentation has attracted much attention; however, this method has many limitations such as low productivity and low solvent tolerance of microorganisms. Despite these problems, biofuels such as bioethanol, biobutanol, and biodiesel are potential energy sources that can help establish a sustainable society.

  7. A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ulrika Wendel

    Full Text Available Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.

  8. Animal Production Research Advances - Vol 5, No 2 (2009)

    African Journals Online (AJOL)

    Predictive ability of boiler production models · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. UE Ogundu, OO Okpala, MU Iloeje. http://dx.doi.org/10.4314/apra.v5i2.49826 ...

  9. Effects of advanced glycation end-products (AGEs) on skin ...

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-06-21

    Jun 21, 2012 ... Abbreviations: AGEs, Glycation end-products; SD, Sprague-. Dawley; STZ, streptozotocin; EGF, epidermal growth factor; NF-. kB, nuclear factor-kappa B. result in significant morbidity. Impaired wound healing is a common vascular complication of diabetes mellitus and constitutes a major clinical problem ...

  10. Comparative Assessment of Advanced Gay Hydrate Production Methods

    Energy Technology Data Exchange (ETDEWEB)

    M. D. White; B. P. McGrail; S. K. Wurstner

    2009-06-30

    Displacing natural gas and petroleum with carbon dioxide is a proven technology for producing conventional geologic hydrocarbon reservoirs, and producing additional yields from abandoned or partially produced petroleum reservoirs. Extending this concept to natural gas hydrate production offers the potential to enhance gas hydrate recovery with concomitant permanent geologic sequestration. Numerical simulation was used to assess a suite of carbon dioxide injection techniques for producing gas hydrates from a variety of geologic deposit types. Secondary hydrate formation was found to inhibit contact of the injected CO{sub 2} regardless of injectate phase state, thus diminishing the exchange rate due to pore clogging and hydrate zone bypass of the injected fluids. Additional work is needed to develop methods of artificially introducing high-permeability pathways in gas hydrate zones if injection of CO{sub 2} in either gas, liquid, or micro-emulsion form is to be more effective in enhancing gas hydrate production rates.

  11. Current advances in biological production of propionic acid.

    Science.gov (United States)

    Eş, Ismail; Khaneghah, Amin Mousavi; Hashemi, Seyed Mohammad Bagher; Koubaa, Mohamed

    2017-05-01

    Propionic acid and its derivatives are considered "Generally Recognized As Safe" food additives and are generally used as an anti-microbial and anti-inflammatory agent, herbicide, and artificial flavor in diverse industrial applications. It is produced via biological pathways using Propionibacterium and some anaerobic bacteria. However, its commercial chemical synthesis from the petroleum-based feedstock is the conventional production process bit results in some environmental issues. Novel biological approaches using microorganisms and renewable biomass have attracted considerable recent attention due to economic advantages as well as great adaptation with the green technology. This review provides a comprehensive overview of important biotechnological aspects of propionic acid production using recent technologies such as employment of co-culture, genetic and metabolic engineering, immobilization technique and efficient bioreactor systems.

  12. Recent advances in screening of natural products for antimicrobial agents.

    Science.gov (United States)

    Zhou, Meng; Luo, Hao; Li, Zhi; Wu, Feng; Huang, Canhua; Ding, Zhenyu; Li, Rui

    2012-05-01

    It has been a very long history for human to resist diseases. During this period, a large number of drugs that could kill or inhibit the growth of microbe has been discovered, most of which were natural products. However, there may still be a large amount of antimicrobial medicines in natural compounds which have not been found yet. The ways of screening for antimicrobial always cost a long time and need a lot of manpower before. However, in recent years, a lot of new antimicrobial targets, antimicrobial drugs and screening methods which are simpler, faster and more efficient have been invented. In this paper the newly discovered targets, natural products and representative technologies were reviewed, which were expected to make some contributions to the research and development of medicines.

  13. Recent Advances in Second Generation Ethanol Production by Thermophilic Bacteria

    OpenAIRE

    Sean Michael Scully; Johann Orlygsson

    2014-01-01

    There is an increased interest in using thermophilic bacteria for the production of bioethanol from complex lignocellulosic biomass due to their higher operating temperatures and broad substrate range. This review focuses upon the main genera of thermophilic anaerobes known to produce ethanol, their physiology, and the relevance of various environmental factors on ethanol yields including the partial pressure of hydrogen, ethanol tolerance, pH and substrate inhibition. Additionally, recent de...

  14. Advances in ethanol reforming for the production of hydrogen

    Directory of Open Access Journals (Sweden)

    Laura Guerrero

    2014-06-01

    Full Text Available Catalytic steam reforming of ethanol (SRE is a promising route for the production of renewable hydrogen (H2. This article reviews the influence of doping supported-catalysts used in SRE on the conversion of ethanol, selectivity for H2, and stability during long reaction periods. In addition, promising new technologies such as membrane reactors and electrochemical reforming for performing SRE are presented.

  15. Production and Recovery of Pyruvic Acid: Recent Advances

    Science.gov (United States)

    Pal, Dharm; Keshav, Amit; Mazumdar, Bidyut; Kumar, Awanish; Uslu, Hasan

    2017-12-01

    Pyruvic acid is an important keto-carboxylic acid and can be manufactured by both chemical synthesis and biotechnological routes. In the present paper an overview of recent developments and challenges in various existing technique for the production and recovery of pyruvic acid from fermentation broth or from waste streams has been presented. The main obstacle in biotechnological production of pyruvic acid is development of suitable microorganism which can provide high yield and selectivity. On the other hand, technical limitation in recovery of pyruvic acid from fermentation broth is that, it could not be separated as other carboxylic acid in the form of salts by addition of alkali. Besides, pyruvic acid cannot be crystallized. Commercial separation by distillation is very expensive because pyruvic acid decomposes at higher temperature. It is also chemically reactive due to its peculiar molecular structure and has tendency to polymerize. Thus, at high concentration the various type of reaction leads to lower yield of the product, and hence, conventional methods are not favorable. Alternate separation technologies viable to both synthetic and biological routes are the current research areas. Latest techniques such as reactive extraction is new to the field of recovery of pyruvic acid. Recent development and future prospects in downstream processing of biochemically produced pyruvic acids has been discussed in this review article.

  16. Simulation of fission products behavior in severe accidents for advanced passive PWR

    International Nuclear Information System (INIS)

    Tong, L.L.; Huang, G.F.; Cao, X.W.

    2015-01-01

    Highlights: • A fission product analysis model based on thermal hydraulic module is developed. • An assessment method for fission product release and transport is constructed. • Fission products behavior during three modes of containment response is investigated. • Source term results for the three modes of containment response are obtained. - Abstract: Fission product behavior for common Pressurized Water Reactor (PWR) has been studied for many years, and some analytical tools have developed. However, studies specifically on the behavior of fission products related to advanced passive PWR is scarce. In the current study, design characteristics of advanced passive PWR influencing fission product behavior are investigated. An integrated fission products analysis model based on a thermal hydraulic module is developed, and the assessment method for fission products release and transport for advanced passive PWR is constructed. Three modes of containment response are simulated, including intact containment, containment bypass and containment overpressure failure. Fission products release from the core and corium, fission products transport and deposition in the Reactor Coolant System (RCS), fission products transport and deposition in the containment considering fission products retention in the in-containment refueling water storage tank (IRWST) and in the secondary side of steam generators (SGs) are simulated. Source term results of intact containment, containment bypass and containment overpressure failure are obtained, which can be utilized to evaluate the radiological consequences

  17. Advanced Decontamination Technologies: High Hydrostatic Pressure on Meat Products

    Science.gov (United States)

    Garriga, Margarita; Aymerich, Teresa

    The increasing demand for “natural” foodstuffs, free from chemical additives, and preservatives has triggered novel approaches in food technology developments. In the last decade, practical use of high-pressure processing (HPP) made this emerging non-thermal technology very attractive from a commercial point of view. Despite the fact that the investment is still high, the resulting value-added products, with an extended and safe shelf-life, will fulfil the wishes of consumers who prefer preservative-free minimally processed foods, retaining sensorial characteristics of freshness. Moreover, unlike thermal treatment, pressure treatment is not time/mass dependant, thus reducing the time of processing.

  18. RAFT technology for the production of advanced photoresist polymers

    Science.gov (United States)

    Sheehan, Michael T.; Farnham, William B.; Okazaki, Hiroshi; Sounik, James R.; Clark, George

    2008-03-01

    Reversible Addition Fragmentation Chain Transfer (RAFT) technology has been developed for use in producing high yield low polydispersity (PD) polymers for many applications. RAFT technology is being used to produce low PD polymers and to allow control of the polymer architecture. A variety of polymers are being synthesized for use in advanced photoresists using this technique. By varying the RAFT reagent used we can modulate the system reactivity of the RAFT reagent and optimize it for use in acrylate or methacrylate monomer systems (193 and 193i photoresist polymers) or for use in styrenic monomer systems (248 nm photoresist polymers) to achieve PD as low as 1.05. RAFT polymerization technology also allows us to produce block copolymers using a wide variety of monomers. These block copolymers have been shown to be useful in self assembly polymer applications to produce unique and very small feature sizes. The mutual compatibilities of all the components within a single layer 193 photoresist are very important in order to achieve low LWR and low defect count. The advent of immersion imaging demands an additional element of protection at the solid/liquid interface. We have used RAFT technology to produce block copolymers comprising a random "resist" block with composition and size based on conventional dry photoresist materials, and a "low surface energy" block for use in 193i lithography. The relative block lengths and compositions may be varied to tune solution behavior, surface energy, contact angles, and solubility in developer. The use of this technique will be explored to produce polymers used in hydrophobic single layer resists as well as additives compatible with the main photoresist polymer.

  19. Recent advances on biological production of difructose dianhydride III.

    Science.gov (United States)

    Zhu, Yingying; Yu, Shuhuai; Zhang, Wenli; Zhang, Tao; Guang, Cuie; Mu, Wanmeng

    2018-04-01

    Difructose dianhydride III (DFA III) is a cyclic difructose containing two reciprocal glycosidic linkages. It is easily generated with a small amount by sucrose caramelization and thus occurs in a wide range of food-stuffs during food processing. DFA III has half sweetness but only 1/15 energy of sucrose, showing potential industrial application as low-calorie sucrose substitute. In addition, it displays many benefits including prebiotic effect, low cariogenicity property, and hypocholesterolemic effect, and improves absorption of minerals, flavonoids, and immunoglobulin G. DFA III is biologically produced from inulin by inulin fructotransferase (IFTase, EC 4.2.2.18). Plenty of DFA III-producing enzymes have been identified. The crystal structure of inulin fructotransferase has been determined, and its molecular modification has been performed to improve the catalytic activity and structural stability. Large-scale production of DFA III has been studied by various IFTases, especially using an ultrafiltration membrane bioreactor. In this article, the recent findings on physiological effects of DFA III are briefly summarized; the research progresses on identification, expression, and molecular modification of IFTase and large-scale biological production of DFA III by IFTase are reviewed in detail.

  20. Recent advances in the elucidation of enzymatic function in natural product biosynthesis.

    Science.gov (United States)

    Tan, Gao-Yi; Deng, Zixin; Liu, Tiangang

    2015-01-01

    With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.

  1. Advanced biomass science and technology for bio-based products: proceedings

    Science.gov (United States)

    Chung Hse; Zehui Jiang; Mon-Lin Kuo

    2009-01-01

    This book was developed from the proceedings of the Advanced Biomass Science and Technology for Bio-Based Products Symposium held in Beijing, China, May 23-25, 2007. The symposium was designed to provide a forum for researchers, producers, and consumers of biomass and bio-based products; to exchange information and ideas; and to stimulate new research and...

  2. Advanced Biofuels and Beyond: Chemistry Solutions for Propulsion and Production.

    Science.gov (United States)

    Leitner, Walter; Klankermayer, Jürgen; Pischinger, Stefan; Pitsch, Heinz; Kohse-Höinghaus, Katharina

    2017-05-08

    Sustainably produced biofuels, especially when they are derived from lignocellulosic biomass, are being discussed intensively for future ground transportation. Traditionally, research activities focus on the synthesis process, while leaving their combustion properties to be evaluated by a different community. This Review adopts an integrative view of engine combustion and fuel synthesis, focusing on chemical aspects as the common denominator. It will be demonstrated that a fundamental understanding of the combustion process can be instrumental to derive design criteria for the molecular structure of fuel candidates, which can then be targets for the analysis of synthetic pathways and the development of catalytic production routes. With such an integrative approach to fuel design, it will be possible to improve systematically the entire system, spanning biomass feedstock, conversion process, fuel, engine, and pollutants with a view to improve the carbon footprint, increase efficiency, and reduce emissions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Advanced Electrochemical Technologies for Hydrogen Production by Alternative Thermochemical Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Lvov, Serguei; Chung, Mike; Fedkin, Mark; Lewis, Michele; Balashov, Victor; Chalkova, Elena; Akinfiev, Nikolay; Stork, Carol; Davis, Thomas; Gadala-Maria, Francis; Stanford, Thomas; Weidner, John; Law, Victor; Prindle, John

    2011-01-06

    Hydrogen fuel is a potentially major solution to the problem of climate change, as well as addressing urban air pollution issues. But a key future challenge for hydrogen as a clean energy carrier is a sustainable, low-cost method of producing it in large capacities. Most of the world's hydrogen is currently derived from fossil fuels through some type of reforming processes. Nuclear hydrogen production is an emerging and promising alternative to the reforming processes for carbon-free hydrogen production in the future. This report presents the main results of a research program carried out by a NERI Consortium, which consisted of Penn State University (PSU) (lead), University of South Carolina (USC), Tulane University (TU), and Argonne National Laboratory (ANL). Thermochemical water decomposition is an emerging technology for large-scale production of hydrogen. Typically using two or more intermediate compounds, a sequence of chemical and physical processes split water into hydrogen and oxygen, without releasing any pollutants externally to the atmosphere. These intermediate compounds are recycled internally within a closed loop. While previous studies have identified over 200 possible thermochemical cycles, only a few have progressed beyond theoretical calculations to working experimental demonstrations that establish scientific and practical feasibility of the thermochemical processes. The Cu-Cl cycle has a significant advantage over other cycles due to lower temperature requirements – around 530 °C and below. As a result, it can be eventually linked with the Generation IV thermal power stations. Advantages of the Cu-Cl cycle over others include lower operating temperatures, ability to utilize low-grade waste heat to improve energy efficiency, and potentially lower cost materials. Another significant advantage is a relatively low voltage required for the electrochemical step (thus low electricity input). Other advantages include common chemical agents and

  4. Advances in aluminium alloy products for structural applications in transportation

    International Nuclear Information System (INIS)

    Staley, J.T.; Lege, D.J.

    1993-01-01

    This paper describes the needs of the aviation and automotive markets for structural materials and presents examples of developments of aluminum alloy products to fill these needs. Designers of aircraft desire materials which will allow them to design lightweight, cost-effective structures which have the performance characteristics of durability and damage tolerance. Their needs are being met by new and emerging materials varying from Al-Li alloys for thick structure, high-strength plate and extrusions for wings, and new monolithic and aluminum-fiber laminates for fuselages. Increase in fuel economy because of lighter weight structure is the driving force for aluminum alloys in the automotive market, and cost is extremely important. Mechanical properties for automotive use also depend on the application, and corrosion resistance must be adequate. For ''hang-on'' components such as fenders and hoods, formability is typically the limiting mechanical property. Strength must be adequate to resist denting at a thickness which offers cost-effective weight savings over steel. Because formability often decreases with increasing yield strength, alloys which are highly formable in the T4 temper and which age harden during the paint bake operation were developed. Alloys such as 6009 and 6010 are now being challenged by 2008, 6111 and 6016. Body structure components must be made from materials which absorb energy and fail gracefully during a crash. Such components for an automotive space frame are being die cast from an Al-Si-Mg alloy. These ductile die castings are joined to thin 6XXX extrusions which must combine formability, strength, ductility and the ability to deform plastically on impact. Bumpers must combine strength and adequate formability; in the event that current alloys are inadequate for future needs, a new 7XXX alloy offers an improved combination of properties. (orig.)

  5. Production of Liquid Synthetic Fuels from Carbon, Water and Nuclear Power on Ships and at Shore Bases for Military and Potential Commercial Applications

    International Nuclear Information System (INIS)

    Locke Bogart, S.; Schultz, Ken; Brown, Lloyd; Russ, Ben

    2006-01-01

    It is demonstrable that synthetic fuels (jet/diesel/gasoline ≅ (CH 2 ) n ) can be produced from carbon, water, and nuclear energy. What remains to be shown is that all system processes are scalable, integrable, and economical. Sources of carbon include but are not limited to CO 2 from the atmosphere or seawater, CO 2 from fossil-fired power plants, and elemental carbon from coal or biomass. For mobile defense (Navy) applications, the ubiquitous atmosphere is our chosen carbon source. For larger-scale sites such as Naval Advance Bases, the atmosphere may still be the choice should other sources not be readily available. However, at many locations suitable for defense and, potentially, commercial syn-fuel production, far higher concentrations of carbon may be available. The rationale for this study was manifold: fuel system security from terrorism and possible oil embargoes; rising demand and, eventually, peaking supply of conventional petroleum; and escalating costs and prices of fuels. For these reasons, the initial parts of the study were directed at Syn-fuel production for mobile Naval platforms and shore sites such as Rokkasho, Japan (as an exemplar). Nuclear reactors would provide the energy for H 2 from water-splitting, Membrane Gas Absorption (MGA) would extract CO 2 from the atmosphere, the Reverse Water-Gas Reaction (RWGR) would convert the CO 2 to CO, and the resultant H 2 and CO feeds would be converted to (CH 2 )n by the Fischer-Tropsch reaction. Many of these processes exist at commercial scale. Some, particularly MGA and RWGR, have been demonstrated at the bench-scale, requiring up-scaling. Likewise, the demonstration of an integrated system at some scale is yet to be done. For ship-based production, it has been shown that the system should be viable and, under reasonable assumptions, both scalable and economical for defense fuels. For the assumptions in the study, fuel cost estimates range from ∼ $2.55 to $4.75 per gallon with a nominal cost of

  6. Contributions to Advances in Blend Pellet Products (BPP) Research on Molecular Structure and Molecular Nutrition Interaction by Advanced Synchrotron and Globar Molecular (Micro)Spectroscopy.

    Science.gov (United States)

    Guevara-Oquendo, VÍctor H; Yu, Peiqiang

    2018-04-13

    To date, advanced synchrotron-based and globar-sourced techniques are almost unknown to food and feed scientists. There has been little application of these advanced techniques to study blend pellet products at a molecular level. This article aims to provide recent research on advanced synchrotron and globar vibrational molecular spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction. How processing induced molecular structure changes in relation to nutrient availability and utilization of the blend pellet products. The study reviews Utilization of co-product components for blend pellet product in North America; Utilization and benefits of inclusion of pulse screenings; Utilization of additives in blend pellet products; Application of pellet processing in blend pellet products; Conventional evaluation techniques and methods for blend pellet products. The study focus on recent applications of cutting-edge vibrational molecular spectroscopy for molecular structure and molecular structure association with nutrient utilization in blend pellet products. The information described in this article gives better insight on how advanced molecular (micro)spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction.

  7. Further advances in the production of membrane proteins in Pichia pastoris.

    Science.gov (United States)

    Hedfalk, Kristina

    2013-01-01

    Membrane proteins have essential cellular functions and are therefore of high interest in both academia and industry. Many efforts have been made on producing those targets in yields allowing crystallization experiments aiming for high resolution structures and mechanistic understanding. The first step of production provides a crucial barrier to overcome, but what we now see, is great progress in membrane protein structural determination in a relatively short time. Achievements on recombinant protein production have been essential for this development and the yeast Pichia pastoris is the most commonly used host for eukaryotic membrane proteins. High-resolution structures nicely illustrate the successes in protein production, and this is the measure used by Ramón and Marin in their review "Advances in the production of membrane proteins in Pichia pastoris" from 2011. Here, additional advances on production and crystallization of eukaryotic membrane proteins are described and reflected on.

  8. Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

    Science.gov (United States)

    Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

    2015-01-01

    In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

  9. Analysis of organizational options for the uranium enrichment enterprise in relation to asset divesture. [BPA; TVA; SYNFUELS; CONRAIL; British TELECOM; COMSTAT

    Energy Technology Data Exchange (ETDEWEB)

    Harrer, B.J.; Hattrup, M.P.; Dase, J.E.; Nicholls, A.K.

    1986-08-01

    This report presents a comparison of the characteristics of some prominent examples of independent government corporations and agencies with respect to the Department of Energy's (DOE) uranium enrichment enterprise. The six examples studied were: the Bonneville Power Administration (BPA); the Tennessee Valley Authority (TVA); the Synthetic Fuels Corporation (SYNFUELS); the Consolidated Rail Corporation (CONRAIL); the British Telecommunications Corporation (British TELECOM); and the Communications Satellite Organization (COMSAT), in order of decreasing levels of government ownership and control. They range from BPA, which is organized as an agency within DOE, to COMSAT, which is privately owned and free from almost all regulations common to government agencies. Differences in the degree of government involvement in these corporations and in many other characteristics serve to illustrate that there are no accepted standards for defining the characteristics of government corporations. Thus, historical precedent indicates considerable flexibility would be available in the development of enabling legislation to reorganize the enrichment enterprise as a government corporation or independent government agency.

  10. Some Nutritional, Technological and Environmental Advances in the Use of Enzymes in Meat Products

    Directory of Open Access Journals (Sweden)

    Anne y Castro Marques

    2010-01-01

    Full Text Available The growing consumer demand for healthier products has stimulated the development of nutritionally enhanced meat products. However, this can result in undesirable sensory consequences to the product, such as texture alterations in low-salt and low-phosphate meat foods. Additionally, in the meat industry, economical aspects have stimulated researchers to use all the animal parts to maximize yields of marketable products. This paper aimed to show some advances in the use of enzymes in meat processing, particularly the application of the proteolytic enzymes transglutaminase and phytases, associated with nutritional, technological, and environmental improvements.

  11. Survey of the Distribution of a Newly Characterized Receptor for Advanced Glycation End Products in Tissues

    OpenAIRE

    Brett, Jerold; Schmidt, Ann Marie; Yan, Shi Du; Zou, Yu Shan; Weidman, Elliott; Pinsky, David; Nowygrod, Roman; Neeper, Michael; Przysiecki, Craig; Shaw, Alan; Migheli, Antonio; Stern, David

    1993-01-01

    Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculatur...

  12. Advances in the Systems and Processes for the Production of Gamma Titanium Aluminide Bars and Powder

    Science.gov (United States)

    Haun, Robert E.

    2017-12-01

    A historical look at the melt processing of gamma titanium aluminides is presented first, followed by recent advances in melting equipment design by Retech to produce 50-mm and 100-mm-diameter ingots up to 1000 mm long. Equipment design for the economical production of gamma titanium aluminide powder is then discussed. The focus in industry has shifted away from basic research to cost-effective production of these titanium alloys for aerospace and automotive engine applications.

  13. Encountering Challenges with the EU Regulation on Advance Therapy Medical Products.

    Science.gov (United States)

    Mansnérus, Juli

    2015-12-01

    This article aims at analysing how well the Advanced Therapy Medical Product Regulation (EC) No. 1394/2007 (ATMP Regulation) meets the needs of small and medium-sized enterprises (SMES), academia and public tissue establishments developing advanced therapy medical products (ATMPS). Benefits and shortcomings of the ATMP Regulation are identified, and possible amendments are proposed to accelerate the translation of research into advanced therapies and to facilitate the commercialisation of ATMPS whilst ensuring safety. It was set up as a lex specialis to ensure the free movement of ATMPS within the EU in order to facilitate their access to the internal market and to foster the competitiveness of European pharmaceutical companies, while guaranteeing the highest level protection of public health. Since the adoption of the ATMP Regulation in late 2008, only 5 ATMPS have been granted marketing authorisations thus far. Hence, there is a need to analyse whether the ATMP Regulation meets its objectives.

  14. Advances in metabolic engineering of yeast Saccharomyces cerevisiae for production of chemicals

    DEFF Research Database (Denmark)

    Borodina, Irina; Nielsen, Jens

    2014-01-01

    Yeast Saccharomyces cerevisiae is an important industrial host for production of enzymes, pharmaceutical and nutraceutical ingredients and recently also commodity chemicals and biofuels. Here, we review the advances in modeling and synthetic biology tools and how these tools can speed up the deve...

  15. The Contribution of Advanced Glycation End product (AGE) accumulation to the decline in motor function

    NARCIS (Netherlands)

    Drenth, Hans; Zuidema, Sytse; Bunt, Steven; Bautmans, Ivan; van der Schans, Cees; Hobbelen, Hans

    2016-01-01

    Diminishing motor function is commonly observed in the elderly population and is associated with a wide range of adverse health consequences. Advanced Glycation End products (AGE's) may contribute to age-related decline in the function of cells and tissues in normal ageing. Although the negative

  16. Receptor for advanced glycation end product expression in experimental diabetic retinopathy

    NARCIS (Netherlands)

    Wang, Yumei; Hagen, Filanziska Vom; Pfister, Frederick; Bierhaus, Angelika; Feng, Yuxi; Gans, Reinhold; Hammes, Hans-Peter; Schleicher, E; Somoza,; Shieberle, P

    2008-01-01

    The advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway is involved in the pathogenesis of diabetic microvascular damage. The special distribution of RAGE and its engagement has an impact on the development of diabetic retinopathy. In the present study, we used immunofluorescence

  17. Effect of collagen turnover on the accumulation of advanced glycation end products

    NARCIS (Netherlands)

    Verzijl, N.; Degroot, J.; Thorpe, S. R.; Bank, R. A.; Shaw, J. N.; Lyons, T. J.; Bijlsma, J. W.; Lafeber, F. P.; Baynes, J. W.; TeKoppele, J. M.

    2000-01-01

    Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE

  18. Production of advanced biofuels: co-processing of upgraded pyrolysis oil in standard refinery units

    NARCIS (Netherlands)

    De Miguel Mercader, F.; de Miguel Mercader, F.; Groeneveld, M.J.; Hogendoorn, Kees; Kersten, Sascha R.A.; Way, N.W.J.; Schaverien, C.J.

    2010-01-01

    One of the possible process options for the production of advanced biofuels is the co-processing of upgraded pyrolysis oil in standard refineries. The applicability of hydrodeoxygenation (HDO) was studied as a pyrolysis oil upgrading step to allow FCC co-processing. Different HDO reaction end

  19. Clinical and prognostic value of advanced glycation end-products in chronic heart failure

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; Voors, Adriaan A.; Schalkwijk, Casper G.; Scheijen, Jean; Smilde, Tom D. J.; Damman, Kevin; Bakker, Stephan J. L.; Smit, Andries J.; van Veldhuisen, Dirk J.

    2007-01-01

    Aims Advanced glycation end-products (AGEs) have been proposed as a novel factor involved in the development and progression of chronic heart failure (CHF). We aimed to determine whether plasma levels of N-epsilon-(carboxymethyl)lysine (CML) and N-epsilon-(carboxyethyl)lysine (CEL), two well-known

  20. Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome

    NARCIS (Netherlands)

    Willemsen, Suzan; Hartog, Jasper W. L.; Heiner-Fokkema, Rebecca; van Veldhuisen, Dirk J.; Voors, Adriaan A.

    The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly

  1. Soluble receptor for advanced glycation end products (sRAGE) and ...

    African Journals Online (AJOL)

    Eman M. Sherif

    2014-07-10

    Jul 10, 2014 ... Abstract Background: Advanced glycation end products (AGEs) are a heterogeneous and com- plex group of biochemical compounds, resulting from nonenzymatic glycation and oxidation of protein, nucleic acids, and lipids. Aim of the study: To assess sRAGE and CIMT in patients with T1DM and their ...

  2. Advanced sorting technologies for optimal wood products and woody biomass utilization

    Science.gov (United States)

    Xiping Wang

    2012-01-01

    Forest materials represent great potential for advancing our goals in the 21st century for sustainable building, energy independence, and carbon sequestration. A critical component of an improved system for producing bioproducts and bioenergr from forest materials is the ability to sort trees, stems, and logs into end-product categories that represent their highest...

  3. Advanced glycation end-products (AGES) and heart failure : Pathophysiology and clinical implications

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; Voors, Adriaan A.; Bakker, Stephan J. L.; Smit, Andries J.; van Veldhuisen, Dirk J.

    2007-01-01

    Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes,

  4. 78 FR 70624 - Guidance on Supervisory Concerns and Expectations Regarding Deposit Advance Products

    Science.gov (United States)

    2013-11-26

    ... deposit advance products and supplements the OCC's existing guidance on payday loans and subprime lending... Subprime Lending Programs'' (2001) states that loans to borrowers who do not demonstrate the capacity to... underwriting requirements. Loans exhibiting subprime credit characteristics are higher-risk loans and may...

  5. 78 FR 70552 - Guidance on Supervisory Concerns and Expectations Regarding Deposit Advance Products

    Science.gov (United States)

    2013-11-26

    ... Subprime Lending Programs'' (2001) states that loans to borrowers who do not demonstrate the capacity to... underwriting requirements. Loans exhibiting subprime credit characteristics are higher- risk loans and may... deposit advance product is a small-dollar, short-term loan or line of credit that a bank makes available...

  6. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia

    NARCIS (Netherlands)

    Achouiti, Ahmed; de Vos, Alex F.; van 't Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W.; Nawroth, Peter P.; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A. D.

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed

  7. Lights, Camera, Action: Advancing Learning, Research, and Program Evaluation through Video Production in Educational Leadership Preparation

    Science.gov (United States)

    Friend, Jennifer; Militello, Matthew

    2015-01-01

    This article analyzes specific uses of digital video production in the field of educational leadership preparation, advancing a three-part framework that includes the use of video in (a) teaching and learning, (b) research methods, and (c) program evaluation and service to the profession. The first category within the framework examines videos…

  8. Skin accumulation of advanced glycation end products is increased in patients with an abdominal aortic aneurysm

    NARCIS (Netherlands)

    Boersema, Jeltje; de Vos, Lisanne C.; Links, Thera P.; Mulder, Douwe J.; Smit, Andries J.; Zeebregts, Clark J.; Lefrandt, Joop D.

    2017-01-01

    Objective: Advanced glycation end products (AGEs) are implicated in the pathogenesis of cardiovascular disease. Accumulation of AGEs is driven by oxidative or glycemic stress and can be assessed by skin autofluorescence (SAF). SAF is increased in patients with peripheral artery disease (PAD) and

  9. The Customized Automatic Processing Framework for HY-2A Satellite Marine Advanced Products

    Directory of Open Access Journals (Sweden)

    Wei Liu

    2016-12-01

    Full Text Available HY-2A, as the first Chinese ocean dynamic environment satellite, provides an effective and efficient way of observing ocean properties. However, in the operational stage, some inconveniences of the existing ground application system have appeared. Based on the review of users’ requirements for data services, the Customized Automatic Processing Framework (CAPF for HY-2A advanced products is proposed and has been developed. As an extension of the existing ground application system, the framework provides interfaces for adding customized algorithms, designing on-demand processing workflows, and scheduling the processing procedures. With the customized processing templates, the framework allows users to easily process the products according to their own expectations, which facilitates the usage of HY-2A satellite advanced products.

  10. Advancing Commercialization of Algal Biofuel through Increased Biomass Productivity and Technical Integration

    Energy Technology Data Exchange (ETDEWEB)

    Anton, David [Cellana, LLC, Kailua-Kona, HI (United States)

    2016-12-31

    The proposed project built on the foundation of over several years years of intensive and ground-breaking R&D work at Cellana's Kona Demonstration Facility (KDF). Phycological and engineering solutions were provided to tackle key cultivation issues and technical barriers limiting algal biomass productivity identified through work conducted outdoors at industrial (1 acre) scale. The objectives of this project were to significantly improve algal biomass productivity and reduce operational cost in a seawater-based system, using results obtained from two top-performing algal strains as the baseline while technically advancing and more importantly, integrating the various unit operations involved in algal biomass production, processing, and refining.

  11. Advanced glycation end-products induce heparanase expression in endothelial cells by the receptor for advanced glycation end products and through activation of the FOXO4 transcription factor.

    Science.gov (United States)

    An, Xiao-Fei; Zhou, Lei; Jiang, Peng-Jun; Yan, Ming; Huang, Yu-Jun; Zhang, Su-Na; Niu, Yun-Fei; Ten, Shi-Chao; Yu, Jiang-Yi

    2011-08-01

    As an endo-β (1-4)-D: -glucuronidase, heparanase can specifically cleave carbohydrate chains of heparan sulfate (HS) and has been implicated in development of endothelial cells dsyfunction. The advanced glycation end products (AGEs) play a pivotal role in the pathology of diabetic complications. In the present study, we investigated the effect of AGE-bovine serum albumin (AGE-BSA) on heparanase expression in human microvascular endothelial cells (HMVECs) and the underlying molecular mechanisms. The results indicated that in vitro direct exposure of HMVECs to AGE-BSA (300, 1000, and 3000 μg/ml) could increase heparanase mRNA and protein expression in a dose and time-dependent manner. The effect of 1000 μg/ml AGE-BSA could be abolished by neutralization with antibody of the receptor for advanced glycation end products (RAGE). Moreover, pretreatment with inhibitors of nuclear factor-κB (NF-κB) or PI3-kinase did not affect heparanase expression induced by AGE-BSA. Nevertheless, small interference RNA (siRNA) for transcriptional factor FOXO4 could reduce the increase of heparanase expression in HMVECs induced by 1000 μg/ml AGE-BSA. These results suggest that AGEs could induce heparanase expression in HMVECs by RAGE and predominantly through activation of the FOXO4 transcription factor.

  12. Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway.

    Science.gov (United States)

    Wu, Qian; Zhong, Zhao-Ming; Zhu, Si-Yuan; Liao, Cong-Rui; Pan, Ying; Zeng, Ji-Huan; Zheng, Shuai; Ding, Ruo-Ting; Lin, Qing-Song; Ye, Qing; Ye, Wen-Bin; Li, Wei; Chen, Jian-Ting

    2016-01-01

    Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. Exposure of chondrocyte to AOPPs activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and increased expression of NADPH oxidase subunits, which was mediated by receptor for advanced glycation end products (RAGE), but not scavenger receptor CD36. Moreover, AOPPs challenge triggered NADPH oxidase-dependent ROS generation which induced mitochondrial dysfunction and endoplasmic reticulum stress resulted in activation of caspase family that eventually lead to apoptosis. Lastly, blockade of RAGE, instead of CD36, largely attenuated these signals. Our study demonstrated first time that AOPPs induce chondrocyte apoptosis via RAGE-mediated and redox-dependent intrinsic apoptosis pathway in vitro. These data implicates that AOPPs may represent a novel pathogenic factor that contributes to RA progression. Targeting AOPPs-triggered cellular mechanisms might emerge as a promising therapeutic option for patients with RA.

  13. Mirror Advanced Reactor Study interim design report

    International Nuclear Information System (INIS)

    1983-04-01

    The status of the design of a tenth-of-a-kind commercial tandem-mirror fusion reactor is described at the midpoint of a two-year study. When completed, the design is to serve as a strategic goal for the mirror fusion program. The main objectives of the Mirror Advanced Reactor Study (MARS) are: (1) to design an attractive tandem-mirror fusion reactor producing electricity and synfuels (in alternate versions), (2) to identify key development and technology needs, and (3) to exploit the potential of fusion for safety, low activation, and simple disposal of radioactive waste. In the first year we have emphasized physics and engineering of the central cell and physics of the end cell. Design optimization and trade studies are continuing, and we expect additional modifications in the end cells to further improve the performance of the final design

  14. Mirror Advanced Reactor Study interim design report

    Energy Technology Data Exchange (ETDEWEB)

    1983-04-01

    The status of the design of a tenth-of-a-kind commercial tandem-mirror fusion reactor is described at the midpoint of a two-year study. When completed, the design is to serve as a strategic goal for the mirror fusion program. The main objectives of the Mirror Advanced Reactor Study (MARS) are: (1) to design an attractive tandem-mirror fusion reactor producing electricity and synfuels (in alternate versions), (2) to identify key development and technology needs, and (3) to exploit the potential of fusion for safety, low activation, and simple disposal of radioactive waste. In the first year we have emphasized physics and engineering of the central cell and physics of the end cell. Design optimization and trade studies are continuing, and we expect additional modifications in the end cells to further improve the performance of the final design.

  15. A Two Stage Solution Procedure for Production Planning System with Advance Demand Information

    Science.gov (United States)

    Ueno, Nobuyuki; Kadomoto, Kiyotaka; Hasuike, Takashi; Okuhara, Koji

    We model for ‘Naiji System’ which is a unique corporation technique between a manufacturer and suppliers in Japan. We propose a two stage solution procedure for a production planning problem with advance demand information, which is called ‘Naiji’. Under demand uncertainty, this model is formulated as a nonlinear stochastic programming problem which minimizes the sum of production cost and inventory holding cost subject to a probabilistic constraint and some linear production constraints. By the convexity and the special structure of correlation matrix in the problem where inventory for different periods is not independent, we propose a solution procedure with two stages which are named Mass Customization Production Planning & Management System (MCPS) and Variable Mesh Neighborhood Search (VMNS) based on meta-heuristics. It is shown that the proposed solution procedure is available to get a near optimal solution efficiently and practical for making a good master production schedule in the suppliers.

  16. Advances in Wound Healing: A Review of Current Wound Healing Products

    Directory of Open Access Journals (Sweden)

    Patrick S. Murphy

    2012-01-01

    Full Text Available Successful wound care involves optimizing patient local and systemic conditions in conjunction with an ideal wound healing environment. Many different products have been developed to influence this wound environment to provide a pathogen-free, protected, and moist area for healing to occur. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. This review of the current state of the art in wound-healing products looks at the latest applications of silver in microbial prophylaxis and treatment, including issues involving resistance and side effects, the latest uses of negative pressure wound devices, advanced dressings and skin substitutes, biologic wound products including growth factor applications, and hyperbaric oxygen as an adjunct in wound healing. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing.

  17. Application of advanced methods for the prognosis of production energy consumption

    International Nuclear Information System (INIS)

    Stetter, R; Witczak, P; Spindler, C; Hertel, J; Staiger, B

    2014-01-01

    This paper, based on a current research project, describes the application of advanced methods that are frequently used in fault-tolerance control and addresses the issue of the prognosis of energy efficiency. Today, the energy a product requires during its operation is the subject of many activities in research and development. However, the energy necessary for the production of goods is very often not analysed in comparable depth. In the field of electronics, studies come to the conclusion that about 80% of the total energy used by a product is from its production [1]. The energy consumption in production is determined very early in the product development process by designers and engineers, for example through selection of raw materials, explicit and implicit requirements concerning the manufacturing and assembly processes, or through decisions concerning the product architecture. Today, developers and engineers have at their disposal manifold design and simulation tools which can help to predict the energy consumption during operation relatively accurately. In contrast, tools with the objective to predict the energy consumption in production and disposal are not available. This paper aims to present an explorative study of the use of methods such as Fuzzy Logic to predict the production energy consumption early in the product development process

  18. Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

    Science.gov (United States)

    Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

    2015-01-01

    With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

  19. Systems biology of yeast: enabling technology for development of cell factories for production of advanced biofuels.

    Science.gov (United States)

    de Jong, Bouke; Siewers, Verena; Nielsen, Jens

    2012-08-01

    Transportation fuels will gradually shift from oil based fuels towards alternative fuel resources like biofuels. Current bioethanol and biodiesel can, however, not cover the increasing demand for biofuels and there is therefore a need for advanced biofuels with superior fuel properties. Novel cell factories will provide a production platform for advanced biofuels. However, deep cellular understanding is required for improvement of current biofuel cell factories. Fast screening and analysis (-omics) methods and metabolome-wide mathematical models are promising techniques. An integrated systems approach of these techniques drives diversity and quantity of several new biofuel compounds. This review will cover the recent technological developments that support improvement of the advanced biofuels 1-butanol, biodiesels and jetfuels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Base Stock Policy in a Join-Type Production Line with Advanced Demand Information

    Science.gov (United States)

    Hiraiwa, Mikihiko; Tsubouchi, Satoshi; Nakade, Koichi

    Production control such as the base stock policy, the kanban policy and the constant work-in-process policy in a serial production line has been studied by many researchers. Production lines, however, usually have fork-type, join-type or network-type figures. In addition, in most previous studies on production control, a finished product is required at the same time as arrival of demand at the system. Demand information is, however, informed before due date in practice. In this paper a join-type (assembly) production line under base stock control with advanced demand information in discrete time is analyzed. The recursive equations for the work-in-process are derived. The heuristic algorithm for finding appropriate base stock levels of all machines at short time is proposed and the effect of advanced demand information is examined by simulation with the proposed algorithm. It is shown that the inventory cost can decreases with little backlogs by using the appropriate amount of demand information and setting appropriate base stock levels.

  1. Biofuels Fuels Technology Pathway Options for Advanced Drop-in Biofuels Production

    Energy Technology Data Exchange (ETDEWEB)

    Kevin L Kenney

    2011-09-01

    Advanced drop-in hydrocarbon biofuels require biofuel alternatives for refinery products other than gasoline. Candidate biofuels must have performance characteristics equivalent to conventional petroleum-based fuels. The technology pathways for biofuel alternatives also must be plausible, sustainable (e.g., positive energy balance, environmentally benign, etc.), and demonstrate a reasonable pathway to economic viability and end-user affordability. Viable biofuels technology pathways must address feedstock production and environmental issues through to the fuel or chemical end products. Potential end products include compatible replacement fuel products (e.g., gasoline, diesel, and JP8 and JP5 jet fuel) and other petroleum products or chemicals typically produced from a barrel of crude. Considering the complexity and technology diversity of a complete biofuels supply chain, no single entity or technology provider is capable of addressing in depth all aspects of any given pathway; however, all the necessary expert entities exist. As such, we propose the assembly of a team capable of conducting an in-depth technology pathway options analysis (including sustainability indicators and complete LCA) to identify and define the domestic biofuel pathways for a Green Fleet. This team is not only capable of conducting in-depth analyses on technology pathways, but collectively they are able to trouble shoot and/or engineer solutions that would give industrial technology providers the highest potential for success. Such a team would provide the greatest possible down-side protection for high-risk advanced drop-in biofuels procurement(s).

  2. Skin autofluorescence, a marker of advanced glycation end products and oxidative stress, is increased in recently preeclamptic women

    NARCIS (Netherlands)

    Blaauw, Judith; Smit, Andries J.; van Pampus, Maria G.; van Doormaal, Jasper J.; Aarnoudse, Jan G.; Rakhorst, Gerhard; Graaff, Reindert

    Objective: Advanced glycation end-products are considered to be markers of oxidative stress and to be involved in the atherosclerotic process. We investigated skin autofluorescence, which reflected advanced glycation end-product accumulation, in recently preeclamptic women and its relationship with

  3. 78 FR 67401 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Advanced Media...

    Science.gov (United States)

    2013-11-12

    ... Production Act of 1993--Advanced Media Workflow Association, Inc. Notice is hereby given that, on September 24, 2013, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et seq. (``the Act''), Advanced Media Workflow Association, Inc. has filed written...

  4. 76 FR 66324 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Advanced Media...

    Science.gov (United States)

    2011-10-26

    ... Production Act of 1993--Advanced Media Workflow Association, Inc. Notice is hereby given that, on September 26, 2011, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et seq. (``the Act''), Advanced Media Workflow Association, Inc. has filed written...

  5. 78 FR 22297 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Advanced Media...

    Science.gov (United States)

    2013-04-15

    ... Production Act of 1993--Advanced Media Workflow Association, Inc. Notice is hereby given that, on March 20, 2013, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et seq. (``the Act''), Advanced Media Workflow Association, Inc. has filed written...

  6. Skin advanced glycation end products in HIV infection are increased and predictive of development of cardiovascular events

    NARCIS (Netherlands)

    Sprenger, Herman G.; Bierman, Wouter F.; Martes, Melanie I.; Graaff, Reindert; van der Werf, Tjip S.; Smit, Andries J.

    2017-01-01

    Objective: HIV-1 infection is associated with an increased cardiovascular disease (CVD) risk. Advanced glycation end products are formed as stable markers of glycaemic and oxidative stress. Skin autofluorescence (SAF) as marker of accumulated advanced glycation end products is increased and

  7. Reference values for the Chinese population of skin autofluorescence as a marker of advanced glycation end products accumulated in tissue

    NARCIS (Netherlands)

    Yue, X.; Hu, H.; Koetsier, M.; Graaff, R.; Han, C.

    Aim Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the

  8. Advanced Multi-Product Coal Utilization By-Product Processing Plant

    Energy Technology Data Exchange (ETDEWEB)

    Thomas Robl; John Groppo

    2009-06-30

    The overall objective of this project is to design, construct, and operate an ash beneficiation facility that will generate several products from coal combustion ash stored in a utility ash pond. The site selected is LG&E's Ghent Station located in Carroll County, Kentucky. The specific site under consideration is the lower ash pond at Ghent, a closed landfill encompassing over 100 acres. Coring activities revealed that the pond contains over 7 million tons of ash, including over 1.5 million tons of coarse carbon and 1.8 million tons of fine (<10 {micro}m) glassy pozzolanic material. These potential products are primarily concentrated in the lower end of the pond adjacent to the outlet. A representative bulk sample was excavated for conducting laboratory-scale process testing while a composite 150 ton sample was also excavated for demonstration-scale testing at the Ghent site. A mobile demonstration plant with a design feed rate of 2.5 tph was constructed and hauled to the Ghent site to evaluate unit processes (i.e. primary classification, froth flotation, spiral concentration, secondary classification, etc.) on a continuous basis to determine appropriate scale-up data. Unit processes were configured into four different flowsheets and operated at a feed rate of 2.5 tph to verify continuous operating performance and generate bulk (1 to 2 tons) products for product testing. Cementitious products were evaluated for performance in mortar and concrete as well as cement manufacture process addition. All relevant data from the four flowsheets was compiled to compare product yields and quality while preliminary flowsheet designs were generated to determine throughputs, equipment size specifications and capital cost summaries. A detailed market study was completed to evaluate the potential markets for cementitious products. Results of the study revealed that the Ghent local fly ash market is currently oversupplied by more than 500,000 tpy and distant markets (i

  9. Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Louise J. N. Jensen

    2015-01-01

    Full Text Available The receptor of advanced glycation end products (RAGE and its ligands are linked to the pathogenesis of coronary artery disease (CAD, and circulating soluble receptor of advanced glycation end products (sRAGE, reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS. The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently.

  10. Advanced concepts for waste management and nuclear energy production in the EURATOM fifth framework programme

    International Nuclear Information System (INIS)

    Hugon, M.; Bhatnagar, V.P.; Martin Bermejo, J.

    2001-01-01

    This paper summarises the objectives of the research projects on Partitioning and Transmutation (P and T) of long lived radionuclides in nuclear waste and advanced systems for nuclear energy production in the key action on nuclear fission of the EURATOM Fifth Framework Programme (FP5) (1998-2002). As these FP5 projects cover the main aspects of P and T, they should provide a basis for evaluating the practicability, on an industrial scale, of P and T for reducing the amount of long lived radionuclides to be disposed of. Concerning advanced concepts, a cluster of projects is addressing the key technical issues to be solved before implementing High Temperature Reactors (HTRs) commercially for energy production. Finally, the European Commission(tm)s proposal for a New Framework Programme (2002-2006) is briefly outlined. (author)

  11. Production of High Energy Aviation Fuels from Advanced Coal Liquids. Phase 1.

    Science.gov (United States)

    1987-04-01

    percentages of those aromatic molecules and may become one of the prime sources of the feedstocks needed for production of advanced fuels. Coal tars ...HRS) was an automated pilot plant capable of studying the processing associated with feedstocks such as petroleum, heavy oils, tars , coal liquids... coal that is rich in aromatics , producing liquids from it under the proper conditions, hydrotreating the aromatics to naphthenes and concentrating

  12. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    OpenAIRE

    Li,D.X.; Deng,T.Z.; Lv,J.; Ke,J.

    2014-01-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts t...

  13. Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS?

    OpenAIRE

    Garg, Deepika; Merhi, Zaher

    2015-01-01

    PCOS is the most common cause of anovulation in reproductive-aged women with 70% experiencing ovulatory problems. Advanced glycation end products are highly reactive molecules that are formed by non-enzymatic reactions of sugars with proteins, nucleic acids and lipids. AGEs are also present in a variety of diet where substantial increase in AGEs can result due to thermal processing and modifications of food. Elevation in bodily AGEs, produced endogenously or absorbed exogenously from high-AGE...

  14. Ultraclean Fuels Production and Utilization for the Twenty-First Century: Advances toward Sustainable Transportation Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Elise B.; Liu, Zhong-Wen; Liu, Zhao-Tie

    2013-11-21

    Ultraclean fuels production has become increasingly important as a method to help decrease emissions and allow the introduction of alternative feed stocks for transportation fuels. Established methods, such as Fischer-Tropsch, have seen a resurgence of interest as natural gas prices drop and existing petroleum resources require more intensive clean-up and purification to meet stringent environmental standards. This review covers some of the advances in deep desulfurization, synthesis gas conversion into fuels and feed stocks that were presented at the 245th American Chemical Society Spring Annual Meeting in New Orleans, LA in the Division of Energy and Fuels symposium on "Ultraclean Fuels Production and Utilization".

  15. Advanced Shape Memory Technology to Reshape Product Design, Manufacturing and Recycling

    Directory of Open Access Journals (Sweden)

    Wen Guang Yang

    2014-08-01

    Full Text Available This paper provides a brief review on the advanced shape memory technology (ASMT with a focus on polymeric materials. In addition to introducing the concept and fundamentals of the ASMT, the potential applications of the ASMT either alone or integrated with an existing mature technique (such as, 3D printing, quick response (QR code, lenticular lens and phenomena (e.g., wrinkling and stress-enhanced swelling effect in product design, manufacturing, and recycling are demonstrated. It is concluded that the ASMT is indeed able to provide a range of powerful approaches to reshape part of the life cycle or the whole life cycle of products.

  16. LLNL medical and industrial laser isotope separation: large volume, low cost production through advanced laser technologies

    International Nuclear Information System (INIS)

    Comaskey, B.; Scheibner, K. F.; Shaw, M.; Wilder, J.

    1998-01-01

    The goal of this LDRD project was to demonstrate the technical and economical feasibility of applying laser isotope separation technology to the commercial enrichment (>lkg/y) of stable isotopes. A successful demonstration would well position the laboratory to make a credible case for the creation of an ongoing medical and industrial isotope production and development program at LLNL. Such a program would establish LLNL as a center for advanced medical isotope production, successfully leveraging previous LLNL Research and Development hardware, facilities, and knowledge

  17. Efficiency and cost advantages of an advanced-technology nuclear electrolytic hydrogen-energy production facility

    Science.gov (United States)

    Donakowski, T. D.; Escher, W. J. D.; Gregory, D. P.

    1977-01-01

    The concept of an advanced-technology (viz., 1985 technology) nuclear-electrolytic water electrolysis facility was assessed for hydrogen production cost and efficiency expectations. The facility integrates (1) a high-temperature gas-cooled nuclear reactor (HTGR) operating a binary work cycle, (2) direct-current (d-c) electricity generation via acyclic generators, and (3) high-current-density, high-pressure electrolyzers using a solid polymer electrolyte (SPE). All subsystems are close-coupled and optimally interfaced for hydrogen production alone (i.e., without separate production of electrical power). Pipeline-pressure hydrogen and oxygen are produced at 6900 kPa (1000 psi). We found that this advanced facility would produce hydrogen at costs that were approximately half those associated with contemporary-technology nuclear electrolysis: $5.36 versus $10.86/million Btu, respectively. The nuclear-heat-to-hydrogen-energy conversion efficiency for the advanced system was estimated as 43%, versus 25% for the contemporary system.

  18. Advanced Chemical Reactor Technologies for Biodiesel Production from Vegetable Oils - A Review

    Directory of Open Access Journals (Sweden)

    Luqman Buchori

    2016-10-01

    Full Text Available Biodiesel is an alternative biofuel that can replace diesel oil without requiring modifications to the engine and advantageously produces cleaner emissions. Biodiesel can be produced through transesterification process between oil or fat and alcohol to form esters and glycerol. The transesterification can be carried out with or without a catalyst. The catalyzed production of biodiesel can be performed by using homogeneous, heterogeneous and enzyme. Meanwhile, non-catalytic transesterification with supercritical alcohol provides a new way of producing biodiesel. Microwave and ultrasound assisted transesterification significantly can reduce reaction time as well as improve product yields. Another process, a plasma technology is promising for biodiesel synthesis from vegetable oils due to very short reaction time, no soap formation and no glycerol as a by-product. This paper reviews briefly the technologies on transesterification reaction for biodiesel production using homogeneous, heterogeneous, and enzyme catalysts, as well as advanced methods (supercritical, microwave, ultrasonic, and plasma technology. Advantages and disadvantages of each method were described comprehensively. Copyright © 2016 BCREC GROUP. All rights reserved Received: 17th May 2016; Revised: 20th September 2016; Accepted: 20th September 2016 How to Cite: Buchori, L., Istadi, I., Purwanto, P. (2016. Advanced Chemical Reactor Technologies for Biodiesel Production from Vegetable Oils - A Review. Bulletin of Chemical Reaction Engineering & Catalysis, 11 (3: 406-430 (doi:10.9767/bcrec.11.3.490.406-430 Permalink/DOI: http://doi.org/10.9767/bcrec.11.3.490.406-430

  19. Advanced Multi-Product Coal Utilization By-Product Processing Plant

    Energy Technology Data Exchange (ETDEWEB)

    Andrew Jackura; John Groppo; Thomas Robl

    2006-12-31

    The objective of the project is to build a multi-product ash beneficiation plant at Kentucky Utilities 2,200-MW Ghent Generating Station, located in Carroll County, Kentucky. This part of the study includes an investigation of the secondary classification characteristics of the ash feedstock excavated from the lower ash pond at Ghent Station. The market study for the products of the processing plant (Subtask 1.6), conducted by Cemex, is reported herein. The study incorporated simplifying assumptions and focused only on pozzolan and ultra fine fly ash (UFFA). It found that the market for pozzolan in the Ghent area was oversupplied, with resultant poor pricing structure. Reachable export markets for the Ghent pozzolan market were mostly locally served with the exception of Florida. It was concluded that a beneficiated material for that market may be at a long term disadvantage. The market for the UFFA was more complex as this material would compete with other beneficiated ash and potential metakaolin and silica fume as well. The study concluded that this market represented about 100,000 tons of sales per year and, although lucrative, represented a widely dispersed niche market.

  20. Advanced Multi-Product Coal Utilization By-Product Processing Plant

    Energy Technology Data Exchange (ETDEWEB)

    Thomas Robl; John Groppo

    2007-03-31

    The objective of the project is to build a multi-product ash beneficiation plant at Kentucky Utilities 2,200-MW Ghent Generating Station, located in Carroll County, Kentucky. Phase 1 was completed successfully, but the project did not continue on to Phase 2 due to withdrawal of CEMEX from the project. Attempts at replacing CEMEX were not successful. Problematic to the continuation of the project was its location in the Ohio Valley which is oversupplied and has low prices for fly ash and the change in CEMEX priorities due to merger and acquisitions. Thus, CAER concurred with the DOE to conclude the project at the end of Budget Period 1, March 31, 2007.

  1. Production and Utilization of Hemicelluloses from Renewable Resources for Sustainable Advanced Products

    DEFF Research Database (Denmark)

    Sárossy, Zsuzsa

    to the possibility of using hemicelluloses for special polysaccharide film applications in the packaging sector, starting from hemicellulose isolations from a side product of agricultural processes, hemicellulose characterization and assessing material properties and the potential use of hemicellulose films in later...... applications. First, water-soluble hemicelluloses of rye bran were extracted with a high-temperature treatment combined with enzymatic starch removal. After the hot water extraction, nonsoluble fibers and protein fractions were separated and the washed fiber fraction was further treated with alkali (Na.......35, while the waterextracted material had an Ara/Xyl ratio of 0.54. In order to analyse the monosaccharide composition of the isolated hemicelluloses, a method based on gas chromatography-mass spectrometry analysis of acetylated methyl glycosides was developed. The derivatives of the monosaccharides...

  2. Development of an advanced, continuous mild gasification process for the production of co-products (Task 1), Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Knight, R.A.; Gissy, J.L.; Onischak, M.; Babu, S.P.; Carty, R.H. (Institute of Gas Technology, Chicago, IL (United States)); Duthie, R.G. (Bechtel Group, Inc., San Francisco, CA (United States)); Wootten, J.M. (Peabody Holding Co., Inc., St. Louis, MO (United States))

    1991-09-01

    Under US DOE sponsorship, a project team consisting of the Institute of Gas Technology, Peabody Holding Company, and Bechtel Group, Inc. has been developing an advanced, mild gasification process to process all types of coal and to produce solid and condensable liquid co-products that can open new markets for coal. The three and a half year program (September 1987 to June 1991) consisted of investigations in four main areas. These areas are: (1) Literature Survey of Mild Gasification Processes, Co-Product Upgrading and Utilization, and Market Assessment; (2) Mild Gasification Technology Development: Process Research Unit Tests Using Slipstream Sampling; (3) Bench-Scale Char Upgrading Study; (4) Mild Gasification Technology Development: System Integration Studies. In this report, the literature and market assessment of mild gasification processes are discussed.

  3. Differential effects between amphoterin and advanced glycation end products on colon cancer cells.

    Science.gov (United States)

    Kuniyasu, Hiroki; Chihara, Yoshitomo; Kondo, Hideaki

    2003-05-10

    Amphoterin is 1 ligand of the receptor for advanced glycation end products (RAGE). We studied expression of amphoterin and RAGE mRNA and proteins in colorectal carcinoma cells and investigated their associations with the invasive activities of cells exposed to advanced glycation end products (AGE). Expression of RAGE and amphoterin was examined in 4 colorectal carcinoma cell lines. All cell lines expressed both RAGE and amphoterin. The effects of RAGE and amphoterin on cell growth (MTT assay), migration (wound healing assay) and invasion (in vitro invasion assay) were tested by treatment of cells with RAGE and amphoterin antisense S-oligodeoxynucleotides (ODNs). Cell growth, migration and invasion were inhibited significantly in Colo320 and WiDr carcinoma cells treated with RAGE and amphoterin antisense S-ODNs compared with sense-treated cells. Differences in ligand activity between amphoterin and AGE were examined with AGE-bovine serum albumin (BSA). AGE-BSA decreased cell growth, migration and invasion of amphoterin antisense S-ODN-treated Colo320 and WiDr cells compared with those of cells treated with Colo320 conditioned medium. Phosphorylation of extracellular signal-regulated kinase-1/2, Rac1 and AKT and production of matrix metalloproteinase 9 were increased to a greater degree by amphoterin than by AGE-BSA. In contrast, production of inducible nitric oxide synthase and nuclear factor-kappaBp65 were increased to a greater degree by AGE-BSA than by amphoterin. Copyright 2003 Wiley-Liss, Inc.

  4. Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference.

    Science.gov (United States)

    Yu, Lawrence X; Baker, Jeffrey; Berlam, Susan C; Boam, Ashley; Brandreth, E J; Buhse, Lucinda; Cosgrove, Thomas; Doleski, David; Ensor, Lynne; Famulare, Joseph; Ganapathy, Mohan; Grampp, Gustavo; Hussong, David; Iser, Robert; Johnston, Gordon; Kesisoglou, Filippos; Khan, Mansoor; Kozlowski, Steven; Lacana, Emanuela; Lee, Sau L; Miller, Stephen; Miksinski, Sarah Pope; Moore, Christine M V; Mullin, Theresa; Raju, G K; Raw, Andre; Rosencrance, Susan; Rosolowsky, Mark; Stinavage, Paul; Thomas, Hayden; Wesdyk, Russell; Windisch, Joerg; Vaithiyalingam, Sivakumar

    2015-07-01

    On September 16 and 17, 2014, the Food and Drug Administration (FDA) and Product Quality Research Institute (PQRI) inaugurated their Conference on Evolving Product Quality. The Conference is conceived as an annual forum in which scientists from regulatory agencies, industry, and academia may exchange viewpoints and work together to advance pharmaceutical quality. This Conference Summary Report highlights key topics of this conference, including (1) risk-based approaches to pharmaceutical development, manufacturing, regulatory assessment, and post-approval changes; (2) FDA-proposed quality metrics for products, facilities, and quality management systems; (3) performance-based quality assessment and clinically relevant specifications; (4) recent developments and implementation of continuous manufacturing processes, question-based review, and European Medicines Agency (EMA)-FDA pilot for Quality-by-Design (QbD) applications; and (5) breakthrough therapies, biosimilars, and international harmonization, focusing on ICH M7 and Q3D guidelines. The second FDA/PQRI conference on advancing product quality is planned for October 5-7, 2015.

  5. Advancing alternatives analysis: The role of predictive toxicology in selecting safer chemical products and processes.

    Science.gov (United States)

    Malloy, Timothy; Zaunbrecher, Virginia; Beryt, Elizabeth; Judson, Richard; Tice, Raymond; Allard, Patrick; Blake, Ann; Cote, Ila; Godwin, Hilary; Heine, Lauren; Kerzic, Patrick; Kostal, Jakub; Marchant, Gary; McPartland, Jennifer; Moran, Kelly; Nel, Andre; Ogunseitan, Oladele; Rossi, Mark; Thayer, Kristina; Tickner, Joel; Whittaker, Margaret; Zarker, Ken

    2017-09-01

    Alternatives analysis (AA) is a method used in regulation and product design to identify, assess, and evaluate the safety and viability of potential substitutes for hazardous chemicals. It requires toxicological data for the existing chemical and potential alternatives. Predictive toxicology uses in silico and in vitro approaches, computational models, and other tools to expedite toxicological data generation in a more cost-effective manner than traditional approaches. The present article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents 4 recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA, adopting a stepwise process to employing predictive toxicology in AA beginning with prioritization of chemicals of concern, leveraging existing resources to advance the integration of predictive toxicology into the practice of AA, and supporting transdisciplinary efforts. The further incorporation of predictive toxicology into AA would advance the ability of companies and regulators to select alternatives to harmful ingredients, and potentially increase the use of predictive toxicology in regulation more broadly. Integr Environ Assess Manag 2017;13:915-925. © 2017 SETAC. © 2017 SETAC.

  6. Acute effects of Advance: a potential reduced exposure product for smokers.

    Science.gov (United States)

    Breland, A B; Evans, S E; Buchhalter, A R; Eissenberg, T

    2002-12-01

    To examine the acute effects of Advance, a potential reduced exposure product (PREP) for smokers marketed as a means to reduce exposure to toxic gases and tobacco specific nitrosamines. Latin square ordered, three condition, laboratory based, crossover design with 20 smokers of light or ultra-light cigarettes (15 or more cigarettes/day). In each 2.5 hour condition, participants completed an 8-puff smoking bout from their own brand, Advance, or an unlit cigarette (that is, sham smoking) every 30 minutes for a total of four bouts. Subject rated measures of tobacco/nicotine withdrawal; carbon monoxide (CO), and heart rate; plasma nicotine concentrations. Relative to own brand, Advance produced similar withdrawal suppression and heart rate increase, lower CO boost, and higher plasma nicotine concentrations. PREPs for smokers need to be evaluated using a comprehensive strategy that includes empirical examination of acute and long term effects. Adequate withdrawal suppression and potentially lower concentrations of CO associated with Advance use are positive factors, although higher nicotine concentrations do not constitute "reduced exposure". Overall, longer exposure periods are necessary to determine carcinogen delivery. PREP evaluation is complex and should be completed objectively.

  7. Advanced Therapy Medicinal Products for Rare Diseases: State of Play of Incentives Supporting Development in Europe

    Directory of Open Access Journals (Sweden)

    Andreas M. Farkas

    2017-05-01

    Full Text Available In 2008, the European Union introduced the Advanced Medicines Regulation aiming to improve regulation of advanced therapy medicinal products (ATMPs. We applied the ATMPs classification definitions in this Regulation to understand the link of this emerging group of medicinal products and the use of the Orphan Regulation. A total of 185 products that can be classified as ATMPs based on this Regulation have been submitted for orphan designation. Prior to its introduction in 2008, 4.5% of the products submitted for orphan designation met these criteria. This percentage went up to 15% after 2008. We analyzed several parameters associated with active ATMP ODDs focusing on sponsor type and EU-Member State origin, therapeutic area targeted, and ATMP classification [i.e., somatic cell therapy medicinal product, tissue-engineered product (TEP, or gene therapy medicinal product (GTMP] and the use of regulatory services linked to incentives such as the use of protocol assistance (PA and other Committees [Committee for Advanced Therapies (CAT and the Pediatric Committee]. The aim here was to gain insight on the use of different services. The UK submits the largest number of ATMPs for ODD representing ~30% of the total to date. Few submissions have been received from central and Eastern European Member States as well as some of the larger Member States such as Germany (3.6%. ATMPs ODDs were primarily GTMPs (48.7% and SCTMPs (43.3%. TEPs only represented 8% of all submissions for this medicinal class. This is different from non-ODDs ATMPs where GTMPs make only 20% of ATMPs. A total of 11.7% of ATMP ODDs had received formal CAT classification. A total of 29.8% of all orphan drug (OD ATMPs requested PA. A total of 71.8% did not have an agreed pediatric investigation plan (PIP. Four products (Glybera one PA; Zalmoxis two; Holoclar one; Strimvelis three have received a marketing authorization (MAA and a 10-year market exclusivity. Strimvelis also completed their

  8. Advanced Therapy Medicinal Products for Rare Diseases: State of Play of Incentives Supporting Development in Europe.

    Science.gov (United States)

    Farkas, Andreas M; Mariz, Segundo; Stoyanova-Beninska, Violeta; Celis, Patrick; Vamvakas, Spiros; Larsson, Kristina; Sepodes, Bruno

    2017-01-01

    In 2008, the European Union introduced the Advanced Medicines Regulation aiming to improve regulation of advanced therapy medicinal products (ATMPs). We applied the ATMPs classification definitions in this Regulation to understand the link of this emerging group of medicinal products and the use of the Orphan Regulation. A total of 185 products that can be classified as ATMPs based on this Regulation have been submitted for orphan designation. Prior to its introduction in 2008, 4.5% of the products submitted for orphan designation met these criteria. This percentage went up to 15% after 2008. We analyzed several parameters associated with active ATMP ODDs focusing on sponsor type and EU-Member State origin, therapeutic area targeted, and ATMP classification [i.e., somatic cell therapy medicinal product, tissue-engineered product (TEP), or gene therapy medicinal product (GTMP)] and the use of regulatory services linked to incentives such as the use of protocol assistance (PA) and other Committees [Committee for Advanced Therapies (CAT) and the Pediatric Committee]. The aim here was to gain insight on the use of different services. The UK submits the largest number of ATMPs for ODD representing ~30% of the total to date. Few submissions have been received from central and Eastern European Member States as well as some of the larger Member States such as Germany (3.6%). ATMPs ODDs were primarily GTMPs (48.7%) and SCTMPs (43.3%). TEPs only represented 8% of all submissions for this medicinal class. This is different from non-ODDs ATMPs where GTMPs make only 20% of ATMPs. A total of 11.7% of ATMP ODDs had received formal CAT classification. A total of 29.8% of all orphan drug (OD) ATMPs requested PA. A total of 71.8% did not have an agreed pediatric investigation plan (PIP). Four products (Glybera one PA; Zalmoxis two; Holoclar one; Strimvelis three) have received a marketing authorization (MAA) and a 10-year market exclusivity. Strimvelis also completed their PIP

  9. Advances in solid-catalytic and non-catalytic technologies for biodiesel production

    International Nuclear Information System (INIS)

    Islam, Aminul; Taufiq-Yap, Yun Hin; Chan, Eng-Seng; Moniruzzaman, M.; Islam, Saiful; Nabi, Md. Nurun

    2014-01-01

    Highlights: • The recent technologies for promoting biodiesel synthesis were elucidated. • The design of catalyst consideration of biodiesel production was proposed. • The recent advances and remaining difficulties in biodiesel synthesis were outlined. • The future research trend in biodiesel synthesis was highlighted. - Abstract: The insecure supply of fossil fuel coerces the scientific society to keep a vision to boost investments in the renewable energy sector. Among the many renewable fuels currently available around the world, biodiesel offers an immediate impact in our energy. In fact, a huge interest in related research indicates a promising future for the biodiesel technology. Heterogeneous catalyzed production of biodiesel has emerged as a preferred route as it is environmentally benign needs no water washing and product separation is much easier. The number of well-defined catalyst complexes that are able to catalyze transesterification reactions efficiently has been significantly expanded in recent years. The activity of catalysts, specifically in application to solid acid/base catalyst in transesterification reaction depends on their structure, strength of basicity/acidity, surface area as well as the stability of catalyst. There are various process intensification technologies based on the use of alternate energy sources such as ultrasound and microwave. The latest advances in research and development related to biodiesel production is represented by non-catalytic supercritical method and focussed exclusively on these processes as forthcoming transesterification processes. The latest developments in this field featuring highly active catalyst complexes are outlined in this review. The knowledge of more extensive research on advances in biofuels will allow a deeper insight into the mechanism of these technologies toward meeting the critical energy challenges in future

  10. Production of advanced materials by methods of self-propagating high-temperature synthesis

    CERN Document Server

    Tavadze, Giorgi F

    2013-01-01

    This translation from the original Russian book outlines the production of a variety of materials by methods of self-propagating high-temperature synthesis (SHS). The types of materials discussed include: hard, refractory, corrosion and wear-resistant materials, as well as other advanced and speciality materials. The authors address the issue of optimal parameters for SHS reactions occurring during processes involving a preliminary metallothermic reduction stage, and they calculate this using thermodynamic approaches. In order to confirm the effectiveness of this approach, the authors describe experiments focussing on the synthesis of elemental crysalline boron, boron carbides and nitrides. Other parts of this brief include theoretical and experimental results on single-stage production of hard alloys on the basis of titanium and zirconium borides, as well as macrokinetics of degassing and compaciton of SHS-products.This brief is suitable for academics, as well as those working in industrial manufacturing com...

  11. Emerging technology: A key enabler for modernizing pharmaceutical manufacturing and advancing product quality.

    Science.gov (United States)

    O'Connor, Thomas F; Yu, Lawrence X; Lee, Sau L

    2016-07-25

    Issues in product quality have produced recalls and caused drug shortages in United States (U.S.) in the past few years. These quality issues were often due to outdated manufacturing technologies and equipment as well as lack of an effective quality management system. To ensure consistent supply of safe, effective and high-quality drug products available to the patients, the U.S. Food and Drug Administration (FDA) supports modernizing pharmaceutical manufacturing for improvements in product quality. Specifically, five new initiatives are proposed here to achieve this goal. They include: (i) advancing regulatory science for pharmaceutical manufacturing; (ii) establishing a public-private institute for pharmaceutical manufacturing innovation; (iii) creating incentives for investment in the technological upgrade of manufacturing processes and facilities; (iv) leveraging external expertise for regulatory quality assessment of emerging technologies; and (v) promoting the international harmonization of approaches for expediting the global adoption of emerging technologies. Published by Elsevier B.V.

  12. Advanced turbine systems program conceptual design and product development. Annual report, August 1994--July 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    This report summarizes the tasks completed under this project during the period from August 1, 1994 through July 31, 1994. The objective of the study is to provide the conceptual design and product development plan for an ultra high efficiency, environmentally superior and cost-competitive industrial gas turbine system to be commercialized by the year 2000. The tasks completed include a market study for the advanced turbine system; definition of an optimized recuperated gas turbine as the prime mover meeting the requirements of the market study and whose characteristics were, in turn, used for forecasting the total advanced turbine system (ATS) future demand; development of a program plan for bringing the ATS to a state of readiness for field test; and demonstration of the primary surface recuperator ability to provide the high thermal effectiveness and low pressure loss required to support the proposed ATS cycle.

  13. Recent advances and strategies in process and strain engineering for the production of butyric acid by microbial fermentation.

    Science.gov (United States)

    Luo, Hongzhen; Yang, Rongling; Zhao, Yuping; Wang, Zhaoyu; Liu, Zheng; Huang, Mengyu; Zeng, Qingwei

    2018-04-01

    Butyric acid is an important platform chemical, which is widely used in the fields of food, pharmaceutical, energy, etc. Microbial fermentation as an alternative approach for butyric acid production is attracting great attention as it is an environmentally friendly bioprocessing. However, traditional fermentative butyric acid production is still not economically competitive compared to chemical synthesis route, due to the low titer, low productivity, and high production cost. Therefore, reduction of butyric acid production cost by utilization of alternative inexpensive feedstock, and improvement of butyric acid production and productivity has become an important target. Recently, several advanced strategies have been developed for enhanced butyric acid production, including bioprocess techniques and metabolic engineering methods. This review provides an overview of advances and strategies in process and strain engineering for butyric acid production by microbial fermentation. Additionally, future perspectives on improvement of butyric acid production are also proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. ADVANCED MULTI-PRODUCT COAL UTILIZATION BY-PRODUCT PROCESSING PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Robert Jewell; Thomas Robl; John Groppo

    2005-03-01

    The objective of the project is to build a multi-product ash beneficiation plant at Kentucky Utilities 2,200-MW Ghent Generating Station, located in Carroll County, Kentucky. This part of the study includes the examination of the feedstocks for the beneficiation plant. The ash, as produced by the plant, and that stored in the lower pond were examined. The ash produced by the plant was found to be highly variable as the plant consumes high and low sulfur bituminous coal, in Units 1 and 2 and a mixture of subbituminous and bituminous coal in Units 3 and 4. The ash produced reflected this consisting of an iron-rich ({approx}24%, Fe{sub 2}O{sub 3}), aluminum rich ({approx}29% Al{sub 2}O{sub 3}) and high calcium (6%-7%, CaO) ash, respectively. The LOI of the ash typically was in the range of 5.5% to 6.5%, but individual samples ranged from 1% to almost 9%. The lower pond at Ghent is a substantial body, covering more than 100 acres, with a volume that exceeds 200 million cubic feet. The sedimentation, stratigraphy and resource assessment of the in place ash was investigated with vibracoring and three-dimensional, computer-modeling techniques. Thirteen cores to depths reaching nearly 40 feet, were retrieved, logged in the field and transported to the lab for a series of analyses for particle size, loss on ignition, petrography, x-ray diffraction, and x-ray fluorescence. Collected data were processed using ArcViewGIS, Rockware, and Microsoft Excel to create three-dimensional, layered iso-grade maps, as well as stratigraphic columns and profiles, and reserve estimations. The ash in the pond was projected to exceed 7 million tons and contain over 1.5 million tons of coarse carbon, and 1.8 million tons of fine (<10 {micro}m) glassy pozzolanic material. The size, quality and consistency of the ponded material suggests that it is the better feedstock for the beneficiation plant.

  15. Advances in the biotechnology of hydrogen production with the microalga Chlamydomonas reinhardtii.

    Science.gov (United States)

    Torzillo, Giuseppe; Scoma, Alberto; Faraloni, Cecilia; Giannelli, Luca

    2015-01-01

    Biological hydrogen production is being evaluated for use as a fuel, since it is a promising substitute for carbonaceous fuels owing to its high conversion efficiency and high specific energy content. The basic advantages of biological hydrogen production over other "green" energy sources are that it does not compete for agricultural land use, and it does not pollute, as water is the only by-product of the combustion. These characteristics make hydrogen a suitable fuel for the future. Among several biotechnological approaches, photobiological hydrogen production carried out by green microalgae has been intensively investigated in recent years. A select group of photosynthetic organisms has evolved the ability to harness light energy to drive hydrogen gas production from water. Of these, the microalga Chlamydomonas reinhardtii is considered one of the most promising eukaryotic H2 producers. In this model microorganism, light energy, H2O and H2 are linked by two excellent catalysts, the photosystem 2 (PSII) and the [FeFe]-hydrogenase, in a pathway usually referred to as direct biophotolysis. This review summarizes the main advances made over the past decade as an outcome of the discovery of the sulfur-deprivation process. Both the scientific and technical barriers that need to be overcome before H2 photoproduction can be scaled up to an industrial level are examined. Actual and theoretical limits of the efficiency of the process are also discussed. Particular emphasis is placed on algal biohydrogen production outdoors, and guidelines for an optimal photobioreactor design are suggested.

  16. Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

    Directory of Open Access Journals (Sweden)

    Abhishek Singh Nayyar

    2013-07-01

    Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

  17. Genetic Resources for Advanced Biofuel Production Described with the Gene Ontology

    Directory of Open Access Journals (Sweden)

    Trudy eTorto-Alalibo

    2014-10-01

    Full Text Available Dramatic increases in research in the area of microbial biofuel production coupled with high-throughput data generation on bioenergy-related microbes has led to a deluge of information in the scientific literature and in databases. Consolidating this information and making it easily accessible requires a unified vocabulary. The Gene Ontology (GO fulfills that requirement, as it is a well-developed structured vocabulary that describes the activities and locations of gene products in a consistent manner across all kingdoms of life. The Microbial Energy Gene Ontology (MENGO: http://www.mengo.biochem.vt.edu project is extending the GO to include new terms to describe microbial processes of interest to bioenergy production. Our effort has added over 600 bioenergy related terms to the Gene Ontology. These terms will aid in the comprehensive annotation of gene products from diverse energy-related microbial genomes. An area of microbial energy research that has received a lot of attention is microbial production of advanced biofuels. These include alcohols such as butanol, isopropanol, isobutanol, and fuels derived from fatty acids, isoprenoids, and polyhydroxyalkanoates. These fuels are superior to first generation biofuels (ethanol and biodiesel esterified from vegetable oil or animal fat, can be generated from non-food feedstock sources, can be used as supplements or substitutes for gasoline, diesel and jet fuels, and can be stored and distributed using existing infrastructure. Here we review the roles of genes associated with synthesis of advanced biofuels, and at the same time introduce the use of the GO to describe the functions of these genes in a standardized way.

  18. TREATMENT OF METAL-LADEN HAZARDOUS WASTES WITH ADVANCED CLEAN COAL TECHNOLOGY BY-PRODUCTS

    Energy Technology Data Exchange (ETDEWEB)

    James T. Cobb, Jr.; Ronald D. Neufeld; Jana Agostini

    1999-06-01

    This sixteenth quarterly report describes work done during the sixteenth three-month period of the University of Pittsburgh's project on the ''Treatment of Metal-Laden Hazardous Wastes with Advanced Clean Coal Technology By-Products.'' This report describes the activities of the project team during the reporting period. The principal work has focused upon new laboratory evaluation of samples from Phase 1, discussions with MAX Environmental Technologies, Inc., on the field work of Phase 2, giving a presentation, and making and responding to several outside contacts.

  19. A sustainable building product: advanced insulation panels obtained by recycling regional sheep’s wool

    Directory of Open Access Journals (Sweden)

    Daniela Bosia

    2011-04-01

    Full Text Available The article deal with an ongoing research aimed at developing an advanced self-bearing panel, fitted for thermal and acoustic insulation of buildings, derived from the reuse and recycling of local sheep wool. The development of a supply chain of environmentally friendly products (a self bearing panel made of 100% wool encourages, on the one hand, the use of a material so far classified in Italy as special waste and, on the one other, provides new opportunities for a sheepfarming that it is now going through an economic recession, with positive effects on the mountain and the hill landscape.

  20. TREATMENT OF METAL-LADEN HAZARDOUS WASTES WITH ADVANCED CLEAN COAL TECHNOLOGY BY-PRODUCTS

    Energy Technology Data Exchange (ETDEWEB)

    James T. Cobb, Jr.; Ronald D. Neufeld; Jana Agostini

    1999-01-01

    This seventeenth quarterly report describes work done during the seventeenth three-month period of the University of Pittsburgh's project on the ''Treatment of Metal-Laden Hazardous Wastes with Advanced Clean Coal Technology By-Products.'' This report describes the activities of the project team during the reporting period. The principal work has focused upon new laboratory evaluation of samples from Phase 1, discussions with MAX Environmental Technologies, Inc., on the field work of Phase 2, giving a presentation, submitting a manuscript and making and responding to one outside contact.

  1. TREATMENT OF METAL-LADEN HAZARDOUS WASTES WITH ADVANCED CLEAN COAL TECHNOLOGY BY-PRODUCTS

    Energy Technology Data Exchange (ETDEWEB)

    James T. Cobb, Jr.; Ronald D. Neufeld; Jana Agostini

    1999-05-11

    This fifteenth quarterly report describes work done during the fifteenth three-month period of the University of Pittsburgh's project on the ''Treatment of Metal-Laden Hazardous Wastes with Advanced Clean Coal Technology By-Products.'' This report describes the activities of the project team during the reporting period. The principal work has focused upon new laboratory evaluation of samples from Phase 1, discussions with MAX Environmental Technologies, Inc., on the field work of Phase 2, preparing and giving presentations, and making and responding to several outside contacts.

  2. Effects of photobleaching on selected advanced glycation end products in the human lens

    DEFF Research Database (Denmark)

    Holm, Thomas; Raghavan, Cibin T; Nahomi, Rooban

    2015-01-01

    BackgroundCataract is the leading cause of blindness, especially in the developing world. To ease access to treatment, we have proposed that cataract could be treated non-invasively by photobleaching of the chemically modified proteins responsible for cataract formation. The present study was aimed...... at examining the optical and biochemical effects of the proposed treatment.MethodsHuman donor lenses were photobleaced using a 445 nm cw laser. Lens optical quality was assessed before and after photobleaching by light transmission and scattering. The concentration of the advanced glycation end products (AGEs...

  3. TREATMENT OF METAL-LADEN HAZARDOUS WASTES WITH ADVANCED CLEAN COAL TECHNOLOGY BY-PRODUCTS

    Energy Technology Data Exchange (ETDEWEB)

    James T. Cobb, Jr.; Ronald D. Neufeld; Jana Agostini

    1999-05-10

    This fourteenth quarterly report describes work done during the fourteenth three-month period of the University of Pittsburgh's project on the ''Treatment of Metal-Laden Hazardous Wastes with Advanced Clean Coal Technology By-Products.'' This report describes the activities of the project team during the reporting period. The principal work has focused upon new laboratory evaluation of samples from Phase 1, discussions with MAX Environmental Technologies, Inc., on the field work of Phase 2, preparing presentations, and making and responding to two outside contacts.

  4. Access to advanced therapy medicinal products in the EU: where do we stand?

    Science.gov (United States)

    Mahalatchimy, A

    2011-05-01

    The European Union has a public health strategy and will generally ensure in all its policies and activities a "high level of human health protection". The new Regulation (EC) n 1394/2007 on advanced therapy medicinal products (ATMP), stems from this global policy and aims to harmonise access to the ATMP market. A real will for the harmonisation is clearly expressed in legal texts and enforced in the implementable procedures and requirements. However, several barriers remain. On the one hand, the scope of the ATMP Regulation is limited. On the other hand, Member States benefit from a wide margin of action.

  5. [Report from the Committee for Advanced Therapies (CAT). Pitfalls on the way from concept to medical treatment with advanced therapy medicinal products].

    Science.gov (United States)

    Reiss, M; Büttel, I C; Schneider, C K

    2011-07-01

    Advanced therapy medicinal products (ATMP) are highly innovative and complex medicines. They comprise gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products (TEP). With the European Regulation on ATMP that came into force in 2008, a consolidated regulatory framework was created, where the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA) plays a central role. This article discusses pitfalls and challenges that the CAT has experienced in its discussions of various procedures. Often ATMPs are developed by small and medium-sized enterprises (SME) which also face nonscientific challenges. The CAT wishes to meet these challenges on a scientific and regulatory level during its 2010-2015 work program.

  6. The association between various smoking behaviors, cotinine biomarkers and skin autofluorescence, a marker for advanced glycation end product accumulation

    NARCIS (Netherlands)

    van Waateringe, Robert P.; Mook-Kanamori, Marjonneke J.; Slagter, Sandra N.; van der Klauw, Melanie M.; van Vliet-Ostaptchouk, Jana V.; Graaff, Reindert; Lutgers, Helen L.; Suhre, Karsten; Selim, Mohammed M. El-Din; Mook-Kanamori, Dennis O.; Wolffenbuttel, Bruce H. R.

    2017-01-01

    BACKGROUND: Skin autofluorescence, a biomarker for advanced glycation end products (AGEs) accumulation, has been shown to predict diabetes-related cardiovascular complications and is associated with several environmental and lifestyle factors. In the present study, we examined the association

  7. Problem of safety in nanoparticle mass production and its solution by means of advanced scanning electron microscopy

    International Nuclear Information System (INIS)

    Maksimov, S K; Maksimov, K S

    2011-01-01

    It is suggested possible approaches to the comprehensive solution of the problem of structural-morphological control in mass production of nanoparticles only by the use of advanced methods of scanning electron microscopy.

  8. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products.

    Science.gov (United States)

    Verardo, Vito; Gómez-Caravaca, Ana Maria; Arráez-Román, David; Hettinga, Kasper

    2017-01-17

    Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed.

  9. Microbial advanced biofuels production: overcoming emulsification challenges for large-scale operation.

    Science.gov (United States)

    Heeres, Arjan S; Picone, Carolina S F; van der Wielen, Luuk A M; Cunha, Rosiane L; Cuellar, Maria C

    2014-04-01

    Isoprenoids and alkanes produced and secreted by microorganisms are emerging as an alternative biofuel for diesel and jet fuel replacements. In a similar way as for other bioprocesses comprising an organic liquid phase, the presence of microorganisms, medium composition, and process conditions may result in emulsion formation during fermentation, hindering product recovery. At the same time, a low-cost production process overcoming this challenge is required to make these advanced biofuels a feasible alternative. We review the main mechanisms and causes of emulsion formation during fermentation, because a better understanding on the microscale can give insights into how to improve large-scale processes and the process technology options that can address these challenges. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products

    Directory of Open Access Journals (Sweden)

    Vito Verardo

    2017-01-01

    Full Text Available Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed.

  11. Advances in cellulosic conversion to fuels: engineering yeasts for cellulosic bioethanol and biodiesel production.

    Science.gov (United States)

    Ko, Ja Kyong; Lee, Sun-Mi

    2018-04-01

    Cellulosic fuels are expected to have great potential industrial applications in the near future, but they still face technical challenges to become cost-competitive fuels, thus presenting many opportunities for improvement. The economical production of viable biofuels requires metabolic engineering of microbial platforms to convert cellulosic biomass into biofuels with high titers and yields. Fortunately, integrating traditional and novel engineering strategies with advanced engineering toolboxes has allowed the development of more robust microbial platforms, thus expanding substrate ranges. This review highlights recent trends in the metabolic engineering of microbial platforms, such as the industrial yeasts Saccharomyces cerevisiae and Yarrowia lipolytica, for the production of renewable fuels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Greening the Grid: Advances in Production Cost Modeling for India Renewable Energy Grid Integration Study

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, Jaquelin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Palchak, David [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-07-12

    The Greening the Grid: Pathways to Integrate 175 Gigawatts of Renewable Energy into India's Electric Grid study uses advanced weather and power system modeling to explore the operational impacts of meeting India's 2022 renewable energy targets and identify actions that may be favorable for integrating high levels of renewable energy into the Indian grid. The study relies primarily on a production cost model that simulates optimal scheduling and dispatch of available generation in a future year (2022) by minimizing total production costs subject to physical, operational, and market constraints. This fact sheet provides a detailed look at each of these models, including their common assumptions and the insights provided by each.

  13. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products

    Science.gov (United States)

    Verardo, Vito; Gómez-Caravaca, Ana Maria; Arráez-Román, David; Hettinga, Kasper

    2017-01-01

    Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed. PMID:28106745

  14. Effect of dietary advanced glycation end products on postprandial appetite, inflammation, and endothelial activation in healthy overweight individuals

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Bak, Monika Judyta; Andersen, Jeanette Marker

    2014-01-01

    Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress.......Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress....

  15. Process modeling and supply chain design for advanced biofuel production based on bio-oil gasification

    Science.gov (United States)

    Li, Qi

    As a potential substitute for petroleum-based fuel, second generation biofuels are playing an increasingly important role due to their economic, environmental, and social benefits. With the rapid development of biofuel industry, there has been an increasing literature on the techno-economic analysis and supply chain design for biofuel production based on a variety of production pathways. A recently proposed production pathway of advanced biofuel is to convert biomass to bio-oil at widely distributed small-scale fast pyrolysis plants, then gasify the bio-oil to syngas and upgrade the syngas to transportation fuels in centralized biorefinery. This thesis aims to investigate two types of assessments on this bio-oil gasification pathway: techno-economic analysis based on process modeling and literature data; supply chain design with a focus on optimal decisions for number of facilities to build, facility capacities and logistic decisions considering uncertainties. A detailed process modeling with corn stover as feedstock and liquid fuels as the final products is presented. Techno-economic analysis of the bio-oil gasification pathway is also discussed to assess the economic feasibility. Some preliminary results show a capital investment of 438 million dollar and minimum fuel selling price (MSP) of $5.6 per gallon of gasoline equivalent. The sensitivity analysis finds that MSP is most sensitive to internal rate of return (IRR), biomass feedstock cost, and fixed capital cost. A two-stage stochastic programming is formulated to solve the supply chain design problem considering uncertainties in biomass availability, technology advancement, and biofuel price. The first-stage makes the capital investment decisions including the locations and capacities of the decentralized fast pyrolysis plants and the centralized biorefinery while the second-stage determines the biomass and biofuel flows. The numerical results and case study illustrate that considering uncertainties can be

  16. Conceptual design study FY 1981: synfuels from fusion - using the tandem mirror reactor and a thermochemical cycle to produce hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Krikorian, O.H. (ed.)

    1982-02-09

    This report represents the second year's effort of a scoping and conceptual design study being conducted for the express purpose of evaluating the engineering potential of producing hydrogen by thermochemical cycles using a tandem mirror fusion driver. The hydrogen thus produced may then be used as a feedstock to produce fuels such as methane, methanol, or gasoline. The main objective of this second year's study has been to obtain some approximate cost figures for hydrogen production through a conceptual design study.

  17. Advanced turbine systems program -- Conceptual design and product development. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-26

    This Final Technical Report presents the accomplishments on Phase 2 of the Advanced Turbine Systems (ATS). The ATS is an advanced, natural gas fired gas turbine system that will represent a major advance on currently available industrial gas turbines in the size range of 1--20 MW. This report covers a market-driven development. The Market Survey reported in Section 5 identified the customer`s performance needs. This market survey used analyses performed by Solar turbine Incorporated backed up by the analyses done by two consultants, Research Decision Consultants (RDC) and Onsite Energy Corporation (Onsite). This back-up was important because it is the belief of all parties that growth of the ATS will depend both on continued participation in Solar`s traditional oil and gas market but to a major extent on a new market. This new market is distributed electrical power generation. Difficult decisions have had to be made to meet the different demands of the two markets. Available resources, reasonable development schedules, avoidance of schedule or technology failures, probable acceptance by the marketplace, plus product cost, performance and environmental friendliness are a few of the complex factors influencing the selection of the Gas Fired Advanced Turbine System described in Section 3. Section 4 entitled ``Conversion to Coal`` was a task which addresses the possibility of a future interruption to an economic supply of natural gas. System definition and analysis is covered in Section 6. Two major objectives were met by this work. The first was identification of those critical technologies that can support overall attainment of the program goals. Separate technology or component programs were begun to identify and parameterize these technologies and are described in Section 7. The second objective was to prepare parametric analyses to assess performance sensitivity to operating variables and to select design approaches to meet the overall program goals.

  18. Role of the receptor for advanced glycation end products in hepatic fibrosis.

    Science.gov (United States)

    Lohwasser, Christina; Neureiter, Daniel; Popov, Yury; Bauer, Michael; Schuppan, Detlef

    2009-12-14

    To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGE-BSA) and N(epsilon)-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-alpha (TNF-alpha). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-alpha. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen alpha1(I) mRNA by AGE-BSA. Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.

  19. Short-term effects of dietary advanced glycation end products in rats

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Andersen, Jeanette Marker; Hedegaard, Rikke Susanne Vingborg

    2016-01-01

    Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW)...... the groups. In conclusion, RAGE and AGER1 expression can be influenced by a high AGE diet after only 2 weeks in proportion to MG-H1 excretion. No other short-term effects were observed.......Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW......) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague-Dawley rats were fed a diet containing 20 % milk powder with different proportions of this being...

  20. Sesamin Ameliorates Advanced Glycation End Products-Induced Pancreatic β-Cell Dysfunction and Apoptosis

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2015-06-01

    Full Text Available Advanced glycation end products (AGEs, the direct modulators of β-cells, have been shown to cause insulin-producing β-cell dysfunction and apoptosis through increase of intracellular reactive oxygen species (ROS production. Sesamin has been demonstrated to possess antioxidative activity. This study was designed to investigate whether sesamin protects against AGEs-evoked β-cell damage via its antioxidant property. The effects of sesamin were examined in C57BL/6J mice and MIN6 cell line. In in vivo studies, mice were intraperitoneally injected with AGEs (120 mg/kg and orally treated with sesamin (160 mg/kg for four weeks. Intraperitoneal glucose tolerance and insulin releasing tests were performed. Insulin content, ROS generation and β-cell apoptosis in pancreatic islets were also measured. In in vitro studies, MIN6 cells were pretreated with sesamin (50 or 100 μM and then exposed to AGEs (200 mg/L for 24 h. Insulin secretion, β-cell death, ROS production as well as expression and activity of NADPH oxidase were determined. Sesamin treatment obviously ameliorated AGE-induced β-cell dysfunction and apoptosis both in vivo and in vitro. These effects were associated with decreased ROS production, down-regulated expression of p67phox and p22phox, and reduced NADPH oxidase activity. These results suggest that sesamin protects β-cells from damage caused by AGEs through suppressing NADPH oxidase-mediated oxidative stress.

  1. Advances in consolidated bioprocessing systems for bioethanol and butanol production from biomass: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Gholamreza Salehi Jouzani

    2015-03-01

    Full Text Available Recently, lignocellulosic biomass as the most abundant renewable resource has been widely considered for bioalcohols production. However, the complex structure of lignocelluloses requires a multi-step process which is costly and time consuming. Although, several bioprocessing approaches have been developed for pretreatment, saccharification and fermentation, bioalcohols production from lignocelluloses is still limited because of the economic infeasibility of these technologies. This cost constraint could be overcome by designing and constructing robust cellulolytic and bioalcohols producing microbes and by using them in a consolidated bioprocessing (CBP system. This paper comprehensively reviews potentials, recent advances and challenges faced in CBP systems for efficient bioalcohols (ethanol and butanol production from lignocellulosic and starchy biomass. The CBP strategies include using native single strains with cellulytic and alcohol production activities, microbial co-cultures containing both cellulytic and ethanologenic microorganisms, and genetic engineering of cellulytic microorganisms to be alcohol-producing or alcohol producing microorganisms to be cellulytic. Moreover, high-throughput techniques, such as metagenomics, metatranscriptomics, next generation sequencing and synthetic biology developed to explore novel microorganisms and powerful enzymes with high activity, thermostability and pH stability are also discussed. Currently, the CBP technology is in its infant stage, and ideal microorganisms and/or conditions at industrial scale are yet to be introduced. So, it is essential to bring into attention all barriers faced and take advantage of all the experiences gained to achieve a high-yield and low-cost CBP process.

  2. [Scientific advice by the national and European approval authorities concerning advanced therapy medicinal products].

    Science.gov (United States)

    Jost, Nils; Schüssler-Lenz, Martina; Ziegele, Bettina; Reinhardt, Jens

    2015-11-01

    The aim of scientific advice is to support pharmaceutical developers in regulatory and scientific questions, thus facilitating the development of safe and efficacious new medicinal products. Recent years have shown that the development of advanced therapy medicinal products (ATMPs) in particular needs a high degree of regulatory support. On one hand, this is related to the complexity and heterogeneity of this group of medicinal products and on the other hand due to the fact that mainly academic research institutions and small- and medium-sized enterprises (SMEs) are developing ATMPs. These often have limited regulatory experience and resources. In 2009 the Paul-Ehrlich-Institut (PEI) initiated the Innovation Office as a contact point for applicants developing ATMPs. The mandate of the Innovation Office is to provide support on regulatory questions and to coordinate national scientific advice meetings concerning ATMPs for every phase in drug development and especially with view to the preparation of clinical trial applications. On the European level, the Scientific Advice Working Party (SAWP) of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicinal Agency (EMA) offers scientific advice. This article describes the concepts of national and EMA scientific advice concerning ATMPs and summarizes the experience of the last six years.

  3. Characterization of anti-advanced glycation end product antibodies to nonenzymatically lysine-derived and arginine-derived glycated products.

    Science.gov (United States)

    Choi, Yeong-Gon; Lim, Sabina

    2009-01-01

    N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) termed advanced glycation end products (AGEs) are known to be produced by nonenzymatic glycation between bovine serum albumin (BSA) and D-glucose. This study is to characterize the immunoreactivity of anti-AGE antibodies including anti-CML and anti-CEL antibodies. Using AGE-modified BSA (AGE-BSA) as an immunogen, a polyclonal anti-AGE immunoglobulin G (IgG) was produced. The anti-AGE IgG could strongly detect AGEs formed on BSA, at least in part, AGEs produced on both residues Lys and Arg due to its immunoreaction with Lys-derived and Arg-derived AGEs produced by NaCNBH(3), a reducing agent, in amino acid glycation analysis, but the pre-immune serum could not. As the anti-CML antibody could also strongly react with AGE-BSA, this suggests that CML is a major nonenzymatically glycated product cross-linked to BSA. Furthermore, CEL is associated with distinguishable polymerization of BSA from CML polymerization of BSA, though weaker than CML and was not produced by Lys glycation analysis. These results indicate that the anti-AGE antibody is effective for detecting both Lys-derived and Arg-derived AGEs, and CML and CEL distinctively polymerize albumin as major AGEs present on AGE-BSA.

  4. Advanced glycation End-products (AGEs): an emerging concern for processed food industries.

    Science.gov (United States)

    Sharma, Chetan; Kaur, Amarjeet; Thind, S S; Singh, Baljit; Raina, Shiveta

    2015-12-01

    The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). The chemistry of the AGEs formation, absorption and bioavailability and their patho-biochemistry particularly in relation to different complications like diabetes and ageing discussed. The concept of AGEs receptor - RAGE is mentioned. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Different methods of detection and quantification along with types of agents used for the treatment of AGEs are reviewed. Generally, ELISA or LC-MS methods are used for analysis of foods and body fluids, however lack of universally established method highlighted. The inhibitory effect of bioactive components on AGEs by trapping variety of chemical moieties discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

  5. Recent advances in the elucidation of enzymatic function in natural product biosynthesis [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Gao-Yi Tan

    2016-02-01

    Full Text Available With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.

  6. Recent advances in the elucidation of enzymatic function in natural product biosynthesis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tan Gao-Yi

    2015-12-01

    Full Text Available With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.

  7. Advanced wind turbine near-term product development. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-01-01

    In 1990 the US Department of Energy initiated the Advanced Wind Turbine (AWT) Program to assist the growth of a viable wind energy industry in the US. This program, which has been managed through the National Renewable Energy Laboratory (NREL) in Golden, Colorado, has been divided into three phases: (1) conceptual design studies, (2) near-term product development, and (3) next-generation product development. The goals of the second phase were to bring into production wind turbines which would meet the cost goal of $0.05 kWh at a site with a mean (Rayleigh) windspeed of 5.8 m/s (13 mph) and a vertical wind shear exponent of 0.14. These machines were to allow a US-based industry to compete domestically with other sources of energy and to provide internationally competitive products. Information is given in the report on design values of peak loads and of fatigue spectra and the results of the design process are summarized in a table. Measured response is compared with the results from mathematical modeling using the ADAMS code and is discussed. Detailed information is presented on the estimated costs of maintenance and on spare parts requirements. A failure modes and effects analysis was carried out and resulted in approximately 50 design changes including the identification of ten previously unidentified failure modes. The performance results of both prototypes are examined and adjusted for air density and for correlation between the anemometer site and the turbine location. The anticipated energy production at the reference site specified by NREL is used to calculate the final cost of energy using the formulas indicated in the Statement of Work. The value obtained is $0.0514/kWh in January 1994 dollars. 71 figs., 30 tabs.

  8. Recent advances and state-of-the-art strategies in strain and process engineering for biobutanol production by Clostridium acetobutylicum.

    Science.gov (United States)

    Xue, Chuang; Zhao, Jingbo; Chen, Lijie; Yang, Shang-Tian; Bai, Fengwu

    Butanol as an advanced biofuel has gained great attention due to its environmental benefits and superior properties compared to ethanol. However, the cost of biobutanol production via conventional acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum is not economically competitive, which has hampered its industrial application. The strain performance and downstream process greatly impact the economics of biobutanol production. Although various engineered strains with carefully orchestrated metabolic and sporulation-specific pathways have been developed, none of them is ideal for industrial biobutanol production. For further strain improvement, it is necessary to develop advanced genome editing tools and a deep understanding of cellular functioning of genes in metabolic and regulatory pathways. Processes with integrated product recovery can increase fermentation productivity by continuously removing inhibitory products while generating butanol (ABE) in a concentrated solution. In this review, we provide an overview of recent advances in C. acetobutylicum strain engineering and process development focusing on in situ product recovery. With deep understanding of systematic cellular bioinformatics, the exploration of state-of-the-art genome editing tools such as CRISPR-Cas for targeted gene knock-out and knock-in would play a vital role in Clostridium cell engineering for biobutanol production. Developing advanced hybrid separation processes for in situ butanol recovery, which will be discussed with a detailed comparison of advantages and disadvantages of various recovery techniques, is also imperative to the economical development of biobutanol. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Spirolactones: Recent Advances in Natural Products, Bioactive Compounds and Synthetic Strategies.

    Science.gov (United States)

    Quintavalla, Arianna

    2018-01-01

    The spirocyclic compounds have always aroused a great interest because this motif is present as structural core in a number of natural products and bioactive compounds. In particular, the spirolactone moiety has been recognized in a wide array of natural and non-natural scaffolds showing a variety of useful pharmacological properties. Extensive literature search using SciFinder (Databases: CA Plus, CAS Registry, CAS React, Chemlist, Chemcat and Medline) and Web of Science (Database: Web of Science Core Collection) was conducted. Nowadays, many efforts are being devoted to the discovery of new natural products containing the promising spirolactone framework and to the disclosure of the potential bioactivities of these chemical entities. Moreover, the medicinal relevance of many spirolactones makes these scaffolds attractive targets for the design and development of innovative and efficient synthetic strategies, enabling the construction of complex and variably substituted products. This review gives an overview on the recent advances in the spirolactones field, in terms of new compounds isolated from natural sources, recently determined bioactivity profiles and innovative synthetic approaches. The collected data demonstrate the key role played by spirolactones in medicinal chemistry and the great attention still devoted by the scientific community to these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Recent advances in analytical determination of cisplatin and its hydrolysis products

    International Nuclear Information System (INIS)

    Ramos Rodriguez, Yalexmiy; Hernandez Castro, Carlos

    2009-01-01

    Cisplatin (cis-diaminedichloroplatinum [II] is a coordination compound, used in the treatment of several solid tumors. Cisplatin and its hydrolysis products exhibit a great pharmacological effect but are very toxic and probably carcinogenic. The present review summarizes the most important advances in the last years in the techniques employed for the detection and quantification of cisplatin and its hydrolysis products and in the different matrixes studied. The new emerging techniques and their modifications recently developed, fundamentally the combined use of detection and separation techniques for the analysis of platinum species and their impact on the speed, sensitivity and specificity of the analytical determination, with regard to the techniques used in the last century are discussed. High-Performance Liquid Chromatography and Capillary Electrophoresis, coupled with detection methods such as Mass Spectrometry, Inductively Coupled Plasma-Mass Spectrometry, Atomic Absorption Spectrometry and more recently, High-Field Asymmetric Waveform Ion Mobility Spectrometry are the methods more employed. The analysis of cisplatin and its hydrolysis products in new and more complex matrixes is also presented

  11. Identification of ionic liquid breakdown products in an advanced oxidation system

    International Nuclear Information System (INIS)

    Czerwicka, M.; Stolte, S.; Mueller, A.; Siedlecka, E.M.; Golebiowski, M.; Kumirska, J.; Stepnowski, P.

    2009-01-01

    Commonly used alkylimidazolium ionic liquids are poorly to negligibly biodegradable, and some are toxic, with the potential to poison typical biological test systems. Therefore, when ionic liquids are present in technological wastewaters they could break through classical wastewater treatment systems into natural waters and become potentially persistent pollutants. A recent study investigating different advanced oxidation processes found that the H 2 O 2 /UV system degraded dissolved imidazolium ionic liquids with the greatest efficiency. In the present study, high performance liquid chromatography was coupled with electrospray mass spectrometry to separate, analyse and identify degradation products following the treatment of ionic liquid solutions with H 2 O 2 in the presence of UV irradiation. It was found that hydroxylation in short-chain entities occurred mainly within the ring moiety, whereas in the case of longer alkylated cations, oxidation of the alkyl chain yielded several products. The potential transformation products were identified structurally by MS/MS analysis and are discussed in the light of their putative toxicity and biodegradability.

  12. Advances in the industrial production of halal and kosher red meat.

    Science.gov (United States)

    Farouk, Mustafa M

    2013-12-01

    The worldwide volume and value of trade in halal and kosher meat and co-products are huge. Muslim countries alone consumed meat estimated to be worth USD 57.2 billion in 2008. The halal and kosher principles that govern the production of red meat have many similarities, as well as some fundamental differences. Perhaps the most significant difference is that at the time of slaughter, the animal needs only to be alive to meet the minimum halal requirement, but must be both alive and conscious for kosher. It is for this reason that reversible pre-slaughter stunning is acceptable only for halal meat, although a compromise form of post-slaughter stunning is now considered kosher in some countries. Extensive research on animal physiology and welfare has characterised and optimised the methods for stunning livestock, and enabled advancement in associated technologies. This forms the basis for harmonising the religious and secular requirements for the protection of animal welfare at slaughter. These technologies and the associated processing practices for the industrial production of halal and kosher meat are reviewed in this paper. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Advanced Therapy Medicinal Products in type I diabetes mellitus: technological and regulatory challenges

    Directory of Open Access Journals (Sweden)

    Camila Leal-Lopes

    2018-02-01

    Full Text Available Introduction: Type 1 Diabetes mellitus (T1DM is an autoimmune disorder which arises from the destruction of insulin-producing pancreatic β-cells. Currently, Brazil’s advanced therapy medicinal products (ATMP, developed for clinical research and therapeutic purposes, take place in the so-called Cellular Technology Centers (CTC, according to the Resolution nº. 9/2011 of the Collegiate Board of Directors (RDC, enacted by the National Health Surveillance Agency (Anvisa. Objective: This study was conducted with the main objective of describing and discussing the development of ATMP for T1DM treatment. Method: A qualitative research, narrative review and critical discussion of the literature were under taken. Results: ATMP promote new therapeutic approaches for Diabetes, holding great potential to restore the patients’ endogenous insulin secretion, improving their life quality, overcoming the chronic complications of Diabetes and reducing the socioeconomic burden. Nowadays, ATMP in T1DM comprise: a cell therapy; b gene therapy products; c tissue engineering and d ATMPassociated to biopharmaceutical products. Conclusions: Further research should contribute to stimulate public and private organizations to effectively act towards reducing the impact of Diabetes on individuals and the society as a whole. It is essential that Brazilian legislation closely follows the biotechnological developments, supporting the scientific progress and benefiting T1DM patients with modern and cutting-edge therapies.

  14. From flavors and pharmaceuticals to advanced biofuels: production of isoprenoids in Saccharomyces cerevisiae.

    Science.gov (United States)

    Tippmann, Stefan; Chen, Yun; Siewers, Verena; Nielsen, Jens

    2013-12-01

    Isoprenoids denote the largest group of chemicals in the plant kingdom and are employed for a wide range of applications in the food and pharmaceutical industry. In recent years, isoprenoids have additionally been recognized as suitable replacements for petroleum-derived fuels and could thus promote the transition towards a more sustainable society. To realize the biofuel potential of isoprenoids, a very efficient production system is required. While complex chemical structures as well as the low abundance in nature demonstrate the shortcomings of chemical synthesis and plant extraction, isoprenoids can be produced by genetically engineered microorganisms from renewable carbon sources. In this article, we summarize the development of isoprenoid applications from flavors and pharmaceuticals to advanced biofuels and review the strategies to design microbial cell factories, focusing on Saccharomyces cerevisiae for the production of these compounds. While the high complexity of biosynthetic pathways and the toxicity of certain isoprenoids still denote challenges that need to be addressed, metabolic engineering has enabled large-scale production of several terpenoids and thus, the utilization of these compounds is likely to expand in the future. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU.

    Science.gov (United States)

    Pellegrini, Graziella; Lambiase, Alessandro; Macaluso, Claudio; Pocobelli, Augusto; Deng, Sophie; Cavallini, Gian Maria; Esteki, Roza; Rama, Paolo

    2016-06-01

    In 1997, the human corneal epithelium was reconstructed in vitro and transplanted on patients. Later, it became a routine treatment, before regulations considered advanced therapy medicinal products and drugs on the same lines. Manufacturing, before and after good manufacturing practice setting, was established in different facilities and the clinical application in several hospitals. Advanced therapy medicinal products, including stem cells, are unique products with different challenges than other drugs: some uncertainties, in addition to benefit, cannot be avoided. This review will focus on all recent developments in the stem cell-based corneal therapy.

  16. Supply chain design under uncertainty for advanced biofuel production based on bio-oil gasification

    International Nuclear Information System (INIS)

    Li, Qi; Hu, Guiping

    2014-01-01

    An advanced biofuels supply chain is proposed to reduce biomass transportation costs and take advantage of the economics of scale for a gasification facility. In this supply chain, biomass is converted to bio-oil at widely distributed small-scale fast pyrolysis plants, and after bio-oil gasification, the syngas is upgraded to transportation fuels at a centralized biorefinery. A two-stage stochastic programming is formulated to maximize biofuel producers' annual profit considering uncertainties in the supply chain for this pathway. The first stage makes the capital investment decisions including the locations and capacities of the decentralized fast pyrolysis plants as well as the centralized biorefinery, while the second stage determines the biomass and biofuels flows. A case study based on Iowa in the U.S. illustrates that it is economically feasible to meet desired demand using corn stover as the biomass feedstock. The results show that the locations of fast pyrolysis plants are sensitive to uncertainties while the capacity levels are insensitive. The stochastic model outperforms the deterministic model in the stochastic environment, especially when there is insufficient biomass. Also, farmers' participation can have a significant impact on the profitability and robustness of this supply chain. - Highlights: • Decentralized supply chain design for advanced biofuel production is considered. • A two-stage stochastic programming is formulated to consider uncertainties. • Farmers' participation has a significant impact on the biofuel supply chain design

  17. Manipulating photorespiration to increase plant productivity: recent advances and perspectives for crop improvement.

    Science.gov (United States)

    Betti, Marco; Bauwe, Hermann; Busch, Florian A; Fernie, Alisdair R; Keech, Olivier; Levey, Myles; Ort, Donald R; Parry, Martin A J; Sage, Rowan; Timm, Stefan; Walker, Berkley; Weber, Andreas P M

    2016-05-01

    Recycling of the 2-phosphoglycolate generated by the oxygenase reaction of Rubisco requires a complex and energy-consuming set of reactions collectively known as the photorespiratory cycle. Several approaches aimed at reducing the rates of photorespiratory energy or carbon loss have been proposed, based either on screening for natural variation or by means of genetic engineering. Recent work indicates that plant yield can be substantially improved by the alteration of photorespiratory fluxes or by engineering artificial bypasses to photorespiration. However, there is also evidence indicating that, under certain environmental and/or nutritional conditions, reduced photorespiratory capacity may be detrimental to plant performance. Here we summarize recent advances obtained in photorespiratory engineering and discuss prospects for these advances to be transferred to major crops to help address the globally increasing demand for food and biomass production. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    Science.gov (United States)

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-12-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80 ± 5.50%, PRAGE participates in and exacerbates periodontium destruction.

  19. [Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells].

    Science.gov (United States)

    Kaji, Yuichi

    2005-11-01

    Corneal endothelial cell loss is a change that occurs with age, but its mechanism is still unclear. We postulated that interaction between advanced glycation end product(AGE) and its receptors is implicated in the corneal endothelial cell loss with age. We investigated the expression of AGE receptors: receptors for AGE(RAGE) and galectin-3 in bovine corneal endothelial cells by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry. In addition, we investigated the effect of AGE on the cultured corneal endothelial cells. Expression of RAGE and galectin-3 was detected in bovine corneal endothelial cells. Galectin-3 was important in the internalization of AGE. In contrast, RAGE was important in the generation of reactive oxygen species and induction of apoptosis. Based on these data, the interaction of AGE in aqueous humor and AGE receptors expressed on the corneal endothelial cells was speculated to have a role in the corneal endothelial cell loss with age.

  20. Recycling of Na in advanced life support: strategies based on crop production systems.

    Science.gov (United States)

    Guntur, S V; Mackowiak, C; Wheeler, R M

    1999-01-01

    Sodium is an essential dietary requirement in human nutrition, but seldom holds much importance as a nutritional element for crop plants. In Advanced Life Support (ALS) systems, recycling of gases, nutrients, and water loops is required to improve system closure. If plants are to play a significant role in recycling of human wastes, Na will need to accumulate in edible tissues for return to the crew diet. If crops fail to accumulate the incoming Na into edible tissues, Na could become a threat to the hydroponic food production system by increasing the nutrient solution salinity. Vegetable crops of Chenopodiaceae such as spinach, table beet, and chard may have a high potential to supply Na to the human diet, as Na can substitute for K to a large extent in metabolic processes of these crops. Various strategies are outlined that include both genetic and environmental management aspects to optimize the Na recovery from waste streams and their resupply through the human diet in ALS.

  1. Advanced glycation end products overload might explain intracellular cobalamin deficiency in renal dysfunction, diabetes and aging.

    Science.gov (United States)

    Obeid, Rima; Shannan, Batool; Herrmann, Wolfgang

    2011-11-01

    Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. EU decision-making for marketing authorization of advanced therapy medicinal products: a case study.

    Science.gov (United States)

    de Wilde, Sofieke; Coppens, Delphi G M; Hoekman, Jarno; de Bruin, Marie L; Leufkens, Hubert G M; Guchelaar, Henk-Jan; Meij, Pauline

    2018-03-21

    A comparative analysis of assessment procedures for authorization of all European Union (EU) applications for advanced therapy medicinal products (ATMPs) shows that negative opinions were associated with a lack of clinical efficacy and identified severe safety risks. Unmet medical need was often considered in positive opinions and outweighed scientific uncertainties. Numerous quality issues illustrate the difficulties in this domain for ATMP development. Altogether, it suggests that setting appropriate standards for ATMP authorization in Europe, similar to elsewhere, is a learning experience. The experimental characteristics of authorized ATMPs urge regulators, industry, and clinical practice to pay accurate attention to post-marketing risk management to limit patient risk. Methodologies for ATMP development and regulatory evaluations need to be continuously evaluated for the field to flourish. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Recent advances in synthetic biology for engineering isoprenoid production in yeast.

    Science.gov (United States)

    Vickers, Claudia E; Williams, Thomas C; Peng, Bingyin; Cherry, Joel

    2017-10-01

    Isoprenoids (terpenes/terpenoids) have many useful industrial applications, but are often not produced at industrially viable level in their natural sources. Synthetic biology approaches have been used extensively to reconstruct metabolic pathways in tractable microbial hosts such as yeast and re-engineer pathways and networks to increase yields. Here we review recent advances in this field, focusing on central carbon metabolism engineering to increase precursor supply, re-directing carbon flux for production of C10, C15, or C20 isoprenoids, and chemical decoration of high value diterpenoids (C20). We also overview other novel synthetic biology strategies that have potential utility in yeast isoprenoid pathway engineering. Finally, we address the question of what is required in the future to move the field forwards. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The receptor for advanced glycation end products (RAGE) and the lung.

    LENUS (Irish Health Repository)

    Buckley, Stephen T

    2010-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

  5. Advances in mixed-integer programming methods for chemical production scheduling.

    Science.gov (United States)

    Velez, Sara; Maravelias, Christos T

    2014-01-01

    The goal of this paper is to critically review advances in the area of chemical production scheduling over the past three decades and then present two recently proposed solution methods that have led to dramatic computational enhancements. First, we present a general framework and problem classification and discuss modeling and solution methods with an emphasis on mixed-integer programming (MIP) techniques. Second, we present two solution methods: (a) a constraint propagation algorithm that allows us to compute parameters that are then used to tighten MIP scheduling models and (b) a reformulation that introduces new variables, thus leading to effective branching. We also present computational results and an example illustrating how these methods are implemented, as well as the resulting enhancements. We close with a discussion of open research challenges and future research directions.

  6. Advanced glycation end products and their receptor contribute to ovarian ageing.

    Science.gov (United States)

    Stensen, Mette Haug; Tanbo, Tom; Storeng, Ritsa; Fedorcsak, Peter

    2014-01-01

    Do advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) affect the cells of the human ovarian follicle? AGE accumulate on the surface of ovarian granulosa-lutein (GL) cells and monocytes by binding to RAGE and other receptors with possible functional effects on these cells. AGE and RAGE are expressed in granulosa and theca cells, as well as in luteinized cells derived from the ovary. In this prospective cohort study, human follicle fluid-derived cells were isolated from aspirates of ovarian follicles of women who underwent assisted reproduction treatment. Immunofluorescence microscopy and multi-colour flow cytometry were used to determine the presence of AGE and RAGE on the surface of follicular fluid-derived cells and to characterize downstream effects of RAGE activation. GL cells and ovarian monocytes were found to contain AGE and RAGE and to bind AGE-bovine serum albumin (BSA) in correlation with the patients' chronological age. AGE-BSA and BSA failed to induce significantly the cleavage of caspase-3, phosphorylation of nuclear factor-κB or the binding of annexin V (the latter was marginally increased). AGE-fibronectin was found to induce detachment of cultured GL cells in vitro. The impact of AGE and RAGE in the ovary, shown here in cells in culture, remains to be affirmed in clinical settings. The ligands of RAGE and their effects in the ovary remain uncertain but this study implies that AGEs in the form of structural long-lived extracellular matrix proteins, rather than soluble AGEs, may play a role in the decline of ovarian function during ageing. The project was funded by the Norwegian Resource Centre for Women's Health, Oslo University Hospital. The authors have no conflicts of interests.

  7. Advanced turbine systems program conceptual design and product development. Annual report, August 1993--July 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-11-01

    This Yearly Technical Progress Report covers the period August 3, 1993 through July 31, 1994 for Phase 2 of the Advanced Turbine Systems (ATS) Program by Solar Turbines Incorporated under DOE Contract No. DE-AC421-93MC30246. As allowed by the Contract (Part 3, Section J, Attachment B) this report is also intended to fulfill the requirements for a fourth quarterly report. The objective of Phase 2 of the ATS Program is to provide the conceptual design and product development plan for an ultra-high efficiency, environmentally superior and cost-competitive industrial gas turbine system to be commercialized in the year 2000. During the period covered by this report, Solar has completed three of eight program tasks and has submitted topical reports. These three tasks included a Project Plan submission of information required by NEPA, and the selection of a Gas-Fueled Advanced Turbine System (GFATS). In the latest of the three tasks, Solar`s Engineering team identified an intercooled and recuperated (ICR) gas turbine as the eventual outcome of DOE`s ATS program coupled with Solar`s internal New Product Introduction (NPI) program. This machine, designated ``ATS50`` will operate at a thermal efficiency (turbine shaft power/fuel LHV) of 50 percent, will emit less than 10 parts per million of NOx and will reduce the cost of electricity by 10 percent. It will also demonstrate levels of reliability, availability, maintainability, and durability (RAMD) equal to or better than those of today`s gas turbine systems. Current activity is concentrated in three of the remaining five tasks a Market Study, GFATS System Definition and Analysis, and the Design and Test of Critical Components.

  8. Advanced glycation end products impair the migration, adhesion and secretion potentials of late endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Li Hong

    2012-04-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPCs, especially late EPCs, play a critical role in endothelial maintenance and repair, and postnatal vasculogenesis. Advanced glycation end products (AGEs have been shown to impair EPC functions, such as proliferation, migration and adhesion. However, their role in the regulation of the production of vasoactive substances in late EPCs is less well defined. Methods Passages of 3~5 EPCs, namely late EPCs, were cultured with different concentrations (0~500 μg/ml of AGEs, and the apoptosis, adhesion and migration were subsequently determined. The release of vasoactive substances, such as stromal cell-derived factor-1 (SDF-1, nitric oxide (NO, prostaglandin I2 (PGI2, plasminogen activator inhibitor-1 (PAI-1, tissue plasminogen activator (tPA, and in addition the activity of superoxide dismutase (SOD, were evaluated by ELISA. At the same time, the gene and protein expressions of CXCR4 were assayed by real-time RT-PCR and western-blot. Results AGEs promoted late EPC apoptosis. Moreover, AGEs impaired late EPC migration and adhesion in a concentration-dependent manner. Accordingly, the production of SDF-1 was decreased by AGEs. Although the CXCR4 expressions of late EPCs were up-regulated for AGE concentrations of 50, 100 or 200 μg/ml, a marked decrease was observed for the higher concentration of 500 μg/ml. Furthermore, co-culturing with AGEs decreased the levels of NO, t-PA, PGI2, and the activity of SOD but up-regulated the production of PAI-1. Conclusion Our data provide evidence that AGEs play an important role in impairing late EPC functions, which could contribute to the development of vascular diseases in diabetes.

  9. PSEUDOAFFINITY CHROMATOGRAPHY ENRICHMENT OF GLYCATED PEPTIDES FOR MONITORING ADVANCED GLYCATION END PRODUCTS (AGES IN METABOLIC DISORDERS

    Directory of Open Access Journals (Sweden)

    Rajasekar R. Prasanna

    2016-09-01

    Full Text Available Advanced Glycation End (AGE products are produced due to diabetic progression and they are responsible for many complications in the diabetic disorder. The diabetic progression is measured, particularly following glycated hemoglobin using specific antibodies. However, the most abundant protein in blood, human serum albumin, is also found to be glycated which has a much shorter half life and gives information on short term glycemic control. In addition, glycated albumins are considered as markers of diabetic complications such as nephropathy, peripheral vascular calcification and also in Alzheimer’s disease. The glycation proceeds from the interaction between aldehyde group of sugar and the free amino group of the protein, resulting in the formation of Schiff’s base, which undergoes a series of modifications leading to generation of imidazoyl derivatives of amino acids known as Amadori rearrangement products. The imidazoyl derivatives from arginine and lysine are the most prominent modifications observed in proteins in the presence of reducing sugar and these imidazoyl derivatives have an affinity towards certain transition metal ions. Based on our earlier exhaustive work on trapping the histidine peptides using transition metal ion, Cu(II linked to imino-diacetate complex, we explored Cu(II immobilized metal affinity chromatography (IMAC as a potential tool for specific detection of glycated peptides of human serum albumin. Our results clearly demonstrate that Cu(II IMAC is able to detect glycated peptides very efficiently while the non-glycated forms were not retained on the Cu (II column as confirmed by LC-MS/MS analysis. We further discuss the utility of IMAC technology to enrich the detection of AGE products in plasma. We anticipate that these studies may provide valuable information on understanding disease pathologies and the potential of AGE products as biomarkers of various diseases including neurodegenerative, renal and

  10. Regulation of advanced therapy medicinal products in Europe and the role of academia.

    Science.gov (United States)

    Pearce, Kim F; Hildebrandt, Martin; Greinix, Hildegard; Scheding, Stefan; Koehl, Ulrike; Worel, Nina; Apperley, Jane; Edinger, Matthius; Hauser, Andrea; Mischak-Weissinger, Eva; Dickinson, Anne M; Lowdell, Mark W

    2014-03-01

    Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them. European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented. Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS. GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field. Copyright © 2014 International Society for Cellular Therapy. All rights reserved.

  11. Reference values for the Chinese population of skin autofluorescence as a marker of advanced glycation end products accumulated in tissue.

    Science.gov (United States)

    Yue, X; Hu, H; Koetsier, M; Graaff, R; Han, C

    2011-07-01

    Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the normal reference value of advanced glycation end products accumulated in tissue measured by the advanced glycation end product reader--skin autofluorescence--and discusses some factors influencing it. The values of autofluorescence in healthy individuals in China were determined by the advanced glycation end product reader; age, gender, skin reflectance, smoking habits and alcohol consumption of the subjects were also recorded. The mean reference values of autofluorescence in healthy Chinese subjects are (95% confidence interval) 20-29 years: 1.54-1.62 arbitrary units; 30-39 years: 1.66-1.75; 40-49 years: 1.78-1.89; 50-59 years: 1.87-2.03; 60-69 years: 1.86-2.09; 70-79 years: 1.97-2.31. The value of autofluorescence is strongly related to age, but no significant difference between males and females were found (all P > 0.05). Autofluorescence was higher in smokers than in non-smokers (P reader reliable for lower skin reflections as well, independently of the skin colour. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  12. Advanced Turbine Systems (ATS) program conceptual design and product development. Quarterly progress report, December 1, 1995--February 29, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    This report describes the overall program status of the General Electric Advanced Gas Turbine Development program, and reports progress on three main task areas. The program is focused on two specific products: (1) a 70-MW class industrial gas turbine based on the GE90 core technology, utilizing a new air cooling methodology; and (2) a 200-MW class utility gas turbine based on an advanced GE heavy-duty machine, utilizing advanced cooling and enhancement in component efficiency. The emphasis for the industrial system is placed on cycle design and low emission combustion. For the utility system, the focus is on developing a technology base for advanced turbine cooling while achieving low emission combustion. The three tasks included in this progress report are on: conversion to a coal-fueled advanced turbine system, integrated program plan, and design and test of critical components. 13 figs., 1 tab.

  13. Hydrogen production methods efficiency coupled to an advanced high temperature accelerator driven system

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez, Daniel González; Lira, Carlos Alberto Brayner de Oliveira [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear; Fernández, Carlos García, E-mail: danielgonro@gmail.com, E-mail: mmhamada@ipen.br [Instituto Superior de Tecnologías y Ciencias aplicadas (InSTEC), La Habana (Cuba)

    2017-07-01

    The hydrogen economy is one of the most promising concepts for the energy future. In this scenario, oil is replaced by hydrogen as an energy carrier. This hydrogen, rather than oil, must be produced in volumes not provided by the currently employed methods. In this work two high temperature hydrogen production methods coupled to an advanced nuclear system are presented. A new design of a pebbled-bed accelerator nuclear driven system called TADSEA is chosen because of the advantages it has in matters of transmutation and safety. For the conceptual design of the high temperature electrolysis process a detailed computational fluid dynamics model was developed to analyze the solid oxide electrolytic cell that has a huge influence on the process efficiency. A detailed flowsheet of the high temperature electrolysis process coupled to TADSEA through a Brayton gas cycle was developed using chemical process simulation software: Aspen HYSYS®. The model with optimized operating conditions produces 0.1627 kg/s of hydrogen, resulting in an overall process efficiency of 34.51%, a value in the range of results reported by other authors. A conceptual design of the iodine-sulfur thermochemical water splitting cycle was also developed. The overall efficiency of the process was calculated performing an energy balance resulting in 22.56%. The values of efficiency, hydrogen production rate and energy consumption of the proposed models are in the values considered acceptable in the hydrogen economy concept, being also compatible with the TADSEA design parameters. (author)

  14. Advanced glycation end products: a link between periodontitis and diabetes mellitus?

    Science.gov (United States)

    Gurav, Abhijit N

    2013-09-01

    Advanced glycation end products (AGEs) are synthesized via the non enzymaticglycation and oxidation of proteins, lipids and nucleic acids. The production of AGEs is particularly enhanced in chronic hyperglycemia, as in diabetes mellitus (DM). The formation of irreversible AGEs affects the tissues by compromising the physiologic and mechanical functions, as a result of defective constitution of the extracellular matrix (ECM) components. Periodontitis is an inflammatory disease of microbial origin, resulting in devastation of the tooth supporting apparatus. This disease condition has severe implicationsin subjects with DM, since the tooth supporting tissuescontain ECM targeted by AGE. There is miniscule literature regarding the contribution of AGE to periodontal disease in patients with DM. The purpose of this review is to address the prejudicial role of AGEs in relation to various tissue components. This paper is an attempt to elucidatethe possible link of AGEs between periodontitis and DM. The exploration of novel therapeutic strategies to target AGEs for the treatment of periodontitis in DM subjects is certainly intriguing.

  15. Production of potato minitubers using advanced environmental control technologies developed for growing plants in space

    Science.gov (United States)

    Britt, Robert G.

    1998-01-01

    Development of plant growth systems for use in outer space have been modified for use on earth as the backbone of a new system for rapid growth of potato minitubers. The automation of this new biotechnology provides for a fully controllable method of producing pathogen-free nuclear stock potato minitubers from tissue cultured clones of varieties of potato in a biomanufacturing facility. These minitubers are the beginning stage of seed potato production. Because the new system provides for pathogen-free minitubers by the tens-of-millions, rather than by the thousands which are currently produced in advanced seed potato systems, a new-dimension in seed potato development, breeding and multiplication has been achieved. The net advantage to earth-borne agricultural farming systems will be the elimination of several years of seed multiplication from the current system, higher quality potato production, and access to new potato varieties resistant to diseases and insects which will eliminate the need for chemical controls.

  16. Recent Advances in Supported Metal Catalysts for Syngas Production from Methane

    Directory of Open Access Journals (Sweden)

    Mohanned Mohamedali

    2018-03-01

    Full Text Available Over the past few years, great attention is paid to syngas production processes from different resources especially from abundant sources, such as methane. This review of the literature is intended for syngas production from methane through the dry reforming (DRM and the steam reforming of methane (SRM. The catalyst development for DRM and SRM represents the key factor to realize a commercial application through the utilization of more efficient catalytic systems. Due to the enormous amount of published literature in this field, the current work is mainly dedicated to the most recent achievements in the metal-oxide catalyst development for DRM and SRM in the past five years. Ni-based supported catalysts are considered the most widely used catalysts for DRM and SRM, which are commercially available; hence, this review has focused on the recent advancements achieved in Ni catalysts with special focus on the various attempts to address the catalyst deactivation challenge in both DRM and SRM applications. Furthermore, other catalytic systems, including Co-based catalysts, noble metals (Pt, Rh, Ru, and Ir, and bimetallic systems have been included in this literature review to understand the observed improvements in the catalytic activities and coke suppression property of these catalysts.

  17. Hydrogen production methods efficiency coupled to an advanced high temperature accelerator driven system

    International Nuclear Information System (INIS)

    Rodríguez, Daniel González; Lira, Carlos Alberto Brayner de Oliveira

    2017-01-01

    The hydrogen economy is one of the most promising concepts for the energy future. In this scenario, oil is replaced by hydrogen as an energy carrier. This hydrogen, rather than oil, must be produced in volumes not provided by the currently employed methods. In this work two high temperature hydrogen production methods coupled to an advanced nuclear system are presented. A new design of a pebbled-bed accelerator nuclear driven system called TADSEA is chosen because of the advantages it has in matters of transmutation and safety. For the conceptual design of the high temperature electrolysis process a detailed computational fluid dynamics model was developed to analyze the solid oxide electrolytic cell that has a huge influence on the process efficiency. A detailed flowsheet of the high temperature electrolysis process coupled to TADSEA through a Brayton gas cycle was developed using chemical process simulation software: Aspen HYSYS®. The model with optimized operating conditions produces 0.1627 kg/s of hydrogen, resulting in an overall process efficiency of 34.51%, a value in the range of results reported by other authors. A conceptual design of the iodine-sulfur thermochemical water splitting cycle was also developed. The overall efficiency of the process was calculated performing an energy balance resulting in 22.56%. The values of efficiency, hydrogen production rate and energy consumption of the proposed models are in the values considered acceptable in the hydrogen economy concept, being also compatible with the TADSEA design parameters. (author)

  18. Recent Advances in Improvement of Forecast Skill and Understanding Climate Processes Using AIRS Version-5 Products

    Science.gov (United States)

    Susskind, Joel; Molnar, Gyula; Iredell, Lena; Rosenberg, Robert

    2012-01-01

    AIRS/AMSU is the state of the art infrared and microwave atmospheric sounding system flying aboard EOS Aqua. These observations, covering the period September 2002 until the present, have been analyzed using the AIRS Science Team Version-5 retrieval algorithm. AIRS is a high spectral resolution infrared grating spectrometer with spect,ral coverage from 650 per centimeter extending to 2660 per centimeter, with low noise and a spectral resolving power of 2400. A brief overview of the AIRS Version-5 retrieval procedure will be presented, including the AIRS channels used in different steps in the retrieval process. Many researchers have used these products to make significant advances in both climate and weather applications. Recent significant results of these experiments will be presented, including results showing that 1) assimilation of AIRS Quality Controlled temperature profiles into a General Circulation Model (GCM) significantly improves the ability to predict storm tracks of intense precipitation events; and 2) anomaly time-series of Outgoing Longwave Radiation (OLR) computed using AIRS sounding products closely match those determined from the CERES instrument, and furthermore explain that the phenomenon that global and especially tropical mean OLR have been decreasing since September 2002 is a result of El Nino/La Nina oscillations during this period.

  19. Do Advanced Glycation End Products (AGEs) Contribute to the Comorbidities of Polycystic Ovary Syndrome (PCOS)?

    Science.gov (United States)

    Rutkowska, Aleksandra Zofia; Diamanti-Kandarakis, Evanthia

    2016-01-01

    Advanced glycation end products (AGEs) are formed both during the endogenous and exogenous reactions and are implicated in the process of ageing, pathogenesis of diabetes, atherosclerosis, female fertility, and cancers. Food and smoking are the most important sources of exogenous AGEs in daily life. The biochemical composition of meal, cooking methods, time and temperature of food preparation may impact AGEs formation, therefore Western-type diet, rich in animal-derived products as well as in fast foods seems to be the main source of AGEs. Both, endogenous and exogenous AGEs can act intracellularly or during serum interaction with cell surface receptors called RAGE influencing variety of molecular pathways. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. The aetiology of this disorder remains unclear, however the environmental and genetic factors may play an important role in its pathogenesis. Nevertheless, PCOS women have increased factors for reproductive and cardiometabolic comorbidities. AGEs can contribute to the pathogenesis of PCOS as well as its consequences. It has been shown that chronic inflammation and increased oxidative stress may be a link between the mechanisms of AGEs action and the metabolic and reproductive consequences of PCOS. This review highlights that high dietary AGEs intake promotes deteriorating biological effects in women with PCOS, whereas AGEs restriction seems to have beneficial impact on women health. Better understanding AGEs formation and biochemistry as well as AGE-mediated pathophysiological mechanisms may open new therapeutic avenues converging to the achievement of the complete treatment of PCOS and its consequences.

  20. Microbial production of polyhydroxyalkanoates (PHAs) and its copolymers: A review of recent advancements.

    Science.gov (United States)

    Anjum, Anbreen; Zuber, Mohammad; Zia, Khalid Mahmood; Noreen, Aqdas; Anjum, Muhammad Naveed; Tabasum, Shazia

    2016-08-01

    Traditional mineral oil based plastics are important commodity to enhance the comfort and quality of life but the accumulation of these plastics in the environment has become a major universal problem due to their low biodegradation. Solution to the plastic waste management includes incineration, recycling and landfill disposal methods. These processes are very time consuming and expensive. Biopolymers are important alternatives to the petroleum-based plastics due to environment friendly manufacturing processes, biodegradability and biocompatibility. Therefore use of novel biopolymers, such as polylactide, polysaccharides, aliphatic polyesters and polyhydroxyalkanoates is of interest. PHAs are biodegradable polyesters of hydroxyalkanoates (HA) produced from renewable resources by using microorganisms as intracellular carbon and energy storage compounds. Even though PHAs are promising candidate for biodegradable polymers, however, the production cost limit their application on an industrial scale. This article provides an overview of various substrates, microorganisms for the economical production of PHAs and its copolymers. Recent advances in PHAs to reduce the cost and to improve the performance of PHAs have also been discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Advanced glycation endproducts in 35 types of seafood products consumed in eastern China

    Science.gov (United States)

    Wang, Jing; Li, Zhenxing; Pavase, Ramesh Tushar; Lin, Hong; Zou, Long; Wen, Jie; Lv, Liangtao

    2016-08-01

    Advanced glycation endproducts (AGEs) have been recognized as hazards in processed foods that can induce chronic diseases such as cardiovascular disease, diabetes, and diabetic nephropathy. In this study, we investigated the AGEs contents of 35 types of industrial seafood products that are consumed frequently in eastern China. Total fluorescent AGEs level and Nɛ-carboxymethyl-lysine (CML) content were evaluated by fluorescence spectrophotometry and gas chromatography-mass spectrometry (GC-MS), respectively. The level of total fluorescent AGEs in seafood samples ranged from 39.37 to 1178.3 AU, and was higher in canned and packaged instant aquatic products that were processed at high temperatures. The CML content in seafood samples ranged from 44.8 to 439.1 mg per kg dried sample, and was higher in roasted seafood samples. The total fluorescent AGEs and CML content increased when seafood underwent high-temperature processing, but did not show an obvious correlation. The present study suggested that commonly consumed seafood contains different levels of AGEs, and the seafood processed at high temperatures always displays a high level of either AGEs or CML.

  2. The role of condensed tannins in ruminant animal production: advances, limitations and future directions

    Directory of Open Access Journals (Sweden)

    Harley D. Naumann

    Full Text Available ABSTRACT Tannins represent one of the most abundant polyphenolic compounds in plants. Tannins exist as a multitude of chemically unique entities in nature. The most commonly occurring tannins are typically divided into two major classes based on chemical structure: hydrolysable (HT or condensed tannins (CT. Hydrolysable tannins are esters of gallic or ellagic acid linked to a polyol core, typically glucose. Condensed tannins or proanthocyanidins consist of flavan-3-ol subunits linked together to form oligomers and polymers. Both HT and CT are defined as astringent, medium-to-high-molecular weight polyphenolic compounds that characteristically bind and precipitate soluble proteins. The objective of this paper was to present recent advances in CT-ruminant interactions, the limitations associated with understanding and using CT in ruminant animal production, and future needs for research to further advance our knowledge of the role of CT in optimization of ruminant animal production. Condensed tannins pose some anti-nutritional problems to ruminants due to their astringent property that reduces feed intake and, consequently, animal performance. Ruminants can, however, tolerate CT by slowly adapting the ruminal microbes to the toxic effects of CT and by releasing CT-binding salivary proteins. The protein-binding ability of CT has some benefits to the ruminant due to complexes formed with essential amino acids, preventing their degradation in the rumen, but releasing them in the lower gut for absorption by the animal. Recent data have suggested increased N retention when CT is given to growing animals. There are potential benefits of using CT and HT for anthelmintic purposes due to their ability to inhibit egg hatching and larval motility of gastrointestinal nematode parasites, especially in small ruminants. Condensed tannins also bind to minerals (Al, Ca, Co, Cu, Fe, Mg, Mn, P, and Zn. Although studies with ruminants have been contradictory, it has

  3. Advancement of highly charged ion beam production by superconducting ECR ion source SECRAL (invited)

    International Nuclear Information System (INIS)

    Sun, L.; Lu, W.; Zhang, W. H.; Feng, Y. C.; Qian, C.; Ma, H. Y.; Zhang, X. Z.; Zhao, H. W.; Guo, J. W.; Yang, Y.; Fang, X.

    2016-01-01

    At Institute of Modern Physics (IMP), Chinese Academy of Sciences (CAS), the superconducting Electron Cyclotron Resonance (ECR) ion source SECRAL (Superconducting ECR ion source with Advanced design in Lanzhou) has been put into operation for about 10 years now. It has been the main working horse to deliver intense highly charged heavy ion beams for the accelerators. Since its first plasma at 18 GHz, R&D work towards more intense highly charged ion beam production as well as the beam quality investigation has never been stopped. When SECRAL was upgraded to its typical operation frequency 24 GHz, it had already showed its promising capacity of very intense highly charged ion beam production. And it has also provided the strong experimental support for the so called scaling laws of microwave frequency effect. However, compared to the microwave power heating efficiency at 18 GHz, 24 GHz microwave heating does not show the ω 2 scale at the same power level, which indicates that microwave power coupling at gyrotron frequency needs better understanding. In this paper, after a review of the operation status of SECRAL with regard to the beam availability and stability, the recent study of the extracted ion beam transverse coupling issues will be discussed, and the test results of the both TE 01 and HE 11 modes will be presented. A general comparison of the performance working with the two injection modes will be given, and a preliminary analysis will be introduced. The latest results of the production of very intense highly charged ion beams, such as 1.42 emA Ar 12+ , 0.92 emA Xe 27+ , and so on, will be presented

  4. The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach.

    Science.gov (United States)

    Salahuddin, Parveen; Rabbani, Gulam; Khan, Rizwan Hasan

    2014-09-01

    Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies have shown that glycation induces the formation of the β-sheet structure in β-amyloid protein, α-synuclein, transthyretin (TTR), copper-zinc superoxide dismutase 1 (Cu, Zn-SOD-1), and prion protein. Aggregation of the β-sheet structure in each case creates fibrillar structures, respectively causing Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, and prion disease. It has been suggested that oligomeric species of glycated α-synuclein and prion are more toxic than fibrils. This review focuses on the pathway of AGE formation, the synthesis of different types of AGE, and the molecular mechanisms by which glycation causes various types of neurodegenerative disease. It discusses several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic and naturally occurring inhibitors. Modulation of the AGE-RAGE axis is now considered promising in the prevention of neurodegenerative diseases. Additionally, the review covers several defense enzymes and proteins in the human body that are important anti-glycating systems acting to prevent the development of neurodegenerative diseases.

  5. Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

    Science.gov (United States)

    Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

    2017-05-01

    Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  6. Dental, Dental Hygiene, and Advanced Dental Students' Use, Knowledge, and Beliefs Regarding Tobacco Products.

    Science.gov (United States)

    Shearston, Jenni A; Shah, Krina; Cheng, Eric; Moosvi, Rizvan; Park, Su Hyun; Patel, Naiya; Spielman, Andrew I; Weitzman, Michael L

    2017-11-01

    Using cigarettes and alternative tobacco products (ATPs) is associated with negative oral health outcomes, and dental health professionals are poised to help patients quit. The aim of this study was to determine dental, dental hygiene, and advanced dental students' use, knowledge, and beliefs about cigarettes and ATPs, including perceptions about their education in tobacco dependence treatment and counseling experience. All 1,783 students enrolled in the dental, dental hygiene, and postdoctoral dental programs at the New York University College of Dentistry were invited to participate in the survey in 2016. A total of 708 students at least partially completed the survey, for a response rate of 39.7%. In the results, 146 of the students (20.1%) reported ever using cigarettes, while 253 (35.7%) reported ever using any ATP. Regarding tobacco use intervention, the students reported they had not received enough training on ATPs, were neutral about cigarettes, and were somewhat confident and not so confident counseling a cigarette smoker or ATP user, respectively. By their fourth year, 77.8% of the dental students reported they had counseled someone to stop smoking cigarettes, but only 40.7% had counseled someone to stop using ATPs. Overall, all groups of students reported feeling more confident and had received more education on interventions for cigarettes than for ATPs (ptobacco and did not perceive they had received enough training on intervening with patients on use of cigarettes and ATPs. These findings call for a revised tobacco education curriculum for dental, dental hygiene, and advanced dental students, focused on building knowledge and confidence for promoting tobacco dependence treatment.

  7. Fission Product Monitoring of TRISO Coated Fuel For The Advanced Gas Reactor -1 Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Dawn M. Scates; John (Jack) K Hartwell; John B. Walter

    2008-09-01

    The US Department of Energy has embarked on a series of tests of TRISO-coated particle reactor fuel intended for use in the Very High Temperature Reactor (VHTR) as part of the Advanced Gas Reactor (AGR) program. The AGR-1 TRISO fuel experiment, currently underway, is the first in a series of eight fuel tests planned for irradiation in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL). The AGR-1 experiment reached a peak compact averaged burn up of 9% FIMA with no known TRISO fuel particle failures in March 2008. The burnup goal for the majority of the fuel compacts is to have a compact averaged burnup greater than 18% FIMA and a minimum compact averaged burnup of 14% FIMA. At the INL the TRISO fuel in the AGR-1 experiment is closely monitored while it is being irradiated in the ATR. The effluent monitoring system used for the AGR-1 fuel is the Fission Product Monitoring System (FPMS). The FPMS is a valuable tool that provides near real-time data indicative of the AGR-1 test fuel performance and incorporates both high-purity germanium (HPGe) gamma-ray spectrometers and sodium iodide [NaI(Tl)] scintillation detector-based gross radiation monitors. To quantify the fuel performance, release-to-birth ratios (R/B’s) of radioactive fission gases are computed. The gamma-ray spectra acquired by the AGR-1 FPMS are analyzed and used to determine the released activities of specific fission gases, while a dedicated detector provides near-real time count rate information. Isotopic build up and depletion calculations provide the associated isotopic birth rates. This paper highlights the features of the FPMS, encompassing the equipment, methods and measures that enable the calculation of the release-to-birth ratios. Some preliminary results from the AGR-1 experiment are also presented.

  8. Advanced turbine systems program conceptual design and product development. Quarterly report, February 1995--April 1995

    Energy Technology Data Exchange (ETDEWEB)

    Karstensen, K.W.

    1995-07-01

    This Quarterly Technical Progress Report covers the period February 1, 1995, through April 30, 1995, for Phase II of the Advanced Turbine Systems (ATS) Program by Solar Turbines Incorporated under DOE contract No. DE-AC21-93MC30246. The objective of Phase II of the ATS Program is to provide the conceptual design and product development plan for an ultra high efficiency, environmentally superior and cost competitive industrial gas turbine system to be commercialized by the year 2000. A secondary objective is to begin early development of technologies critical to the success of ATS. Tasks 1, 2, 3, 5, 6 and 7 of Phase II have been completed in prior quarters. Their results have been discussed in the applicable quarterly reports and in their respective topical reports. With the exception of Task 7, final editions of these topical reports have been submitted to the DOE. This quarterly report, then, addresses only Task 4 and the nine subtasks included in Task 8, {open_quotes}Design and Test of Critical Components.{close_quotes} These nine subtasks address six ATS technologies as follows: (1) Catalytic Combustion - Subtasks 8.2 and 8.5, (2) Recuperator - Subtasks 8.1 and 8.7, (3) Autothermal Fuel Reformer - Subtask 8.3, (4) High Temperature Turbine Disc - Subtask 8.4, (5) Advanced Control System (MMI) - Subtask 8.6, and (6) Ceramic Materials - Subtasks 8.8 and 8.9. Major technological achievements from Task 8 efforts during the quarter are as follows: (1) The subscale catalytic combustion rig in Subtask 8.2 is operating consistently at 3 ppmv of NO{sub x} over a range of ATS operating conditions. (2) The spray cast process used to produce the rim section of the high temperature turbine disc of Subtask 8.4 offers additional and unplanned spin-off opportunities for low cost manufacture of certain gas turbine parts.

  9. The distribution of advanced glycation end products and their receptor in the gastrointestinal tract in the rats

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Gregersen, Hans

    2012-01-01

    To investigate the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the gastrointestinal (GI) tract to provide a basis for further study of the association between AGE/RAGE and diabetic GI dysfunction. METHODS: The distribution of AGEs [N epsilon-(carboxymethyl)......To investigate the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the gastrointestinal (GI) tract to provide a basis for further study of the association between AGE/RAGE and diabetic GI dysfunction. METHODS: The distribution of AGEs [N epsilon...

  10. Purpose, processes, partnerships, and products: four Ps to advance participatory socio-environmental modeling.

    Science.gov (United States)

    Gray, Steven; Voinov, Alexey; Paolisso, Michael; Jordan, Rebecca; BenDor, Todd; Bommel, Pierre; Glynn, Pierre; Hedelin, Beatrice; Hubacek, Klaus; Introne, Josh; Kolagani, Nagesh; Laursen, Bethany; Prell, Christina; Schmitt Olabisi, Laura; Singer, Alison; Sterling, Eleanor; Zellner, Moira

    2018-01-01

    Including stakeholders in environmental model building and analysis is an increasingly popular approach to understanding ecological change. This is because stakeholders often hold valuable knowledge about socio-environmental dynamics and collaborative forms of modeling produce important boundary objects used to collectively reason about environmental problems. Although the number of participatory modeling (PM) case studies and the number of researchers adopting these approaches has grown in recent years, the lack of standardized reporting and limited reproducibility have prevented PM's establishment and advancement as a cohesive field of study. We suggest a four-dimensional framework (4P) that includes reporting on dimensions of (1) the Purpose for selecting a PM approach (the why); (2) the Process by which the public was involved in model building or evaluation (the how); (3) the Partnerships formed (the who); and (4) the Products that resulted from these efforts (the what). We highlight four case studies that use common PM software-based approaches (fuzzy cognitive mapping, agent-based modeling, system dynamics, and participatory geospatial modeling) to understand human-environment interactions and the consequences of ecological changes, including bushmeat hunting in Tanzania and Cameroon, agricultural production and deforestation in Zambia, and groundwater management in India. We demonstrate how standardizing communication about PM case studies can lead to innovation and new insights about model-based reasoning in support of ecological policy development. We suggest that our 4P framework and reporting approach provides a way for new hypotheses to be identified and tested in the growing field of PM. © 2017 by the Ecological Society of America.

  11. Purpose, Processes, Partnerships, and Products: 4Ps to advance Participatory Socio-Environmental Modeling

    Science.gov (United States)

    Gray, S. G.; Voinov, A. A.; Jordan, R.; Paolisso, M.

    2016-12-01

    Model-based reasoning is a basic part of human understanding, decision-making, and communication. Including stakeholders in environmental model building and analysis is an increasingly popular approach to understanding environmental change since stakeholders often hold valuable knowledge about socio-environmental dynamics and since collaborative forms of modeling produce important boundary objects used to collectively reason about environmental problems. Although the number of participatory modeling (PM) case studies and the number of researchers adopting these approaches has grown in recent years, the lack of standardized reporting and limited reproducibility have prevented PM's establishment and advancement as a cohesive field of study. We suggest a four dimensional framework that includes reporting on dimensions of: (1) the Purpose for selecting a PM approach (the why); (2) the Process by which the public was involved in model building or evaluation (the how); (3) the Partnerships formed (the who); and (4) the Products that resulted from these efforts (the what). We highlight four case studies that use common PM software-based approaches (fuzzy cognitive mapping, agent-based modeling, system dynamics, and participatory geospatial modeling) to understand human-environment interactions and the consequences of environmental changes, including bushmeat hunting in Tanzania and Cameroon, agricultural production and deforestation in Zambia, and groundwater management in India. We demonstrate how standardizing communication about PM case studies can lead to innovation and new insights about model-based reasoning in support of environmental policy development. We suggest that our 4P framework and reporting approach provides a way for new hypotheses to be identified and tested in the growing field of PM.

  12. Sulforaphane reduces advanced glycation end products (AGEs)-induced inflammation in endothelial cells and rat aorta.

    Science.gov (United States)

    Matsui, T; Nakamura, N; Ojima, A; Nishino, Y; Yamagishi, S-I

    2016-09-01

    Advanced glycation end products (AGEs)-receptor RAGE interaction evokes oxidative stress and inflammatory reactions, thereby being involved in endothelial cell (EC) damage in diabetes. Sulforaphane is generated from glucoraphanin, a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, by myrosinase. Sulforaphane has been reported to protect against oxidative stress-mediated cell and tissue injury. However, effects of sulforaphane on AGEs-induced vascular damage remain unclear. In this study, we investigated whether and how sulforaphane could inhibit inflammation in AGEs-exposed human umbilical vein ECs (HUVECs) and AGEs-injected rat aorta. Sulforaphane treatment for 4 or 24 h dose-dependently inhibited the AGEs-induced increase in RAGE, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecular-1 (VCAM-1) gene expression in HUVECs. AGEs significantly stimulated MCP-1 production by, and THP-1 cell adhesion to, HUVECs, both of which were prevented by 1.6 μM sulforaphane. Sulforaphane significantly suppressed oxidative stress generation and NADPH oxidase activation evoked by AGEs in HUVECs. Furthermore, aortic RAGE, ICAM-1 and VCAM-1 expression in AGEs-injected rats were increased, which were suppressed by simultaneous infusion of sulforaphane. The present study demonstrated for the first time that sulforaphane could inhibit inflammation in AGEs-exposed HUVECs and AGEs-infused rat aorta partly by suppressing RAGE expression through its anti-oxidative properties. Inhibition of the AGEs-RAGE axis by sulforaphane might be a novel therapeutic target for vascular injury in diabetes. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  13. Advanced oxidative protein products induced human keratinocyte apoptosis through the NOX-MAPK pathway.

    Science.gov (United States)

    Sun, Baihui; Ding, Ruoting; Yu, Wenlin; Wu, Yanhong; Wang, Bulin; Li, Qin

    2016-07-01

    Impaired wound healing is a major diabetes-related complication. Keratinocytes play an important role in wound healing. Multiple factors have been proposed that can induce dysfunction in keratinocytes. The focus of present research is at a more specific molecular level. We investigated the role of advanced oxidative protein products (AOPPs) in inducing human immortalized keratinocyte (HaCaT) cell apoptosis and the cellular mechanism underlying the proapoptotic effect of AOPPs. HaCaT cells were treated with increasing concentrations of AOPP-human serum albumin or for increasing time durations. The cell viability was measured using the thiazolyl blue tetrazolium bromide method, and flow cytometry was used to assess the rate of cell apoptosis. A loss of mitochondrial membrane potential (MMP) and an increase in intracellular reactive oxygen species (ROS) were observed through a confocal laser scanning microscope system, and the level of ROS generation was determined using a microplate reader. Nicotinamide adenine dinucleotide phosphate oxidase (NOX)4, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and apoptosis-related downstream protein interactions were investigated using the Western blot analysis. We found that AOPPs triggered HaCaT cell apoptosis and MMP loss. After AOPP treatment, intracellular ROS generation increased in a time- and dose-dependent manner. Proapoptotic proteins, such as Bax, caspase 9/caspase 3, and poly(ADP-ribose) polymerase (PARP)-1 were activated, whereas anti-apoptotic Bcl-2 protein was downregulated. AOPPs also increased NOX4, ERK1/2, and p38 MAPK expression. Taken together, these findings suggest that extracellular AOPP accumulation triggered NOX-dependent ROS production, which activated ERK1/2 and p38 MAPK, and induced HaCaT cell apoptosis by activating caspase 3 and PARP-1.

  14. Purpose, processes, partnerships, and products: four Ps to advance participatory socio-environmental modeling

    Science.gov (United States)

    Gray, Steven; Voinov, Alexey; Paolisso, Michael; Jordan, Rebecca; BenDor, Todd; Bommel, Pierre; Glynn, Pierre D.; Hedelin, Beatrice; Hubacek, Klaus; Introne, Josh; Kolagani, Nagesh; Laursen, Bethany; Prell, Christina; Schmitt-Olabisi, Laura; Singer, Alison; Sterling, Eleanor J.; Zellner, Moira

    2018-01-01

    Including stakeholders in environmental model building and analysis is an increasingly popular approach to understanding ecological change. This is because stakeholders often hold valuable knowledge about socio-environmental dynamics and collaborative forms of modeling produce important boundary objects used to collectively reason about environmental problems. Although the number of participatory modeling (PM) case studies and the number of researchers adopting these approaches has grown in recent years, the lack of standardized reporting and limited reproducibility have prevented PM's establishment and advancement as a cohesive field of study. We suggest a four-dimensional framework (4P) that includes reporting on dimensions of (1) the Purpose for selecting a PM approach (the why); (2) the Process by which the public was involved in model building or evaluation (the how); (3) the Partnerships formed (the who); and (4) the Products that resulted from these efforts (the what). We highlight four case studies that use common PM software-based approaches (fuzzy cognitive mapping, agent-based modeling, system dynamics, and participatory geospatial modeling) to understand human–environment interactions and the consequences of ecological changes, including bushmeat hunting in Tanzania and Cameroon, agricultural production and deforestation in Zambia, and groundwater management in India. We demonstrate how standardizing communication about PM case studies can lead to innovation and new insights about model-based reasoning in support of ecological policy development. We suggest that our 4P framework and reporting approach provides a way for new hypotheses to be identified and tested in the growing field of PM.

  15. Increased levels of circulating advanced glycation end-products in menopausal women with osteoporosis.

    Science.gov (United States)

    Yang, Deng-Ho; Chiang, Tsay-I; Chang, I-Chang; Lin, Fu-Huang; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-01-01

    Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis.

  16. Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yaw Kuang Chuah

    2013-01-01

    Full Text Available The receptor for advanced glycation end products (RAGE is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.

  17. Receptor for advanced glycation end products (RAGE) knockout reduces fetal dysmorphogenesis in murine diabetic pregnancy.

    Science.gov (United States)

    Ejdesjö, Andreas; Brings, Sebastian; Fleming, Thomas; Fred, Rikard G; Nawroth, Peter P; Eriksson, Ulf J

    2016-07-01

    The receptor for Advanced Glycation End products (RAGE) is implicated in the pathogenesis of diabetic complications, but its importance in diabetic embryopathy is unclear. We therefore investigated the role of RAGE in diabetic embryopathy using streptozotocin induced diabetes in female wild type (WT) C57Bl/6N and RAGE knockout C57Bl/6N (RAGE(-/-)) mice, mated with control males of the same genotype. Maternal diabetes induced more fetal resorption and malformation (facial skeleton, neural tube) in the WT than in the RAGE(-/-) fetuses. Maternal plasma glucose and methylgyoxal concentrations, as well as embryonic N(ε)-carboxymethyl-lysine (CML) levels were increased to the same extent in diabetic WT and RAGE(-/-) pregnancy. However, maternal diabetes induced increased fetal hepatic isoprostane 8-iso-PGF2α levels (oxidative stress marker) and embryonic activation of NFκB in WT only (not in RAGE(-/-) embryos). The association between RAGE knockout and diminished embryonic dysmorphogenesis in diabetic pregnancy suggests that embryonic RAGE activation is involved in diabetic embryopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Receptor for advanced glycation end products (RAGE)-mediated cytotoxicity of 3-hydroxypyridinium derivatives.

    Science.gov (United States)

    Murakami, Yoto; Fujino, Takayuki; Hasegawa, Toshiki; Kurachi, Ryotaro; Miura, Aya; Daikoh, Takumi; Usui, Teruyuki; Hayase, Fumitaka; Watanabe, Hirohito

    2018-02-01

    Advanced glycation end products (AGEs) formed from glyceraldehyde (Gcer) and glycolaldehyde (Gcol) are involved in the pathogenesis of diabetic complications, via interactions with a receptor for AGEs (RAGE). In this study, we aimed to elucidate the RAGE-binding structure in Gcer and Gcol-derived AGEs and identify the minimal moiety recognized by RAGE. Among Gcer and Gcol-derived AGEs, GLAP (glyceraldehyde-derived pyridinium) and GA-pyridine elicited toxicity in PC12 neuronal cells. The toxic effects of GLAP and GA-pyridine were suppressed in the presence of anti-RAGE antibody or the soluble form of RAGE protein. Furthermore, the cytotoxicity test using GLAP analog compounds indicated that the 3-hydroxypyridinium (3-HP) structure is sufficient for RAGE-dependent toxicity. Surface plasmon resonance analysis showed that 3-HP derivatives directly interact with RAGE. These results indicate that GLAP and GA-pyridine are RAGE-binding epitopes, and that 3-HP, a common moiety of GLAP and GA-pyridine, is essential for the interaction with RAGE.

  19. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    International Nuclear Information System (INIS)

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J.

    2014-01-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction

  20. Phosphorene Co-catalyst Advancing Highly Efficient Visible-Light Photocatalytic Hydrogen Production.

    Science.gov (United States)

    Ran, Jingrun; Zhu, Bicheng; Qiao, Shi-Zhang

    2017-08-21

    Transitional metals are widely used as co-catalysts boosting photocatalytic H 2 production. However, metal-based co-catalysts suffer from high cost, limited abundance and detrimental environment impact. To date, metal-free co-catalyst is rarely reported. Here we for the first time utilized density functional calculations to guide the application of phosphorene as a high-efficiency metal-free co-catalyst for CdS, Zn 0.8 Cd 0.2 S or ZnS. Particularly, phosphorene modified CdS shows a high apparent quantum yield of 34.7 % at 420 nm. This outstanding activity arises from the strong electronic coupling between phosphorene and CdS, as well as the favorable band structure, high charge mobility and massive active sites of phosphorene, supported by computations and advanced characterizations, for example, synchrotron-based X-ray absorption near edge spectroscopy. This work brings new opportunities to prepare highly-active, cheap and green photocatalysts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Production of titanium alloys for advanced aerospace systems by powder metallurgy

    Directory of Open Access Journals (Sweden)

    Vinicius André Rodrigues Henriques

    2005-12-01

    Full Text Available Titanium alloys parts are ideally suited for advanced aerospace systems because of their unique combination of high specific strength at both room temperature and moderately elevated temperature, in addition to excellent corrosion resistance. Despite these features, use of titanium alloys in engines and airframes is limited by cost. The alloys processing by powder metallurgy eases the obtainment of parts with complex geometry. In this work, results of the Ti-6Al-4V and Ti-13Nb-13Zr alloys production are presented. Samples were produced by mixing of initial metallic powders followed by uniaxial and cold isostatic pressing with subsequent densification by sintering between 900 up to 1500 °C, in vacuum. Sintered samples were characterized for phase composition, microstructure and microhardness by X-ray diffraction, scanning electron microscopy and Vickers indentation, respectively. It was shown that the samples were sintered to high densities and presented homogeneous microstructure from the elements dissolution with low interstitial pick-up.

  2. Advanced glycation end products (AGEs and their receptor (RAGE induce apoptosis of periodontal ligament fibroblasts

    Directory of Open Access Journals (Sweden)

    D.X. Li

    2014-12-01

    Full Text Available Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL fibroblasts induced by advanced glycation end products (AGEs and their receptor (RAGE. We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA, bovine serum albumin (BSA alone, or given no treatment (control. Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01 and increased apoptosis (11.31±1.73%, P<0.05. Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  3. Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells.

    Science.gov (United States)

    Kaji, Yuichi; Amano, Shiro; Usui, Tomohiko; Oshika, Tetsuro; Yamashiro, Kenji; Ishida, Susumu; Suzuki, Kaori; Tanaka, Sumiyoshi; Adamis, Anthony P; Nagai, Ryoji; Horiuchi, Seiko

    2003-02-01

    The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGEs), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death. First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGEs were added to the culture media of the cultured CECs, and the uptake of AGEs, the generation of reactive oxygen species, and the induction of apoptosis were investigated. Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGEs, the generation of reactive oxygen and the number of apoptotic cells also increased. These results show that the accumulation of AGEs in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGEs in the CECs of elderly patients may be involved in the loss of CECs during the aging process.

  4. Inhibitory effect of GSPE on RAGE expression induced by advanced glycation end products in endothelial cells.

    Science.gov (United States)

    Zhang, Feng-Lei; Gao, Hai-Qing; Shen, Lin

    2007-10-01

    Advanced glycation end products' (AGEs) engagement of a cell-surface receptor for AGEs (RAGE) has been causally implicated in the pathogenesis of diabetic vascular complications via induction of reactive oxygen species (ROS) and subsequent alteration of many gene expressions, including RAGE itself. Grapeseed proanthocyanidin extract (GSPE), which is a naturally occurring polyphenolic compound, has been reported to possess potent radical-scavenging and antioxidant properties and to display significant cardiovascular protective action. In this study, we investigated whether GSPE could inhibit AGE-induced RAGE expression through interference with ROS generation in human umbilical-vein endothelial cells (HUVECs). AGE-modified bovine serum albumin (AGE-BSA) was prepared by incubating BSA with high-concentration glucose. Stimulation of cultured HUVECs with 200 microg/mL of AGE-BSA significantly enhanced intracellular ROS formation and subsequently upregulated the protein and mRNA expression of RAGE; unmodified BSA and GSPE alone had no effect. However, GSPE preincubation markedly downregulated AGE-induced surface expression of RAGE in a time- and concentration-dependent manner. In AGE-stimulated HUVECs, GSPE also dose-dependently decreased RAGE mRNA levels and inhibited AGE-induced ROS generation at defined time periods. These results demonstrate that GSPE can inhibit enhanced RAGE expression in AGE-exposed endothelial cells by suppressing ROS generation, thereby limiting the AGE-RAGE interaction. Hence, GSPE may have therapeutic potential in the prevention and treatment of vascular complications in diabetic patients.

  5. Phytochemicals Against Advanced Glycation End Products (AGEs) and the Receptor System.

    Science.gov (United States)

    Yamagishi, Sho-Ichi; Matsui, Takanori; Ishibashi, Yuji; Isami, Fumiyuki; Abe, Yumi; Sakaguchi, Tatsuya; Higashimoto, Yuichiro

    2017-01-01

    Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. So the AGE-RAGE axis is a novel therapeutic target for numerous devastating disorders. Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGERAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Crop Production for Advanced Life Support Systems - Observations From the Kennedy Space Center Breadboard Project

    Science.gov (United States)

    Wheeler, R. M.; Sager, J. C.; Prince, R. P.; Knott, W. M.; Mackowiak, C. L.; Stutte, G. W.; Yorio, N. C.; Ruffe, L. M.; Peterson, B. V.; Goins, G. D.

    2003-01-01

    The use of plants for bioregenerative life support for space missions was first studied by the US Air Force in the 1950s and 1960s. Extensive testing was also conducted from the 1960s through the 1980s by Russian researchers located at the Institute of Biophysics in Krasnoyarsk, Siberia, and the Institute for Biomedical Problems in Moscow. NASA initiated bioregenerative research in the 1960s (e.g., Hydrogenomonas) but this research did not include testing with plants until about 1980, with the start of the Controlled Ecological Life Support System (CELSS) Program. The NASA CELSS research was carried out at universities, private corporations, and NASA field centers, including Kennedy Space Center (KSC). The project at KSC began in 1985 and was called the CELSS Breadboard Project to indicate the capability for plugging in and testing various life support technologies; this name has since been dropped but bioregenerative testing at KSC has continued to the present under the NASA s Advanced Life Support (ALS) Program. A primary objective of the KSC testing was to conduct pre-integration tests with plants (crops) in a large, atmospherically closed test chamber called the Biomass Production Chamber (BPC). Test protocols for the BPC were based on observations and growing procedures developed by university investigators, as well as procedures developed in plant growth chamber studies at KSC. Growth chamber studies to support BPC testing focused on plant responses to different carbon dioxide (CO2) concentrations, different spectral qualities from various electric lamps, and nutrient film hydroponic culture techniques.

  7. Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

    Science.gov (United States)

    Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

    2017-08-01

    Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

  8. Advanced glycation end products assessed by skin autofluorescence: a new marker of diabetic foot ulceration.

    Science.gov (United States)

    Vouillarmet, Julien; Maucort-Boulch, Delphine; Michon, Paul; Thivolet, Charles

    2013-07-01

    Accumulation of advanced glycation end products (AGEs) may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether AGEs measurement by skin autofluorescence (SAF) would be an additional marker for DFU management. We performed SAF analysis in 66 patients with a history of DFU prospectively included and compared the results with those of 84 control patients with diabetic peripheral neuropathy without DFU. We then assessed the prognostic value of SAF levels on the healing rate in the DFU group. Mean SAF value was significantly higher in the DFU group in comparison with the control group, even after adjustment for other diabetes complications (3.2±0.6 arbitrary units vs. 2.9±0.6 arbitrary units; P=0.001). In the DFU group, 58 (88%) patients had an active wound at inclusion. The mean DFU duration was 14±13 weeks. The healing rate was 47% after 2 months of appropriate foot care. A trend for a correlation between SAF levels and healing time in DFU subjects was observed but was not statistically significant (P=0.06). Increased SAF levels are associated with neuropathic foot complications in diabetes. Use of SAF measurement to assess foot vulnerability and to predict DFU events in high-risk patients appears to be promising.

  9. Role of Reactive Oxygen Species and Advanced Glycation End Products in the Malfunctioning of Dental Implants.

    Science.gov (United States)

    Guo, M; Liu, L; Zhang, J; Liu, M

    2015-09-01

    In the last decade, dental implants have emerged as a crucial modality and serve as an individual form of therapy for dental failure. However, disparities in host responses have led to peri-implantitis and implant failure. The pathological mechanisms driving peri-implantitis remain largely unknown. In this study, we evaluated the role of oxidative stress and advanced glycation end products (AGE) in the progression of peri-implantitis and dental implants failure, compared with chronic periodontal disease. Three patient groups (peri-implantitis, chronic periodontal disease and control), each with 10 subjects (7M/3F) and average age ranging from 40-60 years were selected for analysis. Salivary oxidative stress and tissue AGE levels were analysed by probing for reactive oxygen species (ROS) and Maillard reaction-related fluorescence, respectively. We observed significant increase (> 2-fold) in oxidative stress and AGE levels in patients with peri-implantitis and chronic periodontal disease compared to controls, with chronic periodontal disease having the highest levels. In addition, we observed a strong positive correlation (r = 0.94) between oxidative stress and AGE levels in the patients. We propose that increased AGE levels and oxidative stress, although not the only pathway, are significant mediators in the pathogenesis of peri-implantitis. Altering them may potentially be used in combination with other modalities to manage peri-implantitis.

  10. Advanced glycation end products delay corneal epithelial wound healing through reactive oxygen species generation.

    Science.gov (United States)

    Shi, Long; Chen, Hongmei; Yu, Xiaoming; Wu, Xinyi

    2013-11-01

    Delayed healing of corneal epithelial wounds is a serious complication in diabetes. Advanced glycation end products (AGEs) are intimately associated with the diabetic complications and are deleterious to the wound healing process. However, the effect of AGEs on corneal epithelial wound healing has not yet been evaluated. In the present study, we investigated the effect of AGE-modified bovine serum albumin (BSA) on corneal epithelial wound healing and its underlying mechanisms. Our data showed that AGE-BSA significantly increased the generation of intracellular ROS in telomerase-immortalized human corneal epithelial cells. However, the generation of intracellular ROS was completely inhibited by antioxidant N-acetylcysteine (NAC), anti-receptor of AGEs (RAGE) antibodies, or the inhibitor of NADPH oxidase. Moreover, AGE-BSA increased NADPH oxidase activity and protein expression of NADPH oxidase subunits, p22phox and Nox4, but anti-RAGE antibodies eliminated these effects. Furthermore, prevention of intracellular ROS generation using NAC or anti-RAGE antibodies rescued AGE-BSA-delayed epithelial wound healing in porcine corneal organ culture. In conclusion, our results demonstrated that AGE-BSA impaired corneal epithelial wound healing ex vivo. AGE-BSA increased intracellular ROS generation through NADPH oxidase activation, which accounted for the delayed corneal epithelial wound healing. These results may provide better insights for understanding the mechanism of delayed healing of corneal epithelial wounds in diabetes.

  11. Soft-tissue wound healing by anti-advanced glycation end-products agents.

    Science.gov (United States)

    Chang, P-C; Tsai, S-C; Jheng, Y-H; Lin, Y-F; Chen, C-C

    2014-04-01

    The blocking of advanced glycation end-products (AGE) has been shown to reduce diabetic complications and control periodontitis. This study investigated the pattern of palatal wound-healing after graft harvesting under the administration of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker. Full-thickness palatal excisional wounds (5.0 x 1.5 mm(2)) were created in 72 Sprague-Dawley rats. The rats received daily intraperitoneal injections of normal saline (control), AG, or PTB and were euthanized after 4 to 28 days. The wound-healing pattern was assessed by histology, histochemistry for collagen matrix deposition, immunohistochemistry for AGE and the AGE receptor (RAGE), and the expression of RAGE, as well as inflammation- and recovery-associated genes. In the first 14 days following AG or PTB treatments, wound closure, re-epithelialization, and collagen matrix deposition were accelerated, whereas AGE deposition, RAGE-positive cells, and inflammation were reduced. RAGE and tumor necrosis factor-alpha were significantly down-regulated at day 7, and heme oxygenase-1 was persistently down-regulated until day 14. The levels of vascular endothelial growth factor, periostin, type I collagen, and fibronectin were all increased at day 14. In conclusion, anti-AGE agents appeared to facilitate palatal wound-healing by reducing AGE-associated inflammation and promoting the recovery process.

  12. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-01-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  13. Uptake of advanced glycation end products by proximal tubule epithelial cells via macropinocytosis.

    Science.gov (United States)

    Gallicchio, Marisa A; Bach, Leon A

    2013-12-01

    Chronic hyperglycaemia during diabetes leads to non-enzymatic glycation of proteins to form advanced glycation end products (AGEs) that contribute to nephropathy. We describe AGE uptake in LLC-PK1 and HK2 proximal tubule cell lines by macropinocytosis, a non-specific, endocytic mechanism. AGE-BSA induced dorsal circular actin ruffles and amiloride-sensitive dextran-TRITC uptake, significantly increased AGE-BSA-FITC uptake (167±20% vs BSA control, pmacropinocytosis. PAK1 and PIP5Kγ siRNA significantly decreased AGE-BSA-FITC uptake (81±6% and 64±7%, respectively, pmacropinocytosis inhibitors and a neutralising TGF-β antibody, reversed the AGE-induced decrease in surface Na(+)K(+)ATPase, suggesting AGE uptake by macropinocytosis may contribute to diabetic kidney fibrosis and/or EMT by modulating this pump. Understanding methods of cellular uptake and signalling by AGEs may lead to novel therapies for diabetic nephropathy. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS?

    Directory of Open Access Journals (Sweden)

    Deepika Garg

    2015-12-01

    Full Text Available PCOS is the most common cause of anovulation in reproductive-aged women with 70% experiencing ovulatory problems. Advanced glycation end products are highly reactive molecules that are formed by non-enzymatic reactions of sugars with proteins, nucleic acids and lipids. AGEs are also present in a variety of diet where substantial increase in AGEs can result due to thermal processing and modifications of food. Elevation in bodily AGEs, produced endogenously or absorbed exogenously from high-AGE diets, is further exaggerated in women with PCOS and is associated with ovulatory dysfunction. Additionally, increased expression of AGEs as pro-inflammatory receptors in the ovarian tissue has been observed in women with PCOS. In this review, we summarize the role of dietary AGEs as mediators of metabolic and reproductive alterations in PCOS. Once a mechanistic understanding of the relationship between AGEs and anovulation is established, there is a promise that such knowledge will contribute to the subsequent development of targeted pharmacological therapies that will treat anovulation and improve ovarian health in women with PCOS.

  15. Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS?

    Science.gov (United States)

    Garg, Deepika; Merhi, Zaher

    2015-12-04

    PCOS is the most common cause of anovulation in reproductive-aged women with 70% experiencing ovulatory problems. Advanced glycation end products are highly reactive molecules that are formed by non-enzymatic reactions of sugars with proteins, nucleic acids and lipids. AGEs are also present in a variety of diet where substantial increase in AGEs can result due to thermal processing and modifications of food. Elevation in bodily AGEs, produced endogenously or absorbed exogenously from high-AGE diets, is further exaggerated in women with PCOS and is associated with ovulatory dysfunction. Additionally, increased expression of AGEs as pro-inflammatory receptors in the ovarian tissue has been observed in women with PCOS. In this review, we summarize the role of dietary AGEs as mediators of metabolic and reproductive alterations in PCOS. Once a mechanistic understanding of the relationship between AGEs and anovulation is established, there is a promise that such knowledge will contribute to the subsequent development of targeted pharmacological therapies that will treat anovulation and improve ovarian health in women with PCOS.

  16. Advances in plant proteomics toward improvement of crop productivity and stress resistancex

    Science.gov (United States)

    Hu, Junjie; Rampitsch, Christof; Bykova, Natalia V.

    2015-01-01

    Abiotic and biotic stresses constrain plant growth and development negatively impacting crop production. Plants have developed stress-specific adaptations as well as simultaneous responses to a combination of various abiotic stresses with pathogen infection. The efficiency of stress-induced adaptive responses is dependent on activation of molecular signaling pathways and intracellular networks by modulating expression, or abundance, and/or post-translational modification (PTM) of proteins primarily associated with defense mechanisms. In this review, we summarize and evaluate the contribution of proteomic studies to our understanding of stress response mechanisms in different plant organs and tissues. Advanced quantitative proteomic techniques have improved the coverage of total proteomes and sub-proteomes from small amounts of starting material, and characterized PTMs as well as protein–protein interactions at the cellular level, providing detailed information on organ- and tissue-specific regulatory mechanisms responding to a variety of individual stresses or stress combinations during plant life cycle. In particular, we address the tissue-specific signaling networks localized to various organelles that participate in stress-related physiological plasticity and adaptive mechanisms, such as photosynthetic efficiency, symbiotic nitrogen fixation, plant growth, tolerance and common responses to environmental stresses. We also provide an update on the progress of proteomics with major crop species and discuss the current challenges and limitations inherent to proteomics techniques and data interpretation for non-model organisms. Future directions in proteomics research toward crop improvement are further discussed. PMID:25926838

  17. Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro.

    Science.gov (United States)

    Bansal, Savita; Siddarth, Manushi; Chawla, Diwesh; Banerjee, Basu D; Madhu, S V; Tripathi, Ashok K

    2012-02-01

    Increased oxidative stress (OS) in diabetes mellitus is one of the major factors leading to diabetic pathology. However, the mediators and mechanism that provoke OS in diabetes is not fully understood, and it is possible that accumulation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions may incite circulating polymorphonuclear neutrophils (PMN) to generate reactive oxygen species (ROS). In this report, we aim to investigate the effect of AGE on reactive oxygen and nitrogen species generation and subsequent OS in PMN. AGE-HSA exert dose- and time-dependent enhancement of ROS and reactive nitrogen intermediates (RNI) generation by PMN. Increased ROS and RNI generation were found to be mediated through the upregulation of NADPH oxidase and inducible nitric oxide synthase (iNOS), respectively, as evident from the fact that AGE-treated neutrophils failed to generate ROS and RNI in presence of diphenyleneiodonium, a flavoprotein inhibitor for both enzymes. Further increased generation of ROS and RNI ceased when the cells were incubated with anti-RAGE antibody suggesting the involvement of AGE-RAGE interaction. Also increased malondialdehyde (MDA) and protein carbonyl formation in AGE-exposed PMN suggest induction of OS by AGE. This study provides evidence that AGEs may play a key role in the induction of oxidative stress through the augmentation of PMN-mediated ROS and RNI generation and this may be in part responsible for development of AGE-induced diabetic pathology.

  18. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Science.gov (United States)

    Achouiti, Ahmed; de Vos, Alex F; van 't Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W; Nawroth, Peter P; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A D

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS.

  19. Advanced oxidation protein products and their relationship with cardiovascular risk factors in young apparently healthy people.

    Science.gov (United States)

    Villalpando Sánchez, Diana Carolina; Alvarez Aguilar, Cleto; Gómez García, Anel

    Advanced oxidation protein products (AOPPs) are used as a marker to estimate oxidative stress in plasma proteins. Oxidative stress is considered a factor of cardiovascular risk (CVRF) related to increased blood pressure, and dyslipidaemia. The aim of this study was to evaluate the association between plasma AOPPs and CVRF in apparently healthy young adults. A prospective cross-sectional study was conducted on 120 students of the Faculty of Chemical-Pharmacobiology of the UMSNH. Body mass index (BMI) and blood pressure were determined. A blood specimen was also collected to quantify AOPPs, glucose, total cholesterol, lipoproteins (high, low, and very low density), and triglycerides. Differences were observed in the groups with and without CVRF, with significant differences in BMI, waist, body fat (Pfactor, because their deposition in the atherosclerotic plaque favours the atherogenic process, and thus the development of cardiovascular disease. Quantification of AOPPs contributes to the indirect determination of oxidative status in the body. The study of metabolic and oxidative state of apparently healthy young adults is important in the prevention of cardiovascular disease in later life. More longitudinal studies are required to study its evolution. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Blockade of advanced glycation end product formation attenuates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Liu Dai-Shun

    2009-06-01

    Full Text Available Abstract Background Advanced glycation end products (AGEs have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM-stimulated rat model treated with aminoguanidine (AG, a crosslink inhibitor of AGE formation. Methods Rats were intratracheally instilled with BLM (5 mg/kg and orally administered with AG (40, 80, 120 mg/kg once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47, a collagen specific molecular chaperone, was measured with RT-PCR and Western blot. Moreover, TGFβ1 and its downstream Smad proteins were analyzed by Western blot. Results AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p Conclusion These findings suggest AGE formation may participate in the process of BLM-induced pulmonary fibrosis, and blockade of AGE formation by AG treatment attenuates BLM-induced pulmonary fibrosis in rats, which is implicated in inhibition of HSP47 expression and TGFβ/Smads signaling.

  1. Hurdles in clinical implementation of academic advanced therapy medicinal products: A national evaluation.

    Science.gov (United States)

    de Wilde, Sofieke; Veltrop-Duits, Louise; Hoozemans-Strik, Merel; Ras, Thirza; Blom-Veenman, Janine; Guchelaar, Henk-Jan; Zandvliet, Maarten; Meij, Pauline

    2016-06-01

    Since the implementation of the European Union (EU) regulation for advanced therapy medicinal products (ATMPs) in 2009, only six ATMPs achieved marketing authorization approval in the EU. Recognizing the major developments in the ATMP field, starting mostly in academic institutions, we investigated which hurdles were experienced in the whole pathway of ATMP development towards clinical care. Quality interviews were executed with different stakeholders in The Netherlands involved in the ATMP development field, e.g. academic research groups, national authorities and patient organizations. Based on the hurdles mentioned in the interviews, questionnaires were subsequently sent to the academic principal investigators (PIs) and ATMP good manufacturing practice (GMP) facility managers to quantify these hurdles. Besides the familiar regulatory routes of marketing authorization (MA) and hospital exemption (HE), a part of the academic PIs perceived that ATMPs should become available by the Tissues and Cells Directive or did not anticipate on the next development steps towards implementation of their ATMP towards regular clinical care. The main hurdles identified were: inadequate financial support, rapidly evolving field, study-related problems, lacking regulatory knowledge, lack of collaborations and responsibility issues. Creating an academic environment stimulating and planning ATMP development and licensing as well as investing in expanding the relevant regulatory knowledge in academic institutions seems a prerequisite to develop ATMPs from bench to patient. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  2. Increased advanced glycation end product specific fluorescence in repeatedly heated used cooking oil.

    Science.gov (United States)

    Chhabra, Anupriya; Bhatia, Alka; Ram, Anil Kumar; Goel, Sumit

    2017-07-01

    Repeated heating of cooking oils is known to cause their degradation and generation of toxins. Dietary Advanced glycation end products (dAGEs) are formed when the foods are cooked in dry heat at very high temperatures. dAGEs are believed to contribute significantly to total pool of AGEs in body. In this study, cooking oil samples used for frying snacks were collected from 102 shops. AGEs were extracted using Aqueous-TCA-chloroform method. Fluorescent AGE levels were determined using a fluorescence spectrophotometer and compared with AGEs in corresponding fresh oil samples collected from same shops. Palm oil was most commonly (62.5%) used for cooking. Most of the samples were subjected to several rounds of heating (1-6). AGE specific fluorescence (ASF) in used oil (range = 8.5-745.11) samples was found to be significantly higher in 88/102 as compared to the corresponding fresh oil samples. Treatment with inhibitors like lime concentrate and vitamin C decreased ASF (10/14 and 10/11 samples respectively) of the used oils. The results suggest that cooking oil subjected to repeated heating can contribute to increase in fluorescent AGEs in diet. Simple practices like liberal use of common household substances like lime concentrate may help to reduce these in fried food.

  3. Advanced oxidation protein products are more related to metabolic syndrome components than biomarkers of lipid peroxidation.

    Science.gov (United States)

    Venturini, Danielle; Simão, Andréa Name Colado; Dichi, Isaias

    2015-09-01

    Although advanced oxidation protein products (AOPPs) have been reported as the most appropriate parameter for determination of oxidative stress in patients with metabolic syndrome (MetS), a direct comparison between protein and lipid peroxidation has not been performed yet. The aim of this study was to compare protein peroxidation with lipid peroxidation measured by 2 different methodologies (tert-butyl hydroperoxide-initiated chemiluminescence and ferrous oxidation-xylenol orange assay). The hypothesis of this study was that AOPPs would be more related to MetS than to oxidative markers of lipid peroxidation. This cross-sectional study evaluated 76 patients with MetS and 20 healthy subjects. Prooxidant-antioxidant index (PAI) assessed as AOPP/total radical-trapping antioxidant parameter ratio progressively increased (P protein (r = 0.275, P protein (r = 0.278, P protein peroxidation determined by AOPPs, and especially by PAI, is more related to MetS components than lipid peroxidation. In addition, PAI progressively increased with the number of MetS components. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J. [Department of Stomatology, Air Force General Hospital PLA, Haidian District, Beijing (China)

    2014-09-19

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  5. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products

    Directory of Open Access Journals (Sweden)

    Seoungwoo Shin

    2015-11-01

    Full Text Available The accumulation of free radicals and advanced glycation end products (AGEs in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow’s feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation.

  6. Cloning and characterization of the canine receptor for advanced glycation end products.

    Science.gov (United States)

    Murua Escobar, Hugo; Soller, Jan T; Sterenczak, Katharina A; Sperveslage, Jan D; Schlueter, Claudia; Burchardt, Birgit; Eberle, Nina; Fork, Melanie; Nimzyk, Rolf; Winkler, Susanne; Nolte, Ingo; Bullerdiek, Jörn

    2006-03-15

    Metastasis is one of the major problems when dealing with malignant neoplasias. Accordingly, the finding of molecular targets, which can be addressed to reduce tumour metastasising, will have significant impact on the development of new therapeutic approaches. Recently, the receptor for advanced glycation end products (RAGE)-high mobility group B1 (HMGB1) protein complex has been shown to have significant influence on invasiveness, growth and motility of tumour cells, which are essential characteristics required for metastatic behaviour. A set of in vitro and in vivo approaches showed that blocking of this complex resulted in drastic suppression of tumour cell growth. Due to the similarities of human and canine cancer the dog has joined the common rodent animal model for therapeutic and preclinical studies. However, complete characterisation of the protein complex is a precondition to a therapeutic approach based on the blocking of the RAGE-HMGB1 complex to spontaneously occurring tumours in dogs. We recently characterised the canine HMGB1 gene and protein completely. Here we present the complete characterisation of the canine RAGE gene including its 1384 bp mRNA, the 1215 bp protein coding sequence, the 2835 bp genomic structure, chromosomal localisation, gene expression pattern, and its 404 amino acid protein. Furthermore we compared the CDS of six different canine breeds and screened them for single nucleotide polymorphisms.

  7. Receptor for advanced glycation end-products is a marker of type I lung alveolar cells.

    Science.gov (United States)

    Shirasawa, Madoka; Fujiwara, Naoyuki; Hirabayashi, Susumu; Ohno, Hideki; Iida, Junko; Makita, Koshi; Hata, Yutaka

    2004-02-01

    Lung alveolar epithelial cells are comprised of type I (ATI) and type II (ATII) cells. ATI cells are polarized, although they have very flat morphology. The identification of marker proteins for apical and basolateral membranes of ATI cells is important to investigate into the differentiation of ATI cells. In this paper, we characterized receptor for advanced glycation end-products (RAGE) as a marker for ATI cells. RAGE was localized on basolateral membranes of ATI cells in the immunoelectron microscopy and its expression was enhanced in a parallel manner to the differentiation of ATI cells in vivo and in primary cultures of ATII cells. RAGE and T1 alpha, a well-known ATI marker protein, were targeted to basolateral and apical membranes, respectively, when expressed in polarized Madine Darby canine kidney cells. Moreover, RAGE was expressed in ATI cells after T1 alpha in vivo and in ex in vivo organ cultures. In conclusion, RAGE is a marker for basolateral membranes of well-differentiated ATI cells. ATI cells require some signal provided by the in vivo environment to express RAGE.

  8. TREATMENT OF METAL-LADEN HAZARDOUS WASTES WITH ADVANCED CLEAN COAL TECHNOLOGY BY-PRODUCTS

    Energy Technology Data Exchange (ETDEWEB)

    James T. Cobb, Jr.

    2003-09-12

    Metal-laden wastes can be stabilized and solidified using advanced clean coal technology by-products (CCTBs)--fluid bed combustor ash and spray drier solids. These utility-generated treatment chemicals are available for purchase through brokers, and commercial applications of this process are being practiced by treaters of metal-laden hazardous waste. A complex of regulations governs this industry, and sensitivities to this complex has discouraged public documentation of treatment of metal-laden hazardous wastes with CCTBs. This report provides a comprehensive public documentation of laboratory studies that show the efficacy of the stabilization and solidification of metal-laden hazardous wastes--such as lead-contaminated soils and sandblast residues--through treatment with CCTBs. It then describes the extensive efforts that were made to obtain the permits allowing a commercial hazardous waste treater to utilize CCTBs as treatment chemicals and to install the equipment required to do so. It concludes with the effect of this lengthy process on the ability of the treatment company to realize the practical, physical outcome of this effort, leading to premature termination of the project.

  9. Recent advances on synchronization of ovulation in goats, out of season, for a more sustainable production

    Directory of Open Access Journals (Sweden)

    J. Simões

    2015-06-01

    Full Text Available Goats show marked progressive seasonal reproduction at latitude > 25° and reproductive management should be adapted to market demands. The present review aimed to discuss the synchronization of ovulation for timed artificial insemination concerning new insights regarding a clean, green and ethical meat and milk production. Today, the induction of ovulation during breeding season or transitions periods is mainly based on progestagens/ progesterone (P4 devices intravaginally inserted on females, at least during 11 days, plus equine chorionic gonadotropin (eCG and prostaglandin F2 alfa administration. In last years a reduction to 20 mg of fluorogestone acetate was made and the successful reutilization of devices containing 0.3 g of P4 indicates a possible reduction of their levels. Shortening the period of exogenous progestagens/P4 priming (5 to 7 days is critical for a rational use of hormones. Moreover, the eCG exchange by socio-sexual cues (male effect seems to see a great advance, even if a previous photoperiod treatment, or equivalent method, being necessary in high latitudes. Research trends on these subjects are expected in future using different goats breeds in distinct regions of world.

  10. Accumulation of Advanced Glycation End Products as a Molecular Mechanism for Aging as a Risk Factor in Osteoarthritis

    NARCIS (Netherlands)

    Groot, J. de; Verzijl, N.; Wenting-Wijk, M.J.G. van; Jacobs, K.M.G.; El, B. van; Roermund, P.M. van; Bank, R.A.; Bijlsma, J.W.J.; TeKoppele, J.M.; Lafeber, F.P.J.G.

    2004-01-01

    Objective. Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. Its etiology is largely unknown, but age is the most prominent risk factor. The current study was designed to test whether accumulation of advanced glycation end products (AGEs), which

  11. Association of Polymorphism in the Receptor for Advanced Glycation End Products (RAGE) Gene with Circulating RAGE Levels

    NARCIS (Netherlands)

    Gaens, Katrien H. J.; Ferreira, Isabel; van der Kallen, Carla J. H.; van Greevenbroek, Marleen M. J.; Blaak, Ellen E.; Feskens, Edith J. M.; Dekker, Jacqueline M.; Nijpels, Giel; Heine, Robert J.; 't Hart, Leen M.; de Groot, Philip G.; Stehouwer, Coen D. A.; Schalkwijk, Casper G.

    2009-01-01

    Objective: The receptor for advanced glycation end products (RAGE)-ligand interaction has been linked to vascular complications. The family of soluble forms of RAGE (sRAGE) consists of splice variants and proteolytically cleaved and shed forms of RAGE. sRAGE may be a reflection of cell-bound RAGE.

  12. Receptor for Advanced Glycation End Products Facilitates Host Defense during Escherichia coli-Induced Abdominal Sepsis in Mice

    NARCIS (Netherlands)

    van Zoelen, Marieke A. D.; Schmidt, Ann-Marie; Florquin, Sandrine; Meijers, Joost C.; de Beer, Regina; de Vos, Alex F.; Nawroth, Peter P.; Bierhaus, Angelika; van der Poll, Tom

    2009-01-01

    Background. The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses. Methods. To determine the role of RAGE in the innate immune response to abdominal sepsis caused by Escherichia coli, RAGE-deficient (RAGE(-/-)) and normal wild-type mice were

  13. Advanced glycation end products, measured in skin, vs. HbA1c in children with type 1 diabetes mellitus

    NARCIS (Netherlands)

    Banser, Alena; Naafs, Jolanda C.; Hoorweg-Nijman, Jantine J. G.; van de Garde, Ewoudt M. W.; van der Vorst, Marja M. J.

    2016-01-01

    Background and objectiveAdvanced glycation end products (AGEs) are considered major contributors to microvascular and macrovascular complications in adult patients with diabetes mellitus. AGEs can be measured non-invasively with skin autofluorescence (sAF). The primary aim was to determine sAF

  14. On the Flexibility of Grammatical Advance Planning During Sentence Production: Effects of Cognitive Load on Multiple Lexical Access

    NARCIS (Netherlands)

    Wagner, V.; Jescheniak, J.D.; Schriefers, H.J.

    2010-01-01

    Three picture-word interference experiments addressed the question of whether the scope of grammatical advance planning in sentence production corresponds to some fixed unit or rather is flexible. Subjects produced sentences of different formats under varying amounts of cognitive load. When speakers

  15. The influence of body mass index on the accumulation of advanced glycation end products in hemodialysis patients

    NARCIS (Netherlands)

    Arsov, S.; Trajceska, L.; van Oeveren, W.; Smit, A. J.; Dzekova, P.; Stegmayr, B.; Sikole, A.; Rakhorst, G.; Graaff, R.

    BACKGROUND/OBJECTIVES: The level of skin autofluorescence (AF) at a given moment is an independent predictor of mortality in hemodialysis (HD) patients. Skin AF is a measure of the accumulation of advanced glycation end products (AGEs). The aim of the study was to estimate the influence of nutrition

  16. Biodistribution of the 18F-labelled advanced glycation end products Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL)

    International Nuclear Information System (INIS)

    Bergmann, R.; Helling, R.; Henle, T.; Heichert, C.; Scheunemann, M.; Maeding, P.; Wittrisch, H.; Johannsen, B.

    2002-01-01

    After synthesis of fluorine-18 labelled analogues [ 18 F]fluorobenzoylation at the α-amino group, biodistribution and elimination of individual advanced glycation end products, namely N ε -carboxymethyllysine and N ε -carboxyethyllysine, was studied in comparison to lysine in rats after intravenous injection using positron emission tomography. (orig.)

  17. Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Berg, T J; Snorgaard, O; Faber, J

    1999-01-01

    Impairment of left ventricular diastolic function, possibly caused by increased collagen cross-linking of the cardiac muscle, is common in patients with type 1 diabetes even without coronary artery disease. Advanced glycation end products (AGEs) cross-link tissue collagen and are found within...

  18. Mirror Advanced Reactor Study (MARS): executive summary and overview

    International Nuclear Information System (INIS)

    Logan, B.G.; Perkins, L.J.; Gordon, J.D.

    1984-07-01

    Two self-consistent MARS configurations are discussed - a 1200-MWe commercial electricity-generating plant and a synguels-generating plant that produces hydrogen with an energy equivalent to 26,000 barrels of oil per day. The MARS machine emphasizes the attractive features of the tandem mirror concept, including steady-state operation, a small-diameter high-beta plasma, a linear central cell with simple low-maintenance blankets, low first-wall heat fluxes ( 2 ), no driven plasma currents or associated disruptions, natural halo impurity diversion, and direct conversion of end-loss charged-particle power. The MARS electric plant produces 2600 MW of fusion power in a 130-m-long central cell. Advanced tandem-mirror plasma-engineering concepts, a high-efficiency liquid lithium-lead (Li 17 Pb 83 ) blanket, and efficient direct electrical conversion of end loss power combine to produce a high net plant efficiency of 36%. With a total capital cost of $2.9 billion (constant 1983 dollars), the MARS electric plant produces busbar electricity at approx. 7 cents/kW-hour. The MARS synfuels plant produces 3500 MW of fusion power in a 150-m-long central cell. A helium-gas-cooled silicon carbide pebble-bed blanket provides high-temperature (1000 0 C) heat to a thermochemical water-splitting cycle and the resulting hydrogen is catalytically converted to methanol for distribution. With a total capital cost of $3.6 billion (constant 1983 dollars), the synfuels plant produces methanol fuel at about $1.7/gal. The major features of the MARS reactor include sloshing-ion thermal barrier plugs for efficient plasma confinement, a high efficiency blanket, high-field (24-T) choke cells, drift pumping for trapped plasma species, quasi-optical electron-cyclotron resonant heating (ECRH) systems, and a component gridless direct converter

  19. Advanced linear Fresnel optics for solar thermal energy (STE) production (Conference Presentation)

    Science.gov (United States)

    Collares-Pereira, Manuel

    2016-09-01

    One path towards low electricity cost is the use of ever higher concentration values, since that, in turn, will provide less thermal losses at higher temperatures and high temperature operation means higher thermodynamic efficiency in the conversion of heat into electricity. However concentration has an added value, since it is associated with larger primaries (see below) and thus with a reduction of collector rows in any given collector field. That, in turn, will reduce receiver length, connecting pipe lengths, number of components, thermal losses in pipes, heat transfer fluid mass, pumping power required (thus less parasitics), OM necessary, and all of that will contribute towards a lower electricity production cost. Conventional PT and LFR concentrators are, essentially, focusing optics solutions and thus very far from the concentration limits set by Non Imaging Optics. However if a conventional PT optics is designed to accommodate a second stage concentrator (or, even better, if a parabolic like primary is designed in an optimal way with a secondary concentrator for a given receiver) the result will have a much higher concentration, but also, as a consequence, a much larger size, since available evacuated tubular receivers come in basically one (standard) size : 70mm diameter. Thus from a typical aperture size of 6m and a concentration value of 26, to double the concentration value with n.i.o., would bring the aperture close to 12m, a value which is not practical for manufacture, transportation, field installation and operation (think about wind loads, for instance) . But with LFR technology this size limitation is not there at all, and low concentration values can now be substituted by much higher ones, and primaries between 20 and 30 m can be produced for the same tube. Some LFRs on the market do have second stage concentration and offer primaries of about 12m total mirror width when designed for those evacuated tubes. These correspond to a CPC type second

  20. ROBOTICALLY ENHANCED ADVANCED MANUFACTURING CONCEPTS TO OPTIMIZE ENERGY, PRODUCTIVITY, AND ENVIRONMENTAL PERFORMANCE

    Energy Technology Data Exchange (ETDEWEB)

    Larry L. Keller; Joseph M. Pack; Robert V. Kolarik II

    2007-11-05

    In the first phase of the REML project, major assets were acquired for a manufacturing line for follow-on installation, capability studies and optimization. That activity has been documented in the DE-FC36-99ID13819 final report. In this the second phase of the REML project, most of the major assets have been installed in a manufacturing line arrangement featuring a green cell, a thermal treatment cell and a finishing cell. Most of the secondary and support assets have been acquired and installed. Assets have been integrated with a commercial, machine-tending gantry robot in the thermal treatment cell and with a low-mass, high-speed gantry robot in the finish cell. Capabilities for masterless gauging of product’s dimensional and form characteristics were advanced. Trial production runs across the entire REML line have been undertaken. Discrete event simulation modeling has aided in line balancing and reduction of flow time. Energy, productivity and cost, and environmental comparisons to baselines have been made. Energy The REML line in its current state of development has been measured to be about 22% (338,000 kVA-hrs) less energy intensive than the baseline conventional low volume line assuming equivalent annual production volume of approximately 51,000 races. The reduction in energy consumption is largely attributable to the energy reduction in the REML thermal treatment cell where the heating devices are energized on demand and are appropriately sized to the heating load of a near single piece flow line. If additional steps such as power factor correction and use of high-efficiency motors were implemented to further reduce energy consumption, it is estimated, but not yet demonstrated, that the REML line would be about 30% less energy intensive than the baseline conventional low volume line assuming equivalent annual production volume. Productivity The capital cost of an REML line would be roughly equivalent to the capital cost of a new conventional line. The

  1. Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks

    DEFF Research Database (Denmark)

    Chen, Yun; Nielsen, Jens

    2013-01-01

    Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective...... production. Here we discuss how the development of computational algorithms, novel modules and methods, omics-based techniques combined with modeling refinement are enabling reduction in development time and thus advance the field of industrial biotechnology. We further discuss how recent technological...... developments contribute to the development of novel cell factories for the production of the building block chemicals: adipic acid, succinic acid and 3-hydroxypropionic acid....

  2. Advanced Production Surface Preparation Technology Development for Ultra-High Pressure Diesel Injection

    Energy Technology Data Exchange (ETDEWEB)

    Grant, Marion B.

    2012-04-30

    In 2007, An Ultra High Injection Pressure (UHIP) fueling method has been demonstrated by Caterpillar Fuel Systems - Product Development, demonstrating ability to deliver U.S. Environment Protection Agency (EPA) Tier 4 Final diesel engine emission performance with greatly reduced emissions handling components on the engine, such as without NOx reduction after-treatment and with only a through-flow 50% effective diesel particulate trap (DPT). They have shown this capability using multiple multi-cylinder engine tests of an Ultra High Pressure Common Rail (UHPCR) fuel system with higher than traditional levels of CEGR and an advanced injector nozzle design. The system delivered better atomization of the fuel, for more complete burn, to greatly reduce diesel particulates, while CEGR or high efficiency NOx reduction after-treatment handles the NOx. With the reduced back pressure of a traditional DPT, and with the more complete fuel burn, the system reduced levels of fuel consumption by 2.4% for similar delivery of torque and horsepower over the best Tier 4 Interim levels of fuel consumption in the diesel power industry. The challenge is to manufacture the components in high-volume production that can withstand the required higher pressure injection. Production processes must be developed to increase the toughness of the injector steel to withstand the UHIP pulsations and generate near perfect form and finish in the sub-millimeter size geometries within the injector. This project resulted in two developments in 2011. The first development was a process and a machine specification by which a high target of compressive residual stress (CRS) can be consistently imparted to key surfaces of the fuel system to increase the toughness of the steel, and a demonstration of the feasibility of further refinement of the process for use in volume production. The second development was the demonstration of the feasibility of a process for imparting near perfect, durable geometry to

  3. Expression of receptor for advanced glycation end-products (RAGE) in thymus from myasthenia patients.

    Science.gov (United States)

    Bouchikh, M; Zouaidia, F; Benhaddou, E H A; Mahassini, N; Achir, A; El Malki, H O

    2017-06-01

    The receptor for advanced glycation end-products (RAGE) is a membranous immunoglobulin involved in the pathogenesis of numerous autoimmune diseases and tumors. The aim of this study was to investigate the possible involvement of RAGE in the pathogenesis of myasthenia gravis. This prospective study included 41 cases of myasthenia gravis treated at our institution between 2010 and 2015. There were 18 men and 23 women, with an average age of 36.44±14.47 years. The majority of patients (24.4%) were classified as IIb, according to MGFA scoring, and 21 of them required corticosteroid and/or immunosuppressive treatment. Assessment of RAGE in thymus specimens was done by immunohistochemistry using RAGE antibody (C-term). RAGE expression was assessed according to various clinical, paraclinical and pathological parameters. Histopathological studies found 18 thymomas, 17 hyperplasias and six other types of pathology. Expression of RAGE was negative/weak in 19 cases and moderate/strong in 22 cases. It was more important in thymoma type B2 (P<0.001) and when the duration of myasthenia was short (P=0.04), and was not significantly related to either myasthenia clinical severity or preoperative treatment. Our results suggest that the RAGE pathway is involved in myasthenia gravis pathophysiology, especially at disease onset, and in forms with thymomas. Further studies would be indispensable to explore other aspects of this signaling pathway, especially the potential role of different ligands and soluble forms of RAGE. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Assessment of advanced glycated end product accumulation in skin using auto fluorescence multispectral imaging.

    Science.gov (United States)

    Larsson, Marcus; Favilla, Riccardo; Strömberg, Tomas

    2017-06-01

    Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF). A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, while displaying promising results, it is limited to single-point measurements performed in contact to skin tissue. Furthermore, in vivo imaging of AGE accumulation is virtually unexplored. We proposed a non-invasive, contact-less novel technique for quantifying fluorescent AGE deposits in skin tissue using a multispectral imaging camera setup (MSI) during ultraviolet (UV) exposure. Imaging involved applying a region-of-interest mask, avoiding specular reflections and a simple calibration. Results of a study conducted on 16 subjects with skin types ranging from fair to deeply pigmented skin, showed that AGE measured with MSI in forearm skin was significantly correlated with the AGE reference method (AGE Reader on forearm skin, R=0.68, p=0.005). AGE measured in facial skin was borderline significantly related to AGE Reader on forearm skin (R=0.47, p=0.078). These results support the use of the technique in devices for non-touch measurement of AGE content in either facial or forearm skin tissue over time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia

    Science.gov (United States)

    Achouiti, Ahmed; de Vos, Alex F.; van ‘t Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W.; Nawroth, Peter P.; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A. D.

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated—if any—cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID:26824892

  6. Receptor for Advanced Glycation End Products (RAGE Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

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    Ahmed Achouiti

    Full Text Available Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K. pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/- and normal wild-type (Wt mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS.

  7. Role of advanced glycation end products (AGEs) and oxidative stress in diabetic retinopathy.

    Science.gov (United States)

    Yamagishi, Sho-ichi; Ueda, Seiji; Matsui, Takanori; Nakamura, Kazuo; Okuda, Seiya

    2008-01-01

    Diabetic retinopathy is a common and potentially devastating microvascular complication in diabetes and is a leading cause of acquired blindness among the people of occupational age. However, current therapeutic options for the treatment of sight-threatening proliferative diabetic retinopathy such as photocoagulation and vitrectomy are limited by considerable side effects and far from satisfactory. Therefore, to develop novel therapeutic strategies that specifically target diabetic retinopathy is actually desired for most of the patients with diabetes. Chronic hyperglycemia is a major initiator of diabetic retinopathy. However, recent clinical study has substantiated the concept of 'hyperglycemic memory' in the pathogenesis of diabetic retinopathy. Indeed, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that the reduction in the risk of progressive retinopathy resulting from intensive therapy in patients with type 1 diabetes persisted for at least several years after the DCCT trial, despite increasing hyperglycemia. These findings suggest a long-term beneficial influence of early metabolic control on clinical outcomes in type 1 diabetic patients. Among various biochemical pathways implicated in the pathogenesis of diabetic retinopathy, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. Further, there is a growing body of evidence that AGEs-RAGE (receptor for AGEs) interaction-mediated oxidative stress generation plays an important role in diabetic retinopathy. This article summarizes the role of AGEs and oxidative stress in the development and progression of diabetic retinopathy and the therapeutic interventions that could prevent this devastating disorder. We also discuss here the pathological crosstalk between the AGEs-RAGE and the renin-angiotensin system in

  8. Gingival advanced glycation end-products in diabetes mellitus-associated chronic periodontitis: an immunohistochemical study.

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    Zizzi, A; Tirabassi, G; Aspriello, S D; Piemontese, M; Rubini, C; Lucarini, G

    2013-06-01

    The accumulation of advanced glycation end-products (AGEs) seems to play an important role in the development of diabetes mellitus (DM)-associated periodontitis; however, some aspects of this issue are still scarcely known, such as the expression of AGEs in type 1 DM-associated periodontitis and the clinical factors able to affect their accumulation. This study aimed to clarify these points by evaluating the expression of AGEs in DM-associated periodontitis. Sixteen systemically and periodontally healthy subjects and 48 subjects suffering from generalized, severe, chronic periodontitis (16 with type 1 DM, 16 with type 2 DM and 16 systemically healthy subjects) were studied clinically, periodontally and metabolically. The immunohistochemical expression of AGEs in gingival tissues was also evaluated. Subjects affected with type 1 DM presented a significantly higher percentage of AGE-positive cells than did subjects affected with type 2 DM, not only in the epithelium, but also in vessels and fibroblasts. A positive and significant correlation was found between gingival expression of AGEs and length of time affected with DM both in type 1 and type 2 DM; glycated hemoglobin, lipid profile, body mass index and age did not correlate significantly with gingival AGEs in any of the classes of subjects studied. Gingival AGEs are increased in both type 1 and type 2 DM-associated periodontitis; however, the clinical parameter that determines their accumulation, and therefore their degree of influence on the development of DM-associated periodontitis, may be the duration of DM. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. N -Glycans on the receptor for advanced glycation end products influence amphoterin binding and neurite outgrowth.

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    Srikrishna, Geetha; Huttunen, Henri J; Johansson, Lena; Weigle, Bernd; Yamaguchi, Yu; Rauvala, Heikki; Freeze, Hudson H

    2002-03-01

    In this study we show that embryonic neurite growth-promoting protein amphoterin binds to carboxylated N -glycans previously identified on mammalian endothelial cells. Since amphoterin is a ligand for the receptor for advanced glycation end products (RAGE), and the ligand-binding V-domain of the receptor contains two potential N -glycosylation sites, we hypothesized that N -glycans on RAGE may mediate its interactions with amphoterin. In support of this, anti-carboxylate antibody mAbGB3.1 immunoprecipitates bovine RAGE, and PNGase F treatment reduces its molecular mass by 4.5 kDa, suggesting that the native receptor is a glycoprotein. The binding potential of amphoterin to RAGE decreases significantly in presence of soluble carboxylated glycans or when the receptor is deglycosylated. Oligosaccharide analysis shows that RAGE contains complex type anionic N -glycans with non-sialic acid carboxylate groups, but not the HNK-1 (3-sulfoglucuronyl beta1-3 galactoside) epitope. Consistent with the functional localization of RAGE and amphoterin at the leading edges of developing neurons, mAbGB3.1 stains axons and growth cones of mouse embryonic cortical neurons, and inhibits neurite outgrowth on amphoterin matrix. The carboxylated glycans themselves promote neurite outgrowth in embryonic neurons and RAGE-transfected neuroblastoma cells. This outgrowth requires full-length, signalling-competent RAGE, as cells expressing cytoplasmic domain-deleted RAGE are unresponsive. These results indicate that carboxylated N -glycans on RAGE play an important functional role in amphoterin-RAGE-mediated signalling.

  10. Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel

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    Qiushi Wang

    2015-01-01

    Full Text Available Advanced glycation end-products (AGEs are complex and heterogeneous compounds implicated in diabetes. Sodium reabsorption through the epithelial sodium channel (ENaC at the distal nephron plays an important role in diabetic hypertension. Here, we report that H2S antagonizes AGEs-induced ENaC activation in A6 cells. ENaC open probability (PO in A6 cells was significantly increased by exogenous AGEs and that this AGEs-induced ENaC activity was abolished by NaHS (a donor of H2S and TEMPOL. Incubating A6 cells with the catalase inhibitor 3-aminotriazole (3-AT mimicked the effects of AGEs on ENaC activity, but did not induce any additive effect. We found that the expression levels of catalase were significantly reduced by AGEs and both AGEs and 3-AT facilitated ROS uptake in A6 cells, which were significantly inhibited by NaHS. The specific PTEN and PI3K inhibitors, BPV(pic  and LY294002, influence ENaC activity in AGEs-pretreated A6 cells. Moreover, after removal of AGEs from AGEs-pretreated A6 cells for 72 hours, ENaC PO remained at a high level, suggesting that an AGEs-related “metabolic memory” may be involved in sodium homeostasis. Our data, for the first time, show that H2S prevents AGEs-induced ENaC activation by targeting the ROS/PI3K/PTEN pathway.

  11. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  12. Soluble Receptor for Advanced Glycation End Products Quantifies Lung Injury in Polytraumatized Patients.

    Science.gov (United States)

    Negrin, Lukas L; Halat, Gabriel; Prosch, Helmut; Hüpfl, Michael; Hajdu, Stefan; Heinz, Thomas

    2017-05-01

    Biomarkers caused by blunt chest trauma might leak into the vascular compartment and therefore reflect the severity of parenchymal lung injury (PLI). Five promising proteins were preselected after a literature scan. The objective of our study was to identify a biomarker that is released abundantly into the serum shortly after trauma and reliably quantifies the loss of functional lung tissue. Polytraumatized patients (aged ≥18 years, Injury Severity Score [ISS] ≥16) were included in our prospective observational study if they were admitted directly to our level I trauma center during the first hour after trauma occurred. Immediately after stabilizing the patient's condition, blood samples were taken and a whole-body computed tomographic (CT) scan was obtained. Biomarker levels were measured directly after admission and on day 2. PLI volume was calculated using volumetric analysis. One hundred thirty patients met the inclusion criteria. Compared with a matched healthy control population, median levels of the soluble receptor for advanced glycation end products (sRAGE) was almost 3 times higher and decreased by 41% on day 2. Higher initial median sRAGE levels were detected in patients with PLI compared with patients without PLI and in individuals with severe PLI compared with those with mild PLI. Spearman correlation analysis and a univariate linear log regression model revealed a significant correlation/equation between initial sRAGE levels and relative PLI volume. Receiver operating characteristic (ROC) statistics identified the initial sRAGE level as an indicator of severe PLI. sRAGE levels measured shortly after trauma seem to be a promising diagnostic tool to assess the severity of PLI in polytraumatized patients. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Association between Advanced Glycation End Products and Impaired Fasting Glucose: Results from the SALIA Study.

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    Tom Teichert

    Full Text Available Advanced glycation end products (AGEs may contribute to the development of type 2 diabetes and related complications, whereas their role in the early deterioration of glycaemia is unknown. While previous studies used antibody-based methods to quantify AGEs, data from tandem mass spectrometry coupled liquid chromatography (LC-MS/MS-based measurements are limited to patients with known diabetes. Here, we used the LC-MS/MS method to test the hypothesis that plasma AGE levels are higher in individuals with impaired fasting glucose (IFG than in those with normal fasting glucose (NFG. Secondary aims were to assess correlations of plasma AGEs with quantitative markers of glucose metabolism and biomarkers of subclinical inflammation. This study included on 60 women with NFG or IFG (n = 30 each, mean age 74 years from the German SALIA cohort. Plasma levels of free metabolites (3-deoxyfructose, 3-deoxypentosone, 3-deoxypentulose, two hydroimidazolones, oxidised adducts (carboxymethyllysine, carboxyethyllysine, methionine sulfoxide and Nε-fructosyllysine were measured using LC-MS/MS. Plasma concentrations of all tested AGEs did not differ between the NFG and IFG groups (all p>0.05. Associations between plasma levels of AGEs and fasting glucose, insulin and HOMA-IR as a measure of insulin resistance were weak (r between -0.2 and 0.2, all p>0.05. The association between 3-deoxyglucosone-derived hydroimidazolone with several proinflammatory biomarkers disappeared upon adjustment for multiple testing. In conclusion, plasma AGEs assessed by LC-MS/MS were neither increased in IFG nor associated with parameters of glucose metabolism and subclinical inflammation in our study. Thus, these data argue against strong effects of AGEs in the early stages of deterioration of glucose metabolism.

  14. Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study.

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    van Dooren, Fleur E P; Pouwer, Frans; Schalkwijk, Casper G; Sep, Simone J S; Stehouwer, Coen D A; Henry, Ronald M A; Dagnelie, Pieter C; Schaper, Nicolaas C; van der Kallen, Carla J H; Koster, Annemarie; Denollet, Johan; Verhey, Frans R J; Schram, Miranda T

    2017-01-01

    Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression. Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini-International Neuropsychiatric Interview. Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder. This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression. © 2016 Wiley Periodicals, Inc.

  15. Methylglyoxal, advanced glycation end products and autism: is there a connection?

    Science.gov (United States)

    Maher, P

    2012-04-01

    Autism is a complex and heterogeneous neurodevelopmental disorder of unknown etiology but very likely resulting from both genetic and environmental factors. Recent estimates suggest that it affects 1 in 100-150 individuals in the US. Oxidative stress, inflammation and mitochondrial dysfunction have all been suggested to play key roles in autism and may be linked via alterations in cellular redox homeostasis. The glutathione/glutathione disulfide (GSH/GSSG) redox pair forms the major redox couple in cells and as such plays a critical role in regulating redox-dependent cellular functions. A number of studies have shown that variations in genes involved in GSH metabolism are associated with autism. GSH also modulates the activity of glyoxalase 1 (Glo-1), the rate-limiting enzyme for the removal of reactive dicarbonyls such as methylglyoxal (MG). MG is the major precursor for the formation of advanced glycation end products (AGEs). Both MG and AGEs can induce oxidative stress, inflammation and mitochondrial dysfunction and are implicated in diabetic complications and multiple, age-related neurological diseases. Dietary consumption of AGEs and MG correlates with food intake which has increased 20-30% over the past 20 years. Both MG and AGEs are orally absorbed, leading to increased levels in the blood. Furthermore, in humans, increased MG and AGE levels in maternal blood correlate with increased MG and AGE levels in newborn blood, potentially exposing infants to high oxidative stress and inflammation. It is hypothesized that diet derived MG and AGEs in combination with inborn genetic vulnerabilities that affect the cellular redox status are major contributors to the development of autism and provide a causal link between oxidative stress, inflammation and mitochondrial dysfunction. If future research supports this hypothesis, then by reducing the exposure to these diet-derived factors, it might be possible to decrease the prevalence of at least a subset of autism cases

  16. Impact of Androgen and Dietary Advanced Glycation End Products on Female Rat Liver

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    Eleni Palioura

    2015-09-01

    Full Text Available Background/Aims: Advanced glycation end products (AGEs have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS. The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. Methods: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30 and adult rats (Group B, n=20 that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30. All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Results: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (γGT (p≤0.0002 and indices of AGE immunostaining in liver tissue (pper se constitutes an aggravating factor as demonstrated by the elevated γGT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002 and by the elevated AST and alanine aminotransferase (ALT levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002 followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007. Conclusion: The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions.

  17. Skin autofluorescence (a marker for advanced glycation end products) and erectile dysfunction in diabetes.

    Science.gov (United States)

    Kouidrat, Youssef; Zaitouni, Ahmad; Amad, Ali; Diouf, Momar; Desailloud, Rachel; Loas, Gwenole; Lalau, Jean-Daniel

    2017-01-01

    Although diabetes-related erectile dysfunction (ED) has many etiological factors, little is known about the putative pathophysiological role of advanced glycation end products (AGEs). Skin autofluorescence is a noninvasive marker of AGEs. Recent studies have evidenced a relationship between skin autofluorescence and several complications of diabetes. We hypothesized that AGEs (assessed by skin autofluorescence) are associated with ED in diabetes patients. Between March 2014 and April 2015, 42 patients with type 1 diabetes (T1D) and 44 patients with type 2 diabetes (T2D) were consecutively enrolled in a descriptive, cross-sectional study and compared to 54 healthy controls. ED was evaluated via the 5-item version of the International Index of Erectile Function (IIEF-5). Skin autofluorescence was measured on the volar aspect of the arm with an AGE-Reader. Patients with diabetes had a mean±standard deviation age of 50±15 and a mean duration of diabetes of 16±12years. Skin autofluorescence was strongly and significantly correlated with the IIEF-5 score in the T1D subgroup (r=-0.52; P=0.004), the T2D subgroup (r=-0.32; Pmultivariate analyses that controlled for potentially confounding clinical and biochemical factors, only skin autofluorescence was still significantly correlated with the IIEF-5 score (Panalysis revealed that a skin autofluorescence value ≥3.2AU determined severe ED with a sensitivity of 60% and a specificity of 87% in diabetic patients. Skin autofluorescence is significantly associated with ED in diabetes, independently of classical confounding factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Current advanced therapy cell-based medicinal products for type-1-diabetes treatment.

    Science.gov (United States)

    Cañibano-Hernández, Alberto; Del Burgo, Laura Sáenz; Espona-Noguera, Albert; Ciriza, Jesús; Pedraz, Jose Luis

    2018-03-27

    In the XXI century diabetes mellitus has become one of the main threats to human health with higher incidence in regions such as Europe and North America. Type 1 diabetes mellitus (T1DM) occurs as a consequence of the immune-mediated destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. The administration of exogenous insulin through daily injections is the most prominent treatment for T1DM but its administration is frequently associated to failure in glucose metabolism control, finally leading to hyperglycemia episodes. Other approaches have been developed in the past decades, such as whole pancreas and islet allotransplantation, but they are restricted to patients who exhibit frequent episodes of hypoglycemia or renal failure because the lack of donors and islet survival. Moreover, patients transplanted with either whole pancreas or islets require of immune suppression to avoid the rejection of the transplant. Currently, advanced therapy medicinal products (ATMP), such as implantable devices, have been developed in order to reduce immune rejection response while increasing cell survival. To overcome these issues, ATMPs must promote vascularization, guaranteeing the nutritional contribution, while providing O 2 until vasculature can surround the device. Moreover, it should help in the immune-protection to avoid acute and chronic rejection. The transplanted cells or islets should be embedded within biomaterials with tunable properties like injectability, stiffness and porosity mimicking natural ECM structural characteristics. And finally, an infinitive cell source that solves the donor scarcity should be found such as insulin producing cells derived from mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Several companies have registered their ATMPs and future studies envision new prototypes. In this review, we will discuss the mechanisms and etiology of

  19. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products.

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    Afshin Iram

    Full Text Available Conformational alterations of bovine hemoglobin (Hb upon sequential addition of glyoxal over a range of 0-90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT fluorescence and red shifted Congo Red (CR absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's.

  1. Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth

    International Nuclear Information System (INIS)

    Elangovan, Indira; Thirugnanam, Sivasakthivel; Chen, Aoshuang; Zheng, Guoxing; Bosland, Maarten C.; Kajdacsy-Balla, André; Gnanasekar, Munirathinam

    2012-01-01

    Highlights: ► Targeting RAGE by RNAi induces apoptosis in prostate cancer cells. ► Silencing RAGE expression abrogates rHMGB1 mediated cell proliferation. ► Down regulation of RAGE by RNAi inhibits PSA secretion of prostate cancer cells. ► Knock down of RAGE abrogates prostate tumor growth in vivo. ► Disruption of RAGE expression in prostate tumor activates death receptors. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer.

  2. [The effect of valsartan on the expression of the receptor for advanced glycation end products in human glomerular mesangial cells].

    Science.gov (United States)

    Zhong, Lin-na; Huang, Guo-liang; Feng, Min; Zhang, Ying

    2011-08-01

    To elucidate the effect of valsartan on human glomerular mesangial cells oxidative stress and the expression of the receptor for advanced glycation end products (RAGE) induced by the advanced glycation end-products (AGEs). Human glomerular mesangial cells were treated with advanced glycation end-product-bovine serum albumin (AGE-BSA) in the presence of valsartan. The reactive oxygen species (ROS) in cells were measured by Flow cytometry, and the mRNA of p47 phox, which was the primary subunits of NADPH oxidase, was detected by semi-quantitative reberse transcription polymerase chain reaction (RT-PCR). The mRNA of RAGE was detected by RT-PCR and the RAGE protein was assayed by immunocytochemistry. The product of ROS, and the expression of p47 phox and RAGE in mesangial cells, which were treated with AGE-BSA in the presence of valsartan, were down-regulated compared with the groups treated with AGE-BSA (P RAGE, ROS and p47(phox) in mesangial cells. Valsartan could inhibit RAGE expression through downregulation of oxidative stress.

  3. Role of the advanced glycation end products receptor in Crohn’s disease inflammation

    Science.gov (United States)

    Ciccocioppo, Rachele; Vanoli, Alessandro; Klersy, Catherine; Imbesi, Venerina; Boccaccio, Vincenzo; Manca, Rachele; Betti, Elena; Cangemi, Giuseppina Cristina; Strada, Elena; Besio, Roberta; Rossi, Antonio; Falcone, Colomba; Ardizzone, Sandro; Fociani, Paolo; Danelli, Piergiorgio; Corazza, Gino Roberto

    2013-01-01

    AIM: To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn’s disease (CD). METHODS: Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. RESULTS: In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was

  4. Role of the advanced glycation end products receptor in Crohn's disease inflammation.

    Science.gov (United States)

    Ciccocioppo, Rachele; Vanoli, Alessandro; Klersy, Catherine; Imbesi, Venerina; Boccaccio, Vincenzo; Manca, Rachele; Betti, Elena; Cangemi, Giuseppina Cristina; Strada, Elena; Besio, Roberta; Rossi, Antonio; Falcone, Colomba; Ardizzone, Sandro; Fociani, Paolo; Danelli, Piergiorgio; Corazza, Gino Roberto

    2013-12-07

    To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn's disease (CD). Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band

  5. NOAA JPSS Microwave Integrated Retrieval System (MIRS) Advanced Technology Microwave Sounder (ATMS) Sounding Products from NDE

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains temperature and humidity profiles from the NOAA Microwave Integrated Retrieval System (MIRS) using sensor data from the Advanced Technology...

  6. Advanced glycation end-products (AGEs) and associations with cardio-metabolic, lifestyle, and dietary factors in a general population : The NQplus study

    NARCIS (Netherlands)

    Botros, Nadia; Sluik, Diewertje; van Waateringe, Robert P.; de Vries, Jeanne H. M.; Geelen, Anouk; Feskens, Edith J. M.

    Background: Advanced glycation end-products are a heterogeneous group of molecules that are formed during reactions between reducing sugars and proteins. Advanced glycation end-products are thought to play a role in several diseases, including diabetes mellitus and can be measured non-invasively

  7. Effect of cranberry (Vaccinium macrocarpon) oligosaccharides on the formation of advanced glycation end-products.

    Science.gov (United States)

    Sun, Jiadong; Liu, Weixi; Ma, Hang; Marais, Jannie P J; Khoo, Christina; Dain, Joel A; Rowley, David C; Seeram, Navindra P

    2016-06-16

    BACKGROUND: The formation and accumulation of advanced glycation end-products (AGEs) are implicated in several chronic human illnesses including type-2 diabetes, renal failure, and neurodegenerative diseases. The cranberry ( Vaccinium macrocarpon ) fruit has been previously reported to show anti-AGEs effects, attributed primarily to its phenolic constituents. However, there is lack of similar data on the non-phenolic constituents found in the cranberry fruit, in particular, its carbohydrate constituents. Herein, a chemically characterized oligosaccharide-enriched fraction purified from the cranberry fruit was evaluated for its potential anti-AGEs and free radical scavenging effects. OBJECTIVE: The aim of this study was to evaluate the in vitro anti-AGEs and free radical scavenging effects of a chemically characterized oligosaccharide-enriched fraction purified from the North American cranberry ( Vaccinium macrocarpon ) fruit. METHOD: The cranberry oligosaccharide-enriched fraction was purified from cranberry hull powder and characterized based on spectroscopic and spectrometric (NMR, MALDI-TOF-MS, and HPAEC-PAD) data. The oligosaccharide-enriched fraction was evaluated for its anti-AGEs and free radical scavenging effects by the bovine serum albumin-fructose, and DPPH assays, respectively. RESULTS: Fractionation of cranberry hull material yielded an oligosaccharide-enriched fraction named Cranf1b-CL. The 1 H NMR and MALDI-TOF-MS revealed that Cranf1b-CL consists of oligosaccharides ranging primarily from 6-mers to 9-mers. The monosaccharide composition of Cranf1b-CL was arabinose (25%), galactose (5%), glucose (47%) and xylose (23%). In the bovine serum albumin-fructose assay, Cranf1b-CL inhibited AGEs formation in a concentration-dependent manner with comparable activity to the synthetic antiglycating agent, aminoguanidine, used as the positive control (57 vs. 75%; both at 500μg/mL). In the DPPH free radical scavenging assay, Cranf1b-CL showed superior activity

  8. 2015 Evidence Analysis Library Systematic Review on Advanced Technology in Food Production.

    Science.gov (United States)

    Edge, Marianne Smith; Kunkel, Mary Elizabeth; Schmidt, Jennifer; Papoutsakis, Constantina

    2018-03-08

    In the late 20th century, plant breeders began using molecular biology techniques such as recombinant DNA, also known as genetic engineering, along with traditional cross-breeding. Ten plant and one animal food have been approved for commercialization in the United States. Today, foods and ingredients from genetically engineered (GE) crops are present throughout the food supply, which has led to varying levels of acceptance. Much discussion exists among consumers and health professionals about the believability of statements made regarding benefits or risks of GE foods. The aim of this systematic review was to examine the evidence on the association of consumption of GE foods and ingredients derived from them on human health, specifically allergenicity, food safety, pesticide consumption, nutrient adequacy, inflammation, and antibiotic resistance. An expert panel conducted a systematic review on advanced technology in food production. The 30 developed questions focused on effects of human consumption of GE foods and the effects of human consumption of foods containing pesticide residues on human health. Primary research published from 1994 to 2014 were identified using PubMed and Agricultural Online Access databases. Additional studies were identified by searching references of review articles. Twenty-one studies met the inclusion criteria. Relevant research addressed five of 30 questions. Four questions focused on food allergenicity, the fifth on nutrient adequacy, and all received a Grade III (limited/weak) rating. No human studies addressed 25 questions on the consumption of foods produced using genetic engineering technologies on gene translocation, cancer, food safety, phenotype expression, inflammation and inflammatory markers, or antibiotic resistance. These questions received a Grade V (grade not assignable). Evidence from human studies did not reveal an association between adverse health effects and consumption of foods produced using genetic engineering

  9. Evaluation of advanced glycation end-products in diabetic and inherited canine cataracts.

    Science.gov (United States)

    Bras, I Dineli; Colitz, Carmen M H; Kusewitt, Donna F; Chandler, Heather; Lu, Ping; Gemensky-Metzler, Anne J; Wilkie, David A

    2007-02-01

    The receptor for advanced glycation end-products (RAGE) increases in the human cataract and should correlate with increased DNA damage and proliferation of lens epithelial cells (LECs). The purpose of this study was to measure and immunolocalize RAGE in normal and cataractous canine LECs, and to determine whether there was a correlation between RAGE and DNA damage (gadd45), cell-cycle regulation (p21), and LEC proliferation (proliferating cell nuclear antigen, PCNA). Thirty-two anterior lens capsules from 22 dogs that underwent cataract surgery and 10 lenses from dogs with normal eyes were evaluated. Eleven of the cataractous lenses were from diabetic patients (n=16), and eleven were from patients with inherited cataracts (n=16). Standard immunohistochemical staining was performed using antibodies against RAGE, gadd45, p21, PCNA, alpha-smooth muscle actin, and TGF-beta. Immunostaining intensity for each antibody was given a score of 0-4+. Standard Western blot analysis on normal and cataractous lens capsules was performed using the same antibodies as in the immunohistochemical staining. Comparisons were also made based on age and sex. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for RAGE. There was an increase in RAGE expression with age in normal LECs, but no significant difference was seen when normal adult LECs were compared to cataractous LECs. The stage of the cataract and the presence of LIU were not associated with a significant increase in RAGE expression. There was no age-dependent difference in the normal lenses for gadd45, p21, or PCNA. Significant up-regulation of p21 (P RAGE and PCNA expression did not increase with cataractogenesis, possibly due to overexpression associated with normal aging and constant exposure to oxidative stress from sunlight-related ultraviolet irradiation, respectively. However, p21 and PCNA increased in diabetic cataractogenesis suggesting cell cycle and proliferation dysregulation. This may

  10. Cathepsin D contributes to the accumulation of advanced glycation end products during photoaging.

    Science.gov (United States)

    Xu, Xinya; Zheng, Yue; Huang, Yunfen; Chen, Jian; Gong, Zijian; Li, Yuying; Lu, Chun; Lai, Wei; Xu, Qingfang

    2018-02-19

    The deposition of advanced glycation end products (AGEs) is accelerated in photoaged skin, but the underlying mechanisms remain elusive. Intracellular degradation has been recently considered to play an important role in AGEs removal. Although lysosomal cathepsin D (CatD), B (CatB), L(CatL) and proteasomes are found to degrade internalized AGEs, it remains unknown which protease degrades internalized AGEs in human dermal fibroblasts (HDFs), and whether a decrease in intracellular degradation contributes to enhanced AGEs deposition in photoaged skin. This study aims to investigate the specific proteases that contribute to intracellular AGEs degradation in HDFs and regulate AGEs accumulation in photoaged skin. Repetitive UVA irradiation was used to induce primary HDF photoaging in vitro. Uptake and degradation of AGE-BSA were verified and compared between photoaged and non-photoaged fibroblasts with flow cytometry, ELISA and confocal microscopy. Proteasomal and lysosomal activity, expression of CatD, CatB and CatL were also investigated between photoaged and non-photoaged fibroblasts. Further, the effect of protease inhibitors and CatD overexpression via lentiviral transduction on AGE-BSA degradation was analyzed. Finally, the correlation between CatD expression and AGEs accumulation in sun-exposed and sun-protected skin of people from different age was studied with immunohistochemistry. Fibroblasts underwent photoaging in vitro after repetitive UVA irradiation. AGE-BSA was taken up by both photoaged and non-photoaged fibroblasts, but its degradation was significantly decreased in photoaged cells than that of non-photoaged cells. Although the activity of proteasome, CatB, Cat L and Cat D was significantly reduced in photoaged fibroblasts compared to that of non-photoaged cells, and the expression of CatB, CatL and CatD was profoundly attenuated in photoaged fibroblasts, inhibiting proteasome, CatB and CatL did not affect AGE-BSA degradation in HDFs. In contrast

  11. Methylglyoxal-derived hydroimidazolone-1 evokes inflammatory reactions in endothelial cells via an interaction with receptor for advanced glycation end products.

    Science.gov (United States)

    Ishibashi, Yuji; Matsui, Takanori; Nakamura, Nobutaka; Sotokawauchi, Ami; Higashimoto, Yuichiro; Yamagishi, Sho-Ichi

    2017-09-01

    Glyceraldehyde-derived advanced glycation end products contribute to vascular inflammation in diabetes. However, what advanced glycation end product structure could evoke inflammatory reactions remains unknown. We examined whether and how methylglyoxal-derived hydroimidazolone 1, one of the advanced glycation end products formed from glyceraldehyde, elicits inflammatory reactions in human umbilical vein endothelial cells. Glyceraldehyde-advanced glycation end products-aptamer was prepared using a systemic evolution of ligands by exponential enrichment. The binding affinities of methylglyoxal-derived hydroimidazolone 1 to receptor for advanced glycation end products or advanced glycation end product-aptamer were measured with a quartz crystal microbalance. Intracellular reactive oxygen species generation and THP-1 cell adhesion were evaluated using fluorescent probes. Gene expression was analysed by reverse transcription polymerase chain reaction. Methylglyoxal-derived hydroimidazolone 1 bound to receptor for advanced glycation end products and advanced glycation end product-aptamer with a dissociation constant ( K d ) of 56.7 µM and 1.51 mM, respectively. Methylglyoxal-derived hydroimidazolone 1 at 100 µg/mL significantly increased reactive oxygen species generation in human umbilical vein endothelial cells, which were attenuated by anti-receptor for advanced glycation end products antibody or advanced glycation end product-aptamer. In all, 100 µg/mL methylglyoxal-derived hydroimidazolone 1 significantly increased receptor for advanced glycation end products and intercellular adhesion molecule-1 messenger RNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were blocked by anti-receptor for advanced glycation end products antibody. Our present results indicate that methylglyoxal-derived hydroimidazolone 1 evokes inflammatory reactions in human umbilical vein endothelial cells via receptor for advanced glycation

  12. Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products.

    OpenAIRE

    Schmidt, A M; Yan, S D; Brett, J; Mora, R; Nowygrod, R; Stern, D

    1993-01-01

    Nonenzymatic glycation of proteins occurs at an accelerated rate in diabetes and can lead to the formation of advanced glycation end products of proteins (AGEs), which bind to mononuclear phagocytes (MPs) and induce chemotaxis. We have isolated two cell surface-associated binding proteins that mediate the interaction of AGEs with bovine endothelial cells. One of these proteins is a new member of the immunoglobulin superfamily of receptors (termed receptor for AGEs or RAGE); and the second is ...

  13. Increasing Heavy Oil Reserves in the Wilmington Oil Field Through Advanced Reservoir Characterization and Thermal Production Technologies, Class III

    Energy Technology Data Exchange (ETDEWEB)

    City of Long Beach; Tidelands Oil Production Company; University of Southern California; David K. Davies and Associates

    2002-09-30

    The objective of this project was to increase the recoverable heavy oil reserves within sections of the Wilmington Oil Field, near Long Beach, California through the testing and application of advanced reservoir characterization and thermal production technologies. It was hoped that the successful application of these technologies would result in their implementation throughout the Wilmington Field and, through technology transfer, will be extended to increase the recoverable oil reserves in other slope and basin clastic (SBC) reservoirs.

  14. Extraction, Analytical and Advanced Methods for Detection of Allura Red AC (E129) in Food and Beverages Products

    Science.gov (United States)

    Rovina, Kobun; Siddiquee, Shafiquzzaman; Shaarani, Sharifudin M.

    2016-01-01

    Allura Red AC (E129) is an azo dye that widely used in drinks, juices, bakery, meat, and sweets products. High consumption of Allura Red has claimed an adverse effects of human health including allergies, food intolerance, cancer, multiple sclerosis, attention deficit hyperactivity disorder, brain damage, nausea, cardiac disease and asthma due to the reaction of aromatic azo compounds (R = R′ = aromatic). Several countries have banned and strictly controlled the uses of Allura Red in food and beverage products. This review paper is critically summarized on the available analytical and advanced methods for determination of Allura Red and also concisely discussed on the acceptable daily intake, toxicology and extraction methods. PMID:27303385

  15. Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis.

    Science.gov (United States)

    Paek, Seung-Mann; Jeong, Myeonggyo; Jo, Jeyun; Heo, Yu Mi; Han, Young Taek; Yun, Hwayoung

    2016-07-21

    Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas.

  16. Insight into the product film formed on Ni-advanced weathering steel in a tropical marine atmosphere

    Science.gov (United States)

    Wu, Wei; Cheng, Xuequn; Hou, Huaxing; Liu, Bo; Li, Xiaogang

    2018-04-01

    The product film formed on Ni-advanced weathering steel in a tropical marine environment was investigated in detail through outdoor exposure by using diverse surface analysis techniques combined with electrochemical impedance spectroscopy and scanning kelvin probe measurements. The results showed that the product film was mainly composed of nanophasic goethite in the inner layer and maghemite, akaganeite, and hematite in the outer layer. Moreover, the resistance to atmospheric corrosion gradually increased from the outermost product film to the innermost film. Ni was significantly enriched in the inner layer in the form of the spinel phase NiFe2O4, which transformed lepidocrocite to fine-grained goethite, withstood the invasion of chloridion, and improved the corrosion potential of the product film in a tropical marine atmosphere.

  17. Advanced Therapy Medicinal Products (ATMPand exemptions to the Regulation 1394/2007: how confident can we be? An exploratory analysis.

    Directory of Open Access Journals (Sweden)

    Philippe eVan Wilder

    2012-02-01

    Full Text Available The market authorisation procedure for medicinal products for human use is relying on their demonstrated efficacy, safety and pharmaceutical quality. This applies to all medicinal products whether of chemical or biological origin. Since October 2009, the first advanced therapy medicinal product (ATMP has been authorised through the centralized procedure. ATMPs are gene therapy medicinal products, somatic cell therapy medicinal products or tissue-engineered products.An appropriate ATMP- Regulation is dealing with ATMP requirements.Two exemptions are foreseen to the ATMP-Regulation: a. Products, which were legally on the Community market when the Regulation became applicable, should comply to the Regulation by 30 December 2012. b.the hospital exemption rule for non routine products for an individual patient. In this work we explored whether the actual application of the Regulation on ATMPs is in line with the aim of the Regulation in terms of guaranteeing the highest level of health protection for patients. Based on the analysis of the relative efficacy of the only EC authorized ATMP and its exempted alternatives, there is evidence against this Regulation 1394/2007 assumption.

  18. Advanced Therapy Medicinal Products and Exemptions to the Regulation 1394/2007: How Confident Can We be? An Exploratory Analysis.

    Science.gov (United States)

    Van Wilder, Philippe

    2012-01-01

    The market authorization procedure for medicinal products for human use is relying on their demonstrated efficacy, safety, and pharmaceutical quality. This applies to all medicinal products whether of chemical or biological origin. Since October 2009, the first advanced therapy medicinal product (ATMP) has been authorized through the centralized procedure. ATMPs are gene therapy medicinal products, somatic cell therapy medicinal products or tissue-engineered products. An appropriate ATMP - Regulation is dealing with ATMP requirements. Two exemptions are foreseen to the ATMP Regulation: (a) Products, which were legally on the Community market when the Regulation became applicable, should comply to the Regulation by December 30, 2012. (b) The hospital exemption rule for non-routine products for an individual patient. In this work we explored whether the actual application of the Regulation on ATMPs is in line with the aim of the Regulation in terms of guaranteeing the highest level of health protection for patients. Based on the analysis of the relative efficacy of the only EC authorized ATMP and its exempted alternatives, there is evidence against this Regulation 1394/2007 assumption.

  19. Hydrocarbon production and reservoir management: recent advances in closed-loop optimization technology

    NARCIS (Netherlands)

    Abbink, O.A.; Hanea, R.G.; Nennie, E.D.; Peters, R.C.A.M.

    2009-01-01

    Petroleum production is a relatively inefficient process. For oil production, it is, generally, less than 60 % effective on a macro scale and less than 60 % effective on a micro scale. This results, commonly, in an actual oil recovery of less than 35 %. Optimization of the production process will,

  20. Development of an advanced, continuous mild gasification process for the production of co-products technical evaluation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Ness, R.O. Jr.; Runge, B.; Sharp, L.

    1992-11-01

    The University of North Dakota Energy and Environmental Research Center (EERC) and the AMAX Research and Development Center are cooperating in the development of a Mild Gasification process that will rapidly devolatilize coals of all ranks at relatively low temperatures between 930{degree} and 1470{degree}F (500{degree}and 800{degree}C) and near atmospheric pressure to produce primary products that include a reactive char, a hydrocarbon condensate, and a low-Btu gas. These will be upgraded in a ``coal refinery`` system having the flexibility to optimize products based on market demand. Task 2 of the four-task development sequence primarily covered bench-scale testing on a 10-gram thermogravimetric analyzer (TGA) and a 1 to 4-lb/hr continuous fluidized-bed reactor (CFBR). Tests were performed to determine product yields and qualities for the two major test coals-one a high-sulfur bituminous coal from the Illinois Basin (Indiana No. 3) and the other a low-sulfur subbituminous coal from the Powder River Basin (Wyodak). Results from Task 3, on product upgrading tests performed by AMAX Research and Development (R&D), are also reported. Task 4 included the construction, operation of a Process Research Unit (PRU), and the upgrading of the products. An economic evaluation of a commercial facility was made, based on the data produced in the PRU, CFBR, and the physical cleaning steps.

  1. Development of an advanced, continuous mild gasification process for the production of co-products technical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ness, R.O. Jr.; Runge, B.; Sharp, L.

    1992-11-01

    The University of North Dakota Energy and Environmental Research Center (EERC) and the AMAX Research and Development Center are cooperating in the development of a Mild Gasification process that will rapidly devolatilize coals of all ranks at relatively low temperatures between 930[degree] and 1470[degree]F (500[degree]and 800[degree]C) and near atmospheric pressure to produce primary products that include a reactive char, a hydrocarbon condensate, and a low-Btu gas. These will be upgraded in a coal refinery'' system having the flexibility to optimize products based on market demand. Task 2 of the four-task development sequence primarily covered bench-scale testing on a 10-gram thermogravimetric analyzer (TGA) and a 1 to 4-lb/hr continuous fluidized-bed reactor (CFBR). Tests were performed to determine product yields and qualities for the two major test coals-one a high-sulfur bituminous coal from the Illinois Basin (Indiana No. 3) and the other a low-sulfur subbituminous coal from the Powder River Basin (Wyodak). Results from Task 3, on product upgrading tests performed by AMAX Research and Development (R D), are also reported. Task 4 included the construction, operation of a Process Research Unit (PRU), and the upgrading of the products. An economic evaluation of a commercial facility was made, based on the data produced in the PRU, CFBR, and the physical cleaning steps.

  2. Advanced glycation end product (AGE) accumulation in the skin is associated with depression : The maastricht study

    NARCIS (Netherlands)

    Van Dooren, F.E.P.; Pouwer, F.; Schalkwijk, C.G.; Sep, S.J.S.; Stehouwer, C.D.A.; Henry, R.M.A.; Dagnelie, P.C.; Schaper, N.C.; Van Der Kallen, C.J.H.; Koster, A.; Denollet, J.K.L.; Verhey, F.R.J.; Schram, M.T.

    2017-01-01

    Background: depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced

  3. Research Advances: Paper Batteries, Phototriggered Microcapsules, and Oil-Free Plastic Production

    Science.gov (United States)

    King, Angela G.

    2010-01-01

    Chemists continue to work at the forefront of materials science research. Recent advances include application of bioengineering to produce plastics from renewable biomass instead of petroleum, generation of paper-based batteries, and development of phototriggerable microcapsules for chemical delivery. In this article, the author provides summaries…

  4. Building research capacity and productivity among advanced practice nurses: an evaluation of the Community of Practice model.

    Science.gov (United States)

    Gullick, Janice G; West, Sandra H

    2016-03-01

    The aim of this study was to evaluate Wenger's Community of Practice as a framework for building research capacity and productivity. While research productivity is an expected domain in influential models of advanced nursing practice, internationally it remains largely unmet. Establishment of nursing research capacity precedes productivity and consequently, there is a strong imperative to identify successful capacity-building models for nursing-focussed research in busy clinical environments. Prospective, longitudinal, qualitative descriptive design was used in this study. Bruyn's participant observation framed evaluation of a Community of Practice comprising 25 advanced practice nurses. Data from focus groups, education evaluations, blog/email transcripts and field observations, collected between 2007 and 2014, were analysed using a qualitative descriptive method. The Community of Practice model invited differing levels of participation, allowed for evolution of the research community and created a rhythm of research-related interactions and enduring research relationships. Participants described the value of research for their patients and families and the significance of the developing research culture in providing richness to their practice and visibility of their work to multidisciplinary colleagues. Extensive examples of research dissemination and enrolment in doctoral programmes further confirmed this value. A Community of Practice framework is a powerful model enabling research capacity and productivity evidenced by publication. In developing a solid foundation for a nursing research culture, it should be recognized that research skills, confidence and growth develop over an extended period of time and success depends on skilled coordination and leadership. © 2015 John Wiley & Sons Ltd.

  5. Receptor of advanced glycation end products (RAGE) positively regulates CD36 expression and reactive oxygen species production in human monocytes in diabetes.

    Science.gov (United States)

    Xanthis, A; Hatzitolios, A; Fidani, S; Befani, C; Giannakoulas, G; Koliakos, G

    Advanced glycation end products (AGEs) engagement of a monocyte surface receptor (RAGE) induces atherosclerosis. AGEs also act as CD36 ligands. We studied reactive oxygen species (ROS) and CD36 expression after siRNA inhibition of RAGE expression in human monocytes. We isolated monocytes from: a) 10 type 2 diabetics, and b) 5 age- and sex-matched healthy individuals. CD36 expression and ROS production were evaluated before and after RAGE knockdown. After incubation of monocytes with AGE + bovine serum albumin (BSA), CD36 expression and intracellular ROS increased significantly in all groups. In RAGE-knockdown monocytes, AGE-induced CD36 expression and ROS generation were also significantly inhibited. Blocking RAGE expression using siRNA in human monocytes led to a significant inhibition of CD36 expression and ROS production, suggesting a positive interaction between RAGE, CD36 expression and ROS generation in monocytes.

  6. Development of an advanced, continuous mild gasification process for the production of co-products: Topical report

    Energy Technology Data Exchange (ETDEWEB)

    Cha, C.Y.; Merriam, N.W.; Jha, M.C.; Breault, R.W.

    1988-06-01

    Research on mild gasification is discussed. The report is divided into three sections: literature survey of mild gasification processes; literature survey of char, condensibles, and gas upgrading and utilization methods; and industrial market assessment of products of mild gasification. Recommendations are included in each section. (CBS) 248 refs., 58 figs., 62 tabs.

  7. Advanced Turbine Systems (ATS) program conceptual design and product development. Quarterly report, August 25--November 30, 1993

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    GE has achieved a leadership position in the worldwide gas turbine industry in both industrial/utility markets and in aircraft engines. This design and manufacturing base plus our close contact with the users provides the technology for creation of the next generation advanced power generation systems for both the industrial and utility industries. GE has been active in the definition of advanced turbine systems for several years. These systems will leverage the technology from the latest developments in the entire GE gas turbine product line. These products will be USA based in engineering and manufacturing and are marketed through the GE Industrial and Power Systems. Achieving the advanced turbine system goals of 60% efficiency, 8 ppmvd NOx and 10% electric power cost reduction imposes competing characteristics on the gas turbine system. Two basic technical issues arise from this. The turbine inlet temperature of the gas turbine must increase to achieve both efficiency and cost goals. However, higher temperatures move in the direction of increased NOx emission. Improved coating and materials technologies along with creative combustor design can result in solutions to achieve the ultimate goal.

  8. Advanced Turbine Systems (ATS) program conceptual design and product development. Quarterly report, December 1, 1993--February 28, 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    GE has achieved a leadership position in the worldwide gas turbine industry in both industrial/utility markets and in aircraft engines. This design and manufacturing base plus our close contact with the users provides the technology for creation of the next generation advanced power generation systems for both the industrial and utility industries. GE has been active in the definition of advanced turbine systems for several years. These systems will leverage the technology from the latest developments in the entire GE gas turbine product line. These products will be USA based in engineering and manufacturing and are marketed through the GE Industrial and Power Systems. Achieving the advanced turbine system goals of 60% efficiency, 8 ppmvd NOx and 10% electric power cost reduction imposes competing characteristics on the gas turbine system. Two basic technical issues arise from this. The turbine inlet temperature of the gas turbine must increase to achieve both efficiency and cost goals. However, higher temperatures move in the direction of increased NOx emission. Improved coating and materials technologies along with creative combustor design can result in solutions to achieve the ultimate goal.

  9. Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: Role of the receptor for advanced glycation end products.

    Science.gov (United States)

    Yammani, Raghunatha R; Carlson, Cathy S; Bresnick, Anne R; Loeser, Richard F

    2006-09-01

    S100 proteins have been implicated in various inflammatory conditions, including arthritis. The aims of this study were to determine whether chondrocytes produce S100A4 and whether S100A4 can stimulate the production of matrix metalloproteinase 13 (MMP-13) by articular chondrocytes via receptor for advanced glycation end products (RAGE)-mediated signaling. The expression of chondrocyte S100A4 was analyzed by immunohistochemistry using normal and osteoarthritic (OA) cartilage and by immunoblotting of chondrocyte cell lysates. RAGE signaling was examined by stimulating chondrocytes with S100A4 and monitoring for the activation of MAP kinases and NF-kappaB. Production of MMP-13 was determined in the conditioned medium. A pulldown assay using biotin-labeled S100A4 was used to demonstrate binding to RAGE. S100A4 expression was detected in human articular chondrocytes by immunoblotting and appeared to increase in the cell lysates from OA tissue. Marked positive immunostaining for S100A4 was also noted in sections of human cartilage with changes due to OA. Stimulation of chondrocytes with S100A4 increased the phosphorylation of Pyk-2, MAP kinases, and activated NF-kappaB, followed by increased production of MMP-13 in the conditioned medium. This signaling was inhibited in cells pretreated with soluble RAGE, advanced glycation end product-bovine serum albumin, or the antioxidant Mn(III)tetrakis (4-benzoic acid) porphyrin, or by overexpression of a dominant-negative RAGE construct. A pulldown assay showed that S100A4 binds to RAGE in chondrocytes. This is the first study to demonstrate that S100A4 binds to RAGE and stimulates a RAGE-mediated signaling cascade, leading to increased production of MMP-13. Since both S100A4 and RAGE are up-regulated in OA cartilage, this signaling pathway could contribute to cartilage degradation in OA.

  10. Advancement in bioprocess technology: parallels between microbial natural products and cell culture biologics.

    Science.gov (United States)

    Bandyopadhyay, Arpan A; Khetan, Anurag; Malmberg, Li-Hong; Zhou, Weichang; Hu, Wei-Shou

    2017-05-01

    The emergence of natural products and industrial microbiology nearly eight decades ago propelled an era of bioprocess innovation. Half a century later, recombinant protein technology spurred the tremendous growth of biologics and added mammalian cells to the forefront of industrial producing cells in terms of the value of products generated. This review highlights the process technology of natural products and protein biologics. Despite the separation in time, there is a remarkable similarity in their progression. As the new generation of therapeutics for gene and cell therapy emerges, its process technology development can take inspiration from that of natural products and biologics.

  11. Advance Planning, Programming and Production Control as key Activities Now the Environmental Education

    Directory of Open Access Journals (Sweden)

    Geraldo Cardoso de Oliveira Neto

    2015-06-01

    Full Text Available This work addresses the evolution of Planning, Programming and Control of Production (PPCP as essential activities of the company towards the insertion of environmental education. The approach is based on an exploratory research and a critical bibliographic revision. Two main objectives were established: i a new way of production organization, by considering cleaner production from company utilities to production capacity, technology and outsourcing and ii infrastructure changes related to market attendance and environmental education dissemination. Needs that arise can be grouped as follows: utilities adequacy, cleaner technologies and ecochains implementation; instruction and dissemination of environmental education; and necessity of the adoption of new paradigms.

  12. Oleaginous fungal lipid fermentation on combined acid- and alkali-pretreated corn stover hydrolysate for advanced biofuel production.

    Science.gov (United States)

    Ruan, Zhenhua; Zanotti, Michael; Archer, Steven; Liao, Wei; Liu, Yan

    2014-07-01

    A combined hydrolysis process, which first mixed dilute acid- and alkali-pretreated corn stover at a 1:1 (w/w) ratio, directly followed by enzymatic saccharification without pH adjustment, has been developed in this study in order to minimize the need of neutralization, detoxification, and washing during the process of lignocellulosic biofuel production. The oleaginous fungus Mortierella isabellina was selected and applied to the combined hydrolysate as well as a synthetic medium to compare fungal lipid accumulation and biodiesel production in both shake flask and 7.5L fermentor. Fungal cultivation on combined hydrolysate exhibited comparable cell mass and lipid yield with those from synthetic medium, indicating that the integration of combined hydrolysis with oleaginous fungal lipid fermentation has great potential to improve performance of advanced lignocellulosic biofuel production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Recent advances in microbial production of fuels and chemicals using tools and strategies of systems metabolic engineering

    DEFF Research Database (Denmark)

    Cho, Changhee; Choi, So Young; Luo, Zi Wei

    2015-01-01

    The advent of various systems metabolic engineering tools and strategies has enabled more sophisticated engineering of microorganisms for the production of industrially useful fuels and chemicals. Advances in systems metabolic engineering have been made in overproducing natural chemicals...... and producing novel non-natural chemicals. In this paper, we review the tools and strategies of systems metabolic engineering employed for the development of microorganisms for the production of various industrially useful chemicals belonging to fuels, building block chemicals, and specialty chemicals......, in particular focusing on those reported in the last three years. It was aimed at providing the current landscape of systems metabolic engineering and suggesting directions to address future challenges towards successfully establishing processes for the bio-based production of fuels and chemicals from renewable...

  14. Recent advances in microbial production of fuels and chemicals using tools and strategies of systems metabolic engineering.

    Science.gov (United States)

    Cho, Changhee; Choi, So Young; Luo, Zi Wei; Lee, Sang Yup

    2015-11-15

    The advent of various systems metabolic engineering tools and strategies has enabled more sophisticated engineering of microorganisms for the production of industrially useful fuels and chemicals. Advances in systems metabolic engineering have been made in overproducing natural chemicals and producing novel non-natural chemicals. In this paper, we review the tools and strategies of systems metabolic engineering employed for the development of microorganisms for the production of various industrially useful chemicals belonging to fuels, building block chemicals, and specialty chemicals, in particular focusing on those reported in the last three years. It was aimed at providing the current landscape of systems metabolic engineering and suggesting directions to address future challenges towards successfully establishing processes for the bio-based production of fuels and chemicals from renewable resources. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks.

    Science.gov (United States)

    Chen, Yun; Nielsen, Jens

    2013-12-01

    Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective production. Here we discuss how the development of computational algorithms, novel modules and methods, omics-based techniques combined with modeling refinement are enabling reduction in development time and thus advance the field of industrial biotechnology. We further discuss how recent technological developments contribute to the development of novel cell factories for the production of the building block chemicals: adipic acid, succinic acid and 3-hydroxypropionic acid. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Health Physics experience during production of vitrified waste canisters at Advanced Vitrification System

    International Nuclear Information System (INIS)

    Deokar, U.V.; Mathew, P.; Khot, A.R.; Ganesh, G.; Tripathi, R.M.

    2016-01-01

    In Advanced Vitrification System (AVS-2) High Level Liquid Waste (HLW) from reprocessing plant was vitrified in glass matrix using Joule Heating Ceramic Melter (JHCM). During operation of JHCM health physics unit has developed remote online monitoring system to reduce collective dose and secondary waste. About 28.5 % of authorized collective dose was saved by remote online monitoring system to HP surveyor and plant operator. For measurement of radiation level on overpack the correlation factor of 10 was established between online monitor reading and over pack contact radiation level. This paper summarizes our HP experience during vitrification of 200 canisters at Advance Vitrification System-2 Tarapur. This was achieved by collective dose consumption of 66 % of authorized dose. Our effective radiological monitoring program has significantly reduced the personal exposure and generation of secondary waste

  17. Production of titanium alloys for advanced aerospace systems by powder metallurgy

    OpenAIRE

    Henriques, Vinicius André Rodrigues; Campos, Pedro Paulo de; Cairo, Carlos Alberto Alves; Bressiani, José Carlos

    2005-01-01

    Titanium alloys parts are ideally suited for advanced aerospace systems because of their unique combination of high specific strength at both room temperature and moderately elevated temperature, in addition to excellent corrosion resistance. Despite these features, use of titanium alloys in engines and airframes is limited by cost. The alloys processing by powder metallurgy eases the obtainment of parts with complex geometry. In this work, results of the Ti-6Al-4V and Ti-13Nb-13Zr alloys pro...

  18. 15 CFR 713.4 - Advance declaration requirements for additionally planned production, processing, or consumption...

    Science.gov (United States)

    2010-01-01

    ... additionally planned production, processing, or consumption of Schedule 2 chemicals. 713.4 Section 713.4..., processing, or consumption of Schedule 2 chemicals. (a) Declaration requirements for additionally planned activities. (1) You must declare additionally planned production, processing, or consumption of Schedule 2...

  19. Advances in photobioreactors for intensive microalgal production: configurations, operating strategies and applications

    NARCIS (Netherlands)

    Olivieri, G.; Salatino, P.; Marzocchella, A.

    2014-01-01

    Over the past ten years a great deal of literature has focused on the biotechnological potential of microalgal commercial applications, mainly in the field of biofuel production. However, the biofuel production is not yet competitive, mainly due to the incidence of the photobioreactor technology on

  20. ADVANCED FOREIGN METHODS OF PRODUCT DEVELOPMENT PROGRAM IN THE AIRCRAFT INDUSTRY

    OpenAIRE

    N. G. Ageeva; S. V. Gromov

    2014-01-01

    The state and development prospects of administration methods of production program of product development in the aircraft industry is considered. The modern W model of the design process of life cycle is offered. The modern design technology of construction in the aircraft industry is described.

  1. ADVANCED FOREIGN METHODS OF PRODUCT DEVELOPMENT PROGRAM IN THE AIRCRAFT INDUSTRY

    Directory of Open Access Journals (Sweden)

    N. G. Ageeva

    2014-01-01

    Full Text Available The state and development prospects of administration methods of production program of product development in the aircraft industry is considered. The modern W model of the design process of life cycle is offered. The modern design technology of construction in the aircraft industry is described.

  2. Chapter 3: Omics Advances of Biosynthetic Pathways of Isoprenoid Production in Microalgae

    Energy Technology Data Exchange (ETDEWEB)

    Paniagua-Michel, J.; Subramanian, Venkataramanan

    2017-01-01

    In this chapter, the current status of microalgal isoprenoids and the role of omics technologies, or otherwise specified, in bioproducts optimization and applications are reviewed. Emphasis is focused in the metabolic pathways of microalgae involved in the production of commercially important products, namely, hydrocarbons and biofuels, nutraceuticals, and pharmaceuticals.

  3. Advanced treatment of oilfield production wastewater by an integration of coagulation/flotation, catalytic ozonation and biological processes.

    Science.gov (United States)

    Chen, Ke-Yong; Zhang, Xiao-Bing; Li, Jun

    2016-10-01

    In this study, advanced treatment of heavily polluted oilfield production wastewater (OPW) was investigated employing the combination of coagulation/dissolved air flotation, heterogeneous catalytic ozonation and sequencing batch reactor (SBR) processes. Two SBR reactors were separately set up before and after the ozonation unit. The results show that microbubble flotation was more efficient than macrobubble flotation in pollutant removal. Catalytic ozonation with the prepared Fe/activated carbon catalyst significantly enhanced pollutant removal in the second SBR by improving wastewater biodegradability and reducing wastewater microtoxicity. The treatment technique decreased oil, chemical oxygen demand and NH3-N by about 97%, 88% and 91%, respectively, allowing the discharge limits to be met. Therefore, the integrated process with efficient, economical and sustainable advantages was suitable for advanced treatment of real OPW.

  4. Design manual for management of solid by-products from advanced coal technologies

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-10-01

    Developing coal conversion technologies face major obstacles in byproduct management. This project has developed several management strategies based on field trials of small-scale landfills in an earlier phase of the project, as well as on published/unpublished sources detailing regulatory issues, current industry practice, and reuse opportunities. Field testing, which forms the basis for several of the disposal alternatives presented in this design manual, was limited to byproducts from Ca-based dry SO{sub 2} control technologies, circulating fluidized bed combustion ash, and bubbling bed fluidized bed combustion ash. Data on byproducts from other advanced coal technologies and on reuse opportunities are drawn from other sources (citations following Chapter 3). Field results from the 5 test cases examined under this project, together with results from other ongoing research, provide a basis for predictive modeling of long-term performance of some advanced coal byproducts on exposure to ambient environment. This manual is intended to provide a reference database and development plan for designing, permitting, and operating facilities where advanced coal technology byproducts are managed.

  5. Advanced Process Chains for Prototyping and Pilot Production based on Additive Manufacturing

    DEFF Research Database (Denmark)

    Mischkot, Michael

    2015-01-01

    ). With technological progress and the development of new processes, AM technology now starts to become a serious option for mass production. It enables new options for material choice, shape and internal structure. Productivity in production of e.g. metal parts can be increased due to mass and cost reduction......For many years, Additive Manufacturing (AM) has been a well-established production technology used mainly for rapid prototyping. But the need for increased flexibility and economic low volume production led to the discovery of Additive Manufacturing as a suitable fabrication technique (Mellor 2013...... and better parts functionality (Ponche 2014). Also, the use of AM ma-chines for spare parts can potentially reduce costs and downtime, and lead to a higher robustness to supply chain disruptions (Khajavi 2013). Control and optimization of the involved process chains are crucial for a fast and robust...

  6. Pioglitazone attenuates progression of aortic valve calcification via down-regulating receptor for advanced glycation end products.

    Science.gov (United States)

    Li, Fei; Cai, Zhejun; Chen, Fang; Shi, Xucong; Zhang, Qiao; Chen, Si; Shi, Jiawei; Wang, Dao Wen; Dong, Nianguo

    2012-11-01

    Receptor for advanced glycation end products (RAGE) is associated with inflammation and the progression of cardiovascular diseases. The current study tested the hypothesis that RAGE is involved in the pathogenesis of aortic valve (AV) calcification. Pioglitazone attenuated AV calcification in experimental hypercholesterolemic rabbits via down-regulation of RAGE. Male New Zealand rabbits weighing 2.5-3.0 kg were randomly divided into three groups: control group, high cholesterol + vitamin D(2) (HC + vitD(2)) group and HC + vitD(2) supplemented with pioglitazone group. Compared with HC + vitD(2) group, pioglitazone significantly inhibited the progression of AV calcification assessed by echocardiography. HC + vitD(2) diet markedly increased RAGE expression, oxidative stress, inflammatory cells infiltration and osteopontin expression. These changes were also significantly attenuated by administration of pioglitazone. Cultured porcine aortic valve interstitial cells (VICs) were used as in vitro model. We found that advanced glycation end products of bovine serum albumin markedly increased the expression of RAGE, induced high levels of production of pro-inflammatory cytokines and promoted osteoblastic differentiation of VICs. However, these effects were found to be remarkably suppressed by siRNA silencing of RAGE and pioglitazone as well. Our data provide evidence that RAGE activation-induced inflammation promotes AV calcification in hypercholesterolemic rabbits, which can be attenuated by pioglitazone treatment. This beneficial effect is associated with remarkable down-regulation of RAGE expression.

  7. Engineering propionibacteria as versatile cell factories for the production of industrially important chemicals: advances, challenges, and prospects.

    Science.gov (United States)

    Guan, Ningzi; Zhuge, Xin; Li, Jianghua; Shin, Hyun-Dong; Wu, Jing; Shi, Zhongping; Liu, Long

    2015-01-01

    Propionibacteria are actinobacteria consisting of two principal groups: cutaneous and dairy. Cutaneous propionibacteria are considered primary pathogens to humans, whereas dairy propionibacteria are widely used in the food and pharmaceutical industries. Increasing attention has been focused on improving the performance of dairy propionibacteria for the production of industrially important chemicals, and significant advances have been made through strain engineering and process optimization in the production of flavor compounds, nutraceuticals, and antimicrobial compounds. In addition, genome sequencing of several propionibacteria species has been completed, deepening understanding of the metabolic and physiological features of these organisms. However, the metabolic engineering of propionibacteria still faces several challenges owing to the lack of efficient genome manipulation tools and the existence of various types of strong restriction-modification systems. The emergence of systems and synthetic biology provides new opportunities to overcome these bottlenecks. In this review, we first introduce the major species of propionibacteria and their properties and provide an overview of their functions and applications. We then discuss advances in the genome sequencing and metabolic engineering of these bacteria. Finally, we discuss systems and synthetic biology approaches for engineering propionibacteria as efficient and robust cell factories for the production of industrially important chemicals.

  8. Parametric Evaluation of Large-Scale High-Temperature Electrolysis Hydrogen Production Using Different Advanced Nuclear Reactor Heat Sources

    International Nuclear Information System (INIS)

    Harvego, Edwin A.; McKellar, Michael G.; O'Brien, James E.; Herring, J. Stephen

    2009-01-01

    High Temperature Electrolysis (HTE), when coupled to an advanced nuclear reactor capable of operating at reactor outlet temperatures of 800 C to 950 C, has the potential to efficiently produce the large quantities of hydrogen needed to meet future energy and transportation needs. To evaluate the potential benefits of nuclear-driven hydrogen production, the UniSim process analysis software was used to evaluate different reactor concepts coupled to a reference HTE process design concept. The reference HTE concept included an Intermediate Heat Exchanger and intermediate helium loop to separate the reactor primary system from the HTE process loops and additional heat exchangers to transfer reactor heat from the intermediate loop to the HTE process loops. The two process loops consisted of the water/steam loop feeding the cathode side of a HTE electrolysis stack, and the sweep gas loop used to remove oxygen from the anode side. The UniSim model of the process loops included pumps to circulate the working fluids and heat exchangers to recover heat from the oxygen and hydrogen product streams to improve the overall hydrogen production efficiencies. The reference HTE process loop model was coupled to separate UniSim models developed for three different advanced reactor concepts (a high-temperature helium cooled reactor concept and two different supercritical CO2 reactor concepts). Sensitivity studies were then performed to evaluate the affect of reactor outlet temperature on the power cycle efficiency and overall hydrogen production efficiency for each of the reactor power cycles. The results of these sensitivity studies showed that overall power cycle and hydrogen production efficiencies increased with reactor outlet temperature, but the power cycles producing the highest efficiencies varied depending on the temperature range considered

  9. NOAA JPSS Advanced Technology Microwave Sounder (ATMS)-based Tropical Cyclone (TC) Products from NDE

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The JPSS Microwave Sounder-based Tropical Cyclone (TC) Products provide estimates of tropical cyclone maximum wind speed, minimum sea level pressure, radii of 34,...

  10. Advanced Manufacturing Technologies and Strategically Flexible Production. A Review and Outlook

    DEFF Research Database (Denmark)

    Boer, Harry

    2016-01-01

    to require new rationales to organize and manage production systems. However, the compatibility and coherence between changing organizational paradigms and CIM approaches were not extensively explored nor understood. This paper aims to investigate the interactions between the implementation and integration...

  11. How did the US economy react to shale gas production revolution? An advanced time series approach

    International Nuclear Information System (INIS)

    Bilgili, Faik; Koçak, Emrah; Bulut, Ümit; Sualp, M. Nedim

    2016-01-01

    This paper aims at examining the impacts of shale gas revolution on industrial production in the US. To this end, this paper, first, throughout literature review, exposes the features of shale gas revolution in the US in terms of energy technology and energy markets. However, the potential influences of shale gas extraction on the US economy are not explicit in the existing literature. Thus, considering mainly the output of shale gas revolution on the US economy in this research, later, the paper conducts econometric models to reveal if there exists significant effect(s) of shale gas revolution on the US economy. Therefore, the paper employs unit root tests and cointegration tests by following relevant US monthly data from January 2008 to December 2013. Then, this paper observes long run impact of shale gas production on industrial production in the US through dynamic ordinary least squares estimation with dummy structural breaks and conducts Granger causality test based on vector error correction model. The dynamic ordinary least squares estimator explores that shale gas production has a positive effect on industrial production. Besides, the Granger causality test presents that shale gas production Granger causes industrial production in the long run. Based on the findings of the long run estimations, the paper yields that industrial production is positively related to shale gas production. Eventually, upon its findings, this paper asserts that (i) the shale gas revolution in the US has considerable positive effects on the US economy within the scope of the validity of the growth hypothesis, (ii) new technologies might be developed to mitigate the possible negative environmental effects of shale gas production, (iii) the countries having shale gas reserves, as in US, may follow energy policies to utilize their shale reserves more in the future to meet their energy demand and to increase their economic welfare. - Highlights: • Explores the US shale gas revolution

  12. Advances in Online Shopping Interfaces: Product Catalog Maps and Recommender Systems

    OpenAIRE

    Kagie, Martijn

    2010-01-01

    textabstractOver the past two decades the internet has rapidly become an important medium to retrieve information, maintain social contacts, and to do online shopping. The latter has some important advantages over traditional shopping. Products are often cheaper on the internet, internet companies sell a wider collection of products and consumers can buy items whenever they like without leaving their homes. On the other hand, the current state of online shops still has two major disadvantages...

  13. National Alliance for Advanced Biofuels and Bio-Products Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Olivares, Jose A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Baxter, Ivan [US Dept. of Agriculture (USDA)., Washington, DC (United States); Brown, Judith [Univ. of Arizona, Tucson, AZ (United States); Carleton, Michael [Matrix Genetics, Seattle, WA (United States); Cattolico, Rose Anne [Univ. of Washington, Seattle, WA (United States); Taraka, Dale [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Detter, John C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Devarenne, Timothy P. [Texas Agrilife Research, College Station, TX (United States); Dutcher, Susan K. [Washington Univ., St. Louis, MO (United States); Fox, David T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Goodenough, Ursula [Washington Univ., St. Louis, MO (United States); Jaworski, Jan [Donald Danforth Plant Science Center, St. Louis, MO (United States); Kramer, David [Michigan State Univ., East Lansing, MI (United States); Lipton, Mary S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McCormick, Margaret [Matrix Genetics, Seattle, WA (United States); Merchant, Sabeeha [Univ. of California, Los Angeles, CA (United States); Molnar, Istvan [Univ. of Arizona, Tucson, AZ (United States); Panisko, Ellen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Pellegrini, Matteo [Univ. of California, Los Angeles, CA (United States); Polle, Juergen [City Univ. (CUNY), NY (United States). Brooklyn College; Sabarsky, Martin [Cellana, Inc., San Diego, CA (United States); Sayre, Richard T. [New Mexico Consortium, Los Alamos, NM (United States); Starkenburg,, Shawn [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stormo, Gary [Washington Univ., St. Louis, MO (United States); Twary, Scott N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Unkefer, Clifford J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Unkefer, Pat J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Yuan, Joshua S. [Texas Agrilife Research, College Station, TX (United States); Arnold, Bob [Univ. of Arizona, Tucson, AZ (United States); Bai, Xuemei [Cellana, Inc., San Diego, CA (United States); Boeing, Wiebke [New Mexico State Univ., Las Cruces, NM (United States); Brown, Lois [Texas Agrilife Research, College Station, TX (United States); Gujarathi, Ninad [Reliance Industries Limited, Mumbai (India); Huesemann, Michael [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lammers, Pete [New Mexico State Univ., Las Cruces, NM (United States); Laur, Paul [Eldorado Biofuels, Santa Fe, NM (United States); Khandan, Nirmala [New Mexico State Univ., Las Cruces, NM (United States); Parsons, Ronald [Solix BioSystems, Fort Collins, CO (United States); Samocha, Tzachi [Texas Agrilife Research, College Station, TX (United States); Thomasson, Alex [Texas Agrilife Research, College Station, TX (United States); Unc, Adrian [New Mexico State Univ., Las Cruces, NM (United States); Waller, Pete [Univ. of Arizona, Tucson, AZ (United States); Bonner, James [Clarkson Univ., Potsdam, NY (United States); Coons, Jim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fernando, Sandun [Texas Agrilife Research, College Station, TX (United States); Goodall, Brian [Valicor Renewables, Dexter, MI (United States); Kadam, Kiran [Valicor Renewables, Dexter, MI (United States); Lacey, Ronald [Texas Agrilife Research, College Station, TX (United States); Wei, Liu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marrone, Babs [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Nikolov, Zivko [Texas Agrilife Research, College Station, TX (United States); Trewyn, Brian [Colorado School of Mines, Golden, CO (United States); Albrecht, Karl [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Capareda, Sergio [Texas Agrilife Research, College Station, TX (United States); Cheny, Scott [Diversified Energy, Gilbert, AZ (United States); Deng, Shuguang [New Mexico State Univ., Las Cruces, NM (United States); Elliott, Douglas [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Cesar, Granda [Terrabon, LLC, Bryan, TX (United States); Hallen, Richard [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lupton, Steven [UOP Honeywell Co, LLC, Des Plaines, IL (United States); Lynch, Sharry [UOP Honeywell Co, LLC, Des Plaines, IL (United States); Marchese, Anthony [Colorado State Univ., Fort Collins, CO (United States); Nieweg, Jennifer [Albemarle Catilin, Ames, IA (United States); Ogden, Kimberly [Univ. of Arizona, Tucson, AZ (United States); Oyler, James [Genifuel, Salt Lake City, UT (United States); Reardon, Ken [Colorado State Univ., Fort Collins, CO (United States); Roberts, William [North Carolina State Univ., Raleigh, NC (United States); Sams, David [Albemarle Catilin, Ames, IA (United States); Schaub, Tanner [New Mexico State Univ., Las Cruces, NM (United States); Silks, Pete [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Archibeque, Shawn [Colorado State Univ., Fort Collins, CO (United States); Foster, James [Texas Agrilife Research, College Station, TX (United States); Gaitlan, Delbert [Texas Agrilife Research, College Station, TX (United States); Lawrence, Addison [Texas Agrilife Research, College Station, TX (United States); Lodge-Ivey, Shanna [New Mexico State Univ., Las Cruces, NM (United States); Wickersham, Tyron [Texas Agrilife Research, College Station, TX (United States); Blowers, Paul [Univ. of Arizona, Tucson, AZ (United States); Davis, Ryan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Downes, C. Meghan [New Mexico State Univ., Las Cruces, NM (United States); Dunlop, Eric [Pan Pacific Technologies Pty. Ltd., Adelaide (Australia); Frank, Edward [Argonne National Lab. (ANL), Argonne, IL (United States); Handler, Robert [Michigan Technological Univ., Houghton, MI (United States); Newby, Deborah [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pienkos, Philip [National Renewable Energy Lab. (NREL), Golden, CO (United States); Richardson, James [Texas Agrilife Research, College Station, TX (United States); Seider, Warren [Univ. of Pennsylvania, Philadelphia, PA (United States); Shonnard, David [Michigan Technological Univ., Houghton, MI (United States); Skaggs, Richard [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-09-30

    The main objective of NAABB was to combine science, technology, and engineering expertise from across the nation to break down critical technical barriers to commercialization of algae-based biofuels. The approach was to address technology development across the entire value chain of algal biofuels production, from selection of strains to cultivation, harvesting, extraction, fuel conversion, and agricultural coproduct production. Sustainable practices and financial feasibility assessments ununderscored the approach and drove the technology development.

  14. Advances in the production of isotopes and radiopharmaceuticals at the Atomic Energy Corporation of South Africa

    International Nuclear Information System (INIS)

    Louw, P.A.; De Villiers, W.Y.Z.; Jarvis, N.V.

    1997-01-01

    The Atomic Energy Corporation of South Africa Ltd (AEC) owns and operates the 20 MW research reactor, SAFARI-1. Utilisation of the reactor has in recent years changed from research and materials testing to the production of isotopes. The most important breakthrough achieved in recent years is the production of high quality fission 99Mo. This has been produced routinely since April 1993 and supplied to clients across the world. A capability for the reliable production of 1000 Ci of 99Mo per week (calibrated for six days after production) has been proven. The AEC has also established facilities to produce its own 99mTc generators together with a most of radiopharmaceutical kits for diagnostic nuclear medicine purposes. The production of 153 Sm and 131 I (tellurium oxide route) has been operational for many years. Applications include therapeutic radiopharmaceuticals such as 153 Sm-EDTMP for bone cancer pain palliation, 13' I-Lipiodol for liver cancer and 131 I capsules for thyroid treatment. Facilities for the production of other isotopes such as 131 I (from fission), 32 P and 35 S are in various stages of completion. Extensive analytical methods and equipment have been developed and are routinely used to certify the quality of exported isotopes. Irradiation and encapsulation of 192 Ir is also performed routinely at the AEC. Modern facilities allow for the production of isotopes such as 131 Ba and 140 La on an ad hoc basis. Quality assurance procedures based on ISO9000 were developed for all aspects of the production of the various isotopes. Documentation, such as Drug Master Files, required by authorities in various countries has also been submitted and accepted

  15. Naphthopyrone glucosides from the seeds of Cassia tora with inhibitory activity on advanced glycation end products (AGEs) formation.

    Science.gov (United States)

    Lee, Ga Young; Jang, Dae Sik; Lee, Yun Mi; Kim, Jong Min; Kim, Jin Sook

    2006-07-01

    Three naphthopyrone glucosides, cassiaside (1), rubrofusarin-6-O-beta-D-gentiobioside (2), and toralactone-9-O-beta-D-gentiobioside (3), were isolated from the BuOH-soluble extract of the seeds of Cassia tora as active constituents, using an in vitro bioassay based on the inhibition of advanced glycation end products (AGEs) to monitor chromatographic fractionation. The structures of 1-3 were determined by spectroscopic data interpretation, particularly by extensive 1D and 2D NMR studies. All the isolates (1-3) were evaluated for the inhibitory activity on AGEs formation in vitro.

  16. Modelling of nitric acid production in the Advanced Cold Process Canister due to irradiation of moist air

    International Nuclear Information System (INIS)

    Henshaw, J.

    1994-01-01

    This report summarises the work performed for SKB of Sweden on the modelling of nitric acid production in the gaseous environment of the Advanced Cold Process Canister (ACPC). The model solves the simultaneous chemical rate equations describing the radiation chemistry of He/Ar/N 2 /O 2 /H 2 O gas mixture, involving over 200 chemical reactions. The amount of nitric acid produced as a function of time for typical ACPC conditions has been calculated using the model and the results reported. 11 refs, 11 figs, 1 tab

  17. Low Levels of Serum Soluble Receptors for Advanced Glycation End Products, Biomarkers for Disease State: Myth or Reality

    OpenAIRE

    Prasad, Kailash

    2014-01-01

    Advanced glycation end products (AGEs) interact with the receptor for AGEs (RAGE) on the membrane and induce deleterious effects via activation of nuclear factor kappa-B, and increased oxidative stress and inflammatory mediators. AGEs also combine with circulating soluble receptors (endogenous secretory RAGE [esRAGE] and soluble receptor for RAGE [sRAGE]) and sequester RAGE ligands and act as a cytoprotective agent. esRAGE is secreted from the cells and is a spliced variant of RAGE. The sRAGE...

  18. Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

    DEFF Research Database (Denmark)

    Chen, Peng-Min; Gregersen, Hans; Zhao, Jingbo

    2015-01-01

    AIM: To investigate changes in advanced glycation end products (AGEs) and their receptor (RAGE) expression in the gastrointestinal (GI) tract in type 2 diabetic rats. METHODS: Eight inherited type 2 diabetic rats Goto-Kakizak (GK) and ten age-matched normal rats were used in the study. From 18 wk...... software. RESULTS: The blood glucose concentration (mmol/L) at 18 wk age was highest in the GK group (8.88 ± 1.87 vs 6.90 ± 0.43, P end of the experiment. The wet weight per unit length (mg/cm) increased in esophagus, jejunum and colon from...

  19. Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

    DEFF Research Database (Denmark)

    Sourris, Karly C; Lyons, Jasmine G; Dougherty, Sonia L

    2013-01-01

    Abstract Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective...... was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals. Methods: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males...

  20. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    Science.gov (United States)

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-11-01

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  1. Advanced process monitoring and feedback control to enhance cell culture process production and robustness.

    Science.gov (United States)

    Zhang, An; Tsang, Valerie Liu; Moore, Brandon; Shen, Vivian; Huang, Yao-Ming; Kshirsagar, Rashmi; Ryll, Thomas

    2015-12-01

    It is a common practice in biotherapeutic manufacturing to define a fixed-volume feed strategy for nutrient feeds, based on historical cell demand. However, once the feed volumes are defined, they are inflexible to batch-to-batch variations in cell growth and physiology and can lead to inconsistent productivity and product quality. In an effort to control critical quality attributes and to apply process analytical technology (PAT), a fully automated cell culture feedback control system has been explored in three different applications. The first study illustrates that frequent monitoring and automatically controlling the complex feed based on a surrogate (glutamate) level improved protein production. More importantly, the resulting feed strategy was translated into a manufacturing-friendly manual feed strategy without impact on product quality. The second study demonstrates the improved process robustness of an automated feed strategy based on online bio-capacitance measurements for cell growth. In the third study, glucose and lactate concentrations were measured online and were used to automatically control the glucose feed, which in turn changed lactate metabolism. These studies suggest that the auto-feedback control system has the potential to significantly increase productivity and improve robustness in manufacturing, with the goal of ensuring process performance and product quality consistency. © 2015 Wiley Periodicals, Inc.

  2. Development of an advanced, continuous mild gasification process for the production of co-products (Task 1), Volume 1. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Knight, R.A.; Gissy, J.L.; Onischak, M.; Babu, S.P.; Carty, R.H. [Institute of Gas Technology, Chicago, IL (United States); Duthie, R.G. [Bechtel Group, Inc., San Francisco, CA (United States); Wootten, J.M. [Peabody Holding Co., Inc., St. Louis, MO (United States)

    1991-09-01

    Under US DOE sponsorship, a project team consisting of the Institute of Gas Technology, Peabody Holding Company, and Bechtel Group, Inc. has been developing an advanced, mild gasification process to process all types of coal and to produce solid and condensable liquid co-products that can open new markets for coal. The three and a half year program (September 1987 to June 1991) consisted of investigations in four main areas. These areas are: (1) Literature Survey of Mild Gasification Processes, Co-Product Upgrading and Utilization, and Market Assessment; (2) Mild Gasification Technology Development: Process Research Unit Tests Using Slipstream Sampling; (3) Bench-Scale Char Upgrading Study; (4) Mild Gasification Technology Development: System Integration Studies. In this report, the literature and market assessment of mild gasification processes are discussed.

  3. The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals: a randomized factorial design trial.

    NARCIS (Netherlands)

    Oudegeest-Sander, M.H.; Olde Rikkert, M.G.M.; Smits, P.; Thijssen, D.H.J.; Dijk, A.P.J. van; Levine, B.D.; Hopman, M.T.E.

    2013-01-01

    Aging leads to accumulation of irreversible advanced glycation end-products (AGEs), contributing to vascular stiffening and endothelial dysfunction. When combined with the AGE-crosslink breaker Alagebrium, exercise training reverses cardiovascular aging in experimental animals. This study is the

  4. Micro-structured nuclear fuel and novel nuclear reactor concepts for advanced power production

    International Nuclear Information System (INIS)

    Popa-Simil, Liviu

    2008-01-01

    Many applications (e.g. terrestrial and space electric power production, naval, underwater and railroad propulsion and auxiliary power for isolated regions) require a compact-high-power electricity source. The development of such a reactor structure necessitates a deeper understanding of fission energy transport and materials behavior in radiation dominated structures. One solution to reduce the greenhouse-gas emissions and delay the catastrophic events' occurrences may be the development of massive nuclear power. The actual basic conceptions in nuclear reactors are at the base of the bottleneck in enhancements. The current nuclear reactors look like high security prisons applied to fission products. The micro-bead heterogeneous fuel mesh gives the fission products the possibility to acquire stable conditions outside the hot zones without spilling, in exchange for advantages - possibility of enhancing the nuclear technology for power production. There is a possibility to accommodate the materials and structures with the phenomenon of interest, the high temperature fission products free fuel with near perfect burning. This feature is important to the future of nuclear power development in order to avoid the nuclear fuel peak, and high price increase due to the immobilization of the fuel in the waste fuel nuclear reactor pools. (author)

  5. Use of solar advanced oxidation processes for wastewater treatment: Follow-up on degradation products, acute toxicity, genotoxicity and estrogenicity.

    Science.gov (United States)

    Brienza, M; Mahdi Ahmed, M; Escande, A; Plantard, G; Scrano, L; Chiron, S; Bufo, S A; Goetz, V

    2016-04-01

    Wastewater tertiary treatment by advanced oxidation processes is thought to produce a treated effluent with lower toxicity than the initial influent. Here we performed tertiary treatment of a secondary effluent collected from a Waste Water Treatment Plant via homogeneous (solar/HSO5(-)/Fe(2+)) and heterogeneous (solar/TiO2) solar advanced oxidation aiming at the assessment of their effectiveness in terms of contaminants' and toxicity abatement in a plain solar reactor. A total of 53 organic contaminants were qualitatively identified by liquid chromatography coupled to high-resolution mass spectrometry after solid phase extraction. Solar advanced oxidation totally or partially removed the major part of contaminants detected within 4.5 h. Standard toxicity tests were performed using Vibrio fischeri, Daphnia magna, Pseudokirchneriella subcapitata and Brachionus calyciflorus organisms to evaluate acute and chronic toxicity in the secondary or tertiary effluents, and the EC50% was calculated. Estrogenic and genotoxic tests were carried out in an attempt to obtain an even sharper evaluation of potential hazardous effects due to micropollutants or their degradation by-products in wastewater. Genotoxic effects were not detected in effluent before or after treatment. However, we observed relevant estrogenic activity due to the high sensitivity of the HELN ERα cell line. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Extraction, Analytical and Advanced Methods for Detection of Allura Red AC (E129 in Food and Beverages Products

    Directory of Open Access Journals (Sweden)

    Shafiquzzaman eSiddiquee

    2016-05-01

    Full Text Available Allura Red AC (E129 is an azo dye that widely used in drinks, juices, bakery, meat and sweets products. High consumption of Allura Red has claimed an adverse effects of human health including allergies, food intolerance, cancer, multiple sclerosis, attention deficit hyperactivity disorder (ADHD, brain damage, nausea, cardiac disease and asthma due to the reaction of aromatic azo compounds (R = R' = aromatic. Several countries have banned and strictly controlled the uses of Allura Red in food and beverage products. This review paper is critically summarized on the available analytical and advanced methods for determination of Allura Red and also concisely discussed on the acceptable daily intake (ADI, toxicology and extraction methods.

  7. INCREASING HEAVY OIL RESERVES IN THE WILMINGTON OIL FIELD THROUGH ADVANCED RESERVOIR CHARACTERIZATION AND THERMAL PRODUCTION TECHNOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    Unknown

    2001-08-08

    The objective of this project is to increase the recoverable heavy oil reserves within sections of the Wilmington Oil Field, near Long Beach, California, through the testing and application of advanced reservoir characterization and thermal production technologies. The hope is that successful application of these technologies will result in their implementation throughout the Wilmington Field and, through technology transfer, will be extended to increase the recoverable oil reserves in other slope and basin clastic (SBC) reservoirs. The existing steamflood in the Tar zone of Fault Block II-A (Tar II-A) has been relatively inefficient because of several producibility problems which are common in SBC reservoirs: inadequate characterization of the heterogeneous turbidite sands, high permeability thief zones, low gravity oil and non-uniform distribution of the remaining oil. This has resulted in poor sweep efficiency, high steam-oil ratios, and early steam breakthrough. Operational problems related to steam breakthrough, high reservoir pressure, and unconsolidated sands have caused premature well and downhole equipment failures. In aggregate, these reservoir and operational constraints have resulted in increased operating costs and decreased recoverable reserves. A suite of advanced reservoir characterization and thermal production technologies are being applied during the project to improve oil recovery and reduce operating costs, including: (1) Development of three-dimensional (3-D) deterministic and stochastic reservoir simulation models--thermal or otherwise--to aid in reservoir management of the steamflood and post-steamflood phases and subsequent development work. (2) Development of computerized 3-D visualizations of the geologic and reservoir simulation models to aid reservoir surveillance and operations. (3) Perform detailed studies of the geochemical interactions between the steam and the formation rock and fluids. (4) Testing and proposed application of a

  8. Bio-optic signatures for advanced glycation end products in the skin in streptozotocin (STZ) Induced Diabetes (Conference Presentation)

    Science.gov (United States)

    Saidian, Mayer; Ponticorvo, Adrien; Rowland, Rebecca A.; Balbado, Melisa L.; Lentsch, Griffin; Balu, Mihaela; Alexander, Micheal; Shiri, Li; Lakey, Jonathan R. T.; Durkin, Anthony J.; Kohen, Roni; Tromberg, Bruce J.

    2017-02-01

    Type 1diabetes (T1D) is an autoimmune disorder that occurs due to the rapid destruction of insulin-producing beta cells, leading to insulin deficiency and the inability to regulate blood glucose levels and leads to destructive secondary complications. Advanced glycation end (AGEs) products, the result of the cross-linking of reducing sugars and proteins within the tissues, are one of the key causes of major complications associated with diabetes such as renal failure, blindness, nerve damage and vascular changes. Non-invasive techniques to detect AGEs are important for preventing the harmful effects of AGEs during diabetes mellitus. In this study, we utilized multiphoton microscopy to image biopsies taken from control rats and compared them to biopsies taken from streptozotocin (STZ) induced adult male diabetic rats. This was done at two and four weeks after the induction of hyperglycemia (>400 mg/dL) specifically to evaluate the effects of glycation on collagen. We chose to use an in-situ multiphoton microscopy method that combines multiphoton auto-florescence (AF) and second harmonic generation (SHG) to detect the microscopic influence of glycation. Initial results show high auto-florescence levels were present on the collagen, as a result of the accumulation of AGEs only two weeks after the STZ injection and considerably higher levels were present four weeks after the STZ injection. Future projects could involve evaluating advanced glycation end products in a clinical trial of diabetic patients.

  9. Recent Advances in Exopolysaccharides from Paenibacillus spp.: Production, Isolation, Structure, and Bioactivities

    Science.gov (United States)

    Liang, Tzu-Wen; Wang, San-Lang

    2015-01-01

    This review provides a comprehensive summary of the most recent developments of various aspects (i.e., production, purification, structure, and bioactivity) of the exopolysaccharides (EPSs) from Paenibacillus spp. For the production, in particular, squid pen waste was first utilized successfully to produce a high yield of inexpensive EPSs from Paenibacillus sp. TKU023 and P. macerans TKU029. In addition, this technology for EPS production is prevailing because it is more environmentally friendly. The Paenibacillus spp. EPSs reported from various references constitute a structurally diverse class of biological macromolecules with different applications in the broad fields of pharmacy, cosmetics and bioremediation. The EPS produced by P. macerans TKU029 can increase in vivo skin hydration and may be a new source of natural moisturizers with potential value in cosmetics. However, the relationships between the structures and activities of these EPSs in many studies are not well established. The contents and data in this review will serve as useful references for further investigation, production, structure and application of Paenibacillus spp. EPSs in various fields. PMID:25837984

  10. Production of advanced fuels and of chemicals by yeasts on the basis of second generation feedstocks

    NARCIS (Netherlands)

    Bont, de J.A.M.; Raab, A.; Schilling, M.; Tamame González, M.M.; los Ángeles Santos García, De M.; Martins Dos Santos, V.A.P.; Arjona Antolín, R.; Gutiérrez Gómez, P.

    2014-01-01

    The present invention relates to modified eukaryotic microbial cells that have been engineered for producing fermentation products such as fatty acids, 1-alcohols, [beta]- keto-acids and -alcohols, [beta]-hydroxyacids, 1,3-diols, trans-[Delta]2-fatty acids, alkenes, alkanes and derivatives thereof,

  11. Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing

    DEFF Research Database (Denmark)

    Weber, Jakob; Valiante, Vito; Nødvig, Christina Spuur

    2017-01-01

    is not produced among different isolates. Combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pathway and reconstitute its production in a nonproducing strain. Thus, we present a CRISPR/Cas9-based tool...

  12. Advances in Online Shopping Interfaces: Product Catalog Maps and Recommender Systems

    NARCIS (Netherlands)

    M. Kagie (Martijn)

    2010-01-01

    textabstractOver the past two decades the internet has rapidly become an important medium to retrieve information, maintain social contacts, and to do online shopping. The latter has some important advantages over traditional shopping. Products are often cheaper on the internet, internet companies

  13. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Science.gov (United States)

    2010-01-01

    ... exiting the AMR system for bone solids, bone marrow, spinal cord, and DRG as prescribed in paragraph (c)(1... or bone marrow as measured by the presence of calcium and iron in excess of the requirements in this... nearest 10th, is more than 130.0 mg per 100 g. (ii) Bone marrow. The product's added iron content...

  14. Advanced productivity forecast using petrophysical wireline data calibrated with MDT tests and numerical reservoir simulation

    Energy Technology Data Exchange (ETDEWEB)

    Andre, Carlos de [PETROBRAS, Rio de Janeiro, RJ (Brazil); Canas, Jesus A.; Low, Steven; Barreto, Wesley [Schlumberger, Houston, TX (United States)

    2004-07-01

    This paper describes an integrated and rigorous approach for viscous and middle oil reservoir productivity evaluation using petrophysical models calibrated with permeability derived from mini tests (Dual Packer) and Vertical Interference Tests (VIT) from open hole wire line testers (MDT SLB TM). It describes the process from Dual Packer Test and VIT pre-job design, evaluation via analytical and inverse simulation modeling, calibration and up scaling of petrophysical data into a numerical model, history matching of Dual Packer Tests and VIT with numerical simulation modeling. Finally, after developing a dynamic calibrated model, we perform productivity forecasts of different well configurations (vertical, horizontal and multilateral wells) for several deep offshore oil reservoirs in order to support well testing activities and future development strategies. The objective was to characterize formation static and dynamic properties early in the field development process to optimize well testing design, extended well test (EWT) and support the development strategies in deep offshore viscous oil reservoirs. This type of oil has limitations to flow naturally to surface and special lifting equipment is required for smooth optimum well testing/production. The integrated analysis gave a good overall picture of the formation, including permeability anisotropy and fluid dynamics. Subsequent analysis of different well configurations and lifting schemes allows maximizing formation productivity. The simulation and calibration results are compared to measured well test data. Results from this work shows that if the various petrophysical and fluid properties sources are integrated properly an accurate well productivity model can be achieved. If done early in the field development program, this time/knowledge gain could reduce the risk and maximize the development profitability of new blocks (value of the information). (author)

  15. Land usage attributed to corn ethanol production in the United States: sensitivity to technological advances in corn grain yield, ethanol conversion, and co-product utilization

    Science.gov (United States)

    2014-01-01

    Background Although the system for producing yellow corn grain is well established in the US, its role among other biofeedstock alternatives to petroleum-based energy sources has to be balanced with its predominant purpose for food and feed as well as economics, land use, and environmental stewardship. We model land usage attributed to corn ethanol production in the US to evaluate the effects of anticipated technological change in corn grain production, ethanol processing, and livestock feeding through a multi-disciplinary approach. Seven scenarios are evaluated: four considering the impact of technological advances on corn grain production, two focused on improved efficiencies in ethanol processing, and one reflecting greater use of ethanol co-products (that is, distillers dried grains with solubles) in diets for dairy cattle, pigs, and poultry. For each scenario, land area attributed to corn ethanol production is estimated for three time horizons: 2011 (current), the time period at which the 15 billion gallon cap for corn ethanol as per the Renewable Fuel Standard is achieved, and 2026 (15 years out). Results Although 40.5% of corn grain was channeled to ethanol processing in 2011, only 25% of US corn acreage was attributable to ethanol when accounting for feed co-product utilization. By 2026, land area attributed to corn ethanol production is reduced to 11% to 19% depending on the corn grain yield level associated with the four corn production scenarios, considering oil replacement associated with the soybean meal substituted in livestock diets with distillers dried grains with solubles. Efficiencies in ethanol processing, although producing more ethanol per bushel of processed corn, result in less co-products and therefore less offset of corn acreage. Shifting the use of distillers dried grains with solubles in feed to dairy cattle, pigs, and poultry substantially reduces land area attributed to corn ethanol production. However, because distillers dried grains

  16. Land usage attributed to corn ethanol production in the United States: sensitivity to technological advances in corn grain yield, ethanol conversion, and co-product utilization.

    Science.gov (United States)

    Mumm, Rita H; Goldsmith, Peter D; Rausch, Kent D; Stein, Hans H

    2014-01-01

    Although the system for producing yellow corn grain is well established in the US, its role among other biofeedstock alternatives to petroleum-based energy sources has to be balanced with its predominant purpose for food and feed as well as economics, land use, and environmental stewardship. We model land usage attributed to corn ethanol production in the US to evaluate the effects of anticipated technological change in corn grain production, ethanol processing, and livestock feeding through a multi-disciplinary approach. Seven scenarios are evaluated: four considering the impact of technological advances on corn grain production, two focused on improved efficiencies in ethanol processing, and one reflecting greater use of ethanol co-products (that is, distillers dried grains with solubles) in diets for dairy cattle, pigs, and poultry. For each scenario, land area attributed to corn ethanol production is estimated for three time horizons: 2011 (current), the time period at which the 15 billion gallon cap for corn ethanol as per the Renewable Fuel Standard is achieved, and 2026 (15 years out). Although 40.5% of corn grain was channeled to ethanol processing in 2011, only 25% of US corn acreage was attributable to ethanol when accounting for feed co-product utilization. By 2026, land area attributed to corn ethanol production is reduced to 11% to 19% depending on the corn grain yield level associated with the four corn production scenarios, considering oil replacement associated with the soybean meal substituted in livestock diets with distillers dried grains with solubles. Efficiencies in ethanol processing, although producing more ethanol per bushel of processed corn, result in less co-products and therefore less offset of corn acreage. Shifting the use of distillers dried grains with solubles in feed to dairy cattle, pigs, and poultry substantially reduces land area attributed to corn ethanol production. However, because distillers dried grains with solubles

  17. Secondary Neutron Production from Space Radiation Interactions: Advances in Model and Experimental Data Base Development

    Science.gov (United States)

    Heilbronn, Lawrence H.; Townsend, Lawrence W.; Braley, G. Scott; Iwata, Yoshiyuki; Iwase, Hiroshi; Nakamura, Takashi; Ronningen, Reginald M.; Cucinotta, Francis A.

    2003-01-01

    For humans engaged in long-duration missions in deep space or near-Earth orbit, the risk from exposure to galactic and solar cosmic rays is an important factor in the design of spacecraft, spacesuits, and planetary bases. As cosmic rays are transported through shielding materials and human tissue components, a secondary radiation field is produced. Neutrons are an important component of that secondary field, especially in thickly-shielded environments. Calculations predict that 50% of the dose-equivalent in a lunar or Martian base comes from neutrons, and a recent workshop held at the Johnson Space Center concluded that as much as 30% of the dose in the International Space Station may come from secondary neutrons. Accelerator facilities provide a means for measuring the effectiveness of various materials in their ability to limit neutron production, using beams and energies that are present in cosmic radiation. The nearly limitless range of beams, energies, and target materials that are present in space, however, means that accelerator-based experiments will not provide a complete database of cross sections and thick-target yields that are necessary to plan and design long-duration missions. As such, accurate nuclear models of neutron production are needed, as well as data sets that can be used to compare with, and verify, the predictions from such models. Improvements in a model of secondary neutron production from heavy-ion interactions are presented here, along with the results from recent accelerator-based measurements of neutron-production cross sections. An analytical knockout-ablation model capable of predicting neutron production from high-energy hadron-hadron interactions (both nucleon-nucleus and nucleus-nucleus collisions) has been previously developed. In the knockout stage, the collision between two nuclei result in the emission of one or more nucleons from the projectile and/or target. The resulting projectile and target remnants, referred to as

  18. TECHNOLOGICAL ADVANCEMENT OF DEPOSIT WELDING AND GAS LASER CUTTING TO INCREASE THE EFFICIENCY OF THE BIMETALLIC TOOL PRODUCTION

    Directory of Open Access Journals (Sweden)

    Burlachenko Oleg Vasil’evich

    2017-08-01

    Full Text Available Deposit welding is the application of a layer of metal on the surface of a product using fusion welding. In this paper, we consider the method of improving the technology of gas laser cutting, which makes it possible to achieve a high productivity of manufacturing a bimetallic tool. The present paper is concerned with the advantages of gas laser cutting which allows to consider this particular process of separating materials as highly-productive, low-waste, and advanced method of removing allowances of weld-deposit high-speed steel on the working surfaces of bimetallic tool. Urgency of the use of deposit welding and gas laser cutting to improve the efficiency of production of bimetallic tool is shown. The comparative analysis of gas-laser cutting and other cutting methods is given according to the geometrical parameters of cutting and surface quality. Analysis of the results of experimental studies has confirmed the high technological attractiveness and economic efficiency of manufacturing composite structures of punches and matrices when applying deposit welding of cutting parts with high-speed steels. The cost of dimensional processing of the welded cutting part is reduced by 4 to 6 times, while the manufacturing time is reduced by 6 to 12 times.

  19. Advances on the Chilean Nuclear Energy Commission's Cyclotron Laboratory Program for the production of 18F and 18FDG

    International Nuclear Information System (INIS)

    Avila, M.J; Bustos, Rosario; Pinto, Luis; Ahumada, Luis

    2003-01-01

    The Chilean Nuclear Energy Commission (CCHEN) Cyclotron's Laboratory has begun to produce short-lived positron's emitter radionuclides need for positron emitter tomography (PET) and intended for clinical prognosis. Production trials took place back on February 2003 to calibrate the only existing camera PET in the country at the Hospital Militar. Subsequently, a complex stage of adjustment, corrections and optimizations on the camera itself, as well as, on the accelerator were performed with solely intention to introduce PET technique as clinical tool in the more efficient way as possible. The reported advances on production are linked to the increasing availability of high radionuclidic and radiochemical purity 18 FDG. Because of demand and nuclear medicine declared necessities on this radiopharmaceutical imposes Cyclotron Laboratory to make available 18 FDG as soon as possible, from the earliest production trials. This was accomplished simultaneously with preliminary beam optical and modular synthesis adjustments. During April the availability of 18 FDG for clinical imaging was acceptable to satisfy demand, whereas May actually initiates routinely production (au)

  20. The effect of an insulin releasing agent, BTS 67582, on advanced glycation end product formation in vitro.

    Science.gov (United States)

    Simpson, A E; Jones, R B

    1999-01-01

    BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl) guanidine fumarate) is an insulin-releasing agent currently in phase II clinical trials. Its effect on advanced glycation end product (AGE) formation was measured in the BSA/D-glucose and L-lysine/glucose-6-phosphate assay systems and Amadori product formation was measured in the BSA/D-glucose assay system, following a 3 week incubation period. In the BSA/D-glucose assay system, 200 mM BTS 67582 caused an approximate 70% inhibition in AGE formation (pBTS 67582 and 200 mM aminoguanidine-HCl retarded Amadori product formation by 88% (pBTS 67582 at 20 mM and 2 mM was shown to inhibit Amadori product formation by 67% and 57%, respectively, (pBTS 67582 and 200 mM aminoguanidine-HCl were shown to inhibit AGE formation by about 70% and 96% (p<0.001), respectively. Tolbutamide (200 microM) and glibenclamide (100 microM) had no significant effect on AGE formation.

  1. Advances in animal cell recombinant protein production: GS-NS0 expression system.

    Science.gov (United States)

    Barnes, L M; Bentley, C M; Dickson, A J

    2000-02-01

    The production of recombinant proteins using mammalian cell expression systems is of growing importance within biotechnology, largely due to the ability of specific mammalian cells to carry out post-translational modifications of the correct fidelity. The Glutamine Synthetase-NS0 system is now one such industrially important expression system.Glutamine synthetase catalyses the formation ofglutamine from glutamate and ammonia. NS0 cellscontain extremely low levels of endogenous glutaminesynthetase activity, therefore exogenous glutaminesynthetase can be used efficiently as a selectablemarker to identify successful transfectants in theabsence of glutamine in the media. In addition, theinclusion of methionine sulphoximine, an inhibitor ofglutamine synthetase activity, enables furtherselection of those clones producing relatively highlevels of transfected glutamine synthetase and henceany heterologous gene which is coupled to it. Theglutamine synthetase system technology has been usedfor research and development purposes during thisdecade and its importance is clearly demonstrated nowthat two therapeutic products produced using thissystem have reached the market place.

  2. NREL Advancements in Methane Conversion Lead to Cleaner Air, Useful Products

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    Researchers at NREL leveraged the recent on-site development of gas fermentation capabilities and novel genetic tools to directly convert methane to lactic acid using an engineered methanotrophic bacterium. The results provide proof-of-concept data for a gas-to-liquids bioprocess that concurrently produces fuels and chemicals from methane. NREL researchers developed genetic tools to express heterologous genes in methanotrophic organisms, which have historically been difficult to genetically engineer. Using these tools, researchers demonstrated microbial conversion of methane to lactate, a high-volume biochemical precursor predominantly utilized for the production of bioplastics. Methane biocatalysis offers a means to concurrently liquefy and upgrade natural gas and renewable biogas, enabling their utilization in conventional transportation and industrial manufacturing infrastructure. Producing chemicals and fuels from methane expands the suite of products currently generated from biorefineries, municipalities, and agricultural operations, with the potential to increase revenue and significantly reduce greenhouse gas emissions.

  3. Recent advances in the use of synchrotron radiation for the analysis of coal combustion products

    Energy Technology Data Exchange (ETDEWEB)

    Manowitz, B. [Brookhaven National Lab., Upton, NY (United States)

    1995-11-01

    Two major coal combustion problems are the formation and build-up of slag deposits on heat transfer surfaces and the production and control of toxic species in coal combustion emissions. The use of synchrotron radiation for the analysis of coal combustion products can play a role in the better understanding of both these phenomena. An understanding of the chemical composition of such slags under boiler operating conditions and as a function of the mineral composition of various coals is one ultimate goal of this program. The principal constituents in the ash of many coals are the oxides of Si, Al, Fe, Ca, K, S, and Na. The analytical method required must be able to determine the functional forms of all these elements both in coal and in coal ash at elevated temperatures. One unique way of conducting these analyses is by x-ray spectroscopy.

  4. Technical advance in China's petroleum exploitation and production and its environmental protection

    Energy Technology Data Exchange (ETDEWEB)

    Xingchun, Li; Wei, Fan; Jialin, Wang; Yong, Li

    2010-09-15

    China has gained great development in the fields of petroleum exploitation and production, and these achievements provide reservation for China's energy safety. Some of them may strengthen the environment protection from the source, while some of them may bring certain environmental pressure. This study analyses the opportunities and the challenges brought by the technology development and gives countermeasures for decrease the negative impact of technology development.

  5. Advances in reforming and partial oxidation of hydrocarbons for hydrogen production and fuel cell applications

    OpenAIRE

    Sengodan, Sivaprakash; Lan, Rong; Humphreys, John; Du, Dongwei; Xu, Wei; Wang, Huanting; Tao, Shanwen

    2017-01-01

    One of the most attractive routes for the production of hydrogen or syngas for use in fuel cell applications is the reforming and partial oxidation of hydrocarbons. The use of hydrocarbons in high temperature fuel cells is achieved through either external or internal reforming. Reforming and partial oxidation catalysis to convert hydrocarbons to hydrogen rich syngas plays an important role in fuel processing technology. The current research in the area of reforming and partial oxidation of me...

  6. Energy recovery during advanced wastewater treatment: simultaneous estrogenic activity removal and hydrogen production through solar photocatalysis.

    Science.gov (United States)

    Zhang, Wenlong; Li, Yi; Wang, Chao; Wang, Peifang; Wang, Qing

    2013-03-01

    Simultaneous estrogenic activity removal and hydrogen production from secondary effluent were successfully achieved using TiO(2) microspheres modified with both platinum nanoparticles and phosphates (P-TiO(2)/Pt) for the first time. The coexistence of platinum and phosphate on the surface of TiO(2) microspheres was confirmed by transmission electron microscope, energy-dispersive X-ray and X-ray photoelectron spectroscopy analyses. P-TiO(2)/Pt microspheres showed a significantly higher photocatalytic activity than TiO(2) microspheres and TiO(2) powders (P25) for the removal of estrogenic activity from secondary effluent with the removal ratio of 100%, 58.2% and 48.5% in 200 min, respectively. Moreover, the marked production of hydrogen (photonic efficiency: 3.23 × 10(-3)) was accompanied by the removal of estrogenic activity only with P-TiO(2)/Pt as photocatalysts. The hydrogen production rate was increasing with decreased DO concentration in secondary effluent. Results of reactive oxygen species (ROS) evaluation during P-TiO(2)/Pt photocatalytic process showed that O(2)(-)and OH were dominant ROS in aerobic phase, while OH was the most abundant ROS in anoxic phase. Changes of effluent organic matter (EfOM) during photocatalysis revealed that aromatic, hydrophobic, and high molecular weight fractions of EfOM were preferentially transformed into non-humic, hydrophilic, and low MW fractions (e.g. aldehydes and carboxylic acids), which were continuously utilized as electron donors in hydrogen production process. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology.

    Science.gov (United States)

    Altman, Roy; Bosch, Bill; Brune, Kay; Patrignani, Paola; Young, Clarence

    2015-05-01

    Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. This review illustrates how pharmaceutical technology has been used to modify the pharmacokinetic properties of diclofenac, leading to the creation of novel drug products with improved clinical utility.

  8. Advances on the Measure of Judgment and Meaning of the Product for Brazil

    Directory of Open Access Journals (Sweden)

    Solange Alfinito

    2012-09-01

    Full Text Available The purpose of this paper was the development a measure of judgment and meaning of the product valid for Brazilian consumers. It consisted in a two-stage study including both qualitative and quantitative approaches. In the qualitative stage, focus groups with 16 Brazilian participants allowed the generation of 40 items for a new scale of judgment and meaning of the product. After semantic validation and expert analysis, the found items composed a questionnaire administered to 684 participants in a paper-and-pencil survey. Results suggest that the items performed considerably better when compared to the previous version, indicating their potential of usage not only in Brazil, but also in other countries. The final measure remained with 20 items that were distributed in four factors, as pointed by the literature review. Two factors are related to judgment types (piecemeal and affective, whilst the other two are related to meaning types (utilitarian and symbolic. Additional results, as expected, showed that product's utilitarian meaning is positively correlated to a piecemeal judgment, whereas symbolic meaning is positively related to affective judgment. Managerial implications for marketing, and future research directions are proposed.

  9. Advances of zeolite based membrane for hydrogen production via water gas shift reaction

    Science.gov (United States)

    Makertihartha, I. G. B. N.; Zunita, M.; Rizki, Z.; Dharmawijaya, P. T.

    2017-07-01

    Hydrogen is considered as a promising energy vector which can be obtained from various renewable sources. However, an efficient hydrogen production technology is still challenging. One technology to produce hydrogen with very high capacity with low cost is through water gas shift (WGS) reaction. Water gas shift reaction is an equilibrium reaction that produces hydrogen from syngas mixture by the introduction of steam. Conventional WGS reaction employs two or more reactors in series with inter-cooling to maximize conversion for a given volume of catalyst. Membrane reactor as new technology can cope several drawbacks of conventional reactor by removing reaction product and the reaction will favour towards product formation. Zeolite has properties namely high temperature, chemical resistant, and low price makes it suitable for membrane reactor applications. Moreover, it has been employed for years as hydrogen selective layer. This review paper is focusing on the development of membrane reactor for efficient water gas shift reaction to produce high purity hydrogen and carbon dioxide. Development of membrane reactor is discussed further related to its modification towards efficient reaction and separation from WGS reaction mixture. Moreover, zeolite framework suitable for WGS membrane reactor will be discussed more deeply.

  10. Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs.

    Science.gov (United States)

    Abou-El-Enein, Mohamed; Römhild, Andy; Kaiser, Daniel; Beier, Carola; Bauer, Gerhard; Volk, Hans-Dieter; Reinke, Petra

    2013-03-01

    Advanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities. The "Clean-Room Technology Assessment Technique" (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system. CTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost. CTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. Design and Demonstration of an Advanced Agricultural Feedstock Supply System for Lignocellulosic Bioenergy Production

    Energy Technology Data Exchange (ETDEWEB)

    Clark, Timothy C. [Antares Group Inc., Lanham, MD (United States); Comer, Kevin S. [Antares Group Inc., Lanham, MD (United States); Belden, Jr., William S. [Antares Group Inc., Lanham, MD (United States)

    2016-04-30

    This three-year project developed and demonstrated four innovative, first-of-their-kind pieces of equipment that are aimed at significantly reducing the cost of delivered herbaceous biomass. This equipment included a Self-Propelled Baler (SPB), a Bale Picking Truck (BPT), a Self-Loading Trailer (SLT), and a Heavy Crop Header for harvesting high yielding energy crops. This equipment was designed and fabricated during the first two years of the project and demonstrated on available crops (corn stover, wheat straw, and warm season grasses) across the nation, as available. Operational performance and cost data was collected and analyzed throughout the project to measure the costs of baseline harvesting (using conventional harvesting equipment) and advanced harvesting with the newly developed equipment. This data revealed that the project met its original goal of developing equipment that is realistically capable of reducing the cost of delivered biomass by $13 per dry ton. Each machine was tested after fabrication and put to the test in one or more commercial harvesting seasons. During these tests, operational flaws were found and fixed through upgrades and improvements. The first new SPB, BPT, and two new SLTs were ready for use during the 2013 harvest season. Since then, over 40 SLTs have been ordered and are currently under fabrication. All of the equipment will be commercially available to the industry as demand increases.

  12. Prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease.

    Science.gov (United States)

    Miletić, Jadranka; Drakulić, Dunja; Pejić, Snežana; Petković, Marijana; Ilić, Tihomir V; Miljković, Milica; Stefanović, Aleksandra; Prostran, Milica; Stojanov, Marina

    2017-12-04

    Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity. The aim of this study was to evaluate the levels of the above-mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status. The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant-antioxidant balance (p = 0.02). Relation between oxidant-antioxidant status was further supported by observed positive correlation between 4-hydroxynonenal (p = 0.04) and prooxidant-antioxidant balance (p = 0.03). Finally, the multivariate analysis indicated that prooxidant-antioxidant balance and malondialdehyde were partially determined by gender (10.6% and 7.6%) and Hoehn and Yahr scores (13.6% and 18.8%), while Hoehn and Yahr scores contributed to the variance of advanced oxidation protein products with 13.2%. Our results indicate the higher level of oxidative stress (oxidant-antioxidant imbalance) and possible relation of several markers with gender and disease stage in patients with Parkinson's disease. The analyzed markers could be used to specify the severity of oxidative stress; however, their potential value should be analyzed in further studies.

  13. Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation End-products in Head and Neck Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Nguyen, Austin

    2016-04-01

    Full Text Available Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

  14. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengyu Zhang

    2013-11-01

    Full Text Available Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes.

  15. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE) and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK) Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

    Science.gov (United States)

    Zhang, Zhengyu; Sethiel, Mosha Silas; Shen, Weizhi; Liao, Sentai; Zou, Yuxiao

    2013-01-01

    Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs) in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK) activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes. PMID:24252909

  16. Advanced Intermediate Heat Transport Loop Design Configurations for Hydrogen Production Using High Temperature Nuclear Reactors

    International Nuclear Information System (INIS)

    Chang Oh; Cliff Davis; Rober Barner; Paul Pickard

    2005-01-01

    The US Department of Energy is investigating the use of high-temperature nuclear reactors to produce hydrogen using either thermochemical cycles or high-temperature electrolysis. Although the hydrogen production processes are in an early stage of development, coupling either of these processes to the high-temperature reactor requires both efficient heat transfer and adequate separation of the facilities to assure that off-normal events in the production facility do not impact the nuclear power plant. An intermediate heat transport loop will be required to separate the operations and safety functions of the nuclear and hydrogen plants. A next generation high-temperature reactor could be envisioned as a single-purpose facility that produces hydrogen or a dual-purpose facility that produces hydrogen and electricity. Early plants, such as the proposed Next Generation Nuclear Plant (NGNP), may be dual-purpose facilities that demonstrate both hydrogen and efficient electrical generation. Later plants could be single-purpose facilities. At this stage of development, both single- and dual-purpose facilities need to be understood. A number of possible configurations for a system that transfers heat between the nuclear reactor and the hydrogen and/or electrical generation plants were identified. These configurations included both direct and indirect cycles for the production of electricity. Both helium and liquid salts were considered as the working fluid in the intermediate heat transport loop. Methods were developed to perform thermal-hydraulic evaluations and cycle-efficiency evaluations of the different configurations and coolants. The thermal-hydraulic evaluations estimated the sizes of various components in the intermediate heat transport loop for the different configurations. The relative sizes of components provide a relative indication of the capital cost associated with the various configurations. Estimates of the overall cycle efficiency of the various

  17. Fostering sustainable feedstock production for advanced biofuels on underutilised land in Europe

    Science.gov (United States)

    Mergner, Rita; Janssen, Rainer; Rutz, Dominik; Knoche, Dirk; Köhler, Raul; Colangeli, Marco; Gyuris, Peter

    2017-04-01

    Background In context of growing competition between land uses, bioenergy development is often seen as one of possible contributors to such competition. However, the potential of underutilized land (contaminated, abandoned, marginal, fallow land etc.) which is not used or cannot be used for productive activities is not exhausted and offers an attractive alternative for sustainable production of different biomass feedstocks in Europe. Depending on biomass feedstocks, different remediation activities can be carried out in addition. Bioenergy crops have the potential to be grown profitably on underutilized land and can therefore offer an attractive source of income on the local level contributing to achieving the targets of the Renewable Energy Directive (EC/2009). The FORBIO project The FORBIO project demonstrates the viability of using underutilised land in EU Member States for sustainable bioenergy feedstock production that does not affect the supply of food, feed and land currently used for recreational or conservation purposes. Project activities will serve to build up and strengthen local bioenergy value chains that are competitive and that meet the highest sustainability standards, thus contributing to the market uptake of sustainable bioenergy in the EU. Presented results The FORBIO project will develop a methodology to assess the sustainable bioenergy production potential on available underutilized lands in Europe at local, site-specific level. Based on this methodology, the project will produce multiple feasibility studies in three selected case study locations: Germany (lignite mining and sewage irrigation fields in the metropolis region of Berlin and Brandenburg), Italy (contaminated land from industrial activities in Sulcis, Portoscuso) and Ukraine (underutilised marginal agricultural land in the North of Kiev). The focus of the presentation will be on the agronomic and techno-economic feasibility studies in Germany, Italy and Ukraine. Agronomic

  18. The receptor for advanced glycation end products RAGE is involved in corneal healing.

    Science.gov (United States)

    Nass, Norbert; Trau, Stefanie; Paulsen, Friedrich; Kaiser, Delia; Kalinski, Thomas; Sel, Saadettin

    2017-05-01

    Impaired corneal healing is still a major cause of blindness. As RAGE (receptor for advanced glycation endproducts) is involved in inflammation and wound healing in other tissues, we here investigated its relevance for corneal wound healing. Corneal re-epithelialization after alkaline injury was analysed in an ex-vivo approach with cultured, enucleated eyes from mice either of the C57Bl/6 NChR genotype (RAGE+/+) and mice of the same strain lacking the RAGE gene (RAGE-/-). The wound area was determined time dependently by fluorescence imaging using fluorescein staining. The eyes of RAGE-/- mice showed a significantly slower re-epithelialization than eyes of the RAGE+/- and the RAGE+/+ genotype. In immunohistochemistry, RAGE expression was increased in wounded corneas whereas the abundance of the RAGE ligand HMGB1 was unaffected, but an increase in S100b-like proteins was revealed upon injury. However, neither the addition of the RAGE agonist HMGB1 or an HMGB1 antagonising antibody nor bovine S100b protein to the culture medium of the wounded eyes had an effect on corneal wound closure in ex-vivo. Further gene expression analysis by RT-PCR demonstrated an increase in RAGE expression on the mRNA level, no significant regulation of HMGB1 and a differential regulation of the S100 gene family after alkaline burn of the cornea. In conclusion, RAGE is clearly involved in corneal re-epithelialization most probably mediated by signalling via S100 proteins. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Advances in biofuel production from oil palm and palm oil processing wastes: A review

    Directory of Open Access Journals (Sweden)

    Jundika C. Kurnia

    2016-03-01

    Full Text Available Over the last decades, the palm oil industry has been growing rapidly due to increasing demands for food, cosmetic, and hygienic products. Aside from producing palm oil, the industry generates a huge quantity of residues (dry and wet which can be processed to produce biofuel. Driven by the necessity to find an alternative and renewable energy/fuel resources, numerous technologies have been developed and more are being developed to process oil-palm and palm-oil wastes into biofuel. To further develop these technologies, it is essential to understand the current stage of the industry and technology developments. The objective of this paper is to provide an overview of the palm oil industry, review technologies available to process oil palm and palm oil residues into biofuel, and to summarise the challenges that should be overcome for further development. The paper also discusses the research and development needs, technoeconomics, and life cycle analysis of biofuel production from oil-palm and palm-oil wastes.

  20. Life cycle assessment of advanced bioethanol production from pulp and paper sludge.

    Science.gov (United States)

    Sebastião, Diogo; Gonçalves, Margarida S; Marques, Susana; Fonseca, César; Gírio, Francisco; Oliveira, Ana C; Matos, Cristina T

    2016-05-01

    This work evaluates the environmental performance of using pulp and paper sludge as feedstock for the production of second generation ethanol. An ethanol plant for converting 5400 tons of dry sludge/year was modelled and evaluated using a cradle-to-gate life cycle assessment approach. The sludge is a burden for pulp and paper mills that is mainly disposed in landfilling. The studied system allows for the valorisation of the waste, which due to its high polysaccharide content is a valuable feedstock for bioethanol production. Eleven impact categories were analysed and the results showed that enzymatic hydrolysis and neutralisation of the CaCO3 are the environmental hotspots of the system contributing up to 85% to the overall impacts. Two optimisation scenarios were evaluated: (1) using a reduced HCl amount in the neutralisation stage and (2) co-fermentation of xylose and glucose, for maximal ethanol yield. Both scenarios displayed significant environmental impact improvements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Study on production of useful metabolites by development of advanced cell culture techniques using radiation

    International Nuclear Information System (INIS)

    Chung, Byung Yeoup; Kim, Jinhong; Lee, Seung Sik; Bai, Hyounwoo; An, Byung Chull; Lee, Eun Mi; Lee, Jae Taek; Kim, Mi Ja

    2010-12-01

    The purpose of this project is improvement of investigation, materialization and evaluation techniques on effectiveness for functional natural compounds throughout development of tissue/cell culture techniques for mass production of useful metabolites using radiation. Research scope includes Development of a technique for radiation tissue and cell culture, Database construction for radiation response in plants and radiation effects, Construction of general-purpose national based techniques of cell culture technique using radiation. Main results are as follow: Isolation and identification of radiation induced basI gene; Determination of stresses sensitivities by transformating basI gene into arabidopsis; Isolation and identification of radiation induced chaperon proteins (PaAhpC and yPrxII) from Pseudomonas and yeast, and structural and functional analysis of the proteins; Determination of oxidative and heat resistance by transformating PaAhpC; Isolation and identification of maysin and its derivatives from centipedgrass; Investigation of enhancement technique for improving maysin and its derivatives production using radiation; Investigation of removing undesirable color in maysin and its derivatives using radiation; Determination of the effect of radiation on physiological functions of centipedgrass extracts; Identification of H 2 O 2 removing enzyme in radiation irradiated plant (Spinach); Determination of the effects of centipedgrass extracts on anti-obesity and anti-cancer activities

  2. Pre-treatment technologies for dark fermentative hydrogen production: Current advances and future directions.

    Science.gov (United States)

    Rafieenia, Razieh; Lavagnolo, Maria Cristina; Pivato, Alberto

    2018-01-01

    Hydrogen is regarded as a clean and non-carbon fuel and it has a higher energy content compared to carbon fuels. Dark fermentative hydrogen production from organic wastes is the most promising technology for commercialization among chemical and biological methods. Using mixed microflora is favored in terms of easier process control and substrate conversion efficiencies instead of pure cultures. However, mixed cultures should be first pre-treated in order to select sporulating hydrogen producing bacteria and suppress non-spore forming hydrogen consumers. Various inoculum pre-treatments have been used to enhance hydrogen production by dark fermentation including heat shock, acid or alkaline treatment, chemical inhibition, aeration, irradiation and inhibition by long chain fatty acids. Regarding substrate pre-treatment, that is performed with the aim of enhanced substrate biodegradability, thermal pre-treatment, pH adjustment using acid or base, microwave irradiation, sonication and biological treatment are the most commonly studied technologies. This article reviews the most investigated pre-treatment technologies applied for either inoculum or substrate prior to dark fermentation, the long-term effects of varying pre-treatment methods and the subsequently feasibility of each method for commercialization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The lipid peroxidation product 4-hydroxy-2-nonenal: Advances in chemistry and analysis

    Directory of Open Access Journals (Sweden)

    Corinne M. Spickett

    2013-01-01

    Full Text Available 4-Hydroxy-2-nonenal (HNE is one of the most studied products of phospholipid peroxidation, owing to its reactivity and cytotoxicity. It can be formed by several radical-dependent oxidative routes involving the formation of hydroperoxides, alkoxyl radicals, epoxides, and fatty acyl cross-linking reactions. Cleavage of the oxidized fatty acyl chain results in formation of HNE from the methyl end, and 9-oxo-nonanoic acid from the carboxylate or esterified end of the chain, although many other products are also possible. HNE can be metabolized in tissues by a variety of pathways, leading to detoxification and excretion. HNE-adducts to proteins have been detected in inflammatory situations such as atherosclerotic lesions using polyclonal and monoclonal antibodies, which have also been applied in ELISAs and western blotting. However, in order to identify the proteins modified and the exact sites and nature of the modifications, mass spectrometry approaches are required. Combinations of enrichment strategies with targetted mass spectrometry routines such as neutral loss scanning are now facilitating detection of HNE-modified proteins in complex biological samples. This is important for characterizing the interactions of HNE with redox sensitive cell signalling proteins and understanding how it may modulate their activities either physiologically or in disease.

  4. Premium Fuel Production From Mining and Timber Waste Using Advanced Separation and Pelletizing Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Honaker, R. Q.; Taulbee, D.; Parekh, B. K.; Tao, D.

    2005-12-05

    The Commonwealth of Kentucky is one of the leading states in the production of both coal and timber. As a result of mining and processing coal, an estimated 3 million tons of fine coal are disposed annually to waste-slurry impoundments with an additional 500 million tons stored at a number of disposal sites around the state due to past practices. Likewise, the Kentucky timber industry discards nearly 35,000 tons of sawdust on the production site due to unfavorable economics of transporting the material to industrial boilers for use as a fuel. With an average heating value of 6,700 Btu/lb, the monetary value of the energy disposed in the form of sawdust is approximately $490,000 annually. Since the two industries are typically in close proximity, one promising avenue is to selectively recover and dewater the fine-coal particles and then briquette them with sawdust to produce a high-value fuel. The benefits are i) a premium fuel product that is low in moisture and can be handled, transported, and utilized in existing infrastructure, thereby avoiding significant additional capital investment and ii) a reduction in the amount of fine-waste material produced by the two industries that must now be disposed at a significant financial and environmental price. As such, the goal of this project was to evaluate the feasibility of producing a premium fuel with a heating value greater than 10,000 Btu/lb from waste materials generated by the coal and timber industries. Laboratory and pilot-scale testing of the briquetting process indicated that the goal was successfully achieved. Low-ash briquettes containing 5% to 10% sawdust were produced with energy values that were well in excess of 12,000 Btu/lb. A major economic hurdle associated with commercially briquetting coal is binder cost. Approximately fifty binder formulations, both with and without lime, were subjected to an extensive laboratory evaluation to assess their relative technical and economical effectiveness as binding

  5. Comparison of NF membrane fouling and cleaning by two pretreatment strategies for the advanced treatment of antibiotic production wastewater.

    Science.gov (United States)

    Wang, Jianxing; Li, Kun; Yu, Dawei; Zhang, Junya; Wei, Yuansong; Chen, Meixue; Shan, Baoqing

    2016-01-01

    The nanofiltration (NF) membrane fouling characteristics and cleaning strategies were investigated and compared for treating membrane bioreactor (MBR) effluent and MBR-granular activated carbon (GAC) effluent of an antibiotic production wastewater by DK membrane. Results showed that the fouling of treating MBR effluent was more severe than that of treating MBR-GAC effluent. After filtering for 216 h, the difference of membrane flux decline was obvious between MBR effluent and MBR-GAC effluent, with 14.9% and 10.3% flux decline, respectively. Further study showed that organic fouling is the main NF membrane fouling in the advanced treatment of antibiotic production wastewater for both of the two different effluents. Soluble microbial by-product like and tyrosine-like substances were the dominant components in the foulants, whereas humic-like substances existing in the effluents had little contribution to the NF membrane fouling. A satisfactory efficiency of NF chemical cleaning could be obtained using combination of acid (HCl, pH 2.0-2.5) and alkali (NaOH + 0.3 wt% NaDS, pH 10.0-10.5). The favorable cleaning strategy is acid-alkali for treating the MBR-GAC effluent, while it is alkali-acid for treating the MBR effluent.

  6. Advances in bio-optical sensing on robotic platforms to elucidate ecosystem production in the interior ocean

    Science.gov (United States)

    Walsh, I. D.; Hardman-Mountford, N.; Dufois, F.; Wojtasiewicz, B.; Slawinski, D.; Murphy, D. J.

    2016-02-01

    The global view of ocean productivity has been defined for the past three decades by satellite-derived images of optical properties of the ocean's surface layer. Yet in most of the ocean, zones of enhanced phytoplankton production and nutrient recycling are located at depths below the view of optical satellites. In the subtropical gyres, the almost ubiquitous deep chlorophyll maximum is often located at depths exceeding 100m, along density interfaces at a boundary between the down welling light flux and upward transport of nutrients. Below the chlorophyll maximum heterotrophic production is the dominant process resulting in strong oxygen consumption and dissolved nutrient regeneration. Observing the physical forcing and biogeochemical dynamics that drive this system at the relevant time scales ranging from the diel to the seasonal has been a long-standing challenge in oceanography. In particular, measuring the processes occurring through perturbations to relaxation has often been more happenstance than design. In this presentation we describe advances in sensor systems deployed on autonomous robotic profilers to quantify carbon, oxygen and nutrient cycling within the interior ocean and present examples from the subtropical Indian Ocean, western Mediterranean and Labrador Sea.

  7. Advances in Automated QA/QC for TRISO Fuel Particle Production

    International Nuclear Information System (INIS)

    Hockey, Ronald L.; Bond, Leonard J.; Batishko, Charles R.; Gray, Joseph N.; Saurwein, John J.; Lowden, Richard A.

    2004-01-01

    Fuel in most Generation IV reactor designs typically encompasses billions of the TRISO particles. Present day QA/QC methods, done manually and in many cases destructively, cannot economically test a statistically significant fraction of the large number of the individual fuel particles required. Fully automated inspection technologies are essential to economical TRISO fuel particle production. A combination of in-line nondestructive (NDE) measurements employing electromagnetic induction and digital optical imaging analysis is currently under investigation and preliminary data indicate the potential for meeting the demands of this application. To calibrate high-speed NDE methods, surrogate fuel particle samples are being coated with layers containing a wide array of defect types found to degrade fuel performance and these are being characterized via high-resolution CT and digital radiographic images

  8. Lab interdependencies and the advanced design and production technologies (ADaPT) initiative

    International Nuclear Information System (INIS)

    Hayes, D.

    1995-01-01

    I am delighted to be here today. I was left with a very strong impression this morning about the large degree of integration that has been achieved in the science-based stockpile stewardship program in the last year. When Vic Reis convened this program last February, many of you same people from Energy Research, Defense Programs, and the external community were there. We talked about areas of investments: in credible capability and industrial interaction, the impact on the research community, and so on. The product was the published quality function deployment chart. The activities on the chart were important, but they did not have coherence. In listening to the presentations this morning, particularly the last four, I hear a high degree of coherence and integration, which is very pleasing

  9. Recent Advances in the Discovery and Development of Marine Microbial Natural Products

    Directory of Open Access Journals (Sweden)

    Yong Wang

    2013-03-01

    Full Text Available Marine microbial natural products (MMNPs have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed.

  10. Recent nanoparticle engineering advances in microalgal cultivation and harvesting processes of biodiesel production: a review.

    Science.gov (United States)

    Lee, Young-Chul; Lee, Kyubock; Oh, You-Kwan

    2015-05-01

    Among the various steps entailed in the production of biodiesel from microalgae, the efficiency and cost-reduction of the cultivation and harvesting steps remain key obstacles to its practical commercialization. Recently, in order to overcome the technical bottlenecks and limitations with regard to both steps, nanoparticle engineering based on particles' unique physico-chemical and mechanical properties has been extensively applied as a powerful analytical and practical tool. These applications include the enhancement of cell growth and/or pigments by light back-scattering, the induction of intracellular lipid accumulation by nutritional competition and/or stress environment, the improvement of cell separation efficiency and processing time from culture broth, the multiple reuse of magnetic nanoparticle flocculant, and integrated one-pot harvesting/cell-disruption. This review presents and discusses the recent nanoparticle-engineering-based developments in the implementation of practical microalgal cultivation and harvesting processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Leveraging Advanced Computational Algorithms and Satellite Remote Sensing Products for Flood Forecasting

    Science.gov (United States)

    Aristizabal, F.; Judge, J.; Rangarajan, A.

    2016-12-01

    According to the 2015 World Disasters Report published by the International Federation of Red Cross and Red Crescent Societies, floods, on an average annual reported basis during the period of 2005 to 2014, produced over 5,900 fatalities, over 86 million affected individuals, and over $34 billion in damages. Flood warning and forecasting systems relying on earth observations have generally employed deterministic, process-based hydrology models for near real-time operational applications. Limited research exists examining the application of computational and informatics algorithms for flood forecasting from earth observation data products.The goal of this study is to determine the efficacy of data-driven methodologies for accurately forecasting riverine flooding while exclusively utilizing remotely-sensed, satellite-based observations. Several data-driven spatiotemporal techniques for other applications have been employed such as adaptive resonance theory-MMAP (ART-MMAP) networks and associative neural networks. The initial methodology for flood prediction, similar to ART-MMAP, will be applied to a significant, historical flood spanning a data-rich agricultural area. Existing flood monitoring systems that could be appropriated as dependent data include MODIS Near-Real Time Global Flood Mapping and the Global Flood Detection System. Auxiliary data that are relational and causational to flooding include ground moisture, precipitation, elevation models, and land-cover all which are available from earth observation products. Ground data from observational records and in-situ stream gauges will be used to verify the accuracy of predictions and quantify omission and commission errors.

  12. Phase III Advanced Anodes and Cathodes Utilized in Energy Efficient Aluminum Production Cells

    Energy Technology Data Exchange (ETDEWEB)

    R.A. Christini; R.K. Dawless; S.P. Ray; D.A. Weirauch, Jr.

    2001-11-05

    During Phase I of the present program, Alcoa developed a commercial cell concept that has been estimated to save 30% of the energy required for aluminum smelting. Phase ii involved the construction of a pilot facility and operation of two pilots. Phase iii of the Advanced Anodes and Cathodes Program was aimed at bench experiments to permit the resolution of certain questions to be followed by three pilot cells. All of the milestones related to materials, in particular metal purity, were attained with distinct improvements over work in previous phases of the program. NiO additions to the ceramic phase and Ag additions to the Cu metal phase of the cermet improved corrosion resistance sufficiently that the bench scale pencil anodes met the purity milestones. Some excellent metal purity results have been obtained with anodes of the following composition: Further improvements in anode material composition appear to be dependent on a better understanding of oxide solubilities in molten cryolite. For that reason, work was commissioned with an outside consultant to model the MeO - cryolite systems. That work has led to a better understanding of which oxides can be used to substitute into the NiO-Fe2O3 ceramic phase to stabilize the ferrites and reduce their solubility in molten cryolite. An extensive number of vertical plate bench electrolysis cells were run to try to find conditions where high current efficiencies could be attained. TiB2-G plates were very inconsistent and led to poor wetting and drainage. Pure TiB2 did produce good current efficiencies at small overlaps (shadowing) between the anodes and cathodes. This bench work with vertical plate anodes and cathodes reinforced the importance of good cathode wetting to attain high current efficiencies. Because of those conclusions, new wetting work was commissioned and became a major component of the research during the third year of Phase III. While significant progress was made in several areas, much work needs to be

  13. Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases.

    Science.gov (United States)

    Byun, Kyunghee; Yoo, YongCheol; Son, Myeongjoo; Lee, Jaesuk; Jeong, Goo-Bo; Park, Young Mok; Salekdeh, Ghasem Hosseini; Lee, Bonghee

    2017-09-01

    Advanced glycation end products (AGEs) and their receptor have been implicated in the progressions of many intractable diseases, such as diabetes and atherosclerosis, and are also critical for pathologic changes in chronic degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and alcoholic brain damage. Recently activated macrophages were found to be a source of AGEs, and the most abundant form of AGEs, AGE-albumin excreted by macrophages has been implicated in these diseases and to act through common pathways. AGEs inhibition has been shown to prevent the pathogenesis of AGEs-related diseases in human, and therapeutic advances have resulted in several agents that prevent their adverse effects. Recently, anti-inflammatory molecules that inhibit AGEs have been shown to be good candidates for ameliorating diabetic complications as well as degenerative diseases. This review was undertaken to present, discuss, and clarify current understanding regarding AGEs formation in association with macrophages, different diseases, therapeutic and diagnostic strategy and links with RAGE inhibition. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Advances in hexitol and ethylene glycol production by one-pot hydrolytic hydrogenation and hydrogenolysis of cellulose

    International Nuclear Information System (INIS)

    Li, Yuping; Liao, Yuhe; Cao, Xiaofeng; Wang, Tiejun; Ma, Longlong; Long, Jinxing; Liu, Qiying; Xua, Ying

    2015-01-01

    In this review, recent advances in the one-pot hydrolytic hydrogenation and hydrogenolysis of cellulose to value-added polyols, including hexitols (sorbitol, mannitol, and isosorbide) and 1,2-alkanediols (ethylene glycol and 1,2-propylene glycol), are summarized. Methods for the generation of H + in the first step of cellulose hydrolysis to form intermediate sugars, such as the use of soluble acids (mineral acids and heteropoly acids) and H + produced in situ from functional supports and H 2 dissociation, are classified and analyzed, considering its combination with active metals for the subsequent hydrogenation or hydrogenolysis of sugars to polyols. The interaction of non-noble metals such as nickel, bimetals, and tungsten with support materials in the catalytic conversion of intermediate sugars to hexitols and ethylene glycol is reviewed. The corresponding reaction pathways and mechanisms are discussed, including the conversion process using basic supports and solution conditions. Major challenges and promising routes are also suggested for the future development of the chemocatalytic conversion of cellulose. - Highlights: • Advances in the one-pot hydrolytic hydrogenation/hydrogenolysis of cellulose are summarized. • The interaction of non-noble metals with support materials for cellulose conversion is reviewed. • Method for the generation of in situ H + and effects of the acidic groups on supports are discussed. • Incomplete identification of intermediates/products causes mechanism complications. • Efficient conversion, separation and purification are other concerns for cellulose degrading

  15. The Development and Delivery of On-Demand RADARSAT Constellation Mission Ground Deformation Products Based on Advanced Insar Technology

    Science.gov (United States)

    Samsonov, S. V.; Feng, W.

    2017-12-01

    InSAR-based mapping of surface deformation (displacement) has proven valuable to a variety of geoscience applications within NRCan. Conventional approaches to InSAR analysis require significant expert intervention to separate useful signal from noise and are not suited to the address the opportunities and challenges presented by the large multi-temporal SAR datasets provided by future radar constellations. The Canada Centre for Mapping and Earth Observation (CCMEO) develops, in support of NRCAN and Government of Canada priorities a framework for automatic generation of standard and advanced deformation products based on Interferometric Synthetic Aperture Radar (InSAR) technology from RADARSAT Constellation Mission (RCM) Synthetic Aperture Radar data. We utilize existing processing algorithms that are currently used for processing RADARSAT-2 data and adapt them to RCM specifications. In addition we develop novel advanced processing algorithms that address large data sets made possible by the satellites' rapid revisit cycle and expand InSAR functionality to regional and national scales across a wide range of time scales. Through automation the system makes it possible to extend the mapping of surface deformation to non-SAR experts. The architecture is scalable and expandable to serve large number of clients and simultaneously address multiple application areas including: natural and anthropogenic hazards, natural resource development, permafrost and glacier monitoring, coastal and environmental change and wetlands mapping.

  16. Application of NASA's Advanced Life Support Technologies for Waste Treatment, Water Purification and Recycle, and Food Production in Polar Regions

    Science.gov (United States)

    Bubenheim, David L.; Lewis, Carol E.; Covington, M. Alan (Technical Monitor)

    1995-01-01

    NASA's advanced life support technologies are being combined with Arctic science and engineering knowledge to address the unique needs of the remote communities of Alaska through the Advanced Life Systems for Extreme Environments (ALSEE) project. ALSEE is a collaborative effort involving NASA, the State of Alaska, the University of Alaska, the North Slope Borough of Alaska, and the National Science Foundation (NSF). The focus is a major issue in the state of Alaska and other areas of the Circumpolar North, the health and welfare of its people, their lives and the subsistence lifestyle in remote communities, economic opportunity, and care for the environment. The project primarily provides treatment and reduction of waste, purification and recycling of water. and production of food. A testbed is being established to demonstrate the technologies which will enable safe, healthy, and autonomous function of remote communities and to establish the base for commercial development of the resulting technology into new industries. The challenge is to implement the technological capabilities in a manner compatible with the social and economic structures of the native communities, the state, and the commercial sector. Additional information is contained in the original extended abstract.

  17. In vitro oxidation of fibrinogen promotes functional alterations and formation of advanced oxidation protein products, an inflammation mediator.

    Science.gov (United States)

    Torbitz, Vanessa Dorneles; Bochi, Guilherme Vargas; de Carvalho, José Antônio Mainardi; de Almeida Vaucher, Rodrigo; da Silva, José Edson Paz; Moresco, Rafael Noal

    2015-01-01

    Fibrinogen (FB) is a soluble blood plasma protein and is a key molecule involved in coagulation. Oxidative modification of proteins, such as the formation of advanced oxidation protein products (AOPP), a heterogeneous family of protein compounds structurally modified and derived from oxidative stress, may be associated with the pathophysiology of a number of chronic inflammatory diseases. Therefore, the aim of this study was to determine whether the formation of this mediator of inflammation occurs from FB and whether its generation is associated with structural changes. Results of the present study suggest that the oxidation of FB may provoke the formation of AOPP, which in turn, may promote functional alterations in FB, thus causing changes in its structural domains and increasing its procoagulant activity.

  18. Assessing the quality of a deliberative democracy mini-public event about advanced biofuel production and development in Canada.

    Science.gov (United States)

    Longstaff, Holly; Secko, David M

    2016-02-01

    The importance of evaluating deliberative public engagement events is well recognized, but such activities are rarely conducted for a variety of theoretical, political and practical reasons. In this article, we provide an assessment of the criteria presented in the 2008 National Research Council report on Public Participation in Environmental Assessment and Decision Making (NRC report) as explicit indicators of quality for the 2012 'Advanced Biofuels' deliberative democracy event. The National Research Council's criteria were selected to evaluate this event because they are decision oriented, are the products of an exhaustive review of similar past events, are intended specifically for environmental processes and encompass many of the criteria presented in other evaluation frameworks. It is our hope that the results of our study may encourage others to employ and assess the National Research Council's criteria as a generalizable benchmark that may justifiably be used in forthcoming deliberative events exploring different topics with different audiences. © The Author(s) 2014.

  19. Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides

    Science.gov (United States)

    Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

    2017-01-01

    Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation.

  20. Consumption of a diet low in advanced glycation end products for 4 weeks improves insulin sensitivity in overweight women

    DEFF Research Database (Denmark)

    Mark, Alicja Budek; Poulsen, Malene Wibe; Andersen, Stine

    2014-01-01

    OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs. This parallel intervention study...... investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS Seventy-four overweight women were randomized to follow either a high- or low-AGE diet for 4 weeks, together with consumption...... AGE concentrations were measured (liquid chromatography tandem mass spectrometry) to estimate AGE intake and excretion. RESULTS When adjusted for changes in anthropometric measures during the intervention, the low-AGE diet decreased urinary AGEs, fasting insulin concentrations, and HOMA-IR, compared...

  1. Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension.

    Science.gov (United States)

    Dimitriadis, K; Tsioufis, C; Kasiakogias, A; Miliou, A; Poulakis, M; Kintis, K; Bafakis, I; Benardis, E; Tousoulis, D; Stefanadis, C

    2013-04-01

    Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension. In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p involvement of sRAGE in the progression of hypertensive vascular damage. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Skin advanced glycation end products in HIV infection are increased and predictive of development of cardiovascular events.

    Science.gov (United States)

    Sprenger, Herman G; Bierman, Wouter F; Martes, Melanie I; Graaff, Reindert; van der Werf, Tjip S; Smit, Andries J

    2017-01-14

    HIV-1 infection is associated with an increased cardiovascular disease (CVD) risk. Advanced glycation end products are formed as stable markers of glycaemic and oxidative stress. Skin autofluorescence (SAF) as marker of accumulated advanced glycation end products is increased and predictive of CVD events in diabetes mellitus, chronic kidney disease (CKD), and preexisting CVD. We determined SAF levels in HIV-1 infected patients, testing the hypothesis that SAF predicts CVD events in HIV infection. Single-centre prospective cohort study. In 2010-2011, SAF was measured in 91 patients. Development of CVD events was monitored during a median follow-up of 4.8 years. SAF values of the patients were expressed as a ratio (rSAF) to expected SAF levels in age-matched healthy volunteers. Seventy-nine men and 12 women were included, mean age 47 years; 81 patients were on combination antiretroviral therapy. With a mean rSAF of 1.155, SAF levels in patients were 15.5% higher than predicted for their age (95% confidence interval, 10.0-20.0; P multivariate regression analysis, rSAF was associated with nadir CD4 cell count less than 200 cells/μl (β -0.274; P = 0.01), smoking (β 0.240; P = 0.03), and men who have sex with men (MSM) (β 0.202; P = 0.07). CVD events occurred in six patients (7%). In Cox regression analysis including age, SAF, smoking, diabetes, hypertension and CKD, SAF (P = 0.01), and (Wet Medisch-wetenschappelijk Onderzoek met mensen; WMO) CKD (P = 0.03) remained as independent predictors of CVD events. SAF is increased in HIV-infected patients, and related with smoking, low nadir CD4 cell count, and MSM. Larger studies are needed to confirm whether SAF is an independent predictor of CVD events.

  3. An Analysis of Methanol and Hydrogen Production via High-Temperature Electrolysis Using the Sodium Cooled Advanced Fast Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Shannon M. Bragg-Sitton; Richard D. Boardman; Robert S. Cherry; Wesley R. Deason; Michael G. McKellar

    2014-03-01

    Integration of an advanced, sodium-cooled fast spectrum reactor into nuclear hybrid energy system (NHES) architectures is the focus of the present study. A techno-economic evaluation of several conceptual system designs was performed for the integration of a sodium-cooled Advanced Fast Reactor (AFR) with the electric grid in conjunction with wind-generated electricity. Cases in which excess thermal and electrical energy would be reapportioned within an integrated energy system to a chemical plant are presented. The process applications evaluated include hydrogen production via high temperature steam electrolysis and methanol production via steam methane reforming to produce carbon monoxide and hydrogen which feed a methanol synthesis reactor. Three power cycles were considered for integration with the AFR, including subcritical and supercritical Rankine cycles and a modified supercritical carbon dioxide modified Brayton cycle. The thermal efficiencies of all of the modeled power conversions units were greater than 40%. A thermal efficiency of 42% was adopted in economic studies because two of the cycles either performed at that level or could potentially do so (subcritical Rankine and S-CO2 Brayton). Each of the evaluated hybrid architectures would be technically feasible but would demonstrate a different internal rate of return (IRR) as a function of multiple parameters; all evaluated configurations showed a positive IRR. As expected, integration of an AFR with a chemical plant increases the IRR when “must-take” wind-generated electricity is added to the energy system. Additional dynamic system analyses are recommended to draw detailed conclusions on the feasibility and economic benefits associated with AFR-hybrid energy system operation.

  4. Clinical Development and Commercialization of Advanced Therapy Medicinal Products in the European Union: How Are the Product Pipeline and Regulatory Framework Evolving?

    Science.gov (United States)

    Boráň, Tomáš; Menezes-Ferreira, Margarida; Reischl, Ilona; Celis, Patrick; Ferry, Nicolas; Gänsbacher, Bernd; Krafft, Hartmut; Lipucci di Paola, Michele; Sladowski, Dariusz; Salmikangas, Paula

    2017-09-01

    The research and development of advanced therapy medicinal products (ATMPs) has been active in Europe and worldwide during recent years. Yet, the number of licensed products remains low. The main expected legal change in the near future in the European Union (EU) concerns the regulation on clinical trials (536/2014), which will come into force in 2018. With this new framework, a more harmonized and swift process for approval of clinical trials is anticipated, which is expected to support the entry of new innovations into the EU market. A survey on ATMPs in clinical trials during 2010-2015 in the EU was conducted in order to study the trends of ATMP development since the earlier survey published in 2012. According to the results, the number of clinical trials using ATMPs is slowly increasing in the EU. Yet, the focus is still in early development, and the projects are mainly carried out by small and medium-sized enterprises, academia, and hospitals. Oncology is the main area of clinical development. Yet, the balance between cell-based products and gene therapy medicinal products in this area may be changing in the future due to the new T-cell technologies. Many limitations and challenges are identified for ATMP development, requiring proportionate regulatory requirements. On the other hand, for such a novel field, the developers should be active in considering possible constraints and actively engage with authorities to look for solutions. This article provides up to-date information on forthcoming regulatory improvements and discusses the main challenges hampering the commercialization of ATMPs in the EU.

  5. Assessment of advanced small-scale combined heat and power production

    Energy Technology Data Exchange (ETDEWEB)

    Spitzer, J. [Joanneum Research (Austria)

    1996-12-31

    To increase the share of renewable energy sources, bioenergy has to be used for electricity generation, preferably in combined heat and power (CHP) production systems, besides its traditional use in space heating. The need for small-scale, i.e. below 5 MW{sub el}, CHP production arises from the fact that a considerable portion of the available solid biofuels may not be transported over long distances for economic reasons and that in many cases the heat demand is below 10 MW{sub el} in district heating schemes in communities with less than 10 000 inhabitants. The available technical options have to be assessed with respect to performance, reliability and economy. Such an assessment has been performed in a study where the following options have been compared: Gasification - combustion engine or gas turbine; Combustion - steam turbine/engine; Combustion - hot air turbine; Combustion - Stirling engine. While conventional steam cycle systems are available and reliable they are generally not economical in the power range under consideration. Among the other systems, which are not yet commercially available, the Stirling engine system seems to be attractive in the power range below 500 kW{sub el} and the hot air system could close the gap to the steam cycle systems, i.e. cover the power range between 0.5 and 5.0 MW{sub el}. Gasification schemes seem less suitable: The power generation part (combustion engine and gas turbine) is well established for natural gas, with the combustion engine in the lower (<5 MW{sub el}) and the gas turbine in the higher (>5MW{sub el}) power range. However, the gas quality needed for the operation of a combustion engine requires expensive pre-treatment of the gas from wood gasification so that this scheme is less attractive for the power range under consideration. These conclusions lead to R and D efforts in Austria in two directions: Hot air turbine: A utility demonstration plant is under construction with a power of 1 600 kW{sub el

  6. Advanced Power and Propulsion: Insuring Human Survival and Productivity in Deep Space Missions

    Science.gov (United States)

    Chang-Diaz, Franklin R.

    2001-01-01

    Dr. Chang-Diaz gave an intriguing presentation of his research in advanced rocket propulsion and its relevance for planning and executing crewed deep space explorations. Though not necessarily exclusively Martian, his thrust looks critically at future Mars missions. Initially Dr. Chang-Diaz showed the time constraints of Mars missions due to orbital mechanics and our present chemically powered rocket technology. Since essentially all the energy required to place current generation spacecraft into a Martian trajectory must be expended in the early minutes of a flight, most of such a mission is spent in free-fall drift, captive to the gravitational forces among Earth, the Sun, and Mars. The simple physics of such chemically powered missions requires nearly a year in transit for each direction of a Mars mission. And the optimal orientations of Earth and Mars for rendezvous require further time on or around Mars to await return. These extensions of mission duration place any crew under a three-fold jeopardy: (1) physiological deconditioning (which in some aspects is still unknown and unpreventable), (2) psychological stress, and (3) ionizing radiation. This latter risk is due to exposure of crew members for extended time to the highly unpredictable and potentially lethal radiations of open space. Any gains in shortening mission duration would reap equivalent or greater benefits for these crew concerns. Dr. Chang-Diaz has applied his training and expertise (Ph.D. from Massachusetts Institute of Technology in applied plasma physics) toward development of continuous rocket propulsion which would offer great time advantages in travel, and also more launch options than are now available. He clearly explained the enormous gains from a relatively low thrust accelerative force applied essentially continuously versus the high, but short-lived propulsion of present chemical rockets. In fact, such spacecraft could be powered throughout the mission, accelerating to approximately

  7. Steam pretreatment of Saccharum officinarum L. bagasse by adding of impregnating agents for advanced bioethanol production.

    Science.gov (United States)

    Verardi, A; Blasi, A; De Bari, I; Calabrò, V

    2016-12-01

    The main byproduct of the sugarcane industry, Saccharum officinarum L. bagasse (sugarcane bagasse, SCB), is widely used as lignocellulose biomass for bio-ethanol (EtOH) production. In this research study, SCB was pretreated by steam explosion (SE) method using two different impregnating agents: sulfur dioxide (SD) and hydrogen peroxide (HP). As matter of fact, the use of impregnating agents improves the performance of SE method, increasing the concentrations of fermentable sugars after enzymatic saccharification, and decreasing the inhibitor compounds produced during the steam pretreatment step. The aim of this study was to investigate and compare the use of the two impregnating agents in various SE-conditions in order to optimize pretreatment parameters. For every pretreatment condition, it has been evaluated: concentration of fermentable sugars, glucose and xylose yields, and the effects of the inhibitor compounds on enzymatic hydrolysis step. The obtained results allow to improve the efficiency of the whole process of bio-EtOH synthesis enhancing the amount of fermentable sugars produced and the eco-sustainability of the whole process. Indeed, the optimization of steam pretreatment leads to a reduction of energy requirements and to a lower environmental impact. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Anaerobic gut fungi: Advances in isolation, culture, and cellulolytic enzyme discovery for biofuel production.

    Science.gov (United States)

    Haitjema, Charles H; Solomon, Kevin V; Henske, John K; Theodorou, Michael K; O'Malley, Michelle A

    2014-08-01

    Anaerobic gut fungi are an early branching family of fungi that are commonly found in the digestive tract of ruminants and monogastric herbivores. It is becoming increasingly clear that they are the primary colonizers of ingested plant biomass, and that they significantly contribute to the decomposition of plant biomass into fermentable sugars. As such, anaerobic fungi harbor a rich reservoir of undiscovered cellulolytic enzymes and enzyme complexes that can potentially transform the conversion of lignocellulose into bioenergy products. Despite their unique evolutionary history and cellulolytic activity, few species have been isolated and studied in great detail. As a result, their life cycle, cellular physiology, genetics, and cellulolytic metabolism remain poorly understood compared to aerobic fungi. To help address this limitation, this review briefly summarizes the current body of knowledge pertaining to anaerobic fungal biology, and describes progress made in the isolation, cultivation, molecular characterization, and long-term preservation of these microbes. We also discuss recent cellulase- and cellulosome-discovery efforts from gut fungi, and how these interesting, non-model microbes could be further adapted for biotechnology applications. © 2014 Wiley Periodicals, Inc.

  9. Study on production of useful metabolites by development of advanced cell culture techniques using radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung Yeoup; Kim, Jin Hong; Lee, Seung Sik; Kim, Jae Sung; An, Byung Chull; Moon, Yu Ran; Lee, Eun Mi; Lee, Min Hee; Lee, Jae Tack [KAERI, Daejeon (Korea, Republic of)

    2010-02-15

    The purpose of this project is improvement of investigation, materialization and evaluation techniques on effectiveness for functional natural compounds throughout development of tissue/cell culture techniques for mass production of useful metabolites using radiation. Research scope includes 1) Development of a technique for radiation tissue and cell culture, 2) Database construction for radiation response in plants and radiation effects, 3) Construction of general-purpose national based techniques of cell culture technique using radiation. Main results are as follow: mass culture of the adventitious roots of mountain ginseng (Panax ginseng C. A. Meyer) roots using rare earth elements in bioreactor: characterization of a transcription factor EoP gene from centipedegrass and the transcription regulation of LexA from Synechocystis sp PCC6803 and E. coli: identification of gamma-ray induced hydrogenase synthesis in hox gene transformed E. coli: transformation and the selection of the EoP transgene from Arabidopsis, rice and lettuce: Identification of the maysin and maysin derivatives in centipedegrass: characterization of gamma-ray induced color change in Taxus cuspidata: verification of the expression of antioxidant proteins (POD, APX and CAT) to gamma-ray in Arabidopsis: comparison of the response of the expression level to gamma-ray or H{sub 2}O{sub 2} in Arabidopsis; verification of the responses and effects to gamma-ray from plants (analysis of NPQ and ROS levels): the development method for rapidly enhancing maysin content of centipede grass; establishment of mass culture system for red beet

  10. Study on production of useful metabolites by development of advanced cell culture techniques using radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung Yeoup; Lee, Seung Sik; Bai, Hyounwoo; Singh, Sudhir; Lee, Eun Mi; Hong, Sung Hyun; Park, Chul Hong; Srilatha, B.; Kim, Mi Ja; Lee, Ohchul

    2012-01-15

    The purpose of this project is improvement of investigation, materialization and evaluation techniques on effectiveness for functional natural compounds throughout development of tissue/cell culture techniques for mass production of useful metabolites using radiation. Research scope includes Development of a technique for radiation tissue and cell culture, Database construction for radiation response in plants and radiation effects, Construction of general-purpose national based techniques of cell culture technique using radiation. Main results are as follow: Development of a technique for radiation tissue and cell culture for Erigeron breviscapus (Vant.) Hand. Mazz.; Identification and functional analysis of AtTDX (chaperone and peroxidase activities); Functional analysis of radiation(gamma ray, electron beam, and proton beam) induced chaperon protein activities (AtTDX); Determine the action mechanism of yPrx2; Development of transgenic plant with bas I gene from Arabidopsis; Development of transgenic plant with EoP gene from centipedegrass; Identification of radiation induced multi functional compounds from Aloe; Determination of the effects of radiation on removing undesirable color and physiological activities (Schizandra chinensis baillon, centipedegrass); Determine the action mechanism of transgenic plant with 2-Cys Prx for heat stress resistance; Determination of the effects of centipedegrass extracts on anti-cancer activities; Functional analysis of centipedegrass extracts (anti-virus effects)

  11. Food system advances towards more nutritious and sustainable mantou production in China.

    Science.gov (United States)

    Hu, Xinzhong; Sheng, Xialu; Liu, Liu; Ma, Zhen; Li, Xiaoping; Zhao, Wuqi

    2015-01-01

    Mantou, a traditional Chinese food, is widely consumed in the North China due to its nutritional value and good mouth-feel. However, its current family-style production is impeded due to short shelf-life caused by mold and starch retrogradation. The current packaging and storage methods are not efficient enough for mantou preservation. Recently, a novel, hot online package technology has attracted attention due to its high processing efficiency and low cost. Most importantly, by using this methodology, secondary contamination by microbes can be avoided and starch retrogradation can be markedly delayed, with mantou shelf-life under room temperature extended from a few to at least 90 days without any additives. In this review, the mechanisms of mantou quality deterioration are explained and the advantages of hot package technology addressed and compared with other packaging methods, such as frozen chain storage. In this way, not only wheat, but also other grains (including whole-grains) and ingredients may be mantou constituents, to enhance nutrition of traditional mantou. There is now a technological opportunity for mantou to become a more nutritious, sustainable and affordable foodstuff in local communities.

  12. Cisgenesis and intragenesis in microalgae: promising advancements towards sustainable metabolites production.

    Science.gov (United States)

    Galarza, Janeth I; Delgado, Ninoska; Henríquez, Vitalia

    2016-12-01

    Microalgae are an economically important source of biomolecules and metabolites that can be exploited as feed, nutraceuticals and, potentially, as biofuels, among other biotechnological applications. Microalgae biotechnology involves both culture and metabolic pathways manipulation to obtain high-value products, such as omega-3 fatty acids and carotenoids. However, the introduction of genes and/or foreign regulatory sequences has caused public concern about the effect of genetically modified microalgae to achieve greater secondary metabolite accumulations. To placate these worries, we have focused on two cutting-edge concepts, cisgenesis and intragenesis in order to sustainably produce commercially relevant metabolites. This review provides updated background on current and future uses for microalgae molecular farming. We also discuss the development of genetic tools used in terrestrial plants to obtain genetically modified microalgae free of foreign DNA by means of (i) site-specific mutations, (ii) excision of selectable markers, (iii) zinc-finger nuclease and transcription activator-like effectors, and (iv) CRISPR/Cas9 systems. It is currently important to consider scientific debate not only from a technological standpoint but also in terms of conceptual, socioeconomic, ethical, and legal aspects.

  13. Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products.

    Science.gov (United States)

    Müller, Heinz-Dieter; Cvikl, Barbara; Janjić, Klara; Nürnberger, Sylvia; Moritz, Andreas; Gruber, Reinhard; Agis, Hermann

    2015-11-01

    Proangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp-derived cells (DPCs) and tooth slice organ cultures. In monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology. In monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed. Overall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  14. Accumulation of advanced glycation end (AGEs products in intensive care patients: an observational, prospective study

    Directory of Open Access Journals (Sweden)

    Rommes Johannes H

    2010-05-01

    Full Text Available Abstract Background Oxidative stress plays an important role in the course and eventual outcome in a majority of patients admitted to the intensive care unit (ICU. Markers to estimate oxidative stress are not readily available in a clinical setting. AGEs accumulation has been merely described in chronic conditions, but can also occur acutely due to oxidative stress. Since AGEs have emerged to be stable end products, these can be a marker of oxidative stress. Skin autofluorescence (AF is a validated marker of tissue content of AGEs. We hypothesized that AGEs accumulate acutely in ICU patients. Methods We performed an observational prospective study in a medical surgical ICU in a university affiliated teaching hospital. All consecutively admitted ICU patients in a 2 month period were included. Skin AF was measured using an AGE reader in 35 consecutive ICU patients > 18 yrs. As a comparison, historical data of a control group (n = 231 were used. These were also used to calculate age-adjusted AF-levels (AFadj. Values are expressed as median and interquartile range [P25-P75]. Differences between groups were tested by non parametric tests. P Results AFadj values were higher in ICU patients (0.33 [0.00 - 0.68] than in controls (-0.07 [-0.29 - 0.24]; P adj were observed between acute or planned admissions, or presence of sepsis, nor was skin AFadj related to severity of disease as estimated by APACHE-II score, length of ICU, hospital stay or mortality. Conclusion Acute AGE accumulation in ICU patients was shown in this study, although group size was small. This can possibly reflect oxidative stress in ICU patients. Further studies should reveal whether AGE-accumulation will be a useful parameter in ICU patients and whether skin AF has a predictive value for outcome, which was not shown in this small study.

  15. Development of an Advanced Stimulation / Production Predictive Simulator for Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Pritchett, John W. [Leidos, Inc., San Diego, CA (United States)

    2015-04-15

    projects, not just software designers. It is hoped that, as a result, HeatEx will prove useful during the early stages of the development of EGS technology. The basic objective was to design a tool that could use field data that are likely to become available during the early phases of an EGS project (that is, during initial reconnaissance and fracture stimulation operations) to guide forecasts of the longer-term behavior of the system during production and heat-mining.

  16. Production of Jet Fuels from Coal-Derived Liquids. Volume 11. Production of Advanced Endothermic Fuel Blends from Great Plains Gasification Plant Naphtha By-Product Stream

    Science.gov (United States)

    1989-03-01

    eliminating coking of the heat exchangers and fired heater on the second stage. - 11 - 3.1 Experimental Procedure The hydrotreating process conditions were...sponsored by the DOE. The facility produces more than 125 million cubic feet per day of syngas from North Dakota lignite. As a by-product, nearly 5,000...specific equipment, categories and services: - 91 Heaters Compressor Shelter Vessels and internals Control house Heat Exchange equipment Catalyst

  17. Gaseous Hydrocarbon Synfuels from H2/CO2 based on Renewable Electricity - Kinetics, Selectivity and Fundamentals of Fixed-Bed Reactor Design for Flexible Operation

    OpenAIRE

    Iglesias Gonzalez, Maria

    2015-01-01

    Conversion of electrical energy into chemical energy carriers has the potential to replace fossil fuels and can be attractive as long-term storage. The present work considers different aspects of the electricity-to-fuel process chain using a combination of experimental work and mathematical modelling. This work discusses in detail the production of gaseous hydrocarbons from H2 and CO2 via Fischer-Tropsch synthesis and the potential to operate fixed-bed reactors under flexible conditions.

  18. Dietary Advanced Glycation End Products and Risk Factors for Chronic Disease: A Systematic Review of Randomised Controlled Trials

    Directory of Open Access Journals (Sweden)

    Rachel E. Clarke

    2016-03-01

    Full Text Available Dietary advanced glycation end-products (AGEs form during heating and processing of food products and are widely prevalent in the modern Western diet. Recent systematic reviews indicate that consumption of dietary AGEs may promote inflammation, oxidative stress and insulin resistance. Experimental evidence indicates that dietary AGEs may also induce renal damage, however, this outcome has not been considered in previous systematic reviews. The purpose of this review was to examine the effect of consumption of a high AGE diet on biomarkers of chronic disease, including chronic kidney disease (CKD, in human randomized controlled trials (RCTs. Six databases (SCOPUS, CINHAL, EMBASE, Medline, Biological abstracts and Web of Science were searched for randomised controlled dietary trials that compared high AGE intake to low AGE intake in adults with and without obesity, diabetes or CKD. Twelve dietary AGE interventions were identified with a total of 293 participants. A high AGE diet increased circulating tumour necrosis factor-alpha and AGEs in all populations. A high AGE diet increased 8-isoprostanes in healthy adults, and vascular cell adhesion molecule-1 (VCAM-1 in patients with diabetes. Markers of CKD were not widely assessed. The evidence presented indicates that a high AGE diet may contribute to risk factors associated with chronic disease, such as inflammation and oxidative stress, however, due to a lack of high quality randomised trials, more research is required.

  19. High serum level of pentosidine, an advanced glycation end product (AGE), is a risk factor of patients with heart failure.

    Science.gov (United States)

    Koyama, Yo; Takeishi, Yasuchika; Arimoto, Takanori; Niizeki, Takeshi; Shishido, Tetsuro; Takahashi, Hiroki; Nozaki, Naoki; Hirono, Osamu; Tsunoda, Yuichi; Nitobe, Joji; Watanabe, Tetsu; Kubota, Isao

    2007-04-01

    Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling, causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with end points of cardiac death or rehospitalization. Serum concentration of pentosidine was significantly higher in New York Heart Association (NYHA) Class III/IV patients than in NYHA class I/II patients (P volume, and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure. Patients were divided into 4 groups based on the serum pentosidine levels.

  20. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat

    Energy Technology Data Exchange (ETDEWEB)

    Son, Kuk Hui [Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon (Korea, Republic of); Son, Myeongjoo [Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon (Korea, Republic of); Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon (Korea, Republic of); Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji [Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon (Korea, Republic of); Choi, Chang Hu [Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon (Korea, Republic of); Park, Kook Yang, E-mail: kkyypark@ghil.com [Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon (Korea, Republic of); Byun, Kyunghee, E-mail: khbyun1@gachon.ac.kr [Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon (Korea, Republic of); Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon (Korea, Republic of)

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. - Highlights: • The age-related AGE-albumin accumulation and S100β were more prominent in visceral than subcutaneous fat. • The age-related RAGE expression were more prominent in visceral than subcutaneous fat.

  1. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat

    International Nuclear Information System (INIS)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-01-01

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. - Highlights: • The age-related AGE-albumin accumulation and S100β were more prominent in visceral than subcutaneous fat. • The age-related RAGE expression were more prominent in visceral than subcutaneous fat.

  2. Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction.

    Science.gov (United States)

    Zhuang, Xiuyuan; Pang, Xiufeng; Zhang, Wen; Wu, Wenbin; Zhao, Jingjing; Yang, Huangjian; Qu, Weijing

    2012-01-16

    The present study investigated the effects of ZnCl₂ and MnCl₂ supplementations on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction. Fluorescence detection was used to monitor the Maillard reaction. Inductively coupled plasma optical emission spectroscopy was used to test cellular zinc and manganese levels. Real-time reverse transcription polymerase chain reaction and western blot were used to analyze the expression of endothelial nitric oxide synthase (eNOS), nuclear transcription factor kappa B (NF-κB), and receptor for AGEs (RAGE). Intracellular reactive oxygen species (ROS) and nitric oxide (NO) production, NOS activity were determined by fluorescent probe assay, superoxide dismutase (SOD) activity was determined by water soluble tetrazolium salt assay. MnCl₂ showed excellent inhibitory effect on AGEs formation. Primary cultured bovine aortic endothelial cells (BAECs) were exposed to AGEs for 30 min, followed by trace element treatments. Cell viability and the zinc levels declined due to AGEs exposure, which were improved with the supplementations of ZnCl₂ and MnCl₂. Furthermore, ZnCl₂ supplementation effectively enhanced intracellular NO production, elevated eNOS expression and enzymatic activity, and down-regulated NF-κB activation and RAGE expression. MnCl₂ dose-dependently impaired ROS formation, down-regulated NF-κB protein expression and nuclear translocation, as well as restored Mn-SOD enzymatic capability. Our findings suggested that trace elements relevant to diabetic, such as zinc and manganese played different roles in the formation of AGEs. Both the elements benefited the AGEs-injured BAECs through different mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Higher plasma soluble Receptor for Advanced Glycation End Products (sRAGE) levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes

    DEFF Research Database (Denmark)

    Nin, Johanna W M; Jorsal, Anders; Ferreira, Isabel

    2010-01-01

    To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunct......To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal...

  4. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy.

    Science.gov (United States)

    Forbes, Josephine M; Thorpe, Suzanne R; Thallas-Bonke, Vicki; Pete, Josefa; Thomas, Merlin C; Deemer, Elizabeth R; Bassal, Sahar; El-Osta, Assam; Long, David M; Panagiotopoulos, Sianna; Jerums, George; Osicka, Tanya M; Cooper, Mark E

    2005-08-01

    Recent studies have identified that first-line renoprotective agents that interrupt the renin-angiotensin system not only reduce BP but also can attenuate advanced glycation end product (AGE) accumulation. This study used in vitro, preclinical, and human approaches to explore the potential effects of these agents on the modulation of the receptor for AGE (RAGE). Bovine aortic endothelial cells that were exposed to the angiotensin-converting enzyme inhibitor (ACEi) ramiprilat in the presence of high glucose demonstrated a significant increase in soluble RAGE (sRAGE) secreted into the medium. In streptozotocin-induced diabetic rats, ramipril treatment (ACEi) at 3 mg/L for 24 wk reduced the accumulation of skin collagen-linked carboxymethyllysine and pentosidine, as well as circulating and renal AGE. Renal gene upregulation of total RAGE (all three splice variants) was observed in ACEi-treated animals. There was a specific increase in the gene expression of the splice variant C-truncated RAGE (sRAGE). There were also increases in sRAGE protein identified within renal cells with ACEi treatment, which showed AGE-binding ability. This was associated with decreases in renal full-length RAGE protein from ACEi-treated rats. Decreases in plasma soluble RAGE that were significantly increased by ACEi treatment were also identified in diabetic rats. Similarly, there was a significant increase in plasma sRAGE in patients who had type 1 diabetes and were treated with the ACEi perindopril. Complexes between sRAGE and carboxymethyllysine were identified in human and rodent diabetic plasma. It is postulated that ACE inhibition reduces the accumulation of AGE in diabetes partly by increasing the production and secretion of sRAGE into plasma.

  5. Task 4.0 -- Advanced fuel forms and co-products. Semi-Annual report, April 1--June 30, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, C.M.; Musich, M.A.; Young, B.C.; Timpe, R.C.; Olson, E.S.; Sharma, R.K.

    1993-07-01

    Summarized below is the work carried out over a six-month period on the subtasks Beneficiation for Advanced Systems, Co-Products, and Low-Rank Coal Liquefaction. Hydrothermal drying (hot-water drying and saturated-steam drying) was determined to be an effective method of causing a permanent reduction in the equilibrium moisture of low-rank coals and removing sodium. The development of improved methods is continuing for assessing the propensity of coals to dust generation. Carbonic acid treatment of lignites and subbituminous coals reduced the sodium contents of these coals by 60 to 70 wt%. Float/sink washability testing of low-sulfur subbituminous coals produced ash reductions of 30 to 40 wt% at +95 wt% moisture and ash-free (maf) coal recovery. Ineffective agglomerants were induced to agglomerate low-rank coals by mixing with a polar oil or polar alcohol. Effective agglomeration promoters were crude phenol, m-cresol, cresylic acid, methanol, ethanol, propanol, and butanol. Three coals, a North Dakota Lignite, a North Dakota Leonardite, and an Alaskan subbituminous coal, were pyrolyzed. Proximate analysis showed that the subbituminous char was typically lower in volatiles than the lignite. Adsorption of sulfur dioxide by the chars were indistinguishable from one another. Coal can be effectively solubilized by treatment with CO reductant in an aqueous solvent (CO steam process). In this report, the catalytic hydrotreatment of the solubilized low-severity products from sodium aluminate-catalyzed and uncatalyzed CO/H{sub 2}O reactions of a Wyodak subbituminous coal are compared. Liquefaction with the Co-Me catalyst gave 68% conversion to heptane solubles for both the sodium aluminate and the uncatalyzed low-severity reaction intermediates.

  6. 糖基化终末产物及其受体在糖尿病大鼠胃组织中的分布 (Distribution of advanced glycation end products and their receptor in the stomach of diabetic rats)

    DEFF Research Database (Denmark)

    Tian, Jia Xing; Zhao, Jingbo; Li, Min

    2015-01-01

    AIM: To observe the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the stomach of diabetic rats. METHODS: Diabetes mellitus (DM) and control (CON) rats were reared for eight weeks. Fasting plasma glucose (FPG), glycated serum protein (GSP) and gastric layer...... end products; Receptor for advanced glycation end products...

  7. Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules.

    Science.gov (United States)

    Takahashi, Atsushi; Takabatake, Yoshitsugu; Kimura, Tomonori; Maejima, Ikuko; Namba, Tomoko; Yamamoto, Takeshi; Matsuda, Jun; Minami, Satoshi; Kaimori, Jun-Ya; Matsui, Isao; Matsusaka, Taiji; Niimura, Fumio; Yoshimori, Tamotsu; Isaka, Yoshitaka

    2017-05-01

    Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system that regulates intracellular homeostasis by engulfing cytoplasmic components. We have recently demonstrated that autophagic degradation of damaged lysosomes is indispensable for cellular homeostasis in some settings. In this study, we tested the hypothesis that autophagy could contribute to the degradation of AGEs in the diabetic kidney by modulating lysosomal biogenesis. Both a high-glucose and exogenous AGE overload gradually blunted autophagic flux in the cultured PTECs. AGE overload upregulated lysosomal biogenesis and function in vitro, which was inhibited in autophagy-deficient PTECs because of the impaired nuclear translocation of transcription factor EB. Consistently, streptozotocin-treated, PTEC-specific, autophagy-deficient mice failed to upregulate lysosomal biogenesis and exhibited the accumulation of AGEs in the glomeruli and renal vasculature as well as in the PTECs, along with worsened inflammation and fibrosis. These results indicate that autophagy contributes to the degradation of AGEs by the upregulation of lysosomal biogenesis and function in diabetic nephropathy. Strategies aimed at promoting lysosomal function hold promise for treating diabetic nephropathy. © 2017 by the American Diabetes Association.

  8. Family therapy workshops in the United States: potential abuses in the production of therapy in an advanced capitalist society.

    Science.gov (United States)

    McLean, A

    1986-01-01

    A market for family therapy workshops has mushroomed in recent years. Treatment of families by therapists conducting such workshops, however, can be dispassionate and dehumanizing. Using the distinction between curing and healing, I do not question the curative potential of family therapy, but I question whether this kind of doctor/patient interaction promotes healing. Also, by demonstrating how the systems model tends to objectify patients and alienate therapists from those they treat, this paper challenges claims that family therapy recognizes the social nature of illness. The dehumanizing treatment cannot be attributed solely to the therapists, but requires further interpretation by analyzing the biases of the therapy model, the commodified context of the workshops, and epistemological issues arising from the application of general systems theory to a social model of treatment. Family systems therapy shares epistemological features with biomedicine, and like the biomedical model, alienates therapists from patients. This alienation, ironically, can be even greater when the family systems model is used than in biomedical treatment. Finally, I suggest that family therapy workshops have grown in popularity because the mechanistic features of the treatment model, drawn largely from cybernetics, promote the production and reproduction of a form of therapy compatible with the emphasis on 'functional health' favored in an advanced capitalist society.

  9. Regulation of Receptor for Advanced Glycation End Products (RAGE) Ectodomain Shedding and Its Role in Cell Function*

    Science.gov (United States)

    Braley, Alex; Kwak, Taekyoung; Jules, Joel; Harja, Evis; Landgraf, Ralf; Hudson, Barry I.

    2016-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that can undergo proteolysis at the cell surface to release a soluble ectodomain. Here we observed that ectodomain shedding of RAGE is critical for its role in regulating signaling and cellular function. Ectodomain shedding of both human and mouse RAGE was dependent on ADAM10 activity and induced with chemical activators of shedding (ionomycin, phorbol 12-myristate 13-acetate, and 4-aminophenylmercuric acetate) and endogenous stimuli (serum and RAGE ligands). Ectopic expression of the splice variant of RAGE (RAGE splice variant 4), which is resistant to ectodomain shedding, inhibited RAGE ligand dependent cell signaling, actin cytoskeleton reorganization, cell spreading, and cell migration. We found that blockade of RAGE ligand signaling with soluble RAGE or inhibitors of MAPK or PI3K blocked RAGE-dependent cell migration but did not affect RAGE splice variant 4 cell migration. We finally demonstrated that RAGE function is dependent on secretase activity as ADAM10 and γ-secretase inhibitors blocked RAGE ligand-mediated cell migration. Together, our data suggest that proteolysis of RAGE is critical to mediate signaling and cell function and may therefore emerge as a novel therapeutic target for RAGE-dependent disease states. PMID:27022018

  10. Modeling the Interaction between Quinolinate and the Receptor for Advanced Glycation End Products (RAGE): Relevance for Early Neuropathological Processes

    Science.gov (United States)

    Serratos, Iris N.; Castellanos, Pilar; Pastor, Nina; Millán-Pacheco, César; Rembao, Daniel; Pérez-Montfort, Ruy; Cabrera, Nallely; Reyes-Espinosa, Francisco; Díaz-Garrido, Paulina; López-Macay, Ambar; Martínez-Flores, Karina; López-Reyes, Alberto; Sánchez-García, Aurora; Cuevas, Elvis; Santamaria, Abel

    2015-01-01

    The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor involved in neurodegenerative and inflammatory disorders. RAGE induces cellular signaling upon binding to a variety of ligands. Evidence suggests that RAGE up-regulation is involved in quinolinate (QUIN)-induced toxicity. We investigated the QUIN-induced toxic events associated with early noxious responses, which might be linked to signaling cascades leading to cell death. The extent of early cellular damage caused by this receptor in the rat striatum was characterized by image processing methods. To document the direct interaction between QUIN and RAGE, we determined the binding constant (Kb) of RAGE (VC1 domain) with QUIN through a fluorescence assay. We modeled possible binding sites of QUIN to the VC1 domain for both rat and human RAGE. QUIN was found to bind at multiple sites to the VC1 dimer, each leading to particular mechanistic scenarios for the signaling evoked by QUIN binding, some of which directly alter RAGE oligomerization. This work contributes to the understanding of the phenomenon of RAGE-QUIN recognition, leading to the modulation of RAGE function. PMID:25757085

  11. Regulation of Receptor for Advanced Glycation End Products (RAGE) Ectodomain Shedding and Its Role in Cell Function.

    Science.gov (United States)

    Braley, Alex; Kwak, Taekyoung; Jules, Joel; Harja, Evis; Landgraf, Ralf; Hudson, Barry I

    2016-06-03

    The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that can undergo proteolysis at the cell surface to release a soluble ectodomain. Here we observed that ectodomain shedding of RAGE is critical for its role in regulating signaling and cellular function. Ectodomain shedding of both human and mouse RAGE was dependent on ADAM10 activity and induced with chemical activators of shedding (ionomycin, phorbol 12-myristate 13-acetate, and 4-aminophenylmercuric acetate) and endogenous stimuli (serum and RAGE ligands). Ectopic expression of the splice variant of RAGE (RAGE splice variant 4), which is resistant to ectodomain shedding, inhibited RAGE ligand dependent cell signaling, actin cytoskeleton reorganization, cell spreading, and cell migration. We found that blockade of RAGE ligand signaling with soluble RAGE or inhibitors of MAPK or PI3K blocked RAGE-dependent cell migration but did not affect RAGE splice variant 4 cell migration. We finally demonstrated that RAGE function is dependent on secretase activity as ADAM10 and γ-secretase inhibitors blocked RAGE ligand-mediated cell migration. Together, our data suggest that proteolysis of RAGE is critical to mediate signaling and cell function and may therefore emerge as a novel therapeutic target for RAGE-dependent disease states. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Lateral diffusion and signaling of receptor for advanced glycation end-products (RAGE): a receptor involved in chronic inflammation.

    Science.gov (United States)

    Syed, Aleem; Zhu, Qiaochu; Smith, Emily A

    2018-01-01

    Membrane diffusion is one of the key mechanisms in the cellular function of receptors. The signaling of receptors for advanced glycation end-products (RAGE) has been extensively studied in the context of several pathological conditions, however, very little is known about RAGE diffusion. To fill this gap, RAGE lateral diffusion is probed in native, cholesterol-depleted, and cytoskeleton-altered cellular conditions. In native GM07373 cellular conditions, RAGE has a 90% mobile fraction and an average diffusion coefficient of 0.3 μm 2 /s. When depolymerization of the actin cytoskeleton is inhibited with the small molecule jasplakinolide (Jsp), the RAGE mobile fraction and diffusion coefficient decrease by 22 and 37%, respectively. In contrast, depolymerizing the filamentous actin cytoskeleton using the small molecule cytochalasin D (CD) does not alter the RAGE diffusion properties. There is a 70 and 50% decrease in phosphorylation of extracellular signal-regulated kinase (p-ERK) when the actin cytoskeleton is disrupted by CD or Jsp, respectively, in RAGE-expressing GM07373 cells. Disrupting the actin cytoskeleton in GM07373 cells that do not express detectable amounts of RAGE results in no change in p-ERK. Cholesterol depletion results in no statistically significant change in the diffusion properties of RAGE or p-ERK. This work presents a strong link between the actin cytoskeleton and RAGE diffusion and downstream signaling, and serves to further our understanding of the factors influencing RAGE lateral diffusion.

  13. Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling

    International Nuclear Information System (INIS)

    Li, Guofeng; Xu, Jingren; Li, Zengchun

    2012-01-01

    Highlights: ► RAGE overexpression suppresses cell proliferation in MC3T3-E1 cells. ► RAGE overexpression decreases Wnt/β-catenin signaling. ► RAGE overexpression decreases ERK and PI3K signaling. ► Inhibition of Wnt signaling abolishes PI3K signaling restored by RAGE blockade. ► Inhibition of Wnt signaling abolishes ERK signaling restored by RAGE blockade. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in bone metabolism. However, the role of RAGE in the control of osteoblast proliferation is not yet evaluated. In the present study, we demonstrate that RAGE overexpression inhibits osteoblast proliferation in vitro. The negative regulation of RAGE on cell proliferation results from suppression of Wnt, PI3K and ERK signaling, and is restored by RAGE neutralizing antibody. Prevention of Wnt signaling using Sfrp1 or DKK1 rescues RAGE-decreased PI3K and ERK signaling and cell proliferation, indicating that the altered cell growth in RAGE overexpressing cells is in part secondary to alterations in Wnt signaling. Consistently, RAGE overexpression inhibits the expression of Wnt targets cyclin D1 and c-myc, which is partially reversed by RAGE blockade. Overall, these results suggest that RAGE inhibits osteoblast proliferation via suppression of Wnt, PI3K and ERK signaling, which provides novel mechanisms by which RAGE regulates osteoblast growth.

  14. UV-Visible Spectrooelectrochemistry of the Reduction Products of Anthraquinone in Dimethylformamide Solutions: An Advanced Undergraduate Experiment

    Science.gov (United States)

    Babaei, Ali; Connor, Paul A.; McQuillan, A. James; Umapathy, Siva

    1997-10-01

    The redox properties of anthraquinone (AQ) may be used to model the behaviour of quinones in biological systems. AQ undergoes two successive one-electron reductions in aprotic solvents to form a stable radical anion (AQ.-) and a stable dianion (AQ2-) but this behaviour is altered in the presence of a proton donor. This advanced undergraduate experiment shows how cyclic voltammetry, digital simulations of cyclic voltammograms, and UV-visible spectroelectrochemistry may be used to examine the reduction behaviour of AQ in dimethylformamide (DMF), both in the absence and presence of benzoic acid. The cyclic voltammetry of AQ in DMF shows two reversible one-electron reductions. This allows the UV-visible spectra of AQ.- and of AQ2- to be determined using an optically transparent thin layer electrode (OTTLE) cell. AQH- may also be detected in the spectra if there are proton impurities. When benzoic acid is added to the DMF, the cyclic voltammograms are markedly altered with almost all the reduction occurring near the AQ/AQ.- potential and the corresponding oxidation at rather more positive potentials. The UV-visible spectroelectrochemistry shows AQH2 as the stable reduction product under these conditions while digital simulations of the cyclic voltammograms support a mechanism involving protonation of AQ.- followed by AQH. disproportionation.

  15. Beneficial effects of metformin and irbesartan on advanced glycation end products (AGEs)-RAGE-induced proximal tubular cell injury.

    Science.gov (United States)

    Ishibashi, Yuji; Matsui, Takanori; Takeuchi, Masayoshi; Yamagishi, Sho-ichi

    2012-03-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) axis contributes to diabetic nephropathy. An oral hypoglycemic agent, metformin may have a potential effect on the inhibition of glycation reactions. Further, since a pathophysiological crosstalk between renin-angiotensin system (RAS) and AGEs-RAGE axis is involved in diabetic nephropathy, it is conceivable that metformin and irbesartan additively could protect against the AGEs-RAGE-induced tubular cell injury. In this study, we addressed the issues. Metformin dose-dependently inhibited the formation of AGEs modification of bovine serum albumin (BSA). Compared with AGEs-modified BSA prepared without metformin (AGEs-MF0), those prepared in the presence of 30 mM or 100 mM metformin (AGEs-MF30 or AGEs-MF100) significantly reduced RAGE mRNA level, reactive oxygen species (ROS) generation, apoptosis, monocyte chemoattractant protein-1 and transforming growth factor-β mRNA level in tubular cells. Irbesartan further inhibited the harmful effects of AGEs-MF0 or AGEs-MF30 on tubular cells. Our present study suggests that combination therapy with metformin and irbesartan may have therapeutic potential in diabetic nephropathy; it could play a protective role against tubular injury in diabetes not only by inhibiting AGEs formation, but also by attenuating the deleterious effects of AGEs via down-regulating RAGE expression and subsequently suppressing ROS generation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development.

    Science.gov (United States)

    Ishiguro, Hitoshi; Nakaigawa, Noboru; Miyoshi, Yasuhide; Fujinami, Kiyoshi; Kubota, Yoshinobu; Uemura, Hiroji

    2005-06-15

    Advanced glycation end products (AGE) are produced with normal aging. Recently, some reports indicated that the interaction between AGE and the cognate receptor (RAGE) has a role in cancer dependent. We investigated RAGE and amphoterin mRNA expression in prostate cancer cell lines (DU145, PC-3, and LNCaP cells), hormone-refractory prostate cancer tissues, and paired untreated primary prostate cancer and normal prostate (including benign prostatic hypertrophy (BPH)) tissues using real-time quantitative PCR. Moreover, to confirm the AGE-RAGE interaction in prostate cancer, DU145 cells stimulated with AGE-bovine serum albumin (AGE-BSA) were examined by in vitro matrigel assay, cell viability assay, MTT assay, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot. DU145 cells, a hormone-independent prostate cancer cell line, showed the highest RAGE mRNA expression. Amphoterin mRNA was expressed in all three cell lines. In prostate tissues, untreated prostate cancer tissue and hormone-refractory prostate cancer tissue showed higher RAGE and amphoterin mRNA expression than normal prostate tissue. The AGE-RAGE interaction induced the invasion and growth in DU145 cells stimulated with AGE-BSA. The AGE-RAGE interaction is important in prostate cancer development, and inhibition of this interaction has potential as a new molecular target for cancer therapy or prevention.

  17. [Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells].

    Science.gov (United States)

    Feng, Min; Xu, Cheng-Bo; Wen, Jun-Ping; Lin, Gui-Fang; Lv, Qi; Huang, Guo-Liang

    2014-07-01

    To investigate the effects of advanced glycosylation end products (AGEs) modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs). HRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours, or with AGE-BSA (200 mg/L) for different times (12, 24, 48, 72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR) after treatment with AGE-BSA or BSA. The protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE, while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG. The expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.

  18. Early plasma soluble receptor for advanced glycation end-product levels are associated with bronchiolitis obliterans syndrome.

    Science.gov (United States)

    Shah, R J; Bellamy, S L; Lee, J C; Cantu, E; Diamond, J M; Mangalmurti, N; Kawut, S M; Ware, L B; Christie, J D

    2013-03-01

    Early epithelial injury after lung transplantation may contribute to development of bronchiolitis obliterans syndrome (BOS). We evaluated the relationship between early postoperative soluble receptor for advanced glycation end-product (sRAGE) levels, a marker of type I alveolar cell injury and BOS. We performed a cohort study of 106 lung transplant recipients between 2002 and 2006 at the University of Pennsylvania with follow-up through 2010. Plasma sRAGE was measured 6 and 24 h after transplantation. Cox proportional hazards models were used to evaluate the association between sRAGE and time to BOS, defined according to ISHLT guidelines. Sixty (57%) subjects developed BOS. The average time to BOS was 3.4 years. sRAGE levels measured at 6 h (HR per SD of sRAGE: 1.69, 95% CI: 1.11, 2.57, p = 0.02) and 24 h (HR per SD of sRAGE: 1.74, 95% CI: 1.14, 2.65, p = 0.01) were associated with an increased hazard of BOS. Multivariable Cox regression indicated this relationship was independent of potential confounders. Elevated plasma sRAGE levels measured in the immediate postoperative period are associated with the development of BOS. Early epithelial injury after transplantation may contribute to the development of fibrosis in BOS. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Xian Jin

    2015-01-01

    Full Text Available Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation.

  20. Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

    Science.gov (United States)

    Jin, Xian; Yao, Tongqing; Zhou, Zhong'e; Zhu, Jian; Zhang, Song; Hu, Wei; Shen, Chengxing

    2015-01-01

    Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation. PMID:26114112