WorldWideScience

Sample records for park gmp research

  1. [The Contribution of GMP-grade Hospital Preparation to Translational Research].

    Science.gov (United States)

    Yonezawa, Atsushi; Kajiwara, Moto; Minami, Ikuko; Omura, Tomohiro; Nakagawa, Shunsaku; Matsubara, Kazuo

    2015-01-01

    Translational research is important for applying the outcomes of basic research studies to practical medical treatments. In exploratory early-phase clinical trials for an innovative therapy, researchers should generally manufacture investigational agents by themselves. To provide investigational agents with safety and high quality in clinical studies, appropriate production management and quality control are essential. In the Department of Pharmacy of Kyoto University Hospital, a manufacturing facility for sterile drugs was established, independent of existing manufacturing facilities. Manuals on production management and quality control were developed according to Good Manufacturing Practices (GMP) for Investigational New Drugs (INDs). Advanced clinical research has been carried out using investigational agents manufactured in our facility. These achievements contribute to both the safety of patients and the reliability of clinical studies. In addition, we are able to do licensing-out of our technique for the manufacture of investigational drugs. In this symposium, we will introduce our GMP grade manufacturing facility for sterile drugs and discuss the role of GMP grade hospital preparation in translational research.

  2. Perceived Health Benefits and Willingness to Pay for Parks by Park Users: Quantitative and Qualitative Research

    Directory of Open Access Journals (Sweden)

    Claire Henderson-Wilson

    2017-05-01

    Full Text Available Whilst a growing body of evidence demonstrates people derive a range of health and wellbeing benefits from visiting parks, only a limited number of attempts have been made to provide a complementary economic assessment of parks. The aim of this exploratory study was to directly estimate the perceived health and wellbeing benefits attained from parks and the economic value assigned to parks by park users in Victoria, Australia. The research employed a mixed methods approach (survey and interviews to collect primary data from a selection of 140 park users: 100 from two metropolitan parks in Melbourne and 40 from a park on the urban fringe of Melbourne, Victoria. Our findings suggest that park users derive a range of perceived physical, mental/spiritual, and social health benefits, but park use was predominantly associated with physical health benefits. Overall, our exploratory study findings suggest that park users are willing to pay for parks, as they highly value them as places for exercising, socialising, and relaxing. Importantly, most people would miss parks if they did not exist. The findings aim to provide park managers, public health advocates, and urban policy makers with evidence about the perceived health and wellbeing benefits of park usage and the economic value park visitors place on parks.

  3. Now that you want to take your HIV/AIDS vaccine/biological product research concept into the clinic: what are the "cGMP"?

    Science.gov (United States)

    Sheets, Rebecca L; Rangavajhula, Vijaya; Pullen, Jeffrey K; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael

    2015-04-08

    The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd.

  4. Business to Business Marketing Research for Angry Birds Park Vuokatti

    OpenAIRE

    Leppävuori, Liisa

    2014-01-01

    This thesis was developed to acquire information about companies’ attitudes towards recreational days for their employees and their families. The research was commissioned by Angry Birds Park Vuokatti/ SuperPark Oy. The theoretical background for this thesis includes theory of marketing research, branding and enhancing working life balance. The theory of marketing research discusses the differences and benefits of quantitative and qualitative research, as well as using questionnaires in r...

  5. Characteristics of urban parks associated with park use and physical activity: a review of qualitative research.

    Science.gov (United States)

    McCormack, Gavin R; Rock, Melanie; Toohey, Ann M; Hignell, Danica

    2010-07-01

    Given that recent literature reviews on physical activity in urban parks deliberately excluded qualitative findings, we reviewed qualitative research on this topic informed by a published classification scheme based on quantitative research. Twenty-one studies met our inclusion criteria. These studies relied mainly on semi-structured interviews with individuals or in focus groups; only five studies involved in situ observation. Our synthesis aligns with previous quantitative research showing that attributes including safety, aesthetics, amenities, maintenance, and proximity are important for encouraging park use. Furthermore, our synthesis of qualitative research suggests that perceptions of the social environment entwine inextricably with perceptions of the physical environment. If so, physical attributes of parks as well as perceptions of these attributes (formed in relation to broader social contexts) may influence physical activity patterns. Both qualitative and quantitative methods provide useful information for interpreting such patterns, and in particular, when designing and assessing interventions intended to improve the amount and intensity of physical activity. 2010 Elsevier Ltd. All rights reserved.

  6. Legotalk in the Research Park. Commentary.

    Science.gov (United States)

    Webb, Nick

    1997-01-01

    Utilizes Uwe Poerksen's concept of "plastic words" to examine and criticize the preeminence given to research in art education. "Plastic words" refers to vague technical jargon that suggests meaning without actually providing it (e.g., development, process, goal-setting). Argues that this usage inherently corrupts and diverts any productive…

  7. Survey, Research And Prospect Of Signage Systems In National Parks In Yunnan Province

    Directory of Open Access Journals (Sweden)

    wenjuan XU

    2018-01-01

    Full Text Available The Signage System is essential to establishing a national park. The authors conducted surveys, analysis and research of identification signs, informational sign, directional signs and functional signs from the signage systems adopted by five national parks in Yunnan Province. Relying on the results, with reference to industry experience, years of research related to national park, successful cases of overseas national parks and the current signage systems across China’s national parks, the paper aims to explore future development strategies of national park signage systems that are suitable for China.

  8. The role of science and technology parks in communication processes between research institutions and industry

    Directory of Open Access Journals (Sweden)

    Paweł Sobkowicz

    2013-12-01

    Full Text Available Among the ways to bridge the gap between the research communities and the industry, one of the best known are the Science and Technology Parks. The scope of the offered services, the scale of operations and their revenues vary considerably. The largest parks gather companies, whose revenues may reach billions of dollars. Achieving such success requires, from the park operators, much more than offering attractive prices for office space. Moreover, it requires well-coordinated activities, based on a long term vision, from the central governments. The paper presents an analysis of the factors determining the success or fiasco of science and technology parks, both in worldwide and Polish context.

  9. 78 FR 13081 - Draft Environmental Impact Statement for General Management Plan, Everglades National Park, Florida

    Science.gov (United States)

    2013-02-26

    ... visitor use in the Park. The GMP will provide updated management direction for the entire park. The EEWS....YP0000] Draft Environmental Impact Statement for General Management Plan, Everglades National Park... the General Management Plan (GMP) and East Everglades Wilderness Study (EEWS) for Everglades National...

  10. Implementation of Good Maufacturing Practices (GMP) in the Kitchen Hospital

    OpenAIRE

    Sari, Fitria Novita

    2016-01-01

    Abstract: Food safety is one of the important thing in public health improvement in Indonesia. Hospitals are required to keep food safety for patients by conducting the principle Good Manufacturing Practices (GMP). The purpose of this research to -identify the application of GMP in Installation Nutrition Hospital. Design of this study was using descriptive research in observational method with cross sectional design. Variables the treatment were the physical building, utility, equipment, stor...

  11. Fact Sheet on EPA's Science, Technology, Engineering & Math (STEM) Outreach Program in Research Triangle Park

    Science.gov (United States)

    Employees from EPA’s Research Triangle Park (RTP) campus serve as guest speakers at local schools and in the community. Hands-on activities and interactive discussions supplement classroom instruction and promote environmental awareness

  12. Report: Results of Technical Network Vulnerability Assessment: EPA’s Research Triangle Park Finance Center

    Science.gov (United States)

    Report #09-P-0227, August 31, 2009. Vulnerability testing conducted in April 2009 of EPA’s Research Triangle Park Finance Center network identified Internet Protocol addresses with several highrisk vulnerabilities.

  13. Description of the terrestrial ecology of the Oak Ridge Environmental Research Park

    Energy Technology Data Exchange (ETDEWEB)

    Kitchings, T.; Mann, L.K.

    1976-10-01

    The Environmental Sciences Division at Oak Ridge National Laboratory has begun to develop research and administrative foundations necessary to establish and operate an Environmental Research Park (ERP) on the Energy Research and Development Administration Reservation at Oak Ridge, Tennessee. Important in developing a functional research area is a description and inventory of the species and ecosystems which comprise the Research Park. This report describes some of the floral and faunal components of the Oak Ridge Reservation. Emphasis is placed on the relationship of faunal communities to the vegetation type in which they occur. Unique vegetational areas and rare and endangered species are also discussed.

  14. Description of the terrestrial ecology of the Oak Ridge Environmental Research Park

    International Nuclear Information System (INIS)

    Kitchings, T.; Mann, L.K.

    1976-10-01

    The Environmental Sciences Division at Oak Ridge National Laboratory has begun to develop research and administrative foundations necessary to establish and operate an Environmental Research Park (ERP) on the Energy Research and Development Administration Reservation at Oak Ridge, Tennessee. Important in developing a functional research area is a description and inventory of the species and ecosystems which comprise the Research Park. This report describes some of the floral and faunal components of the Oak Ridge Reservation. Emphasis is placed on the relationship of faunal communities to the vegetation type in which they occur. Unique vegetational areas and rare and endangered species are also discussed

  15. Assessment of Nonnative Invasive Plants in the DOE Oak Ridge National Environmental Research Park

    Energy Technology Data Exchange (ETDEWEB)

    Drake, S.J.

    2002-11-05

    The Department of Energy (DOE) National Environmental Research Park at Oak Ridge, Tennessee, is composed of second-growth forest stands characteristic of much of the eastern deciduous forest of the Ridge and Valley Province of Tennessee. Human use of natural ecosystems in this region has facilitated the establishment of at least 167 nonnative, invasive plant species on the Research Park. Our objective was to assess the distribution, abundance, impact, and potential for control of the 18 most abundant invasive species on the Research Park. In 2000, field surveys were conducted of 16 management areas on the Research Park (14 Natural Areas, 1 Reference Area, and Walker Branch Watershed) and the Research Park as a whole to acquire qualitative and quantitative data on the distribution and abundance of these taxa. Data from the surveys were used to rank the relative importance of these species using the ''Alien Plant Ranking System, Version 5.1'' developed by the U.S. Geological Survey. Microstegium (Microstegium vimineum) was ranked highest, or most problematic, for the entire Research Park because of its potential impact on natural systems, its tendency to become a management problem, and how difficult it is to control. Microstegium was present in 12 of the 16 individual sites surveyed; when present, it consistently ranked as the most problematic invasive species, particularly in terms of its potential impact on natural systems. Japanese honeysuckle (Lonicera japonica) and Chinese privet (Ligustrum sinense) were the second- and third-most problematic plant species on the Research Park; these two species were present in 12 and 9 of the 16 sites surveyed, respectively, and often ranked second- or third-most problematic. Other nonnative, invasive species, in decreasing rank order, included kudzu (Pueraria montma), multiflora rose (Rosa multiflora), Chinese lespedeza (Lespedeza cuneara), and other species representing a variety of life forms and growth

  16. Gauging and visualizing c-di-GMP levels in pseudomonas aeruginosa using fluorescence-based biosensors

    DEFF Research Database (Denmark)

    Rybtke, Morten; Chua, Song Lin; Yam, Joey Kuok Hoong

    2017-01-01

    Recent research has shown that the molecule c-di-GMP is an important second messenger regulating various functions in bacteria. In particular, the implication of c-di-GMP as a positive regulator of adhesion and biofilm formation has gained momentum as a highly relevant research topic, as detailed...... knowledge about the underlying regulatory mechanisms may enable the development of measures to control biofilms in both industrial and medical settings. Accordingly, it is in many cases of interest to measure the c-di-GMP level in bacteria under specific conditions or in specific mutant strains. We have...... developed a collection of fluorescence-based c-di-GMP biosensors capable of gauging the c-di-GMP level in Pseudomonas aeruginosa and closely related bacteria. Here, we describe protocols for the use of these biosensors in gauging and visualizing cellular c-di-GMP levels of P. aeruginosa both in in vitro...

  17. ENVIRONMENTAL PUBLIC HEALTH OUTCOMES WORKSHOP PROCEEDINGS -RESEARCH TRIANGLE PARK, NC, 7/30-31/2002

    Science.gov (United States)

    To better define ORD's Environmental Public Health Outcomes (EPHO) research agenda, a workshop was held 7/30-31/2002 at EPA facilities in Research Triangle Park, NC. The intent of this workshop was to engage federal and other organizations in a dialog that will assist ORD in deve...

  18. Some aspects of identity, meaning and park sustainability research, with special reference to Kamenički park

    Directory of Open Access Journals (Sweden)

    Bajić Luka

    2011-01-01

    Full Text Available One of the main goals of urban planning by principles of sustainable development is the pursuit of diversity in structure, form and function in planning and design of urban public space. It is therefore necessary to redefine the concept and function of urban green areas and city parks, with the recommendation of identity preservation and promotion of social cohesion of this type of public space. In a theoretical sense, there is a problem of planning and designing urban parks in Serbia. This is due to failure to recognize the complexity underlying the possible role of urban public parks as an engine of urban renewal in the city or of any of his districts. Example of Kamenički park was chosen because of its complexity - in addition to being the largest green space in the city, this park also has high natural and cultural values (the park is protected as a cultural and natural heritage. The results indicate the reduced use of urban space. Based on existing theory and insights into the local planning process, general recommendations for improving its quality is the improvement of form/design of the park and it is necessary to define and promote the identity of space through the spatial analysis. The ultimate goal is to successfully respond to existing and potential customers' needs and thus define environmental, economic, cultural and social sustainability, which are key factors in managing the park.

  19. Proceedings of the fourth conference on research in California's National Parks

    Science.gov (United States)

    Veirs, Stephen D.; Stohlgren, Thomas; Schonewald-Cox, Christine

    1993-01-01

    The papers in this proceedings were selected from the 63 presentations given at the Fourth Biennial Conference on Research in National Parks in California. The overall theme for this meeting was a recurring one: “The Integration of Research into National Park Service Resource Management Decisions.” The conference was held at the University of California, Davis, on 10-12 September 1991 and was sponsored by the National Park Service Cooperative Park Studies Unit and the Institute of Ecology at the University of California, Davis. This proceedings highlights a variety of research and resource management efforts to improve the stewardship of our most treasured landscapes. In the future, it will become increasingly more important for federal and state agencies, university scientists and students, and the public to cooperate fully to improve the quantity and quality of science and resource management programs in units of the National Park System. As many of the papers in this proceedings attest, we must look beyond the political boundaries of protected landscapes to incorporate entire ecosystems. Competing resource uses inside and outside parklands must be reexamined to weave a common thread of biological conservation. As scientists, our studies must bridge the gap from plots to landscapes and from landscapes to regions. Our studies must built on information from species and populations to ecosystems and the processes that influence them. The papers in this proceedings are modest but important contribution to those ideals. Each paper represents original research and has been peer-reviewed. Many agencies, institutions, and individuals contributed in the development of this product. In the planning stages, National Park Service Western Region scientists provided advice and assistance in structuring the conference format. University of California, Davis, graduate students, directed by Sharon Lynch, assisted with logistics at the meeting, and provided general assistance

  20. Specificity of the Cyclic GMP-Binding Activity and of a Cyclic GMP-Dependent Cyclic GMP Phosphodiesterase in Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Walsum, Hans van; Meer, Rob C. van der; Bulgakov, Roman; Konijn, Theo M.

    1982-01-01

    The nucleotide specificity of the cyclic GMP-binding activity in a homogenate of Dictyostelium discoideum was determined by competition of cyclic GMP derivatives with [8-3H] cyclic GMP for the binding sites. The results indicate that cyclic GMP is bound to the binding proteins by hydrogen bonds at

  1. KAJIAN PENERAPAN GOOD MANUFACTURING PRACTICE (GMP DI INDUSTRI RAJUNGAN PT.KELOLA MINA LAUT MADURA

    Directory of Open Access Journals (Sweden)

    Bhiaztika Ristyanadi

    2016-11-01

    Full Text Available Good manufacturing practice is the first step implementation of food safety regulation. PT. Kelola Mina Laut is one of chilled sea crab producers in Madura. It has four branches in Madura,those are in Tanjung Bumi, Noreh, Sampang, and Lobuk. The objective of this research is to assess the effectiveness GMP in four branches of PT. Kelola Mina Laut. The research  uses field observation, data analysis and GMP development as the method. Based on GMP analysis, four branches of PT. Kelola Mina Laut appear to have a cummulative score between 337-369, in which Lobuk has the highest score. Therefore, it can be concluded that PT. Kelola Mina Laut has applied most of GMP elements

  2. ASEAN GMP and pharmaceutical industries in Indonesia.

    Science.gov (United States)

    Soesilo, S; Sitorus, U

    1995-01-01

    Indonesia was appointed by the ASEAN Technical Cooperation in Pharmaceutical as a focal point and to coordinate the development of practical guidelines for the implementation of GMP. The ASEAN GMP Guidelines were endorsed by the ASEAN Technical Cooperation in Pharmaceutical in 1988, which among others required separation of Beta-Lactam dedicated facilities and three degrees of cleanliness for production areas. As it was realised that drug manufacturers in developing countries need more detailed guidelines to be able to implement the GMP, an Operational Manual for GMP was also prepared for providing examples of SOPs lay-outs, documentation etc. It was agreed by the technical cooperation group to leave the implementation of GMP to each member country. However, the ASEAN Manual for Inspection of GMP was drafted and endorsed by the group and training of ASEAN Drug Inspectors was organized to support the implementation. The ASEAN GMP is being implemented in Indonesia through a five-year, stepwise implementation plan, starting in 1989.

  3. 75 FR 28055 - General Management Plan; Joshua Tree National Park; San Bernardino and Riverside Counties, CA...

    Science.gov (United States)

    2010-05-19

    ... kinds of resource management activities, visitor activities, and developments that would be appropriate... DEPARTMENT OF THE INTERIOR National Park Service General Management Plan; Joshua Tree National... National Park Service is updating the General Management Plan (GMP) for Joshua Tree National Park...

  4. When Disney Meets the Research Park: Metaphors and Models for Engineering an Online Learning Community of Tomorrow

    Science.gov (United States)

    Chenail, Ronald J.

    2004-01-01

    It is suggested that educators look to an environment in which qualitative research can be learned in more flexible and creative ways--an online learning community known as the Research Park Online (RPO). This model, based upon Walt Disney's 1966 plan for his "Experimental Prototype Community of Tomorrow" (EPCOT) and university cooperative…

  5. National Parks

    Data.gov (United States)

    Department of Transportation — National Park Service unit boundaries (NTAD). These park boundaries signify legislative boundary definitions and local park names have been consolidated according to...

  6. Research Coordination Network: Geothermal Biology and Geochemistry in Yellowstone National Park

    Science.gov (United States)

    Inskeep, W. P.; Young, M. J.; Jay, Z.

    2006-12-01

    The number and diversity of geothermal features in Yellowstone National Park (YNP) represent a fascinating array of high temperature geochemical environments that host a corresponding number of unique and potentially novel organisms in all of the three recognized domains of life: Bacteria, Archaea and Eukarya. The geothermal features of YNP have long been the subject of scientific inquiry, especially in the fields of microbiology, geochemistry, geothermal hydrology, microbial ecology, and population biology. However, there are no organized forums for scientists working in YNP geothermal areas to present research results, exchange ideas, discuss research priorities, and enhance synergism among research groups. The primary goal of the YNP Research Coordination Network (GEOTHERM) is to develop a more unified effort among scientists and resource agencies to characterize, describe, understand and inventory the diverse biota associated with geothermal habitats in YNP. The YNP RCN commenced in January 2005 as a collaborative effort among numerous university scientists, governmental agencies and private industry. The YNP RCN hosted a workshop in February 2006 to discuss research results and to form three working groups focused on (i) web-site and digital library content, (ii) metagenomics of thermophilic microbial communities and (iii) development of geochemical methods appropriate for geomicrobiological studies. The working groups represent one strategy for enhancing communication, collaboration and most importantly, productivity among the RCN participants. If you have an interest in the geomicrobiology of geothermal systems, please feel welcome to join and or participate in the YNP RCN.

  7. Research and Implementation of Automatic Fuzzy Garage Parking System Based on FPGA

    Directory of Open Access Journals (Sweden)

    Wang Kaiyu

    2016-01-01

    Full Text Available Because of many common scenes of reverse parking in real life, this paper presents a fuzzy controller which accommodates front and back adjustment of vehicle’s body attitude, and based on chaotic-genetic arithmetic to optimize the membership function of this controller, and get a vertical parking fuzzy controller whose simulation result is good .The paper makes the hardware-software embedded design for system based on Field-Programmable Gate Array (FPGA, and set up a 1:10 verification platform of smart car to verify the fuzzy garage parking system with real car. Verification results show that, the system can complete the parking task very well.

  8. Hanford National Environmental Research Park (NERP): a descriptive summary of the site and site-related research programs, 1952--1977

    International Nuclear Information System (INIS)

    Vaughan, B.E.; Rickard, W.H.

    1977-11-01

    The Hanford National Environmental Research Park site is described in general terms and major plant communities and special habitats are discussed. Important bird, mammal, and fish populations are listed. Current research programs on aquatic and terrestrial ecosystems and radioecology are reviewed briefly. A list is included of some 100 publications that report results of research studies in detail

  9. Transient Kinetics of a cGMP-dependent cGMP-specific Phosphodiesterase from Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Lookeren Campagne, Michiel M. van

    1984-01-01

    Chemotactic stimulation of Dictyostelium discoideum cells induces a fast transient increase of cGMP levels which reach a peak at 10 s. Prestimulation levels are recovered in ~30 s, which is achieved mainly by the action of a guanosine 3',5'-monophosphate cGMP-specific phosphodiesterase. This enzyme

  10. Design and research on the electronic parking brake system of the medium and heavy duty vehicles

    Directory of Open Access Journals (Sweden)

    Hongliang WANG

    2015-04-01

    Full Text Available Focusing on auto control of parking brake system of the medium and heavy duty vehicles, the key problems are studied including the system design and control strategies. The structure and working principle of the parking brake system of the medium and heavy duty vehicles are analyzed. The functions of EPB are proposed. The important information of the vehicle are analyzed which could influence the EPB system. The overall plan of the pneumatic EPB system is designed, which adopts the two-position three-way electromagnetic valve with double coil as actuator. The system could keep the vehicle parking brake status or parking release status for a long time without power supply. The function modules of the system are planned, and the control strategies of automatic parking brake and parking release are made. The experiment is performed on a medium-sized commercial vehicle which is experimentally modified. The overall plan of the pneumatic EPB system and the automatic parking function are proved through real vehicle tests.

  11. Exploration of Science Parks

    Institute of Scientific and Technical Information of China (English)

    Xiong Huibing; Sun Nengli

    2005-01-01

    Science parks have developed gready in the world, whereas empirical researches have showed that science parks based on linear model cannot guarantee the creation of innovation. Hi-tech innovation is derived from flow and management of information. The commercial and social interactions between in-parks and off-park firms and research institutions act as the key determinant for innovation.Industrial clustering is the rational choice for further developing Chinese science parks and solving some problems such as the lack of dear major industries and strong innovation sense, etc.

  12. Scoping Review on Research on Food conducted in the Faculty of Social Sciences. Including other Institutions in the Norwich Research Park and Beyond

    OpenAIRE

    Howard Wilsher, Stephanie

    2014-01-01

    Executive summary The scoping review was commissioned to examine what research on food has been conducted in the Faculty of Social Sciences (SSF) at the University of East Anglia (UEA) since 2005. The aim of the report is to facilitate collaborative research between SSF and the rest of the Norwich Research Park (NRP), in particular, the Institute of Food Research (IFR). However, it is important to contextualise this beyond the NRP as the Eastern Academic Research Consortium (EARC) provides fu...

  13. Guanylin peptides: cyclic GMP signaling mechanisms

    Directory of Open Access Journals (Sweden)

    Forte L.R.

    1999-01-01

    Full Text Available Guanylate cyclases (GC serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin, two disulfides (guanylin and uroguanylin and three disulfides (E. coli stable toxin, ST. The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

  14. Viewshed and sense of place as conservation features: A case study and research agenda for South Africa's national parks

    Directory of Open Access Journals (Sweden)

    Jaco Barendse

    2016-08-01

    Full Text Available Sense of place (SoP refers to the meanings and values that people attach to places. The concept can be used to frame how people engage or form a connection with the natural environment. At a sensory level, SoP is influenced by people’s visual experiences, which in turn can be linked to the concept of viewsheds. Viewsheds can be transformed, either abruptly (e.g. by infrastructure development such as wind turbines or more gradually (e.g. by non-native trees invading a landscape. In this study, we focus on the Garden Route National Park to explore the potential importance of viewsheds as a conservation feature, specifically in the context of non-native (especially invasive tree species. Using mixed information sources, we explore the potential role of invasive trees on experiences of visitors to this protected area and speculate on how viewsheds may shape SoP associations and how such associations may inform protected area management. Our investigation shows that people’s experiences regarding natural and modified viewsheds are varied and intricate. Both SoP and viewsheds have the potential to inform conservation action, and these concepts should form an integral part of objective hierarchies and management plans for national parks. However, while legislation and park management plans make provision for the use of these concepts, associated research in South Africa is virtually non-existent. We conclude by proposing a conceptual model and research agenda to promote the use of viewsheds and SoP in the management of national parks in South Africa. Conservation implications: Viewshed and sense of place can be used as boundary concepts to (1 facilitate interdisciplinary research between social and natural scientists, (2 help understand the connectedness and feedbacks between people and nature and (3 promote communication between science, management and stakeholders regarding desired conditions of landscapes in and around parks.

  15. Environmental Survey Report for ORNL: Small Mammal Abundance and Distribution Survey Oak Ridge National Environmental Research Park 2009 - 2010

    Energy Technology Data Exchange (ETDEWEB)

    Giffen, Neil R [ORNL; Reasor, R. Scott [Oak Ridge Institute for Science and Education (ORISE); Campbell, Claire L. [Oak Ridge Institute for Science and Education (ORISE)

    2009-12-01

    This report summarizes a 1-year small mammal biodiversity survey conducted on the Oak Ridge National Environmental Research Park (OR Research Park). The task was implemented through the Oak Ridge National Laboratory (ORNL) Natural Resources Management Program and included researchers from the ORNL Environmental Sciences Division, interns in the Oak Ridge Institute for Science and Education Higher Education Research Experiences Program, and ORNL Environmental Protection Services staff. Eight sites were surveyed reservation wide. The survey was conducted in an effort to determine species abundance and diversity of small mammal populations throughout the reservation and to continue the historical inventory of small mammal presence for biodiversity records. This data collection effort was in support of the approved Wildlife Management Plan for the Oak Ridge Reservation, a major goal of which is to maintain and enhance wildlife biodiversity on the Reservation. Three of the sites (Poplar Creek, McNew Hollow, and Deer Check Station Field) were previously surveyed during a major natural resources inventory conducted in 1996. Five new sites were included in this study: Bearden Creek, Rainy Knob (Natural Area 21), Gum Hollow, White Oak Creek and Melton Branch. The 2009-2010 small mammal surveys were conducted from June 2009 to July 2010 on the Oak Ridge National Environmental Research Park (OR Research Park). The survey had two main goals: (1) to determine species abundance and diversity and (2) to update historical records on the OR Research Park. The park is located on the Department of Energy-owned Oak Ridge Reservation, which encompasses 13,580 ha. The primary focus of the study was riparian zones. In addition to small mammal sampling, vegetation and coarse woody debris samples were taken at certain sites to determine any correlations between habitat and species presence. During the survey all specimens were captured and released using live trapping techniques including

  16. Using integrated research and interdisciplinary science: Potential benefits and challenges to managers of parks and protected areas

    Science.gov (United States)

    van Riper, Charles; Powell, Robert B.; Machlis, Gary; van Wagtendonk, Jan W.; van Riper, Carena J.; von Ruschkowski, Eick; Schwarzbach, Steven E.; Galipeau, Russell E.

    2012-01-01

    Our purpose in this paper is to build a case for utilizing interdisciplinary science to enhance the management of parks and protected areas. We suggest that interdisciplinary science is necessary for dealing with the complex issues of contemporary resource management, and that using the best available integrated scientific information be embraced and supported at all levels of agencies that manage parks and protected areas. It will take the commitment of park managers, scientists, and agency leaders to achieve the goal of implementing the results of interdisciplinary science into park management. Although such calls go back at least several decades, today interdisciplinary science is sporadically being promoted as necessary for supporting effective protected area management(e.g., Machlis et al. 1981; Kelleher and Kenchington 1991). Despite this history, rarely has "interdisciplinary science" been defined, its importance explained, or guidance provided on how to translate and then implement the associated research results into management actions (Tress et al. 2006; Margles et al. 2010). With the extremely complex issues that now confront protected areas (e.g., climate change influences, extinctions and loss of biodiversity, human and wildlife demographic changes, and unprecedented human population growth) information from more than one scientific discipline will need to be brought to bear in order to achieve sustained management solutions that resonate with stakeholders (Ostrom 2009). Although interdisciplinary science is not the solution to all problems, we argue that interdisciplinary research is an evolving and widely supported best practice. In the case of park and protected area management, interdisciplinary science is being driven by the increasing recognition of the complexity and interconnectedness of human and natural systems, and the notion that addressing many problems can be more rapidly advanced through interdisciplinary study and analysis.

  17. The concept for development of the research network for the measurements of modern tectonic movements in Ksiaz Landscape Park

    Directory of Open Access Journals (Sweden)

    Damian Kasza

    2013-09-01

    Full Text Available The paper presents the concept for the development of research network for measurements of effects related to modern tectonic activity in the area of Ksiaz Landscape Park. The first evidences for the existence of displacements on the surfaces of discontinuity with event characteristic and the instruments used in the study were described. The way and shape of development of Ksiaz geodynamic polygon were characterized as well as the methodology and purpose of observations.

  18. Partial reconstitution of photoreceptor cGMP phosphodiesterase characteristics in cGMP phosphodiesterase-5.

    Science.gov (United States)

    Granovsky, A E; Artemyev, N O

    2001-06-15

    Photoreceptor cGMP phosphodiesterases (PDE6) are uniquely qualified to serve as effector enzymes in the vertebrate visual transduction cascade. In the dark-adapted photoreceptors, the activity of PDE6 is blocked via tight association with the inhibitory gamma-subunits (Pgamma). The Pgamma block is removed in the light-activated PDE6 by the visual G protein, transducin. Transducin-activated PDE6 exhibits an exceptionally high catalytic rate of cGMP hydrolysis ensuring high signal amplification. To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. PDE5 is insensitive to Pgamma and has a more than 100-fold lower k(cat) for cGMP hydrolysis. Our mutational analysis of chimeric PDE5/PDE6alpha' enzymes revealed that the inhibitory interaction of cone PDE6 catalytic subunits (PDE6alpha') with Pgamma is mediated primarily by three hydrophobic residues at the entry to the catalytic pocket, Met(758), Phe(777), and Phe(781). The maximal catalytic rate of PDE5 was enhanced by at least 10-fold with substitutions of PDE6alpha'-specific glycine residues for the corresponding PDE5 alanine residues, Ala(608) and Ala(612). The Gly residues are adjacent to the highly conserved metal binding motif His-Asn-X-X-His, which is essential for cGMP hydrolysis. Our results suggest that the unique Gly residues allow the PDE6 metal binding site to adopt a more favorable conformation for cGMP hydrolysis.

  19. Research and Implementation of Automatic Fuzzy Garage Parking System Based on FPGA

    OpenAIRE

    Wang Kaiyu; Yu Zongmin; Guan Sanghai; Yang Xing; Sheng Menglin; Tang Zhenan

    2016-01-01

    Because of many common scenes of reverse parking in real life, this paper presents a fuzzy controller which accommodates front and back adjustment of vehicle’s body attitude, and based on chaotic-genetic arithmetic to optimize the membership function of this controller, and get a vertical parking fuzzy controller whose simulation result is good .The paper makes the hardware-software embedded design for system based on Field-Programmable Gate Array (FPGA), and set up a 1:10 verification platfo...

  20. 40 CFR 230.54 - Parks, national and historical monuments, national seashores, wilderness areas, research sites...

    Science.gov (United States)

    2010-07-01

    ....54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION 404(b... Human Use Characteristics § 230.54 Parks, national and historical monuments, national seashores... -managed. Note: Possible actions to minimize adverse impacts regarding site or material characteristics can...

  1. A bibliometric analysis to illustrate the role of an embedded research capability in South African National Parks

    CSIR Research Space (South Africa)

    Van Wilgen, BW

    2016-04-01

    Full Text Available analysis to illustrate the role of an embedded research capability in South African National Parks Brian W. van Wilgen1 , Nelius Boshoff2 , Izak P. J. Smit3,4 , Sofia Solano-Fernandez5 , Luanita van der Walt6 1 Centre for Invasion Biology..., Department of Botany and Zoology, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa 2 Centre for Research on Evaluation, Science and Technology and DST/NRF CoE in Scientometrics and Science, Technology and Innovation Policy...

  2. Cellular signaling with nitric oxide and cyclic GMP

    Directory of Open Access Journals (Sweden)

    F. Murad

    1999-11-01

    Full Text Available During the past two decades, nitric oxide signaling has been one of the most rapidly growing areas in biology. This simple free radical gas can regulate an ever growing list of biological processes. In most instances nitric oxide mediates its biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis. However, the identification of effects of nitric oxide that are independent of cyclic GMP is also growing at a rapid rate. The effects of nitric oxide can mediate important physiological regulatory events in cell regulation, cell-cell communication and signaling. Nitric oxide can function as an intracellular messenger, neurotransmitter and hormone. However, as with any messenger molecule, there can be too much or too little of the substance and pathological events ensue. Methods to regulate either nitric oxide formation, metabolism or function have been used therapeutically for more than a century as with nitroglycerin therapy. Current and future research should permit the development of an expanded therapeutic armamentarium for the physician to manage effectively a number of important disorders. These expectations have undoubtedly fueled the vast research interests in this simple molecule.

  3. Microbiological criteria for good manufacturing practice (GMP)

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, J [Inst. of Preservation and Livestock Products Technology, Univ. of Horticulture and Food Industry, Budapest (Hungary); Zukal, E [Inst. of Preservation and Livestock Products Technology, Univ. of Horticulture and Food Industry, Budapest (Hungary)

    1992-01-01

    Good manufacturing practice (GMP) consist of an effective manufacturing operation and an effective application of food control. GMP is best supported by the Hazard Analysis Critical Control Point system (HACCP) of the preventive quality assurance, which requires that food irradiation as any food processing technology should be used only with foods of an acceptable quality and adequate handling and storage procedures should precede and follow the processing. The paper concentrates on the first element of the HACCP system for an irradiation plant: the incoming product control, i.e. whether GMP of foods to be irradiated can be assessed by establishing microbiological criteria for their previous good manufacturing practice. In this regard, it summarizes considerations and findings of a ''Consultation on Microbiological Criteria for Foods to be Further Processed Including by Irradiation'' held in 1989 by the International Consultative Group on Food irradiation at the Headquarters of the World Health Organization, Geneva. Difficulties in establishing reference values and defining good manufacturing practices will be pointed out. (orig.)

  4. Microbiological criteria for good manufacturing practice (GMP)

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, J. (Inst. of Preservation and Livestock Products Technology, Univ. of Horticulture and Food Industry, Budapest (Hungary)); Zukal, E. (Inst. of Preservation and Livestock Products Technology, Univ. of Horticulture and Food Industry, Budapest (Hungary))

    1992-01-01

    Good manufacturing practice (GMP) consist of an effective manufacturing operation and an effective application of food control. GMP is best supported by the Hazard Analysis Critical Control Point system (HACCP) of the preventive quality assurance, which requires that food irradiation as any food processing technology should be used only with foods of an acceptable quality and adequate handling and storage procedures should precede and follow the processing. The paper concentrates on the first element of the HACCP system for an irradiation plant: the incoming product control, i.e. whether GMP of foods to be irradiated can be assessed by establishing microbiological criteria for their previous good manufacturing practice. In this regard, it summarizes considerations and findings of a ''Consultation on Microbiological Criteria for Foods to be Further Processed Including by Irradiation'' held in 1989 by the International Consultative Group on Food irradiation at the Headquarters of the World Health Organization, Geneva. Difficulties in establishing reference values and defining good manufacturing practices will be pointed out. (orig.)

  5. Microbiological criteria for good manufacturing practice (GMP)

    International Nuclear Information System (INIS)

    Farkas, J.; Zukal, E.

    1992-01-01

    Good manufacturing practice (GMP) consist of an effective manufacturing operation and an effective application of food control. GMP is best supported by the Hazard Analysis Critical Control Point system (HACCP) of the preventive quality assurance, which requires that food irradiation as any food processing technology should be used only with foods of an acceptable quality and adequate handling and storage procedures should precede and follow the processing. The paper concentrates on the first element of the HACCP system for an irradiation plant: the incoming product control, i.e. whether GMP of foods to be irradiated can be assessed by establishing microbiological criteria for their previous good manufacturing practice. In this regard, it summarizes considerations and findings of a ''Consultation on Microbiological Criteria for Foods to be Further Processed Including by Irradiation'' held in 1989 by the International Consultative Group on Food irradiation at the Headquarters of the World Health Organization, Geneva. Difficulties in establishing reference values and defining good manufacturing practices will be pointed out. (orig.) [de

  6. History of pronghorn population monitoring, research, and management in Yellowstone National Park

    Science.gov (United States)

    Keating, Kim A.

    2002-01-01

    Pronghorn antelope in Yellowstone National Park (YNP) persist in a small population that historically has experienced recurrent, sometimes dramatic declines. They apparently are isolated from other pronghorns, depend partly on private lands for winter range, experience heavy predation of fawns, and concentrate during winter in a relatively small area, thereby increasing their vulnerability to factors like disease or locally extreme weather. Overall, the situation raises serious concerns about the long-term viability of this population. Although such concerns are not new, evidence of a dramatic population decline since 1991 and continued poor recruitment has created a renewed sense of urgency.

  7. The Influence of Philosophical Perspectives in Integrative Research: a Conservation Case Study in the Cairngorms National Park

    Directory of Open Access Journals (Sweden)

    Anna C. Evely

    2008-12-01

    Full Text Available The benefits of increasing the contribution of the social sciences in the fields of environmental and conservation science disciplines are increasingly recognized. However, integration between the social and natural sciences has been limited, in part because of the barrier caused by major philosophical differences in the perspectives between these research areas. This paper aims to contribute to more effective interdisciplinary integration by explaining some of the philosophical views underpinning social research and how these views influence research methods and outcomes. We use a project investigating the motivation of volunteers working in an adaptive co-management project to eradicate American Mink from the Cairngorms National Park in Scotland as a case study to illustrate the impact of philosophical perspectives on research. Consideration of different perspectives promoted explicit reflection of the contributing researcher's assumptions, and the implications of his or her perspectives on the outcomes of the research. We suggest a framework to assist conservation research projects by: (1 assisting formulation of research questions; (2 focusing dialogue between managers and researchers, making underlying worldviews explicit; and (3 helping researchers and managers improve longer-term strategies by helping identify overall goals and objectives and by identifying immediate research needs.

  8. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

    Science.gov (United States)

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

    2017-09-15

    Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and

  9. Research on Park Ji-Won in China%朴趾源研究在中国

    Institute of Scientific and Technical Information of China (English)

    张丽娜

    2012-01-01

    朴趾源研究是韩国古典文学研究的一个热点和重点。总体上看,研究队伍中名家济济,以汉文形式发表的研究成果较多。学界对朴趾源的研究主要集中在其思想、小说创作上,《热河日记》是研究的一个焦点。对于朴趾源诗歌、散文和《燕岩集》的整体研究有所欠缺,全面、系统、客观地研究评价朴趾源在韩国文学史、思想史上的地位的专著尚未出现。%Research on Park Ji-Won is a key and hit of Korean classical literature. On the whole, there are many famous experts in the field and lots of research achievements in Chinese. Academic studies focus on his ideas and novels, of which ReHe Diary is a focus. However, an overall study of his poetries, proses and YanYan Collection is not enough. Comprehensive, systematic and objective works have not yet appeared, which study and assess Park Ji -Won's position in the history of Korean literature and intellectual

  10. Exploring en-route parking type and parking-search route choice

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Bekhor, Sholomo

    2011-01-01

    This paper describes the first phase of an on-going research investigating the joint choice of parking type, parking facility and cruising-for-parking route. The importance of this issue derives from the significant share of cruising-for-parking traffic in urban areas, the relevance of parking po...

  11. Quality Risk Management: Putting GMP Controls First.

    Science.gov (United States)

    O'Donnell, Kevin; Greene, Anne; Zwitkovits, Michael; Calnan, Nuala

    2012-01-01

    This paper presents a practical way in which current approaches to quality risk management (QRM) may be improved, such that they better support qualification, validation programs, and change control proposals at manufacturing sites. The paper is focused on the treatment of good manufacturing practice (GMP) controls during QRM exercises. It specifically addresses why it is important to evaluate and classify such controls in terms of how they affect the severity, probability of occurrence, and detection ratings that may be assigned to potential failure modes or negative events. It also presents a QRM process that is designed to directly link the outputs of risk assessments and risk control activities with qualification and validation protocols in the GMP environment. This paper concerns the need for improvement in the use of risk-based principles and tools when working to ensure that the manufacturing processes used to produce medicines, and their related equipment, are appropriate. Manufacturing processes need to be validated (or proven) to demonstrate that they can produce a medicine of the required quality. The items of equipment used in such processes need to be qualified, in order to prove that they are fit for their intended use. Quality risk management (QRM) tools can be used to support such qualification and validation activities, but their use should be science-based and subject to as little subjectivity and uncertainty as possible. When changes are proposed to manufacturing processes, equipment, or related activities, they also need careful evaluation to ensure that any risks present are managed effectively. This paper presents a practical approach to how QRM may be improved so that it better supports qualification, validation programs, and change control proposals in a more scientific way. This improved approach is based on the treatment of what are called good manufacturing process (GMP) controls during those QRM exercises. A GMP control can be considered

  12. Specific GMP guidelines for radiopharmaceutical products

    International Nuclear Information System (INIS)

    2000-01-01

    These guidelines are intended to complement those provided in ''Good manufacturing practices for pharmaceutical products'', as well as the GMP for sterile pharmaceutical products. The regulatory procedures necessary to control radiopharmaceutical products are in large part determined by the sources of products and methods of manufacture. Manufacturing procedures within the scope of these guidelines include: preparation of radiopharmaceuticals in hospital radiopharmacies, preparation of radiopharmaceuticals in centralized radiopharmacies, production of radiopharmaceuticals in nuclear centres, institutes or industrial manufacturers, preparation and production of radiopharmaceuticals in Positron Emission Tomography (PET) centres

  13. Production of GMP certified herbal products in Malaysian Nuclear Agency

    International Nuclear Information System (INIS)

    Daryl Jesus Arapoc; Bohari Yaacob; Zainah Adam

    2015-01-01

    This paper will discuss on up scaling production of herbal product. A pilot scale production plant were developed in Block 37 and equipped with automated and semi-automated production machines which have the capacity to produce 100 thousand pieces of tablet per hour. In order to ensure the quality of the products, raw material inspections, IPQC and FPQC will be done on each batch. Besides that, certification of GMP will be done concurrently. One of the products that will be launch soon is the Mas Cotek tablet. This product is the result of numerous years of researches that had been done in BTP. This includes formulation and production of the product itself. It is hope that more herbal products can be produce in near future. (author)

  14. Changes of platelet GMP-140 in diabetic nephropathy and its multi-factor regression analysis

    International Nuclear Information System (INIS)

    Wang Zizheng; Du Tongxin; Wang Shukui

    2001-01-01

    The relation of platelet GMP-140 and its related factors with diabetic nephropathy was studied. 144 patients of diabetic mellitus without nephropathy (group without DN, mean suffering duration of 25.5 +- 18.6 months); 80 with diabetic nephropathy (group DN, mean suffering duration of 58.7 +- 31.6 months) and 50 normal controls were chosen in the research. Platelet GMP-140, plasma α 1 -MG, β 2 -MG, and 24 hour urine albumin (ALB), IgG, α 1 -MG, β 2 -MG were detected by RIA, while HBA 1 C via chromatographic separation and FBG, PBG, Ch, TG, HDL, FG via biochemical methods. All the data had been processed with software on computer with t-test and linear regression, and multi-factor analysis were done also. The levels of platelet GMP-140, FG, DBP, TG, HBA 1 C and PBG in group DN were significantly higher than those of group without DN and normal control (P 0.05), while they were higher than those of normal controls. Multi-factor analysis of platelet GMP-140 with TG, DBP and HBA 1 C were performed in 80 patients with DN (P 1 C are the independent factors enhancing the activation of platelets. The disturbance of lipid metabolism in type II diabetic mellitus may also enhance the activation of platelets. Elevation of blood pressure may accelerate the initiation and deterioration of DN in which change of platelet GMP-140 is an independent factor. Elevation of HBA 1 C and blood glucose are related closely to the diabetic nephropathy

  15. About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use.

    Science.gov (United States)

    Hartmann-Fritsch, Fabienne; Marino, Daniela; Reichmann, Ernst

    2016-09-01

    The treatment of severe full-thickness skin defects represents a significant and common clinical problem worldwide. A bio-engineered autologous skin substitute would significantly reduce the problems observed with today's gold standard. Within 15 years of research, the Tissue Biology Research Unit of the University Children's Hospital Zurich has developed autologous tissue-engineered skin grafts based on collagen type I hydrogels. Those products are considered as advanced therapy medicinal products (ATMPs) and are routinely produced for clinical trials in a clean room facility following the guidelines for good manufacturing practice (GMP). This article focuses on hurdles observed for the translation of ATMPs from research into the GMP environment and clinical application. Personalized medicine in the field of rare diseases has great potential. However, ATMPs are mainly developed and promoted by academia, hospitals, and small companies, which face many obstacles such as high financial burdens.

  16. Park It!

    Science.gov (United States)

    Sartorius, Tara Cady

    2010-01-01

    Many artists visit national parks to draw, paint and take photographs of some of the most amazing scenery on earth. Raw nature is one of the greatest inspirations to an artist, and artists can be credited for helping inspire the government to create the National Park System. This article features Thomas Moran (1837-1926), one of the artists who…

  17. Onion Park Research Natural Area: Botanical and ecological resources inventory, mapping and analysis with recommendations towards the development of a long-term monitoring and research program

    Science.gov (United States)

    Earle F. Layser

    1992-01-01

    Onion Park is a floristically rich naturally occurring mountain meadow and wetland complex which is surrounded by subalpine forest. The grass- and wetlands comprising the Park contribute biological diversity to an otherwise predominantly lodgepole pine-forested, subalpine setting. Onion Park is located at 7400' elevation in the Little Belt Mountains, five miles...

  18. Parks & benefits

    DEFF Research Database (Denmark)

    Brandt, Jesper; Christensen, Andreas Aagaard; Holmes, Esbern

    2011-01-01

    conservation. Increasing visitor flows and cuts in staff resources has put focus on the management of visitor carrying capacities and their relation to landscape structure and zoning. At the same time park authorities face falling public appropriations and receding focus on their conservation functions...... compared to recreation and settlement. The constant priority of the balancing of nature protection and economic utilization gives rise to various experience with land use and visitor management relevant for sustainable development also outside the parks. In European nature parks the handling of visitor...... carrying capacities related to Natura2000-sites and their included habitat type areas is a priority theme for the sustainable management of nature parks. A comparative analysis of conditions and initiatives related to visitor carrying capacities in 8 nature parks in the Baltic region has been carried out...

  19. Multiple Degradation Pathways of Chemoattractant Mediated Cyclic GMP Accumulation in Dictyostelium

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Lookeren Campagne, Michiel M. van; Kesbeke, Fanja

    1983-01-01

    Chemoattractants induce a transient accumulation of cGMP levels in Dictyostelium. Intracellular cGMP levels reach a peak at 10 s and prestimulated cGMP levels are recovered at about 30 s. Intracellular and extracellular cGMP levels were detected simultaneously after stimulation of D. lacteum cells

  20. Guidelines for negotiating social research in communities living adjacent to transboundary protected areas: Kruger National Park

    NARCIS (Netherlands)

    B.N. Tapela (Barbara); B.E. Büscher (Bram); L. Maluleke (Lamson); W.C. Twine (Wayne); C. Steenkamp (Conrad)

    2009-01-01

    textabstractThe objective with these Guidelines is to assist local people and social researchers to negotiate equitable research agreements. This document lays out the purpose of the guidelines, provides some background information about the process that led to this document, and provides some

  1. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-01-01

    positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking

  2. Fire management and research in the Kruger National Park, with suggestions on the detection of thresholds of potential concern

    Directory of Open Access Journals (Sweden)

    B.W. Van Wilgen

    1998-07-01

    Full Text Available This paper reviews the options for management of the savanna ecosystems of the Kruger National Park using fire. The major goals of management have shifted from attempts to use fire to achieve a stable vegetation composition, to one of recognising that savanna ecosystems are in constant flux. Fire is a major form of disturbance that helps to maintain a state of flux, and thus to conserve biodiversity. Three candidate approaches for fire management have been put forward@the lightning fire approach, the patch mosaic burning approach, and an approach based on the assessment of ecological criteria. These approaches differ in their underlying philosophies, but not necessarily in their outcomes, although this cannot be predicted with confidence. We propose, therefore, that patterns of fire frequency, season, intensity and spatial distribution be recorded and monitored, and that these patterns should serve as surrogate measures of biodiversity. Guidelines for the definition of thresholds of potential concern with regard to these patterns are discussed. The monitoring of both fire patterns and trends in plant and animal populations can be used to identify interactions between fire and the components of the ecosystem, and these in turn can be used to define a relevant research agenda. The role of management in monitoring and assessing fire patterns (previously regarded as a research responsibility is emphasised. Convergence in the patterns of fire that result from the different management approaches could also serve as a basis for merging some or all of these approaches in order to simplify management.

  3. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    KAUST Repository

    Kim, Jeong Joo

    2016-04-09

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

  4. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

    KAUST Repository

    Kim, Jeong  Joo; Lorenz, Robin; Arold, Stefan T.; Reger, Albert  S.; Sankaran, Banumathi; Casteel, Darren  E.; Herberg, Friedrich  W.; Kim, Choel

    2016-01-01

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

  5. Communicating Climate Change through Place Based Engagement: Methods, Research, and Applications to Parks and Protected Area

    Science.gov (United States)

    Davis, Shawn Kyle

    2014-01-01

    This research explored the connections between place attachment and resident perceptions of tourism. Aspects of place attachment such as place identity and place dependence were tested against tourism dependence for strength of correlation and relationship to perceived impacts of tourism. Survey data were collected from residents of eight…

  6. Public transportation research study : price elasticity of rideshare : commuter fringe benefits & parking cash-out

    Science.gov (United States)

    2004-06-01

    The goal of this research project was to determine the price elasticity of rideshare with specific objectives of helping to assess what the effect on ridership would be if the effective price paid by the traveler was substantially reduced (i.e., incr...

  7. Park Districts

    Data.gov (United States)

    Vermont Center for Geographic Information — The Parks Districts layer is part of a dataset contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes feature classes for...

  8. Finding the Value of Urban Parking : An Analysis of the Impacts of Smart Parking Systems on Congestion and Land Values in Downtown Houston, Final Report

    Science.gov (United States)

    2018-01-01

    For this report, researchers have examined smart parking, which is a parking management tool that uses various technologies to aid drivers in efficiently locating and paying for available parking. Smart parking systems allow drivers to know where the...

  9. 2006 USGS/NPS/NASA Experimental Advanced Airborne Research Lidar (EAARL): Jean Lafitte National Historical Park and Preserve

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A first surface/bare earth elevation map (also known as a Digital Elevation Model, or DEM) of the Jean Lafitte National Historical Park and Preserve in Louisiana was...

  10. Heterogeneous Parking Market Subject to Parking Rationing

    Directory of Open Access Journals (Sweden)

    Saeed Asadi Bagloee

    2015-01-01

    Full Text Available Different types of drivers and parking spaces delineate a heterogeneous parking market for which the literature has yet to provide a model applicable to the real world. The main obstacle is computational complexities of considering various parking restrictions along with traffic congestion on the road network. In this study, the heterogeneity aspects are considered within a Logit parking choice model. A mathematical programming problem was introduced to explicitly consider parking capacities and parking rationing constraints. The parking rationing is defined as any arrangement to reserve parking space for some specific demand such as parking permit, private parking, VIP parking, and different parking durations. Introduction of parking rationing in the presence of other constraints is a unique factor in this study which makes the model more realistic. The algorithm was tested on a central business district case study. The results prove that the algorithm is able to converge rapidly. Among the algorithm’s output are shadow prices of the parking capacity and parking rationing constraints. The shadow prices contain important information which is key to addressing a variety of parking issues, such as the location of parking shortages, identification of fair parking charges, viability of parking permits, and the size of reserved parking.

  11. ParkIndex

    DEFF Research Database (Denmark)

    Kaczynski, Andrew T; Schipperijn, Jasper; Hipp, J Aaron

    2016-01-01

    using ArcGIS 9.3 and the Community Park Audit Tool. Four park summary variables - distance to nearest park, and the number of parks, amount of park space, and average park quality index within 1 mile were analyzed in relation to park use using logistic regression. Coefficients for significant park......, planners, and citizens to evaluate the potential for park use for a given area. Data used for developing ParkIndex were collected in 2010 in Kansas City, Missouri (KCMO). Adult study participants (n=891) reported whether they used a park within the past month, and all parks in KCMO were mapped and audited...

  12. Maryon Park

    OpenAIRE

    Bertoli, Giasco

    2018-01-01

    Tiré du site Internet de Onestar Press: "Maryon Park is the place Michelangelo Antonioni chose, in 1966, to shoot the scenes that would become cult images from his film "Blow Up", and deservedly so. The park is located in Charlton, southeast of London, a place that's hardly changed since Antonioni shot there. I first went there to shoot a series of photos on March 7 and 8, 2007. I returned again on March 7, 2014. I called the series “Maryon Park”. I used a medium format, six by seven inch col...

  13. Smart Parking Management Field Test: A Bay Area Rapid Transit (BART) District Parking Demonstration

    OpenAIRE

    Shaheen, Susan

    2005-01-01

    In almost every major city in the U.S. and internationally, parking problems are ubiquitous. It is well known that the limited availability of parking contributes to roadway congestion, air pollution, and driver frustration and that the cost of expanding traditional parking capacity is frequently prohibitive. However, less research has addressed the effect of insufficient parking at transit stations on transit use. In the San Francisco Bay Area, parking has recently been at or near capacity a...

  14. Environmental Assessment for Lease of Land for the Development of a Research Park at Los Alamos National Laboratory, Los Alamos, New Mexico - Final Document

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    1997-10-07

    As part of its initiative to fulfill its responsibilities to provide support for the incorporated County of Los Alamos (the County) as an Atomic Energy Community, while simultaneously fulfilling its obligations to enhance the self-sufficiency of the County under authority of the Atomic Energy Community Act of 1955 and the Defense Authorization Act, the U.S. Department of Energy (DOE) proposes to lease undeveloped land in Los Alamos, New Mexico, to the County for private sector use as a research park. The Proposed Action is intended to accelerate economic development activities within the County by creating regional employment opportunities through offering federal land for private sector lease and use. As a result of the proposed land lease, any government expenditures for providing infrastructure to the property would be somewhat supplemented by tenant purchase of Los Alamos National Laboratory (LANL) expertise in research and development activities. The presence of a research park within LANL boundaries is expected to allow private sector tenants of the park to be able to quickly and efficiently call upon LANL scientific expertise and facility and equipment capabilities as part of their own research operations and LANL research personnel, in turn, would be challenged in areas complementary to their federally funded research. In this way a symbiotic relationship would be enjoyed by both parties while simultaneously promoting economic development for the County through new job opportunities at the Research Park and at LANL, new indirect support opportunities for the community at large, and through payment of the basic building space leases. A ''sliding-scale'' approach (DOE 1993) is the basis for the analysis of effects in this Environmental Assessment (EA). That is, certain aspects of the Proposed Action have a greater potential for creating adverse environmental effects than others; therefore, they are discussed in greater detail in this EA

  15. Nitrogen–use efficiency in different vegetation type at Cikaniki Research Station, Halimun-Salak Mountain National Park, West Java

    Directory of Open Access Journals (Sweden)

    SUHARNO

    2007-10-01

    Full Text Available A research about nitrogen–use efficiency (NUE and trees identification was conducted at different vegetation type at Cikaniki, Halimun-Salak National Park, West Java. Plot quadrate methods (20 x 50 m was used to analyze trees vegetation and Kjeldahl methods was used to analyze leaf nitrogen. The width and length of the leaf was also measured to obtain the leaf surface area. The result showed that there are 61 individual trees which consisted of 24 species was identified. The species which have 5 highest important value are Altingia excelsa (64,657, Castanopsis javanica (39,698, Platea latifolia (27,684, Garcinia rostrata (21,151, and Schima walichii (16,049. Futhermore Eugenia lineata (13,967, Melanochyla caesa (12,241, Quercus lineata (10,766, platea excelsa (10,766 have lower important value. Other trees have important value less than 10. Morphological and nitrogen content analyze were done on 4 species : Quercus lineata, G. rostrata, A. excelsa, and E. lineata. Among them, Quercus lineata has highest specific leaf area (SLA (0,01153, followed by G. rostrata (0,00821, A. excelsa (0,00579, and E. lineata (0,00984 g/cm2. The highest number of stomata was found on A. excelsa (85,10/mm2, followed by E. lineata (74,40/mm2, Q. lineata (53,70/mm2, and G. rostrata (18,4 /mm2. The emergent species (A. excelsa and Q. lineata have higher nitrogen content than the underlayer species (G. rostrata and E. lineata. A. excelsa have highest nitrogen use efficiency (28,19% compare to E. lineata (23,81% , Q. lineata (19,09%, and G. rostrata (14,87%. Although not significant, emergen species have higher NUE than underlayer species.

  16. Uranium and the park : or how to research and assess the environmental impact of a uranium mine on an adjacent park that features on the world heritage list

    International Nuclear Information System (INIS)

    Fry, R.M.

    1988-01-01

    The activities of the Office of the Supervising Scientist, established to protect the Alligator Rivers Region in the Northern Territory of Australia from the potential effects of uranium mining operations, are described. Research which accounts for 75 per cent of the Office's biology, plant ecology, environmental chemistry, environmental radioactivity and man, environmental modelling and geomorphology

  17. Automated Car Park Management System

    Science.gov (United States)

    Fabros, J. P.; Tabañag, D.; Espra, A.; Gerasta, O. J.

    2015-06-01

    This study aims to develop a prototype for an Automated Car Park Management System that will increase the quality of service of parking lots through the integration of a smart system that assists motorist in finding vacant parking lot. The research was based on implementing an operating system and a monitoring system for parking system without the use of manpower. This will include Parking Guidance and Information System concept which will efficiently assist motorists and ensures the safety of the vehicles and the valuables inside the vehicle. For monitoring, Optical Character Recognition was employed to monitor and put into list all the cars entering the parking area. All parking events in this system are visible via MATLAB GUI which contain time-in, time-out, time consumed information and also the lot number where the car parks. To put into reality, this system has a payment method, and it comes via a coin slot operation to control the exit gate. The Automated Car Park Management System was successfully built by utilizing microcontrollers specifically one PIC18f4550 and two PIC16F84s and one PIC16F628A.

  18. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    KAUST Repository

    Wheeler, Janet I.

    2017-05-08

    The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation. Therefore, the guanylate cyclase activity of BRI1 is modulated by the kinase while cGMP, the product of the guanylate cyclase, in turn inhibits BRI1 kinase activity. Furthermore, we show using Arabidopsis root cell cultures that cGMP rapidly potentiates phosphorylation of the downstream substrate BRASSINOSTEROID SIGNALING KINASE 1 (BSK1). Taken together, our results suggest that cGMP acts as a modulator that enhances downstream signaling while dampening signal generation from the receptor. This article is protected by copyright. All rights reserved.

  19. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    KAUST Repository

    Wheeler, Janet I.; Wong, Aloysius Tze; Marondedze, Claudius; Groen, Arnoud J.; Kwezi, Lusisizwe; Freihat, Lubna; Vyas, Jignesh; Raji, Misjudeen; Irving, Helen R.; Gehring, Christoph A

    2017-01-01

    The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation. Therefore, the guanylate cyclase activity of BRI1 is modulated by the kinase while cGMP, the product of the guanylate cyclase, in turn inhibits BRI1 kinase activity. Furthermore, we show using Arabidopsis root cell cultures that cGMP rapidly potentiates phosphorylation of the downstream substrate BRASSINOSTEROID SIGNALING KINASE 1 (BSK1). Taken together, our results suggest that cGMP acts as a modulator that enhances downstream signaling while dampening signal generation from the receptor. This article is protected by copyright. All rights reserved.

  20. fantsika National Park

    African Journals Online (AJOL)

    Station, a dry deciduous forest within Ankarafantsika National. Park. We set Sherman ... dry deciduous forests compared to research in the eastern rainforests (Goodman et al. .... the ground, this rat was observed on both the ground and trees. We tentatively .... Conservation International, Washington DC. Carleton, M. D. ...

  1. Lucas Heights technology park

    International Nuclear Information System (INIS)

    1987-01-01

    The proposed Lucas Heights Technology Park will pound together the applied research programs of Government, tertiary and industry sectors, aiming to foster technology transfer particularly to the high-technology manufacturing industry. A description of the site is given along with an outline of the envisaged development, existing facilities and expertise. ills

  2. Outdoor physical activity for older people-the senior exercise park: Current research, challenges and future directions.

    Science.gov (United States)

    Levinger, Pazit; Sales, Myrla; Polman, Remco; Haines, Terry; Dow, Briony; Biddle, Stuart J H; Duque, Gustavo; Hill, Keith D

    2018-03-14

    Exercising outdoors provide beneficial effect on mental and physical health for all ages. However, few older people exercise outdoors other than walking. While outdoor gyms have become increasingly common in Australia, limited outdoor exercise equipment specifically designed for older people is available in public spaces. We have set up and evaluated a unique purpose-built outdoor exercise park for older people in the community setting and demonstrated positive physical and well-being outcomes associated with the provision of this unique exercise mode and social programme. This study is a reflective narrative describing this innovative exercise approach and reports challenges associated with establishment of the exercise park, conducting the randomised trial, strategies adopted to address these challenges and recommendations for future implementation of this approach in the community. Many challenges were encountered, including securing appropriate land to locate the exercise park, control of environmental factors for safety (non-slippery ground and equipment) as well as logistics in running the exercise programme itself. Several adjustments in the equipment were also required to ensure safe use by older people. The inclusion of outdoor equipment for older people in public spaces or urban parks is important and careful consideration needs to be taken by local/public authorities to provide access, amenities and safety for all as well as activities to suit all ages. SO WHAT?: Seniors' exercise parks can be installed in public places and may provide an enjoyable and effective approach to engage older individuals in a more active and healthier lifestyle. © 2018 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.

  3. C-di-GMP regulates antimicrobial peptide resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chua, Song Lin; Tan, Sean Yang-Yi; Rybtke, Morten Theil

    2013-01-01

    Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger which controls the life styles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes...... a planktonic lifestyle. Here, we used expression of different reporters to show that planktonic cells (PCells), biofilm cells (BCells) and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced...... the expression of proteins required for the virulence and development of antimicrobial peptide resistance in P. aeruginosa. In accordance, P. aeruginosa cells with low c-di-GMP levels were found to be more resistant to colistin than P. aeruginosa cells with high c-di-GMP levels. This contradicts the current...

  4. Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

    OpenAIRE

    Škrnjug, Ivana; Guzmán, Carlos Alberto; Ruecker, Christine

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice....

  5. Seremban Urban Park, Malaysia: a Preference Study

    OpenAIRE

    Maulan, Suhardi

    2002-01-01

    Unlike the West, where many studies have explored how peopleâ s needs are fulfilled by urban parks, Malaysia has received very little attention from researchers. One reason for this is the fact that Malaysia has only a short public park tradition. Although folk art and stories have chronicled a long history of gardens and other parks, these spaces were only accessible to royal family members and autocrats. In Malaysia, the concept of free public parks is relatively recent, having been introd...

  6. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-05-06

    Various methods and systems are provided for smart parking barriers. In one example, among others, a smart parking barrier system includes a movable parking barrier located at one end of a parking space, a barrier drive configured to control positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking space and a second position that allows access to the parking space. The parking controller can initiate movement of the movable parking barrier in response to a positive identification of an individual allowed to use the parking space. The parking controller can identify the individual through, e.g., a RFID tag, a mobile device (e.g., a remote control, smartphone, tablet, etc.), an access card, biometric information, or other appropriate identifier.

  7. Implementation of good manufacturing practices (GMP) on human blood irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: cboghi@uol.com.br; cmnapoli@ipen.br; dancarde@ig.com.br; prela@ipen.br; Zarate, Herman S. [Comission Chilena de Energia Nuclear, Santiago (Chile)]. E-mail: hzarate@cchen.cl

    2007-07-01

    The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO{sub 4}: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

  8. Implementation of good manufacturing practices (GMP) on human blood irradiation

    International Nuclear Information System (INIS)

    Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto; Zarate, Herman S.

    2007-01-01

    The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO 4 : Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

  9. cGMP signalling : different ways to create a pathway

    NARCIS (Netherlands)

    Roelofs, Jeroen; Smith, Janet L.; Haastert, Peter J.M. van

    Recently, a novel cGMP signalling cascade was uncovered in Dictyostelium, a eukaryote that diverged from the lineage leading to metazoa after plants and before yeast. In both Dictyostelium and metazoa, the ancient cAMP-binding (cNB) motif of bacterial CAP has been modified and assembled with other

  10. Good manufacturing practices (GMP utilized on human blood irradiation process

    Directory of Open Access Journals (Sweden)

    Cláudio Boghi

    2008-01-01

    Full Text Available Irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease, a rare but devastating adverse effect of leukocytes present in blood components for immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25Gy to 50Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO4: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation.

  11. Cyclic GMP alters Ca exchange in vascular smooth muscle

    International Nuclear Information System (INIS)

    Magliola, L.; Bailey, B.; Jones, A.W.

    1986-01-01

    Contraction and 42 K efflux from vascular smooth muscle stimulated either by norepinephrine (NE) or by K-depolarization is dependent on an increase in cytosolic Ca concentration. The purpose of this study was to determine if cyclic GMP (cGMP) inhibited these processes and if inhibition was secondary to the action of cGMP on Ca movements. Basal cGMP content of rat aorta was 1.2 fmol/mg wet wt. Sodium nitroprusside (NP) increased cGMP ∼2-fold at 1 nM and ∼750-fold at 1 μM with no effect on cAMP levels. A 5 min pretreatment with NP (1 μM) completely prevented tension development induced by 3 μM NE. The same concentration of NP also inhibited NE-stimulated 42 K and 45 Ca efflux > 90 and > 80%, respectively. Removal of NP in the continued presence of NE (3 μM) caused recovery of the 42 K efflux response to ∼75% of control with a half-time of ∼2.5 min. NP (1 μM) also caused a rapid relaxation of aorta contracted with 3 μM NE and a loss of the 42 K efflux response with half-times of 2-3 min. In contrast, 100 μM NP produced only a 50% inhibition of contraction induced by high K (55 mM). Also, NP (1 μM) inhibited K-stimulated 42 K efflux only ∼25%. These results demonstrate both a concentration- and a time-dependent relationship between increases in cGMP induced by NP and decreases in NE-stimulated contraction, 42 K and 45 Ca effluxes. They also indicate that the sensitivity of NE-induced contraction and 42 K efflux to NP is greater than that induced by high K. These studies suggest that cGMP modulates the control sites for Ca exchange in the plasma membrane and sarcoplasmic reticulum

  12. Reduced intracellular c-di-GMP content increases expression of quorum sensing-regulated genes in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chua, Song Lin; Liu, Yang; Li, Yingying

    2017-01-01

    Cyclic-di-GMP (c-di-GMP) is an intracellular secondary messenger which controls the biofilm life cycle in many bacterial species. High intracellular c-di-GMP content enhances biofilm formation via the reduction of motility and production of biofilm matrix, while low c-di-GMP content in biofilm...... cells leads to increased motility and biofilm dispersal. While the effect of high c-di-GMP levels on bacterial lifestyles is well studied, the physiology of cells at low c-di-GMP levels remains unclear. Here, we showed that Pseudomonas aeruginosa cells with high and low intracellular c-di-GMP contents...... possessed distinct transcriptome profiles. There were 535 genes being upregulated and 432 genes downregulated in cells with low c-di-GMP, as compared to cells with high c-di-GMP. Interestingly, both rhl and pqs quorum-sensing (QS) operons were expressed at higher levels in cells with low intracellular c-di-GMP...

  13. Design of GMP compliance radiopharmaceutical production facility in MINT

    International Nuclear Information System (INIS)

    Anwar Abd Rahman; Shaharum Ramli; M Rizal Mamat Ibrahim; Rosli Darmawan; Yusof Azuddin Ali; Jusnan Hashim

    2005-01-01

    In 1985, MINT built the only radiopharmaceutical production facility in Malaysia. The facility was designed based on IAEA (International Atomic Energy Agency) standard guidelines which provide radiation safety to the staff and the surrounding environment from radioactive contamination. Since 1999, BPFK (Biro Pengawalan Farmaseutikal Kebangsaan) has used the guidelines from Pharmaceutical Inspection Convention Scheme (PICS) to meet the requirements of the Good Manufacturing Practice (GMP) for Pharmaceutical Products. In the guidelines, the pharmaceutical production facility shall be designed based on clean room environment. In order to design a radiopharmaceutical production facility, it is important to combine the concept of radiation safety and clean room to ensure that both requirements from GMP and IAEA are met. The design requirement is necessary to set up a complete radiopharmaceutical production facility, which is safe, has high production quality and complies with the Malaysian and International standards. (Author)

  14. Changing perspectives in urban park management

    DEFF Research Database (Denmark)

    Chan, Chung-shing; Marafa, Lawal M.; Konijnendijk, Cecil Cornelis

    2015-01-01

    managers in Hong Kong have encountered different challenges over time, and the quest for changing park managerial strategies. In 2004, a set of indicators for urban park management in Hong Kong was produced as part of a Master's research. Local park managers were asked about their views on the respective......Urban parks provide numerous benefits to our society. In densely populated metropolises such as Hong Kong, urban parks are in high demand. A variety of indicators can be used as tools for improving park planning and management. Facing a dynamic society and increasing user expectations, urban park...... importance and performance (I–P) of the indicators. In 2012, a follow-up questionnaire survey was conducted with the managers to study if their views regarding these indicators and their performance had changed. Results from the 2004 and 2012 surveys revealed changing perceptions regarding both I...

  15. Identification and Characterization of c-di-GMP Metabolic Enzymes of Leptospira interrogans and c-di-GMP Fluctuations After Thermal Shift and Infection

    Directory of Open Access Journals (Sweden)

    Guohui Xiao

    2018-04-01

    Full Text Available Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species. The most common species, Leptospira interrogans, can transfer from contaminated soil or water to the human body. It is able to survive these changing environments through sensing and responding to the changes of environmental cues. Cyclic di-GMP (c-di-GMP is a special secondary messenger in bacteria, which can respond to the environment and regulate diverse bacterial behaviors. The c-di-GMP levels in bacterial cells are regulated by diguanylatecyclases (DGC and phosphodiesterases (PDE, which are responsible for synthesizing or hydrolyzing c-di-GMP, respectively. In this study, distribution and phylogenetics of c-di-GMP metabolic genes among 15 leptospiral species were systematically analyzed. Bioinformatics analysis revealed that leptospiral species contain a multitude of c-di-GMP metabolic genes. C-di-GMP metabolic genes in L. interrogans strain Lai 56601 were further analyzed and the results showed that these genes have very diverse expression patterns. Most of the putative DGCs and PDEs possess enzymatic activities, as determined by riboswitch-based dual-fluorescence reporters in vivo or HPLC in vitro. Furtherer analysis of subdomains from GGDEF-containing proteins revealed that the ability to synthesize c-di-GMP was lost when the GAF domain from LA1483 and PAS domain from LA2932 were deleted, while deletion of the REC domain from LA2528 did not affect its ability to synthesize c-di-GMP. Furthermore, high temperatures generally resulted in low c-di-GMP concentrations in L. interrogans and most of the c-di-GMP metabolic genes exhibited differential temperature regulation. Also, infection of murine J774A.1 cells resulted in reduced c-di-GMP levels, while no significant change of c-di-GMP metabolic genes on transcriptional levels were observed during the infection of J774A.1 cells. Taken together, these results provide a basic platform for future studies of c-di-GMP

  16. Specificity of Good Manufacturing Practice (GMP) for Biomedical Cell Products.

    Science.gov (United States)

    Tulina, M A; Pyatigorskaya, N V

    2018-03-01

    The article describes special aspects of Good Manufacturing Practice (GMP) for biomedical cell products (BMCP) that imply high standards of aseptics throughout the entire productio process, strict requirements to donors and to the procedure of biomaterial isolation, guaranty of tracing BMCP products, defining processing procedures which allow to identify BMCP as minimally manipulated; continuous quality control and automation of the control process at all stages of manufacturing, which will ensure product release simultaneously with completion of technological operations.

  17. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    CSIR Research Space (South Africa)

    Wheeler, J

    2017-06-01

    Full Text Available ) with the ll PickUp Injection mode using the loading pump at 15 ll min�1 flow rate for 3 min. Samples were then loaded on a RSLC, 75 lm 9 500 mm, nanoVi- per, C18, 2 lm, 100 �A column (Acclaim, PepMap) retrofitted to an EASY-spray source with a flow rate of 300... receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling Janet I. Wheeler1,2,†, Aloysius Wong3,4, Claudius Marondedze3,5, Arnoud J. Groen5, Lusisizwe Kwezi1,6, Lubna Freihat1, Jignesh Vyas1, Misjudeen A. Raji7, Helen R. Irving1...

  18. Implementation of ergonomics in the management of parking increasing the quality of living parking park in mall Robinson Denpasar city

    Science.gov (United States)

    Sutapa, I. K.; Sudiarsa, I. M.

    2018-01-01

    The problems that often arise in the area of Denpasar City mostly caused by parking problems at the centers of activities such as shopping centers. The problems that occur not only because of the large number of vehicles that parked but also the result of the condition of parking officers who have not received attention, there is no concern about the physical condition of parking attendants because doing night guard duty. To improve the quality of parking officer, ergonomic parking lot is improved through the application of appropriate technology with systemic, holistic, interdisciplinary and participatory approach. The general objective of the research is to know the implementation of ergonomics in parking management on the improvement of the quality of parking officer in Robinson shopping center. The indicator of the quality of the parking officer work is the decrease of musculoskeletal complaints, fatigue, workload, boredom and increasing work motivation. The study was conducted using the same subject design, involving 10 subjects as a simple random sample. Intervention is done by arrangement of ergonomic basement motorcycle parking. Measurements done before and after repair. Washing out (WO) for 14 days. The data obtained were analyzed descriptively, tested normality (shapirowilk) and homogeneity (Levene Test). For normal and homogeneous distribution data, different test with One Way Anova, different test between Period with Post Hoc. Normally distributed and non-homogeneous data, different test with Friedman Test, different test between periods using Wilcoxon test. Data were analyzed with significance level of 5%. The results showed that the implementation of ergonomic in the management of parking area of the court decreased musculoskeletal complaints by 15.10% (p management of the parking lot improves the quality of the parking officer work from: (1) decrease of musculoskeletal complaints, (2) decrease of melting rate, (3) decrease of parking workload

  19. Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.

    Science.gov (United States)

    Kato, Kazuki; Omura, Hiroki; Ishitani, Ryuichiro; Nureki, Osamu

    2017-06-20

    The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

  20. Experiences of using the GMP audit preparation tool in pharmaceutical contract manufacturer audits.

    Science.gov (United States)

    Linna, Anu; Korhonen, Mirka; Airaksinen, Marja; Juppo, Anne Mari

    2010-06-01

    Use of external contractors is nowadays inevitable in the pharmaceutical industry. Therefore the amount of current good manufacturing practice audits has been increasing. During the audit, a large amount of items should be covered in a limited amount of time. Consequently, pharmaceutical companies should have systematic and effective ways to manage and prepare for the audits. This study is a continuation to the earlier study, where a tool for the preparation of cGMP audit was developed and its content was validated. The objective of this study was to evaluate the usefulness of the developed tool in audit preparation and during the actual cGMP audit. Three qualitative research methods were used in this study (observation, interviews, and opinion survey). First, the validity of the information given through the tool was examined by comparing the responses to the actual conditions observed during the contract manufacturer audits (n = 15). Additionally the opinions of the contract manufacturers of the tool were gathered (n = 10) and the auditors were interviewed (n = 2). The developed tool was proven to be useful in audit preparation phase from both the auditor's and the contract manufacturers' point of view. Furthermore, using the tool can also save some time when performing the audit. The results show that using the tool can give significant support in audit preparation phase and also during the actual audit.

  1. A study on relations between the levels of GMP-140 and microangiopathy in NIDDM

    International Nuclear Information System (INIS)

    Du Tongxin; Wang Zizheng; Shi Hongzhen

    1995-01-01

    The relations between the level of GMP-140 and microangiopathy in NIDDM for earlier diagnosis or better treatment are investigated, the level of GMP-140 in both platelet and plasma was measured. The level of GMP-140 in both platelet and plasma in 104 cases with NIDDM (55 with and 49 without microagiopathy) and 38 controls were assayed by RIA and also simultaneously with direct platelet count. The level of GMP-140 in both platelet and plasma in NIDDM was remarkably higher than that in controls (P 1 = 0.69, r 2 = 0.75). No differences existed in platelet count between NIDDM and controls. The level of GMP-140 and ophthalmoscopic study had no change after decreasing the concentration of blood glucose (<7.8 mmol/L) and administrating aspirin for 6 months. Microangiopathy in NIDDM had close relation with platelet function and the level of GMP-140

  2. Correlative intravital imaging of cGMP signals and vasodilation in mice

    Directory of Open Access Journals (Sweden)

    Martin eThunemann

    2014-10-01

    Full Text Available Cyclic guanosine monophosphate (cGMP is an important signaling molecule and drug target in the cardiovascular system. It is well known that stimulation of the vascular nitric oxide (NO-cGMP pathway results in vasodilation. However, the spatiotemporal dynamics of cGMP signals themselves and the cGMP concentrations within specific cardiovascular cell types in health, disease, and during pharmacotherapy with cGMP-elevating drugs are largely unknown. To facilitate the analysis of cGMP signaling in vivo, we have generated transgenic mice that express fluorescence resonance energy transfer (FRET-based cGMP sensor proteins. Here, we describe two models of intravital FRET/cGMP imaging in the vasculature of cGMP sensor mice: (1 epifluorescence-based ratio imaging in resistance-type vessels of the cremaster muscle and (2 ratio imaging by multiphoton microscopy within the walls of subcutaneous blood vessels accessed through a dorsal skinfold chamber. Both methods allow simultaneous monitoring of NO-induced cGMP transients and vasodilation in living mice. Detailed protocols of all steps necessary to perform and evaluate intravital imaging experiments of the vasculature of anesthetized mice including surgery, imaging, and data evaluation are provided. An image segmentation approach is described to estimate FRET/cGMP changes within moving structures such as the vessel wall during vasodilation. The methods presented herein should be useful to visualize cGMP or other biochemical signals that are detectable with FRET-based biosensors, such as cyclic adenosine monophosphate or Ca2+, and to correlate them with respective vascular responses. With further refinement and combination of transgenic mouse models and intravital imaging technologies, we envision an exciting future, in which we are able to ‘watch’ biochemistry, (patho physiology, and pharmacotherapy in the context of a living mammalian organism.

  3. Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

    Science.gov (United States)

    Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.

    2013-01-01

    ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760

  4. Metal loading in Soda Butte Creek upstream of Yellowstone National Park, Montana and Wyoming; a retrospective analysis of previous research; and quantification of metal loading, August 1999

    Science.gov (United States)

    Boughton, G.K.

    2001-01-01

    Acid drainage from historic mining activities has affected the water quality and aquatic biota of Soda Butte Creek upstream of Yellowstone National Park. Numerous investigations focusing on metals contamination have been conducted in the Soda Butte Creek basin, but interpretations of how metals contamination is currently impacting Soda Butte Creek differ greatly. A retrospective analysis of previous research on metal loading in Soda Butte Creek was completed to provide summaries of studies pertinent to metal loading in Soda Butte Creek and to identify data gaps warranting further investigation. Identification and quantification of the sources of metal loading to Soda Butte Creek was recognized as a significant data gap. The McLaren Mine tailings impoundment and mill site has long been identified as a source of metals but its contribution relative to the total metal load entering Yellowstone National Park was unknown. A tracer-injection and synoptic-sampling study was designed to determine metal loads upstream of Yellowstone National Park.A tracer-injection and synoptic-sampling study was conducted on an 8,511-meter reach of Soda Butte Creek from upstream of the McLaren Mine tailings impoundment and mill site downstream to the Yellowstone National Park boundary in August 1999. Synoptic-sampling sites were selected to divide the creek into discrete segments. A lithium bromide tracer was injected continuously into Soda Butte Creek for 24.5 hours. Downstream dilution of the tracer and current-meter measurements were used to calculate the stream discharge. Stream discharge values, combined with constituent concentrations obtained by synoptic sampling, were used to quantify constituent loading in each segment of Soda Butte Creek.Loads were calculated for dissolved calcium, silica, and sulfate, as well as for dissolved and total-recoverable iron, aluminum, and manganese. Loads were not calculated for cadmium, copper, lead, and zinc because these elements were infrequently

  5. Renovated Parks Improve Physical Activity

    Centers for Disease Control (CDC) Podcasts

    We know that children who are physically active every day are less likely to develop chronic diseases as adults, including obesity. Dr. Sandy Slater, a researcher with the University of Illinois, Chicago Prevention Research Center, discusses how a park improvement project in Chicago helped engage communities to improve areas for play and activity.

  6. Capacity Analysis Of Parking Lot And Volume Of Vehicle Toward Sustainable Parking Convenience

    Science.gov (United States)

    Herdiansyah, Herdis; Sugiyanto; Guntur Octavianto, Andrew; Guntur Aritonang, Edison; Nova Imaduddin, Malya; Dedi; Rilaningrum, Magfira

    2017-10-01

    The development of human's population is having effect on the increase of facilities and transportation needs. One of the primary problems is the availability of parking area. This has occurred in Universitas Indonesia (UI), mainly in Salemba Campus. The availability of land is not as equal as the number of vehicles, which are to be parked, that is why the convenience of students, lecturers and employees at UI is unsatisfactory. The purpose of this paper is to know the level of parking convenience that is affected by the capacity of parking lots and the volume of vehicles in UI Salemba Campus. The results of this research indicate Salemba campus's parking index. The motor index is still in the category of medium (index 0.945) and the car parking index has less category with a parking index 0.485. While with the location of research object being behind the UI Salemba campus, the results obtained were both the motor and the car are still in the category of “enough” with the parking index of, that is 0.657 for the motor and 0.777 for the car. So theoretically, the parking management at Salemba Campus is in an unsustainable parking degree because, if there is no long-term solution, it will increase congestion in the surrounding area and intensify the dissatisfaction of existing parking users.

  7. c-di-GMP Regulates Various Phenotypes and Insecticidal Activity of Gram-Positive Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    Yang Fu

    2018-02-01

    Full Text Available C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis, a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs and c-di-GMP-degrading enzyme phosphodiesterases (PDEs in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera. Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium.

  8. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis.

    Science.gov (United States)

    Shaw, Catherine A; Webb, David J; Rossi, Adriano G; Megson, Ian L

    2009-05-07

    Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMvarphi), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR) spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMvarphi. Resultant MDMvarphi were treated for 24 h with DETA/NO (100 - 1000 muM) or GEA-3162 (10 - 300 muM) in the presence or absence of BAY 41-2272 (1 muM), isobutylmethylxanthine (IBMX; 1 muM), 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 muM) or 8-bromo-cGMP (1 mM). Apoptosis in MDMvarphi was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO) had no effect on cell viability, but ONOO- (GEA-3162) caused a concentration-dependent induction of apoptosis in MDMvarphi. Preconditioning of MDMvarphi with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX), or the NO-independent stimulator of soluble guanylate cyclase, BAY 41-2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner. These results

  9. Captive solvent [11C]acetate synthesis in GMP conditions

    International Nuclear Information System (INIS)

    Soloviev, Dmitri; Tamburella, Claire

    2006-01-01

    Reliable procedure for the production of 1-[ 11 C]acetate in GMP conditions was developed based on a combination of the captive-solvent Grignard reaction conducted in the sterile catheter followed by the convenient solid-phase extraction purification on a series of ion-exchange cartridges. The described procedure proved to be reliable in more than 30 patient productions. The process provides stable radiochemical yields (65% EOB) of sodium acetate (1-[ 11 C]) of the Ph.Eur. quality (radiochemical purity better than 95%) in a short time (5 min)

  10. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  11. Resource management plan for the Oak Ridge Reservation. Volume 30, Oak Ridge National Environmental Research Park natural areas and reference areas--Oak Ridge Reservation environmentally sensitive sites containing special plants, animals, and communities

    Energy Technology Data Exchange (ETDEWEB)

    Pounds, L.R. [Univ. of Tennessee, Knoxville, TN (US); Parr, P.D.; Ryon, M.G. [Oak Ridge National Lab., TN (United States)

    1993-08-01

    Areas on the Oak Ridge Reservation (ORR) that contain rare plant or animal species or are special habitats are protected through National Environmental Research Park Natural Area (NA) or Reference Area (RA) designations. The US Department of Energy`s Oak Ridge National Environmental Research Park program is responsible for identifying species of vascular plants that are endangered, threatened, or rare and, as much as possible, for conserving those areas in which such species grow. This report includes a listing of Research Park NAs and RAs with general habitat descriptions and a computer-generated map with the areas identified. These are the locations of rare plant or animal species or special habitats that are known at this time. As the Reservation continues to be surveyed, it is expected that additional sites will be designated as Research Park NAs or RAs. This document is a component of a larger effort to identify environmentally sensitive areas on ORR. This report identifies the currently known locations of rare plant species, rare animal species, and special biological communities. Floodplains, wetlands (except those in RAs or NAs), and cultural resources are not included in this report.

  12. Stimulation of cyclic GMP efflux in human melanocytes by hypergravity generated by centrifugal acceleration

    NARCIS (Netherlands)

    Ivanova, Krassimira; Zadeh, Nahid Hamidi; Block, Ingrid; Das, Pranab K.; Gerzer, Rupert

    2004-01-01

    Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic

  13. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Novak

    2014-05-01

    Full Text Available In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

  14. Understanding the link between GMP and dough: from glutenin particles in flour towards developed dough

    NARCIS (Netherlands)

    Don, C.; Lichtendonk, W.J.; Plijter, J.J.; Hamer, R.J.

    2003-01-01

    Clear correlations exist for glutenin macropolymer (GMP) quantity and rheological properties vs. wheat quality and dough rheological properties, but real insight in understanding these links is still missing. The observation that GMP consists of glutenin particles opens up new possibilities to

  15. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

    Directory of Open Access Journals (Sweden)

    Robert W Moon

    2009-09-01

    Full Text Available The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta, unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta, showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.

  16. Understanding the link between GMP and dough: From glutenin particles in flour towards developed dough

    NARCIS (Netherlands)

    Don, C.; Lichtendonk, W.J.; Plijter, J.J.; Hamer, R.J.

    2003-01-01

    Clear correlations exist for glutenin macropolymer (GMP) quantity and rheological properties vs. wheat quality and dough rheological properties, but real insight in understanding these links is still missing. The observation that GMP consists of glutenin particles opens up new possibilities to

  17. c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection

    Science.gov (United States)

    Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.

    2009-01-01

    Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167

  18. Modelling Space Appropriation in Public Parks

    NARCIS (Netherlands)

    Ostermann, F.O.; Timpf, S.; Wachowicz, Monica; Bodum, Lars

    2007-01-01

    Sustainable park management encompasses the requirement to provide equal opportunities for access and usage of the park, regardless of age, gender or nationality of the visitors. It thereby presents opportunities as well as problems for today’s heterogeneous global cities. The research presented

  19. Parks of Chapel Hill

    Data.gov (United States)

    Town of Chapel Hill, North Carolina — Hours, location, and amenity information for Chapel Hill parks as shown on the Town of Chapel Hill's website. Includes a map with points for each park location.

  20. State Park Trails

    Data.gov (United States)

    Minnesota Department of Natural Resources — This data set is a collection of ArcView shapefiles (by park) of trails within statutory boundaries of individual MN State Parks, State Recreation Areas and State...

  1. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  2. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Science.gov (United States)

    Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  3. Purification and characterization of cGMP binding protein-phosphodiesterase from rat lung

    International Nuclear Information System (INIS)

    Francis, S.H.; Walseth, T.F.; Corbin, J.D.

    1986-01-01

    The cGMP binding protein-phosphodiesterase (cG-BPP) with a phosphodiesterase specific activity of 7 μM/min/mg has been purified from rat lung by sequential chromatography on DEAE-cellulose, Blue-Sepharose, zinc chelate affinity adsorbent and HPLC-DEAE. Migration of the major band on SDS-PAGE corresponds to a MW of ∼93,000. Both cGMP phosphodiesterase activity and cGMP binding from the HPLC-DEAE profile correlate with this band. Since the authors previous work has determined the native MW to be ∼177,000, this suggests a dimeric structure comprised of two 93,000 MW subunits for the rat lung cG-BPP. At low cGMP concentrations, cGMP binding is stimulated ∼20-fold by histone and ∼5-fold by 3-isobutyl-1-methylxanthine(IBMX). The purified protein has one component of cGMP dissociation with a rate constant of 0.045/min. Photolysis of the purified protein in the presence of 32 P-cGMP labels the 93,000 MW band and this labeling is increased by IBMX, indicating that the 93,000 MW band is a subunit of the cGMP-BPP. This implies that the enzyme preparation is nearly homogeneous, a conclusion also supported by a minimum [ 3 H]-cGMP binding stoichiometry of 0.5 mol per 93,000 subunit. An additional protein band with a MW of ∼90,000 also occurs in these preparations which exhibits behavior similar to the 93,000 MW protein. N 2 -Hexyl-cGMP inhibits phosphodiesterase activity by competing with cGMP for hydrolysis at the catalytic site but not at the binding site. N 2 -Hexyl cGMP actually increases cGMP binding. This provides the first evidence that cGMP binding is increased by compounds hydrolyzed at the catalytic site. This interaction between the binding and phosphodiesterase sites could be important in the regulation of the functions of these sites in vivo

  4. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation

    OpenAIRE

    Moreira, Ricardo N.; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M.

    2017-01-01

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms...

  5. Radioimmunoassay for platelet activation specific protein GMP-140 on the platelet surface and in plasma

    International Nuclear Information System (INIS)

    Wu Guoxin; Li Jianyong; Ruan Changgeng

    1991-08-01

    Using monoclonal antibody (McAb) SZ-51 which is specific for an alpha-granule membrane protein (GMP-140) on the surface of human activated platelets, the platelet GMP-140 expression in fixed whole blood was measured by direct radioimmunoassay and GMP-140 microparticles in plasma was measured by sandwich method. The GMP-140 molecules per platelet or milliliter (mL) were calculated for the following subjects; acute myocardial infarction; cerebro thrombosis; diabetic mellitus; asthma attack; epidemic hemorrhagic fever etc.. By comparing with the concentration of thromboxane B 2 (TXB 2 ) and von Willebrand factor (vWF) in plasma, it is confirmed that the measurement of GMP-140 molecules is better than that of TXB 2 and vWF. It is a sensitive and specific method for evaluating the platelet activation degree in vivo. The establishment of this method will be useful to diagnosing the thrombotic disorders and studying the pathogenesis of some other diseases

  6. SMART VEHICLE PARKING

    OpenAIRE

    S.Bharath Ram

    2016-01-01

    The goal of this project is to count the number of empty car parking areas and to display them in a Website. This system consists of sensors attached to several parking areas. These sensors located in different parking area’s detects the presence of vehicle and sends information to Microcontroller, which calculates the number of available empty parking areas and uploads them in a website. This basically works on the principle of Internet of Things here the sensors are connected to internet.

  7. Interview with Steve Parks

    Science.gov (United States)

    Hitchcock, Jennifer

    2016-01-01

    Jennifer Hitchcock interviews community activist and director of Syracuse University's Composition and Cultural Rhetoric doctoral program, Steve Parks. They discuss Parks's working-class background, career path, influences, and activism. Parks also considers the direction of the field of composition and rhetoric and expresses optimism for the…

  8. Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles.

    Science.gov (United States)

    Shuhaibar, Leia C; Egbert, Jeremy R; Norris, Rachael P; Lampe, Paul D; Nikolaev, Viacheslav O; Thunemann, Martin; Wen, Lai; Feil, Robert; Jaffe, Laurinda A

    2015-04-28

    Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates receptors in the mural granulosa cells of the ovarian follicle. Prior work has established the central role of cyclic GMP (cGMP) from the granulosa cells in maintaining meiotic arrest, but it is not clear how binding of LH to receptors that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real-time in live follicles from mice expressing a FRET sensor, we show that diffusion of cGMP through gap junctions is responsible not only for maintaining meiotic arrest, but also for rapid transmission of the signal that reinitiates meiosis from the follicle surface to the oocyte. Before LH exposure, the cGMP concentration throughout the follicle is at a uniformly high level of ∼2-4 μM. Then, within 1 min of LH application, cGMP begins to decrease in the peripheral granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink provided by the large granulosa cell volume, such that by 20 min the cGMP concentration in the follicle is uniformly low, ∼100 nM. The decrease in cGMP in the oocyte relieves the inhibition of the meiotic cell cycle. This direct demonstration that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions could provide a general mechanism for diverse cellular processes.

  9. Evaluation of GMP-compliant culture media for in vitro expansion of human bone marrow mesenchymal stromal cells.

    Science.gov (United States)

    Wuchter, Patrick; Vetter, Marcel; Saffrich, Rainer; Diehlmann, Anke; Bieback, Karen; Ho, Anthony D; Horn, Patrick

    2016-06-01

    Mesenchymal stromal cells (MSCs) from human bone marrow serve as a resource for cell-based therapies in regenerative medicine. Clinical applications require standardized protocols according to good manufacturing practice (GMP) guidelines. Donor variability as well as the intrinsic heterogeneity of MSC populations must be taken into consideration. The composition of the culture medium is a key factor in successful MSC expansion. The aim of this study was to comparatively assess the efficiency of xeno-free human platelet lysate (HPL)-based cell expansion with two commercially available media-StemPro MSC SFM CTS (for human ex vivo tissue and cell culture processing applications) and MSCGM (non-GMP-compliant, for research only)-in an academic setting as the first optimization step toward GMP-compliant manufacturing. We report the feasibility of MSC expansion up to the yielded cell number with all three media. MSCs exhibited the typical fibroblastoid morphology, with distinct differences in cell size depending on the medium. The differentiation capacity and characteristic immunophenotype were confirmed for all MSC populations. Proliferation was highest using StemPro MSC SFM CTS, whereas HPL medium was more cost-effective and its composition could be adjusted individually according to the respective needs. In summary, we present a comprehensive evaluation of GMP-compatible culture media for MSC expansion. Both StemPro and HPL medium proved to be suitable for clinical application and allowed sufficient cell proliferation. Specific differences were observed and should be considered according to the intended use. This study provides a detailed cost analysis and tools that may be helpful for the establishment of GMP-compliant MSC expansion. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  10. Tourism package preferences of West Virginia state park visitors

    Science.gov (United States)

    William Gravley; John Dengler; Roy Ramthun; Chad Pierskalla

    2009-01-01

    This study was a preliminary examination of the activity and spending behavior of visitors to Pipestem State Park in West Virginia. This state park is being used as a case study area to determine whether a new fish stocking program accompanied by appropriate marketing activities can increase park visitation by anglers and other sports-oriented people. The research was...

  11. Family structure and park use among parents.

    Science.gov (United States)

    Fan, Yingling; French, Simone A; Das, Kirti V

    2012-11-01

    Despite the increasingly diversified family structure in the U.S., little research examines differences in park use between nontraditional and traditional family structures. This study examines family-structure differences in parent park use. It was hypothesized that working single parents and dual-worker parents have lower levels of park use than parents in two-parent, single-worker families. Data from a 2010 park-use survey in three urban neighborhoods in Minneapolis MN (N=261 parents) were analyzed in 2012. Multiple variables of park use were developed, including recalled measures over the past 3 days and over the past year. Family-structure differences in these variables were examined using multivariate regression analyses. After controlling for spatial clustering effects and confounding factors, working single parents reported 32.6% (pparents in two-parent, single-worker families. Dual-worker parents did not report fewer park visits in the past 3 days than parents in two-parent, single-worker families, yet the length of time they spent in parks during these visits was 41.5% (psingle parents and dual-worker parents is needed in descriptive and intervention research aiming to promote park use among families with children. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  12. High-Performance Liquid Chromatography (HPLC)-Based Detection and Quantitation of Cellular c-di-GMP.

    Science.gov (United States)

    Petrova, Olga E; Sauer, Karin

    2017-01-01

    The modulation of c-di-GMP levels plays a vital role in the regulation of various processes in a wide array of bacterial species. Thus, investigation of c-di-GMP regulation requires reliable methods for the assessment of c-di-GMP levels and turnover. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis has become a commonly used approach to accomplish these goals. The following describes the extraction and HPLC-based detection and quantification of c-di-GMP from Pseudomonas aeruginosa samples, a procedure that is amenable to modifications for the analysis of c-di-GMP in other bacterial species.

  13. Parking Navigation for Alleviating Congestion in Multilevel Parking Facility

    OpenAIRE

    Kenmotsu, Masahiro; Sun, Weihua; Shibata, Naoki; Yasumoto, Keiichi; Ito, Minoru

    2012-01-01

    Finding a vacant parking space in a large crowded parking facility takes long time. In this paper, we propose a navigation method that minimizes the parking time based on collected real-time positional information of cars. In the proposed method, a central server in the parking facility collects the information and estimates the occupancy of each parking zone. Then, the server broadcasts the occupancy data to the cars in the parking facility. Each car then computes a parking route with the sh...

  14. 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

    Science.gov (United States)

    Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

    2017-09-01

    In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

  15. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

    Directory of Open Access Journals (Sweden)

    Shi-qi An

    2014-10-01

    Full Text Available Bis-(3',5' cyclic di-guanylate (cyclic di-GMP is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc. This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d∼2 µM. Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  16. The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

    DEFF Research Database (Denmark)

    Groizeleau, Julie; Rybtke, Morten; Andersen, Jens Bo

    2016-01-01

    Current antibiotic treatments are insufficient in eradicating bacterial biofilms, which represent the primary cause of chronic bacterial infections. Thus, there is an urgent need for new strategies to eradicate biofilm infections. The second messenger c-di-GMP is a positive regulator of biofilm...... formation in many clinically relevant bacteria. It is hypothesized that drugs lowering the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. To identify compounds capable of lowering c-di-GMP levels in Pseudomonas aeruginosa, we screened 5000 compounds...... for their potential c-di-GMP-lowering effect using a recently developed c-di-GMP biosensor strain. Our screen identified the anti-cancerous drug doxorubicin as a potent c-di-GMP inhibitor. In addition, the drug decreased the transcription of many biofilm-related genes. However, despite its effect on the c-di-GMP...

  17. Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High Affinity Ligand for STING

    OpenAIRE

    Zhang, Xu; Shi, Heping; Wu, Jiaxi; Zhang, Xuewu; Sun, Lijun; Chen, Chuo; Chen, Zhijian J.

    2013-01-01

    The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2′-OH of GMP and 5′-phosphate of AMP, and the other between 3′-OH of AMP and 5′-phosphate of GMP. This mo...

  18. Domestic parking estimation using remotely sensed data

    Science.gov (United States)

    Ramzi, Ahmed

    2012-10-01

    Parking is an integral part of the traffic system everywhere. Provision of parking facilities to meet peak of demands parking in cities of millions is always a real challenge for traffic and transport experts. Parking demand is a function of population and car ownership which is obtained from traffic statistics. Parking supply in an area is the number of legal parking stalls available in that area. The traditional treatment of the parking studies utilizes data collected either directly from on street counting and inquiries or indirectly from local and national traffic censuses. Both methods consume time, efforts, and funds. Alternatively, it is reasonable to make use of the eventually available data based on remotely sensed data which might be flown for other purposes. The objective of this work is to develop a new approach based on utilization of integration of remotely sensed data, field measurements, censuses and traffic records of the studied area for studying domestic parking problems in residential areas especially in informal areas. Expected outcomes from the research project establish a methodology to manage the issue and to find the reasons caused the shortage in domestics and the solutions to overcome this problems.

  19. Pulsars at Parkes

    OpenAIRE

    Manchester, R. N.

    2012-01-01

    The first pulsar observations were made at Parkes on March 8, 1968, just 13 days after the publication of the discovery paper by Hewish and Bell. Since then, Parkes has become the world's most successful pulsar search machine, discovering nearly two thirds of the known pulsars, among them many highly significant objects. It has also led the world in pulsar polarisation and timing studies. In this talk I will review the highlights of pulsar work at Parkes from those 1968 observations to about ...

  20. Evidence for a Messenger Function of Cyclic GMP During Phosphodiesterase Induction in Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Pasveer, Frank J.; Meer, Rob C. van der; Heijden, Paul R. van der; Walsum, Hans van; Konijn, Theo M.

    1982-01-01

    Chemotactic stimulation of vegetative or aggregative Dictyostelium discoideum cells induced a transient elevation of cyclic GMP levels. The addition of chemoattractants to postvegetative cells by pulsing induced phosphodiesterase activity. The following lines of evidence suggest a messenger function

  1. The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation

    DEFF Research Database (Denmark)

    Kruuse, Christina; Rybalkin, S D; Khurana, T S

    2001-01-01

    The aim was to investigate the presence and activity of cGMP hydrolysing phosphodiesterases in guinea pig basilar arteries and the effect of selective and non-selective phosphodiesterase inhibitors on cerebral artery dilatation involving the nitric oxide (NO)-guanosine cyclic 3'5-monophosphate (cGMP...... a close relation to the nitric oxide-cGMP pathway. The responses to zaprinast and dipyridamole, however, were not only moderately affected, but also restored by sodium nitroprusside (0.1 microM) pretreatment. At high concentrations, the dilatory effects of zaprinast and dipyridamole were partly caused...... by cGMP-independent mechanisms. Targeting the phosphodiesterases present in cerebral arteries, with selective inhibitors or activators of phosphodiesterase, may be a possible new way of treating cerebrovascular disease....

  2. Supercritical fluid chromatography for GMP analysis in support of pharmaceutical development and manufacturing activities.

    Science.gov (United States)

    Hicks, Michael B; Regalado, Erik L; Tan, Feng; Gong, Xiaoyi; Welch, Christopher J

    2016-01-05

    Supercritical fluid chromatography (SFC) has long been a preferred method for enantiopurity analysis in support of pharmaceutical discovery and development, but implementation of the technique in regulated GMP laboratories has been somewhat slow, owing to limitations in instrument sensitivity, reproducibility, accuracy and robustness. In recent years, commercialization of next generation analytical SFC instrumentation has addressed previous shortcomings, making the technique better suited for GMP analysis. In this study we investigate the use of modern SFC for enantiopurity analysis of several pharmaceutical intermediates and compare the results with the conventional HPLC approaches historically used for analysis in a GMP setting. The findings clearly illustrate that modern SFC now exhibits improved precision, reproducibility, accuracy and robustness; also providing superior resolution and peak capacity compared to HPLC. Based on these findings, the use of modern chiral SFC is recommended for GMP studies of stereochemistry in pharmaceutical development and manufacturing. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Correspondence of perceived vs. objective proximity to parks and their relationship to park-based physical activity

    Directory of Open Access Journals (Sweden)

    Kaczynski Andrew T

    2009-08-01

    Full Text Available Abstract Background Parks are key environmental resources for encouraging population-level physical activity (PA. In measuring availability of parks, studies have employed both self-reported and objective indicators of proximity, with little correspondence observed between these two types of measures. However, little research has examined how the degree of correspondence between self-reported and objectively-measured distance to parks is influenced by individual, neighborhood, and park-related variables, or which type of measure is more strongly related to physical activity outcomes. Methods We used data from 574 respondents who reported the distance to their closest park and compared this with objective measurements of proximity to the closest park. Both indicators were dichotomized as having or not having a park within 750 m. Audits of all park features within this distance were also conducted and other personal characteristics and neighborhood context variables (safety, connectedness, aesthetics were gleaned from participants' survey responses. Participants also completed detailed seven-day PA log booklets from which measures of neighborhood-based and park-based PA were derived. Results Agreement was poor in that only 18% of respondents achieved a match between perceived and objective proximity to the closest park (kappa = 0.01. Agreement was higher among certain subgroups, especially those who reported engaging in at least some park-based PA. As well, respondents with a greater number of parks nearby, whose closest park had more features, and whose closest park contained a playground or wooded area were more likely to achieve a match. Having a ball diamond or soccer field in the closest park was negatively related to achieving a match between perceived and objective proximity. Finally, engaging in at least some park-based PA was not related to either perceived or objective proximity to a park, but was more likely when a match between and

  4. Fulfillment of GMP standard, halal standard, and applying HACCP for production process of beef floss (Case study: Ksatria enterprise)

    Science.gov (United States)

    A'diat, Arkan Addien Al; Liquiddanu, Eko; Laksono, Pringgo Widyo; Sutopo, Wahyudi; Suletra, I. Wayan

    2018-02-01

    Along with the increasing number of the modern retail business in Indonesia, give an opportunity to small and medium enterprise (SME) to sell its products through the modern retailer. There are some obstacles faced by the SMEs, one of them is about product standard. Product standard that must be owned by SMEs are GMP standard and halal standard. This research was conducted to know the fulfillment by the beef floss enterprise in jagalan in fulfilling the GMP standard and halal. In addition, Hazard Analysis and Critical Control Points (HACCP) system was applied to analyze the process. HACCP which used in this research was based on the seven principles in SNI (Indonesian National Standard) 01-4852-1998. The seven principles included hazard analysis, critical control point (CCP) determination, critical limit establishment, CCP monitor system establishment, corrective action establishment, verification, and also documentation establishment that must be applied in preparing HACCP plan. Based on this case study, it is concluded that there were 5 CCPs : the boiling process, roasting process, frying process, the beef floss draining process, and the packaging process.

  5. The role of cGMP signalling in regulating life cycle progression of Plasmodium.

    OpenAIRE

    Hopp, CS; Bowyer, PW; Baker, DA

    2012-01-01

    The 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regu...

  6. Property values, parks, and crime: a hedonic analysis in Baltimore, MD

    Science.gov (United States)

    Austin Troy; J. Morgan Grove

    2008-01-01

    While urban parks are generally considered to be a positive amenity, past research suggests that some parks are perceived as a neighborhood liability. Using hedonic analysis of property data in Baltimore, MD, we attempted to determine whether crime rate mediates how parks are valued by the housing market. Transacted price was regressed against park proximity, area-...

  7. Protecting resources: Assessing visitor harvesting of wild morel mushrooms in two national capital region parks

    Science.gov (United States)

    Elizabeth S. Barron; Marla R. Emery

    2009-01-01

    Anecdotal reports have sparked concerns that morel mushroom populations may be declining at National Park sites in the greater Washington, D.C. area. The research reported here focuses on two of these parks, Catoctin Mountain Park (CATO) and the Chesapeake and Ohio Canal National Historical Park (CHOH). Oral histories conducted with 41 harvesters in 2005 and 2007 had...

  8. NURE and the National Park Service

    International Nuclear Information System (INIS)

    Weaver, T.A.

    1979-01-01

    Under the National Resource Evaluation (NURE), massive amounts of geological, geochemical, and geophysical data, covering the entire conterminous 48 states and Alaska, are being collected and made public. In addition to NURE goals, these data are applicable to various other researches on and in the vicinity of lands controlled by the National Park Service. Airborne geophysical and hydrogeochemical survey NURE data have been made public for the majority of the area in the combined Mt. McKinley National Park and Denali National Monument. Besides indicating potential raw material deposits, these data are also useful for geologic mapping, water quality, pollution and othe geological, biological, and environmental studies in the park

  9. iPark

    DEFF Research Database (Denmark)

    Yang, Bin; Fantini, Ernesto Nicolas; Jensen, Christian S.

    2013-01-01

    where the geo-spatial aspect is not just a tag on other content, but is the primary content, e.g., a city street map with up-to-date road construction data. Along these lines, the iPark system aims to turn volumes of GPS data obtained from vehicles into information about the locations of parking spaces...

  10. THE SCHOOL PARK.

    Science.gov (United States)

    FISCHER, JOHN H.

    TO ASSIST IN DESEGREGATION, VARIOUS MODELS FOR THE SCHOOL PARK ARE PROPOSED--(1) ASSEMBLING ALL STUDENTS AND SCHOOLS OF A SMALL OR MEDIUM-SIZED COMMUNITY ON A SINGLE CAMPUS, (2) SERVING ONE SECTION OF A LARGE CITY, (3) CENTERING ALL SCHOOL FACILITIES FOR A SINGLE LEVEL OF EDUCATION ON A SINGLE SITE, AND (4) ESTABLISHING RINGS OF SCHOOL PARKS ABOUT…

  11. Parking Space Verification

    DEFF Research Database (Denmark)

    Høg Peter Jensen, Troels; Thomsen Schmidt, Helge; Dyremose Bodin, Niels

    2018-01-01

    system, based on a Convolutional Neural Network, that is capable of determining if a parking space is occupied or not. A benchmark database consisting of images captured from different parking areas, under different weather and illumination conditions, has been used to train and test the system...

  12. Bicycle Parking and Locking

    DEFF Research Database (Denmark)

    Larsen, Jonas

    2017-01-01

    . This article contributes with new insights into parking and locking - ‘moorings’ - to cycling literature. It presents an ethnography of ‘design moorings’ and practices associated with parking and locking bikes. The main case study is the very pro-cycling city of Copenhagen. Yet to explore what is unique about...

  13. The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP

    DEFF Research Database (Denmark)

    Almblad, Henrik; Harrison, Joe J; Rybtke, Morten

    2015-01-01

    infection give rise to rugose small colony variants (RSCVs), which are hyper-biofilm-forming mutants that commonly possess mutations that increase production of the biofilm-promoting secondary messenger cyclic di-GMP (c-di-GMP). We show that RSCVs display a decreased production of acute virulence factors...... as a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (c......AMP), which is decreased in response to a high level of c-di-GMP. Mutations that cause reversion of the RSCV phenotype concomitantly reactivate Vfr-cAMP signaling. Attempts to uncover the mechanism underlying the observed c-di-GMP-mediated lowering of cAMP content provided evidence that it is not caused...

  14. cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

    Science.gov (United States)

    Bork, Nadja I.; Nikolaev, Viacheslav O.

    2018-01-01

    The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

  15. Parks and their users

    Directory of Open Access Journals (Sweden)

    Barbara Goličnik

    2008-01-01

    Full Text Available This paper is concerned with urban parks and their use(rs. It focuses on usage-spatial relationships from two different angles. Firstly, it discusses the actual uses mapped in places, using repeated observation on different days, times and weather conditions. Secondly, it addresses designers’ views and beliefs about usage and design of urban parks. However, the paper shows that designers’ beliefs and awareness about uses in places, in some aspects, differ from actual use. It stresses the use of empirical knowledge about usage-spatial relationships, which can be gained by using observation and behavioural mapping, in decision-making processes for parks design.

  16. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    Science.gov (United States)

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Regulation of the Na(+)-K(+)-2Cl(-) cotransporter by cGMP/cGMP-dependent protein kinase I after furosemide administration.

    Science.gov (United States)

    Limmer, Franziska; Schinner, Elisabeth; Castrop, Hayo; Vitzthum, Helga; Hofmann, Franz; Schlossmann, Jens

    2015-10-01

    Sodium chloride reabsorption in the thick ascending limb of the loop of Henle is mediated by the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). The loop diuretic furosemide is a potent inhibitor of NKCC2. However, less is known about the mechanism regulating the electrolyte transporter. Considering the well-established effects of nitric oxide on NKCC2 activity, cGMP is likely involved in this regulation. cGMP-dependent protein kinase I (cGKI; PKGI) is a cGMP target protein that phosphorylates different substrates after activation through cGMP. We investigated the potential correlation between the cGMP/cGKI pathway and NKCC2 regulation. We treated wild-type (wt) and cGKIα-rescue mice with furosemide. cGKIα-rescue mice expressed cGKIα only under the control of the smooth muscle-specific transgelin (SM22) promoter in a cGKI deficient background. Furosemide treatment increased the urine excretion of sodium and chloride in cGKIα-rescue mice compared to that in wt mice. We analyzed the phosphorylation of NKCC2 by western blotting and immunostaining using the phosphospecific antibody R5. The administration of furosemide significantly increased the phosphorylated NKCC2 signal in wt but not in cGKIα-rescue mice. NKCC2 activation led to its phosphorylation and membrane translocation. To examine whether cGKI was involved in this process, we analyzed vasodilator-stimulated phosphoprotein, which is phosphorylated by cGKI. Furosemide injection resulted in increased vasodilator-stimulated phosphoprotein phosphorylation in wt mice. We hypothesize that furosemide administration activated cGKI, leading to NKCC2 phosphorylation and membrane translocation. This cGKI-mediated pathway could be a mechanism to compensate for the inhibitory effect of furosemide on NKCC2. © 2015 FEBS.

  18. Spatial analysis related to the location characteristics of park supply. Case study: Music Park and Pendawa Park, Bandung City, Indonesia

    Science.gov (United States)

    Malik, A.; Akbar, R.; Maryati, S.; Natalivan, P.

    2018-05-01

    Public space plays a role in defining the character of a city and is a valuable asset for a city and one of the indicators in assessing whether a city is considered successful or not. In the context of urban sociology, high-quality public spaces with well-maintained environments can improve the quality of the heterogeneous life of urban social communities by creating economic, social, or environmental value-added. Urban societies tend to be heterogeneous, individualistic, and characterized by high competition that often causes conflicts. Another reason for conflicts is the relatively high social differentiation because of the level of religious differences, customs, languages, and sociocultural aspects brought by immigrants from various regions. In the context of space, the city is a system that does not stand alone because internally the city is a unified system of functional activities in it. Meanwhile, externally, the city is influenced by its surrounding environment. As part of the public space, park has an important role in the environmental, aesthetic, recreational, psychological, social, educational, and economic aspects of the city. Public space can be understood as open spaces in urban areas, where everyone regardless their interests and backgrounds can be intersectional and have social contact and serve as an “urban regenerator” including educational functions through innovation and technological intervention. Moreover, park can also absorb carbon dioxide emissions, produce oxygen, improve air and water quality, regulate the microclimate, reduce noise, protect soil and water, and maintain biodiversity. However, many things cause the function of parks to decrease. One reason relates to the distribution of parks related to the characteristics of their location. Research has not seen many studies on the characteristics of locations in the planning of public space. The provision of public space should consider these location characteristics. This study

  19. Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

    Science.gov (United States)

    Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

    2018-03-01

    Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Versailles' park taasavatud

    Index Scriptorium Estoniae

    2000-01-01

    Osa Pariisi lähedase Versailles' lossi pargist avati jaanuari alguses uuesti publikule. 17.-18. sajandi prantsuse stiilis park suleti avalikkusele detsembris 1999 pärast parki laastanud hiigeltormi, mis murdis ligemale 10000 puud.

  1. New Mexico Parks

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This dataset provides an initial version of the locations of parks in New Mexico, in point form, with limited attributes, compiled using available data from a...

  2. New Mexico State Parks

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This dataset provides an initial version of the generalized physical boundaries of New Mexico State Parks, in polygonal form with limited attributes, compiled using...

  3. Allegheny County Parks Outlines

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Shows the size and shape of the nine Allegheny County parks. If viewing this description on the Western Pennsylvania Regional Data Center’s open data portal...

  4. State Park Statutory Boundaries

    Data.gov (United States)

    Minnesota Department of Natural Resources — Legislative statutory boundaries for sixty six state parks, six state recreation areas, and eight state waysides. These data are derived principally from DNR's...

  5. Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation.

    Science.gov (United States)

    Lutton, Rebecca E M; Moore, Jessica; Larrañeta, Eneko; Ligett, Stephen; Woolfson, A David; Donnelly, Ryan F

    2015-08-01

    With interest in microneedles as a novel drug transdermal delivery system increasing rapidly since the late 1990s (Margetts and Sawyer Contin Educ Anaesthesia Crit Care Pain. 7(5):171-76, 2007), a diverse range of microneedle systems have been fabricated with varying designs and dimensions. However, there are still very few commercially available microneedle products. One major issue regarding microneedle manufacture on an industrial scale is the lack of specific quality standards for this novel dosage form in the context of Good Manufacturing Practice (GMP). A range of mechanical characterisation tests and microneedle insertion analysis techniques are used by researchers working on microneedle systems to assess the safety and performance profiles of their various designs. The lack of standardised tests and equipment used to demonstrate microneedle mechanical properties and insertion capability makes it difficult to directly compare the in use performance of candidate systems. This review highlights the mechanical tests and insertion analytical techniques used by various groups to characterise microneedles. This in turn exposes the urgent need for consistency across the range of microneedle systems in order to promote innovation and the successful commercialisation of microneedle products.

  6. Auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism

    Science.gov (United States)

    Cai, Weiming; Hu, Liwei; Hu, Xiangyang; Cui, Dayong; Cai, Weiming

    Gravitropism is the asymmetric growth or curvature of plant organs in response to gravistimulation. There is a complex signal transduction cascade which involved in the differential growth of plants in response to changes in the gravity vector. The role of auxin in gravitropism has been demonstrated by many experiments, but little is known regarding the molecular details of such effects. In our studies before, mediation of the gravitropic bending of soybean roots and rice leaf sheath bases by nitric oxide, cGMP and gibberellins, are induced by auxin. The asymmetrical distribution of nitric oxide, cGMP and gibberellins resulted from the asymmetrical synthesis of them in bending sites. In soybean roots, inhibitions of NO and cGMP synthesis reduced differential NO and cGMP accumulation respectively, which both of these effects can lead to the reduction of gravitropic bending. Gibberellin-induced OsXET, OsEXPA4 and OsRWC3 were also found involved in the gravitropic bending. These data indicated that auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism. More experiments need to prove the more detailed mechanism of them.

  7. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

    International Nuclear Information System (INIS)

    Carvalho-Costa, P.G.; Branco, L.G.S.; Leite-Panissi, C.R.A.

    2014-01-01

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress

  8. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho-Costa, P.G. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Branco, L.G.S. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Leite-Panissi, C.R.A. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-09-19

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.

  9. SCIENCE AND TECHNOLOGY PARKS

    Directory of Open Access Journals (Sweden)

    Miroslav Milutinović

    2014-04-01

    Full Text Available The establishment of science and technology parks is necessarily accompanied by the establishment of a base of professional staff as the foundation of the park and the base of the potential management that will manage the park and the professional staff. Science and Technology Park is a broader term used to describe a variety of attempts directed at enhancing the entrepreneurship development by means of establishing knowledge – based, small and medium-sized enterprises. The enterprise at the top of the technology pyramid receives support in the form of capital, administration, space and access to new information technologies. The overall objective of the development of industrial enterprises in the technology park is the introduction of economically profitable production with the efficient usage of nonrenewable resources and the application of the highest environmental standards. Achieving the primary developmental objective of the Technology Park includes: creating a favorable business atmosphere in the local community, attractive to both foreign and domestic investors – providing support to the establishment of small and medium-sized enterprises using different models of joint ventures and direct foreign investment.

  10. Factors That Influence Park Use and Physical Activity in Predominantly Hispanic and Low-Income Neighborhoods.

    Science.gov (United States)

    Dolash, Karry; He, Meizi; Yin, Zenong; Sosa, Erica T

    2015-04-01

    Park features' association with physical activity among predominantly Hispanic communities is not extensively researched. The purpose of this study was to assess factors associated with park use and physical activity among park users in predominantly Hispanic neighborhoods. Data were collected across 6 parks and included park environmental assessments to evaluate park features, physical activity observations to estimate physical activity energy expenditure as kcal/kg/ minute per person, and park user interviews to assess motivators for park use. Quantitative data analysis included independent t tests and ANOVA. Thematic analysis of park user interviews was conducted collectively and by parks. Parks that were renovated had higher physical activity energy expenditure scores (mean = .086 ± .027) than nonrenovated parks (mean = .077 ± .028; t = -3.804; P motivation to be physically active, using the play spaces in the park, parks as the main place for physical activity, and social support for using parks. Renovations to park amenities, such as increasing basketball courts and trail availability, could potentially increase physical activity among low-socioeconomic-status populations.

  11. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S

    2004-01-01

    Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from...... migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce...

  12. Receptors and cGMP signalling mechanism for E. coli enterotoxin in opossum kidney

    International Nuclear Information System (INIS)

    Forte, L.R.; Krause, W.J.; Freeman, R.H.

    1988-01-01

    Receptors for the heat-stable enterotoxin produced by Escherichia coli were found in the kidney and intestine of the North American opossum and in cultured renal cell lines. The enterotoxin markedly increased guanosine 3',5'-cyclic monophosphate (cGMP) production in slices of kidney cortex and medulla, in suspensions of intestinal mucosa, and in the opossum kidney (OK) and rat kangaroo kidney (PtK-2) cell lines. In contrast, atrial natriuretic factor elicited much smaller increases in cGMP levels of kidney, intestine, or cultured kidney cell lines. The enterotoxin receptors in OK cells had a molecular mass of approximately 120 kDa when measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of receptors crosslinked with 125 I-enterotoxin. The occurrence of receptors for the E. coli peptide in OK implies that these receptors may be involved in the regulation of renal tubular function in the opossum. E. coli enterotoxin caused a much larger increase in urine cGMP excretion than did atrial natriuretic factor when these peptides were injected intravenously into opossums. However, atrial natriuretic factor elicited a marked diuresis, natriuresis, and increased urinary excretion of calcium, phosphate, potassium, and magnesium. In contrast, the enterotoxin did not acutely influence OK fluid and electrolyte excretion. Thus the substantial increase in cGMP synthesis produced by the bacterial peptide in OK cortex and medulla in vitro and the increased renal excretion of cGMP in vivo were not associated with changes in electrolyte or water excretion. Whether cGMP represents a second messenger molecule in the kidney is an interesting question that was raised but not answered in this series of experiments

  13. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

    Science.gov (United States)

    Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

    2002-11-01

    Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

  14. The role of cGMP signalling in regulating life cycle progression of Plasmodium.

    Science.gov (United States)

    Hopp, Christine S; Bowyer, Paul W; Baker, David A

    2012-08-01

    The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  15. cGMP-dependent protein kinase I, the circadian clock, sleep and learning

    OpenAIRE

    Feil, Robert; Hölter, Sabine M; Weindl, Karin; Wurst, Wolfgang; Langmesser, Sonja; Gerling, Andrea; Feil, Susanne; Albrecht, Urs

    2009-01-01

    The second messenger cGMP controls cardiovascular and gastrointestinal homeostasis in mammals. However, its physiological relevance in the nervous system is poorly understood.1 Now, we have reported that the cGMP-dependent protein kinase type I (PRKG1) is implicated in the regulation of the timing and quality of sleep and wakefulness.2 Prkg1 mutant mice showed altered distribution of sleep and wakefulness as well as reduction in rapid-eye-movement sleep (REMS) duration and in non-REMS consoli...

  16. PDE1A inhibition elicits cGMP-dependent relaxation of rat mesenteric arteries

    DEFF Research Database (Denmark)

    Khammy, Makhala Michell; Dalsgaard, Thomas; Larsen, Peter Hjorringgaard

    2017-01-01

    (EC50 = 32 nM). Inhibition of NOS with L-NAME, soluble GC with ODQ, or PKG with Rp-8-Br-PET-cGMP all attenuated PDE1 inhibition-induced relaxation, whereas PKA inhibition with H89 had no effect. CONCLUSION AND IMPLICATIONS: Pde1a was the dominant PDE1 isoform present in VSMC and relaxation mediated...... by PDE1A-inhibition was predominantly driven by enhanced cGMP signalling. These results imply that isoform-selective PDE1 inhibitors are powerful investigative tools allowing examination of physiological and pathological roles of PDE1 isoforms....

  17. Biophysical Techniques for Detection of cAMP and cGMP in Living Cells

    Directory of Open Access Journals (Sweden)

    Viacheslav O. Nikolaev

    2013-04-01

    Full Text Available Cyclic nucleotides cAMP and cGMP are ubiquitous second messengers which regulate myriads of functions in virtually all eukaryotic cells. Their intracellular effects are often mediated via discrete subcellular signaling microdomains. In this review, we will discuss state-of-the-art techniques to measure cAMP and cGMP in biological samples with a particular focus on live cell imaging approaches, which allow their detection with high temporal and spatial resolution in living cells and tissues. Finally, we will describe how these techniques can be applied to the analysis of second messenger dynamics in subcellular signaling microdomains.

  18. A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Aalkjær, Christian; Nilsson, Holger

    2004-01-01

    We have previously demonstrated the presence of a cyclic GMP (cGMP)-dependent calcium-activated inward current in vascular smooth-muscle cells, and suggested this to be of importance in synchronizing smooth-muscle contraction. Here we demonstrate the characteristics of this current. Using......M) in the pipette solution. The current was found to be a calcium-activated chloride current with an absolute requirement for cyclic GMP (EC50 6.4 microM). The current could be activated by the constitutively active subunit of PKG. Current activation was blocked by the protein kinase G antagonist Rp-8-Br-PET-cGMP...... differed from those of the calcium-activated chloride current in pulmonary myocytes, which was cGMP-independent, exhibited a high sensitivity to inhibition by niflumic acid, was unaffected by zinc ions, and showed outward current rectification as has previously been reported for this current. Under...

  19. Scour Forecasting for Offshore Wind Parks

    DEFF Research Database (Denmark)

    Hartvig, Peres Akrawi

    In an effort to minimize the costs of offshore wind parks, the present research deals with optimizing a certain aspect of the support structure, namely the approach to scour. Scour is the phenomenon of seabed changes in the vicinity of the support structure that arises when the support structure......, scour forecasts facilitate the comparison between a scour design based on either deployment of scour-protection or enhanced structural design. The broad goal is to develop a method that produces accurate scour forecasts for offshore wind parks. The present research investigates more specifically which...

  20. The Open Space Sculptures Used in the Gençlik Park towards Visual Perception of Park Users

    Directory of Open Access Journals (Sweden)

    Ahmet Polat

    2012-11-01

    Full Text Available Urban parks are the most important areas that allow recreational activities in our towns. Increasing the visual quality of urban parks provides positive impacts on urban quality. Besides the artistic and technical features of open space sculptures which are used for urban park designs are the visual perceptions and preferences of park users are also important. In the context of this study, six sculptures in Gençlik Park which is in the boundaries Ankara have been considered. The aim of the study, to measure the visual quality of the sculptures in the urban parks through park users and to reveal the relationship between visual landscape indicators (of being interesting, coherence, complexity, meaningfulness, and mystery and the visual quality. For this purpose, the six pieces in Ankara Youth Park of sculpture were evaluated the scope of research. According to the results of the study; it was realized that park users like sculptures visually. A statistically significant relationship was found between the visual quality of the sculptures and some landscape indicators (to be interesting, mystery and harmony. In addition to these, some suggestions were made regarding the use of sculptures in urban parks.

  1. Dependence of Parking Pricing on Land Use and Time of Day

    Directory of Open Access Journals (Sweden)

    Fang Zong

    2015-07-01

    Full Text Available A key strategy of sustainable transportation, parking pricing can directly contribute to decreased greenhouse gas emissions and air pollution. This paper describes an optimal structure of parking rates in terms of parking locations and time of day. A two-level parking model based on game theory is established using parking survey data collected in Beijing in 2014. The model was estimated based on Stackelberg game and the Nash equilibrium. Using the two-level parking model, the optimal structure of parking rates for inside/outside business zones and during peak/off-peak hours was calculated. In addition, the relationship between the government (which represents the public benefit and car users, as well as the relationships among car users in the parking system were investigated. The results indicate that equilibrium among all of the agents in the parking system can be obtained using the proposed parking rate structure. The findings provide a better understanding of parking behavior, and the two-level parking model presented in the paper can be used to determine the optimal parking rate to balance the temporal and spatial distribution of parking demand in urban areas. This research helps reduce car use and the parking-related cruising time and thus contributes to the reduction of carbon emissions and air pollution.

  2. Geology of National Parks

    Science.gov (United States)

    Stoffer, Philip W.

    2008-01-01

    This is a set of two sheets of 3D images showing geologic features of many National Parks. Red-and-cyan viewing glasses are need to see the three-dimensional effect. A search on the World Wide Web will yield many sites about anaglyphs and where to get 3D glasses. Red-blue glasses will do but red-cyan glasses are a little better. This publication features a photo quiz game: Name that park! where you can explore, interpret, and identify selected park landscapes. Can you identify landscape features in the images? Can you explain processes that may have helped form the landscape features? You can get the answers online.

  3. A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24).

    Science.gov (United States)

    Ruth, P; Kamm, S; Nau, U; Pfeifer, A; Hofmann, F

    1996-01-01

    Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein PKI are very potent inhibitors of cAMP-dependent protein kinase, but are extremely weak inhibitors of cGMP-dependent protein kinase. In this study, we tried to confer PKI sensitivity to cGMP kinase by site-directed mutagenesis. The molecular requirements for high affinity inhibition by PKI were deduced from the crystal structure of the cAMP kinase/PKI complex. A prominent site of interaction are residues Tyr235 and Phe239 in the catalytic subunit, which from a sandwich-like structure with Phe10 of the PKI(5-24) peptide. To increase the sensitivity for PKI, the cGMP kinase codons at the corresponding sites, Ser555 and Ser559, were changed to Tyr and Phe. The mutant cGMP kinase was stimulated half maximally by cGMP at 3-fold higher concentrations (240 nM) than the wild type (77 nM). Wild type and mutant cGMP kinase did not differ significantly in their Km and Vmax for three different substrate peptides. The PKI(5-24) peptide inhibited phosphotransferase activity of the mutant cGMP kinase with higher potency than that of wild type, with Ki values of 42 +/- .3 microM and 160 +/- .7 microM, respectively. The increased affinity of the mutant cGMP kinase was specific for the PKI(5-24) peptide. Mutation of the essential Phe10 in the PKI(5-24) sequence to an Ala yielded a peptide that inhibited mutant and wild type cGMP kinase with similar potency, with Ki values of 160 +/- 11 and 169 +/- 27 microM, respectively. These results suggest that the mutations Ser555Tyr and Ser559Phe are required, but not sufficient, for high affinity inhibition of cGMP kinase by PKI.

  4. GMP scale-up and banking of pluripotent stem cells for cellular therapy applications.

    Science.gov (United States)

    Ausubel, Lara J; Lopez, Patricia M; Couture, Larry A

    2011-01-01

    Human pluripotent stem cells (PSCs), which include human embryonic stem cells (ESCs) as well as induced pluripotent stem cells (iPSCs), represent an important source of cellular therapies in regenerative medicine and the study of early human development. As such, it is becoming increasingly important to develop methods for the large-scale banking of human PSC lines. There are several well-established methods for the propagation of human PSCs. The key to development of a good manufacturing practice (GMP) bank is to determine a manufacturing method that is amenable to large-scale production using materials that are fully documented. We have developed several banks of hESCs using animal feeder cells, animal-based matrices, or animal-free matrices. Protocols for growing hESCs on mouse embryonic fibroblasts (MEFs) are well established and are very helpful for producing research grade banks of cells. As most human ESCs cultured by research laboratories have been exposed to xenogeneic reagents, it is not imperative that all materials used in the production of a master cell bank be animal-free in origin. Nevertheless, as the field develops, it will no doubt become increasingly important to produce a bank of cells for clinical use without xenogeneic reagents, particularly nonhuman feeder cells which might harbor viruses with potential risk to human health or cell product integrity. Thus, even for cell lines previously exposed to xenogeneic reagents, it is important to minimize any subsequent exposure of the cell lines to additional adventitious agents. We have specifically described procedures for the growth of hESCs on Matrigel, an animal-matrix, and CELLstart, an animal-free matrix, and these can be used to produce hESCs as part of a clinical manufacturing process.

  5. Examining winter visitor use in Yellowstone National Park

    Science.gov (United States)

    Mae A. Davenport; Wayne A. Freimund; William T. Borrie; Robert E. Manning; William A. Valliere; Benjamin Wang

    2000-01-01

    This research was designed to assist the managers of Yellowstone National Park (YNP) in their decision making about winter visitation. The focus of this report is on winter use patterns and winter visitor preferences. It is the author’s hope that this information will benefit both the quality of winter experiences and the stewardship of the park resources. This report...

  6. Tourists' motivations for visiting Kakum National Park, Ghana

    African Journals Online (AJOL)

    Department of Hospitality &Tourism Management, University of Cape Coast, Ghana E. ... The concept of matching in tourism requires that recreational opportunities offered in parks .... of tourism research, as it provides a useful strategy for identifying different groupings ..... of satisfaction: The case of Pirongia Forest Park.

  7. Physical activity in Georgia state parks: A pilot study

    Science.gov (United States)

    Lincoln R. Larson; Jason W. Whiting; Gary T. Green

    2012-01-01

    This pilot study assessed the role of Georgia State Parks in the promotion of physical activity among different racial/ethnic and age groups. Data were collected at three state parks in north Georgia during the summer of 2009 using two research methods: behavior observations (N=2281) and intercept surveys (N=473).

  8. "South Park" vormistab roppused muusikalivormi

    Index Scriptorium Estoniae

    2000-01-01

    Animafilm "South Park : suurem, pikem ja lõikamata" ("South Park . Bigger, Longer & Uncut") : Stsenaristid Trey Parker, Matt Stone ja Pam Brady : režissöör Trey Parker : Ameerika Ühendriigid 1999

  9. Allegheny County Park Rangers Outreach

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Launched in June 2015, the Allegheny County Park Rangers program reached over 48,000 people in its first year. Park Rangers interact with residents of all ages and...

  10. Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

    Science.gov (United States)

    Kandasamy, S. B.; Williaes, B. A.

    1983-01-01

    It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

  11. A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function

    Directory of Open Access Journals (Sweden)

    Aileen Balkow

    2015-08-01

    Conclusions: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes.

  12. cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants.

    Directory of Open Access Journals (Sweden)

    Lorena Olivares-González

    Full Text Available Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2 for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions.

  13. HMW-GS affect the properties of glutenin particles in GMP and thus flour quality

    NARCIS (Netherlands)

    Don, C.; Mann, G.; Bekes, F.; Hamer, R.J.

    2006-01-01

    Using a unique set of deletion lines, (Olympic×Gabo, varying in high molecular weight glutenin subunit (HMW-GS) composition, but with the same genetic background) it was shown that the presence of glutenin particles in glutenin macropolymer (GMP) is directly related to the presence of certain

  14. The added value of Good Manufacturing Practices (GMP) in the production of radiopharmaceuticals

    NARCIS (Netherlands)

    Gerrits, Edwin; Woerdenbag, Herman; Luurtsema, Geert; de Hooge, Marjolijn; Boersma, Hendrikus

    2017-01-01

    Manufacturers of medicinal products including radiopharmaceuticals have to follow regulations from their governmental organizations as well as professional societies to ensure built-in quality combined with patient safety issues. This chapter is a concise review of Good Manufacturing Practices (GMP)

  15. GMP and AMP as methyl radical traps in the reaction with pentaamminemethylcobalt(III)

    DEFF Research Database (Denmark)

    Kofod, Pauli

    2004-01-01

    as the PBN/13??H3 adduct (PBN = phenyl-N-tert-butylnitrone). When the purine nucleotide was used in large excess, the efficiency of the trapping by the C8 atom was determined by integration of the 13C NMR signals to be 20-25% for GMP and 15-20% for AMP, respectively, at 37??C. ?? 2004 Elsevier Inc. All...

  16. Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts

    Directory of Open Access Journals (Sweden)

    Marija Marinko

    2015-06-01

    Full Text Available As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV and human internal mammary artery (HIMA, this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC, ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (KV channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.

  17. Structural and functional characteristics of cGMP-dependent methionine oxidation in Arabidopsis thaliana proteins

    KAUST Repository

    Marondedze, Claudius; Turek, Ilona; Parrott, Brian Jonathan; Thomas, Ludivine; Jankovic, Boris R.; Lilley, Kathryn S; Gehring, Christoph A

    2013-01-01

    molecule, the cell-permeant second messenger analogue, 8-bromo-3,5-cyclic guanosine monophosphate (8-Br-cGMP), results in a time-dependent increase in the content of oxidised methionine residues. Interestingly, the group of proteins affected by c

  18. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    International Nuclear Information System (INIS)

    Leitman, D.C.

    1988-01-01

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using 125 I-ANP 8-33 . Specific 125 I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP

  19. Design And Implementation Of Smart Parking System Using Peripheral Interface Controllers And Infrared Sensors

    Directory of Open Access Journals (Sweden)

    May Thaw Htet

    2015-08-01

    Full Text Available With the increase in world population and vehicle production parking spaces and facilities are required. As the numbers of vehicles on the road are increasing day by day parking problems which are increasing at an alarming rate in every major city cause drivers frustration traffic congestion and time wasting especially during the peak business hours. Lot of researches was being done all over the world to implement better parking management system which reduces parking problems. SPARK Smart Parking is parking garage system that utilizes various technologies to implement best parking system. The proposed system is aimed to inform drivers about the number of available parking spaces without any parking difficulties. This system is designed for two- level parking slots with twenty six parking spaces and one aisle on each floor. The condition of parking slots is detected by IR sensors and is reported periodically to main controller via floor controllers and self controllers. PIC 18F4550 is chosen to be used as controllers because it is suitable for the proposed system. Each floor contains LCD display which will show available parking spaces of that floor. LCD display at the entrance gate will show overall available parking slots of two floors. In this paper a new parking system called Smart Parking system is proposed to help drivers getting the real-time parking information and to find vacant spaces in a car park in a shorter time. This kind of system minimizes not only traffic congestion problems but also staff requirements to control the traffic in the car park.

  20. Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.

    Directory of Open Access Journals (Sweden)

    Ming He

    2011-06-01

    Full Text Available Cyclic dimeric GMP (c-di-GMP is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1, which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol. To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.

  1. fantsika National Park

    African Journals Online (AJOL)

    We often observed domestic mammals such as cattle, cats and dogs in the forest at Ampijoroa. Although the primary forest in Ampijoroa is managed by Madagascar National Parks, local people leave these domestic animals in the forest. Introduced animals may be a threat to endemic animals. Cattle can be transmitters of ...

  2. Pro-survival Effects of 17β-Estradiol on Osteocytes Are Mediated by Nitric Oxide/cGMP via Differential Actions of cGMP-dependent Protein Kinases I and II*

    Science.gov (United States)

    Marathe, Nisha; Rangaswami, Hema; Zhuang, Shunhui; Boss, Gerry R.; Pilz, Renate B.

    2012-01-01

    Estrogens promote bone health in part by increasing osteocyte survival, an effect that requires activation of the protein kinases Akt and ERK1/2, but the molecular mechanisms involved are only partly understood. Because estrogens increase nitric oxide (NO) synthesis and NO can have anti-apoptotic effects, we examined the role of NO/cGMP signaling in estrogen regulation of osteocyte survival. Etoposide-induced death of MLO-Y4 osteocyte-like cells, assessed by trypan blue staining, caspase-3 cleavage, and TUNEL assays, was completely prevented when cells were pre-treated with 17β-estradiol. This protective effect was mimicked when cells were pre-treated with a membrane-permeable cGMP analog and blocked by pharmacological inhibitors of NO synthase, soluble guanylate cyclase, or cGMP-dependent protein kinases (PKGs), supporting a requirement for NO/cGMP/PKG signaling downstream of 17β-estradiol. siRNA-mediated knockdown and viral reconstitution of individual PKG isoforms demonstrated that the anti-apoptotic effects of estradiol and cGMP were mediated by PKG Iα and PKG II. Akt and ERK1/2 activation by 17β-estradiol required PKG II, and cGMP mimicked the effects of estradiol on Akt and ERK, including induction of ERK nuclear translocation. cGMP induced BAD phosphorylation on several sites, and experiments with phosphorylation-deficient BAD mutants demonstrated that the anti-apoptotic effects of cGMP and 17β-estradiol required BAD phosphorylation on Ser136 and Ser155; these sites were targeted by Akt and PKG I, respectively, and regulate BAD interaction with Bcl-2. In conclusion, 17β-estradiol protects osteocytes against apoptosis by activating the NO/cGMP/PKG cascade; PKG II is required for estradiol-induced activation of ERK and Akt, and PKG Iα contributes to pro-survival signaling by directly phosphorylating BAD. PMID:22117068

  3. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

    Directory of Open Access Journals (Sweden)

    Alexandre Dumoulin

    2018-04-01

    Full Text Available Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα. In the absence of any one of these components, neurons in dorsal root ganglia (DRG and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

  4. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.

    Science.gov (United States)

    Dumoulin, Alexandre; Ter-Avetisyan, Gohar; Schmidt, Hannes; Rathjen, Fritz G

    2018-04-24

    Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

  5. The participation of elevated levels of cyclic GMP in the recovery from radiation-induced mitotic delay

    International Nuclear Information System (INIS)

    Daniel, J.W.; Oleinick, N.L.

    1984-01-01

    The levels of cyclic AMP and cyclic GMP have been measured in Physarum plasmodia before and after treatment with gamma-radiation, 2 mM caffeine, or combinations of the two agents compared to the length of the radiation-induced mitotic delay. Caffeine alone produces a rapid transient elevation of cyclic AMP and a slower delayed elevation of cyclic GMP. Irradiation elicits an immediate transient increase in cyclic AMP and a later cyclic GMP increase which accompanies or precedes the delayed mitosis. A composite pattern is produced by combinations of radiation and caffeine, a distinctive feature of which is an elevated level of cyclic GMP near the time of the radiation-delayed and caffeine-promoted mitosis. With pretreatment by caffeine, the least radiation-induced mitotic delay occurs when plasmodia are irradiated during the caffeine-elicited increase in cyclic GMP. The plasmodium becomes refractory to the reduction of mitotic delay by caffeine at approximately the time it becomes refractory to the further elevation of cyclic GMP by caffeine. The data support a role for cyclic AMP in the onset of and for cyclic GMP in the recovery from mitotic delay induced by ionizing radiation. (author)

  6. The crucial role of cyclic GMP in the eclosion hormone mediated signal transduction in the silkworm metamorphoses.

    Science.gov (United States)

    Shibanaka, Y; Hayashi, H; Okada, N; Fujita, N

    1991-10-31

    The signal transduction of the peptide, eclosion hormone, in the silkworm Bombyx mori appears to be mediated via the second messenger cyclic GMP throughout their life cycle. Injection of 8-bromo-cGMP induced the ecdysis behavior in pharate adults with similar latency to eclosion hormone-induced ecdysis; the moulting occurred 50-70 min after the injection. The potency of 8Br-cGMP was 10(2) fold higher than that of cGMP and the efficacy was increased by the co-injection of the phosphodiesterase inhibitor IBMX. On the other hand, in the silkworm pupal ecdysis the eclosion hormone and also 8Br-cGMP induced the moulting behavior in a dose-dependent manner. The adult development of the ability to respond to 8Br-cGMP took place concomitantly with the response to the eclosion hormone. Both the developmental time courses were shifted by a shift of light and dark cycles. Accordingly, the sensitivities to the peptide and cyclic nucleotide developed correspondently under the light and dark circadian rhythm. Thus throughout the silkworm life cycle, eclosion hormone is effective to trigger the ecdysis behavior and cGMP plays a crucial role as the second messenger in the eclosion hormone-mediated signal transduction.

  7. Single amino acids in the carboxyl terminal domain of aquaporin-1 contribute to cGMP-dependent ion channel activation

    Directory of Open Access Journals (Sweden)

    Yool Andrea J

    2003-10-01

    Full Text Available Abstract Background Aquaporin-1 (AQP1 functions as an osmotic water channel and a gated cation channel. Activation of the AQP1 ion conductance by intracellular cGMP was hypothesized to involve the carboxyl (C- terminus, based on amino acid sequence alignments with cyclic-nucleotide-gated channels and cGMP-selective phosphodiesterases. Results Voltage clamp analyses of human AQP1 channels expressed in Xenopus oocytes demonstrated that the nitric oxide donor, sodium nitroprusside (SNP; 3–14 mM activated the ionic conductance response in a dose-dependent manner. Block of soluble guanylate cyclase prevented the response. Enzyme immunoassays confirmed a linear dose-dependent relationship between SNP and the resulting intracellular cGMP levels (up to 1700 fmol cGMP /oocyte at 14 mM SNP. Results here are the first to show that the efficacy of ion channel activation is decreased by mutations of AQP1 at conserved residues in the C-terminal domain (aspartate D237 and lysine K243. Conclusions These data support the idea that the limited amino acid sequence similarities found between three diverse classes of cGMP-binding proteins are significant to the function of AQP1 as a cGMP-gated ion channel, and provide direct evidence for the involvement of the AQP1 C-terminal domain in cGMP-mediated ion channel activation.

  8. case study of ramat park benin city

    African Journals Online (AJOL)

    user

    SETTLEMENT: CASE STUDY OF RAMAT PARK BENIN CITY. E. S. Okonofua1, R. ... region on a daily basis. The movement of ... with major road networks [2]. In order to ease ... led to series of research and development of traffic noise models.

  9. Cohesive Properties of the Caulobacter crescentus Holdfast Adhesin Are Regulated by a Novel c-di-GMP Effector Protein

    Directory of Open Access Journals (Sweden)

    Kathrin S. Sprecher

    2017-03-01

    Full Text Available When encountering surfaces, many bacteria produce adhesins to facilitate their initial attachment and to irreversibly glue themselves to the solid substrate. A central molecule regulating the processes of this motile-sessile transition is the second messenger c-di-GMP, which stimulates the production of a variety of exopolysaccharide adhesins in different bacterial model organisms. In Caulobacter crescentus, c-di-GMP regulates the synthesis of the polar holdfast adhesin during the cell cycle, yet the molecular and cellular details of this control are currently unknown. Here we identify HfsK, a member of a versatile N-acetyltransferase family, as a novel c-di-GMP effector involved in holdfast biogenesis. Cells lacking HfsK form highly malleable holdfast structures with reduced adhesive strength that cannot support surface colonization. We present indirect evidence that HfsK modifies the polysaccharide component of holdfast to buttress its cohesive properties. HfsK is a soluble protein but associates with the cell membrane during most of the cell cycle. Coincident with peak c-di-GMP levels during the C. crescentus cell cycle, HfsK relocalizes to the cytosol in a c-di-GMP-dependent manner. Our results indicate that this c-di-GMP-mediated dynamic positioning controls HfsK activity, leading to its inactivation at high c-di-GMP levels. A short C-terminal extension is essential for the membrane association, c-di-GMP binding, and activity of HfsK. We propose a model in which c-di-GMP binding leads to the dispersal and inactivation of HfsK as part of holdfast biogenesis progression.

  10. Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

    Science.gov (United States)

    Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

    2017-07-19

    High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory. SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

  11. Are TODs Over-Parked?

    OpenAIRE

    Cervero, Robert; Adkins, Arlie; Sullivan, Cathleen

    2009-01-01

    This study empirically investigates the proposition that TOD, and specifically housing near suburban rail stops, is “over-parked†in the U.S. This is done by comparing parking generation rates for 31 housing complexes near rail stops in the San Francisco Bay Area and Portland, Oregon with on-site parking supplies and with ITE parking generation rates. Factors that explain parking demand for transit-oriented housing are also investigated, both statistically and through case analyses. The re...

  12. Antidepressant-like properties of sildenafil in a genetic rat model of depression: Role of cholinergic cGMP-interactions

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Brink, Christiaan; Brand, Linda

    2008-01-01

    Background: The N-methyl-D-aspartate (NMDA)/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway has been implicated in the neurobiology of depression. Recently we suggested a possible complex interaction between the cholinergic and NO-cGMP pathways in the antidepressant-like response....... Conclusions: Using a genetic animal model of depression, we have confirmed the antidepressant-like property of sildenafil following “unmasking” by concomitant block of muscarinic receptors. These findings hint at a novel interaction between the cGMP and cholinergic systems in depression, and suggest...

  13. High-throughput screening for compounds that modulate the cellular c-di-GMP level in bacteria

    DEFF Research Database (Denmark)

    Groizeleau, Julie; Andersen, Jens Bo; Givskov, Michael

    2017-01-01

    . The secondary messenger c-di-GMP is a positive regulator of biofilm formation in many clinically relevant bacteria, and it is assumed that drugs that lower the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. We describe a protocol for high......-throughput screening of chemical libraries for compounds that lower the c-di-GMP level in bacteria, and potentially can serve as lead compounds in the development of novel biofilm dismantling drugs....

  14. The Tourism Experience Offered by Religious Theme Parks: Taman Tamadun Islam (TTI) in Malaysia

    OpenAIRE

    Moal - Ulvoas, Gaëlle M

    2016-01-01

    Theme parks are major drivers of tourism development and experience is a central concept in tourism research. This study investigates the experience potential associated with religious theme parks which offer a combination of religious and secular activities. The experiences of visitors to Taman Tamadun Islam (TTI), a Muslim theme park based in Malaysia, are identified through the analysis of visitors’ feedback on Tripadvisor.

  15. From landscapes to soundscapes: understanding and managing natural quiet in the national parks

    Science.gov (United States)

    Robert Manning; William Valliere; Jeffery Hallo; Peter Newman; Ericka Pilcher; Michael Savidge; Dan Dugan

    2007-01-01

    Research at Muir Woods Natural Monument suggests that soundscapes are an important component of parks and outdoor recreation, that human-caused noise is a potentially important indicator of quality for park soundscapes, and that visitors have normative standards for the maximum acceptable level of human-caused noise in parks. Formulating indicators and standards of...

  16. Social science in the national park service: an evolving mission and program

    Science.gov (United States)

    Richard H. Briceland

    1992-01-01

    In 1988 the director of the National Park Service requested that a social science program be established. Since that time a number of new research initiatives have been developed to address this need. This paper describes seven major steps taken thus far to meet social science needs of park superintendents, program managers, and park planners. Specific examples are...

  17. Modelling parking behaviour considering heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    San Martin, G.A.; Ibeas Portilla, A.; Alonso Oreña, B.; Olio, L. del

    2016-07-01

    Most of motorized trips in cities of middle and small size are made in public transport and mainly in private vehicle, this has caused a saturation in parking systems of the cities, causing important problems to society, one of the most important problems is high occupancy of public space by parking systems. Thus, is required the estimation of models that reproduce users’ behaviour when they are choosing for parking in cities, to carry out transport policies to improve transport efficiency and parking systems in the cities. The aim of this paper is the specification and estimation of models that simulate users’ behaviour when they are choosing among alternatives of parking that there are in the city: free on street parking, paid on street parking, paid on underground parking and Park and Ride (now there isn´t). For this purpose, is proposed a multinomial logit model that consider systematic and random variations in tastes. Data of users’ behaviour from the different alternatives of parking have been obtained with a stated preference surveys campaign which have been done in May 2015 in the principal parking zones of the city of Santander. In this paper, we provide a number of improvements to previously developed methodologies because of we consider much more realism to create the scenarios stated preference survey, obtaining better adjustments. (Author)

  18. Design And Implementation Of Smart Parking System Using Peripheral Interface Controllers And Infrared Sensors

    OpenAIRE

    May Thaw Htet; Chaw Myat New; Hla Myo Tun

    2015-01-01

    With the increase in world population and vehicle production parking spaces and facilities are required. As the numbers of vehicles on the road are increasing day by day parking problems which are increasing at an alarming rate in every major city cause drivers frustration traffic congestion and time wasting especially during the peak business hours. Lot of researches was being done all over the world to implement better parking management system which reduces parking problems. SPARK Smart Pa...

  19. The regulatory role of the NO/cGMP signal transduction cascade during larval attachment and metamorphosis of the barnacle Balanus (=Amphibalanus) amphitrite

    KAUST Repository

    Zhang, Y.

    2012-08-01

    The barnacle Balanus amphitrite is among the most dominant fouling species on intertidal rocky shores in tropical and subtropical areas and is thus a target organism in antifouling research. After being released from adults, the swimming nauplius undertakes six molting cycles and then transforms into a cyprid. Using paired antennules, a competent cyprid actively explores and selects a suitable substratum for attachment and metamorphosis (collectively known as settlement). This selection process involves the reception of exogenous signals and subsequent endogenous signal transduction. To investigate the involvement of nitric oxide (NO) and cyclic GMP (cGMP) during larval settlement of B. amphitrite, we examined the effects of an NO donor and an NO scavenger, two nitric oxide synthase (NOS) inhibitors and a soluble guanylyl cyclase (sGC) inhibitor on settling cyprids. We found that the NO donor sodium nitroprusside (SNP) inhibited larval settlement in a dose-dependent manner. In contrast, both the NO scavenger carboxy-PTIO and the NOS inhibitors aminoguanidine hemisulfate (AGH) and S-methylisothiourea sulfate (SMIS) significantly accelerated larval settlement. Suppression of the downstream guanylyl cyclase (GC) activity using a GC-selective inhibitor ODQ could also significantly accelerate larval settlement. Interestingly, the settlement inhibition effects of SNP could be attenuated by ODQ at all concentrations tested. In the developmental expression profiling of NOS and sGC, the lowest expression of both genes was detected in the cyprid stage, a crucial stage for the larval decision to attach and metamorphose. In summary, we concluded that NO regulates larval settlement via mediating downstream cGMP signaling.

  20. The regulatory role of the NO/cGMP signal transduction cascade during larval attachment and metamorphosis of the barnacle Balanus (=Amphibalanus) amphitrite

    KAUST Repository

    Zhang, Y.; He, L.-S.; Zhang, G.; Xu, Y.; Lee, O.-O.; Matsumura, K.; Qian, P.-Y.

    2012-01-01

    The barnacle Balanus amphitrite is among the most dominant fouling species on intertidal rocky shores in tropical and subtropical areas and is thus a target organism in antifouling research. After being released from adults, the swimming nauplius undertakes six molting cycles and then transforms into a cyprid. Using paired antennules, a competent cyprid actively explores and selects a suitable substratum for attachment and metamorphosis (collectively known as settlement). This selection process involves the reception of exogenous signals and subsequent endogenous signal transduction. To investigate the involvement of nitric oxide (NO) and cyclic GMP (cGMP) during larval settlement of B. amphitrite, we examined the effects of an NO donor and an NO scavenger, two nitric oxide synthase (NOS) inhibitors and a soluble guanylyl cyclase (sGC) inhibitor on settling cyprids. We found that the NO donor sodium nitroprusside (SNP) inhibited larval settlement in a dose-dependent manner. In contrast, both the NO scavenger carboxy-PTIO and the NOS inhibitors aminoguanidine hemisulfate (AGH) and S-methylisothiourea sulfate (SMIS) significantly accelerated larval settlement. Suppression of the downstream guanylyl cyclase (GC) activity using a GC-selective inhibitor ODQ could also significantly accelerate larval settlement. Interestingly, the settlement inhibition effects of SNP could be attenuated by ODQ at all concentrations tested. In the developmental expression profiling of NOS and sGC, the lowest expression of both genes was detected in the cyprid stage, a crucial stage for the larval decision to attach and metamorphose. In summary, we concluded that NO regulates larval settlement via mediating downstream cGMP signaling.

  1. Mount Rainier National Park

    Science.gov (United States)

    Hoffman, Robert; Woodward, Andrea; Haggerty, Patricia K.; Jenkins, Kurt J.; Griffin, Paul C.; Adams, Michael J.; Hagar, Joan; Cummings, Tonnie; Duriscoe, Dan; Kopper, Karen; Riedel, Jon; Samora, Barbara; Marin, Lelaina; Mauger, Guillaume S.; Bumbaco, Karen; Littell, Jeremy S.

    2014-01-01

    Natural Resource Condition Assessments (NRCAs) evaluate current conditions for a subset of natural resources and resource indicators in national parks. NRCAs also report on trends in resource condition (when possible), identify critical data gaps, and characterize a general level of confidence for study findings. The resources and indicators emphasized in a given project depend on the park’s resource setting, status of resource stewardship planning and science in identifying high-priority indicators, and availability of data and expertise to assess current conditions for a variety of potential study resources and indicators. Although the primary objective of NRCAs is to report on current conditions relative to logical forms of reference conditions and values, NRCAs also report on trends, when appropriate (i.e., when the underlying data and methods support such reporting), as well as influences on resource conditions. These influences may include past activities or conditions that provide a helpful context for understanding current conditions and present-day threats and stressors that are best interpreted at park, watershed, or landscape scales (though NRCAs do not report on condition status for land areas and natural resources beyond park boundaries). Intensive cause-andeffect analyses of threats and stressors, and development of detailed treatment options, are outside the scope of NRCAs. It is also important to note that NRCAs do not address resources that lack sufficient data for assessment. For Mount Rainier National Park, this includes most invertebrate species and many other animal species that are subject to significant stressors from climate change and other anthropogenic sources such as air pollutants and recreational use. In addition, we did not include an analysis of the physical hydrology associated with streams (such as riverine landforms, erosion and aggradation which is significant in MORA streams), due to a loss of staff expertise from the USGS

  2. Urban Park: an Integral Part of Welfare for Citizens — A Case Study of Shangzhi and Qinbin Parks in Harbin Metropolis, China

    DEFF Research Database (Denmark)

    Yang, Binzhang; Zhao, Chunli

    2008-01-01

    Abstract: As a key part of the urban green spaces, urban park plays important role in city citizens’ life. The significances of park treating as a green lung in urban area demonstrate its unique contribution to people’s life not only in physical and tangible aspects such as environment, ecology a...... management and service have been contributed by this study. Specifically, the awareness for treating the urban park as an integral part of citizens’ welfare should be arose and educated in entire society. Key words: Harbin Metropolis, urban park, activity, public life...... in their daily life, second one tries to learn what problems they meet during their visit and using, third one focuses on what problems and challenges of urban park need to be resolved by administrative officers and park managers. The research samples, Shanzhi Park and Qingbin Park, were selected in two...... spaces in both numbers and sizes as the form of park. It also showed some problems and challenges faced in park design and management had to be enhanced. Finally, some suggestions aimed to improve the situation of urban spaces included constructing new urban parks and promoting the quality of park...

  3. Similar expression patterns of bestrophin-4 and cGMP dependent Ca2+-activated chloride channel activity in the vasculature

    DEFF Research Database (Denmark)

    Bouzinova, Elena V.; Larsen, Per; Matchkov, Vladimir

    2008-01-01

    (abstract by Matchkov et. al) that siRNA mediated downregulation of bestrophin-4 is associated with the disappearance of a recently demonstrated2 cGMP-dependent Ca2+-activated Cl- current in vascular smooth muscle cells (SMCs). Here we study the distribution of bestrophin-4-and cGMP dependent Cl- channel...... expressed epitope) Western blot detected a ~65 kDa band in cell lysates from rat mesenteric small arteries and aorta, which was not seen in pulmonary arteries and when preincubated with the immunizing peptide. The distribution of bestrophin-4 mRNA and protein has a pattern similar to the cGMP-dependent Cl......- current in SMCs of different origins. Immunohistochemistry identified bestrophin-4 both in endothelial and SMCs of the vascular tree in the brain, heart, kidney and mesentery, but not in the lungs. We suggest that bestrophin-4 is important for the cGMP dependent, Ca2+ activated Cl- conductance in many...

  4. [Aging reduces contents of endogenous CO, cAMP and cGMP in rat penile tissues].

    Science.gov (United States)

    Qin, Wen-Bo; Wang, Shu-Qiu; Li, Ming; Kang, Yu-Ming; Gui, Shi-Liang; Chi, Bao-Jin

    2009-02-01

    To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.

  5. Mathematical model of parking space unit for triangular parking area

    Science.gov (United States)

    Syahrini, Intan; Sundari, Teti; Iskandar, Taufiq; Halfiani, Vera; Munzir, Said; Ramli, Marwan

    2018-01-01

    Parking space unit (PSU) is an effective measure for the area size of a vehicle, including the free space and the width of the door opening of the vehicle (car). This article discusses a mathematical model for parking space of vehicles in triangular shape area. An optimization model for triangular parking lot is developed. Integer Linear Programming (ILP) method is used to determine the maximum number of the PSU. The triangular parking lot is in isosceles and equilateral triangles shape and implements four possible rows and five possible angles for each field. The vehicles which are considered are cars and motorcycles. The results show that the isosceles triangular parking area has 218 units of optimal PSU, which are 84 units of PSU for cars and 134 units of PSU for motorcycles. Equilateral triangular parking area has 688 units of optimal PSU, which are 175 units of PSU for cars and 513 units of PSU for motorcycles.

  6. The Barriers to Millennials Visiting Rouge Urban National Park

    Directory of Open Access Journals (Sweden)

    Gillian Ramsay

    2017-05-01

    Full Text Available Intensified urbanization has led to more populated cities and less green spaces which are vital to community health, wellbeing and conservation. Rouge Urban National Park in Toronto has recently become Canada’s first urban national park. This park is ideally suited to the millennial population, offering outdoor recreation and green space that this growing market generally desires. There is, however, a lack of research into visitor motivations to urban parks and more specifically millennial motivations. Findings from 280 quantitative surveys found three main barriers to visiting the Urban National Park: distance, transportation, and awareness. The lack of public transport combined with road congestion and fewer millennials owning cars creates issues with accessibility. Poor branding and knowledge through electronic media creates low awareness within a demographic market so tied to technology.

  7. Park Planning for Ageing Adults Using Grounded Theory Methodology

    Directory of Open Access Journals (Sweden)

    Bernie Dahl

    2004-06-01

    Full Text Available The importance of understanding park planning issues and implementing planning strategies for ageing adults was the driving force for this study. Literature reviews have identified a variety of scholarly work from fields such as gerontology, psychology, sociology and economics, all of which provide valuable information regarding the special needs of ageing adults. Very few researchers, however, have investigated the leisure behaviours of older adults in outdoor recreation (Croskeys, Tinsley and Tinsley, 2002 and the use of grounded theory methodology has essentially been unexplored in this area. Ageing adults are projected to live more than 20 percent of their life in retirement (MRP, 1998, cited in Croskeys, Tinsley and Tinsley, 2002, allowing for an increased amount of discretionary time. This offers opportunities for ageing adults to participate in outdoor recreational activities and will undoubtedly increase their leisure time. However, with limited research in recreational needs and inclusion for older adults, it is difficult for park planners and administrators to meet the growing needs of this population. Therefore, this research is necessary in order to determine whether ageing adults are being accounted for in park and outdoor recreational planning. The objective of this study was to use grounded theory research methodology to identify and examine ageing adult needs in relation to outdoor leisure activities in a regional park setting. Ten Midwestern regional park visitors (aged 65-75 years old and four park employees were interviewed. Our research attempts to fill in the gaps between the perceptions of ageing park users and those of park planners, using a methodology that relies primarily on direct contact with park visitors.

  8. Prospects and sustainability of ecotourism in Finima Nature Park ...

    African Journals Online (AJOL)

    Journal of Research in Forestry, Wildlife and Environment ... Similarly, the occupation (χ2=151.880) and level of education (χ2=51.952) of tourists had ... Keyword: Finima Nature Park, Biodiversity conservation, Bonny Island, Ecotourism, ...

  9. A Survey of Intelligent Car Parking System

    OpenAIRE

    Faheem; S.A. Mahmud; G.M. Khan; M. Rahman; H. Zafar

    2013-01-01

    The industrialization of the world, increase in population, slow paced city development and mismanagement of the available parking space has resulted in parking related problems. There is a dire need for a secure, intelligent, efficient and reliable system which can be used for searching the unoccupied parking facility, guidance towards the parking facility, negotiation of the parking fee, along with the proper management of the parking facility. Intelligent Parking Service is a part of Intel...

  10. Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets.

    Science.gov (United States)

    Makhoul, Stephanie; Walter, Elena; Pagel, Oliver; Walter, Ulrich; Sickmann, Albert; Gambaryan, Stepan; Smolenski, Albert; Zahedi, René P; Jurk, Kerstin

    2018-06-01

    Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome. We also showed that the sGC stimulator riociguat is in vitro a highly specific inhibitor, via cGMP, of various functions of human platelets. Here, we review the regulatory role of the cGMP/protein kinase G (PKG) system in human platelet function, and our current approaches to establish and analyze the phosphoproteome after selective stimulation of the sGC/cGMP pathway by NO donors and riociguat. Present data indicate an extensive and diverse NO/riociguat/cGMP phosphoproteome, which has to be compared with the cAMP phosphoproteome. In particular, sGC/cGMP-regulated phosphorylation of many membrane proteins, G-proteins and their regulators, signaling molecules, protein kinases, and proteins involved in Ca 2+ regulation, suggests that the sGC/cGMP system targets multiple signaling networks rather than a limited number of PKG substrate proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. 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.

  12. parkITsmart: minimization of cruising for parking

    OpenAIRE

    Tsiaras, Christos; Hobi, Livio; Hofstetter, Fabian; Liniger, Samuel; Stiller, Burkhard

    2015-01-01

    Finding a parking space in urban areas is a daily challenge for drivers across the world, due to the increasing amount of vehicles and the limited amount of parking spaces. Drivers who are looking for a parking space in peak hours are often forced to drive around city blocks until they spot a free parking space. This process is termed in literature “cruising for parking” and is proven to (a) cost a lot of time and gas for drivers, (b) generate unnecessary traffic load, and (c) affect the envi...

  13. An observational study of defensible space in the neighbourhood park

    Science.gov (United States)

    Marzukhi, M. A.; Afiq, M. A.; Zaki, S. Ahmad; Ling, O. H. L.

    2018-02-01

    The planning of neighborhood park is important to provide space for interaction, leisure, and recreation among residents in any neighbourhood area. However, on an almost daily basis, newspapers report inappropriate incidents such as snatch theft, robbery and street attack that occurred in the neighborhood park. These cases reflect the significance of physical planning and design of neighborhood park that directly affect the safety and comfort of the users. Thus, this study attempts to engage with the defensible space concept in ensuring the security elements be applied in the planning of the recreational area. This study adopts a qualitative method form of research that is retrofitted to an observational study. The observational study is significant for revealing the condition of a neighbourhood park in the ‘real-world,’ in which direct observation is conducted on Taman Tasik Puchong Perdana. The observer focused on four elements or variables of defensible space concept including the provision of facilities in the neighborhood park, territoriality, surveillance, image and milieu. The findings revealed that the planning of Taman Tasik Puchong Perdana does not deliberate the defensible space elements, which may contribute to the crime activities in the park. In these circumstances, the planning of neighbourhood park needs to include proposals for the implementation of defensible space in response to the challenges underpinned by crime problems. Besides, the awareness among the residents needs to be emphasized with the support from local authorities and other organizations to manage and sustain the safety environment in the neighborhood park.

  14. Improvements in the automated radioimmunoassay for cAMP or cGMP

    International Nuclear Information System (INIS)

    Brooker, G.

    1988-01-01

    The work others in developing antibodies and the original radioimmunoassay for cyclic nucleotides provides the basis for these sensitive assays. The acetylation radioimmunoassay for cyclic nucleotides has enabled the measurement of cyclic AMP and cyclic GMP in very small biological samples. This is because accurate determinations can be made in samples containing less than 1 fmol of cyclic AMP or cyclic GMP. The Gamma-Flo automated radioimmunoassay system has been adapted to these assays such that cyclic nucleotides can be automatically measured at a rate of about 60 samples/hr. The Gamma-Flo instrument provides high-precision assays and eliminates human intervention in all steps of the radioimmunoassay. The automated assay has been in continuous operation in our laboratory over the last 10 years and this chapter summarizes the methodology and delineates improvements which have occurred over that time frame. Details for the preparation of the radioligands apply also to the manual acetylated radioimmunoassay for cyclic nucleotides

  15. IL-4 induces cAMP and cGMP in human monocytic cells

    Directory of Open Access Journals (Sweden)

    B. Dugas

    1995-01-01

    Full Text Available Human monocytes, preincubated with IFN-γ respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 – 3 min and cAMP (20 – 25 min in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors. These results suggest that: (1 IL-4 may stimulate different NOS isoforms in resting and IFN-γ activated monocytes, and (2 cAMP accumulation may be partially dependent on the NO pathway. By RT-PCR, a type III constitutive NOS mRNA was detected in U937 monocytic cells. IL-4 also increased the [Ca2+]i in these cells. Different NOS may thus be expressed in monocytic cells depending on their differentiation and the signals they receive.

  16. cGMP signaling as a target for the prevention and treatment of breast cancer.

    Science.gov (United States)

    Windham, Perrin F; Tinsley, Heather N

    2015-04-01

    One in eight women in the United States will be diagnosed with invasive breast cancer in her lifetime. Advances in therapeutic strategies, diagnosis, and improved awareness have resulted in a significant reduction in breast cancer related mortality. However, there is a continued need for more effective and less toxic drugs for both the prevention and the treatment of breast cancer in order to see a continued decline in the morbidity and mortality associated with this disease. Recent studies suggest that the cGMP signaling pathway may be aberrantly regulated in breast cancer. As such, this pathway may serve as a source of novel targets for future breast cancer drug discovery efforts. This review provides an overview of cGMP signaling in normal physiology and in breast cancer as well as current strategies being investigated for targeting this pathway in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Enhancing Visitor Experiences Using Thematic Interpretation in Park Guiding Service in Sarawak National Parks

    Directory of Open Access Journals (Sweden)

    Amin Victor Luna

    2014-01-01

    Full Text Available Enhancing visitor experiences is arguably the primary and most important goal for interpretation by many protected area managers and tourism business. However, little research has been conducted in Sarawak, Malaysia to directly quantify the effects of thematic interpretation has on tourist experiences. Drawing on the TORE-model of interpretation and through the inception of Park Guiding Training and Licensing System in Sarawak since 2007, this quantitative study examines the effectiveness of thematic interpretive guided tours delivered by park guides at Bako National Park, Sarawak, with the assumption that it will further enhance visitor experiences. A descriptive analysis and Pearson's product-moment correlation analysis of sub-indicators of the global evaluation of interpretation of site, and sub-indicators of elaboration surveyed from visitors of purposively sampled park guides revealed a strong measurement and correlation coefficients of visitors’ overall quality of thematic intepretive guided tours effecting visitor satisfaction and experiences. These findings provide empirical evidence that good thematic interpretive guided tour makes a positive impacts on visitor experiences, thus making training of tourism businesses' employees as park guides as a good investment. The suggestions for further research in influencing visitor attitude and shaping visitor behaviour are offered.

  18. VICTORIA PARK: A DEMOCTRATIC PUBLIC OPEN SPACE FOR INDONESIA DOMESTIC HELPERS (TKW

    Directory of Open Access Journals (Sweden)

    Parmonangan Manurung

    2016-01-01

    Full Text Available Victoria Park is the largest city park in Hong Kong. This city park is not only known in Hong Kong, but also very well known in Indonesia as a gathering place for Indonesia domestic helpers (TKW in Hong Kong. This research tried to find out some determinant factors that have been affected the public open spac of Victoria Park to be a gathering place for thousands of TKW in Sunday and holidays as their day off. In order to get the results of research, some methodological research had been conducted such as: observation (survey, mapping, interviews and literature studies. The results showed that Victoria Park has a number of factors capable of meeting the needs of domestic help-ers in Hong Kong, these factors consist of internal factors and external factors. Internally, the character and functions held Victoria Park became a very influential factor, while externally, the accessibility and support functions around Victoria Park also has a considerable influence.

  19. C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth

    DEFF Research Database (Denmark)

    Chua, Song Lin; Sivakumar, Krishnakumar; Rybtke, Morten Levin

    2015-01-01

    tellurite (TeO3(2-)) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO3(2-) further...... increased P. aeruginosa biofilm formation and resistance to TeO3(2-). P. aeruginosa ΔsadCΔsiaD and PAO1/p(lac)-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO3(2-) exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed...... to TeO3(2-). Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth....

  20. Cyclic GMP-AMP Synthase is an Innate Immune Sensor of HIV and Other Retroviruses

    OpenAIRE

    Gao, Daxing; Wu, Jiaxi; Wu, You-Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J.

    2013-01-01

    Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic-GMP-AMP (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type-I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse transcribed HIV DNA triggers the...

  1. The plant natriuretic peptide receptor is a guanylyl cyclase and enables cGMP-dependent signaling

    KAUST Repository

    Turek, Ilona

    2016-03-05

    The functional homologues of vertebrate natriuretic peptides (NPs), the plant natriuretic peptides (PNPs), are a novel class of peptidic hormones that signal via guanosine 3′,5′-cyclic monophosphate (cGMP) and systemically affect plant salt and water balance and responses to biotrophic plant pathogens. Although there is increasing understanding of the complex roles of PNPs in plant responses at the systems level, little is known about the underlying signaling mechanisms. Here we report isolation and identification of a novel Leucine-Rich Repeat (LRR) protein that directly interacts with A. thaliana PNP, AtPNP-A. In vitro binding studies revealed that the Arabidopsis AtPNP-A binds specifically to the LRR protein, termed AtPNP-R1, and the active region of AtPNP-A is sufficient for the interaction to occur. Importantly, the cytosolic part of the AtPNP-R1, much like in some vertebrate NP receptors, harbors a catalytic center diagnostic for guanylyl cyclases and the recombinant AtPNP-R1 is capable of catalyzing the conversion of guanosine triphosphate to cGMP. In addition, we show that AtPNP-A causes rapid increases of cGMP levels in wild type (WT) leaf tissue while this response is significantly reduced in the atpnp-r1 mutants. AtPNP-A also causes cGMP-dependent net water uptake into WT protoplasts, and hence volume increases, whereas responses of the protoplasts from the receptor mutant are impaired. Taken together, our results suggest that the identified LRR protein is an AtPNP-A receptor essential for the PNP-dependent regulation of ion and water homeostasis in plants and that PNP- and vertebrate NP-receptors and their signaling mechanisms share surprising similarities. © 2016 Springer Science+Business Media Dordrecht

  2. Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High Affinity Ligand for STING

    Science.gov (United States)

    Zhang, Xu; Shi, Heping; Wu, Jiaxi; Zhang, Xuewu; Sun, Lijun; Chen, Chuo; Chen, Zhijian J.

    2013-01-01

    The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2′-OH of GMP and 5′-phosphate of AMP, and the other between 3′-OH of AMP and 5′-phosphate of GMP. This molecule, termed 2′3′-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages. The crystal structure of STING bound to 2′3′-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation. PMID:23747010

  3. Gibberellic acid and cGMP-dependent transcriptional regulation in arabidopsis thaliana

    KAUST Repository

    Bastian, René

    2010-03-01

    An ever increasing amount of transcriptomic data and analysis tools provide novel insight into complex responses of biological systems. Given these resources we have undertaken to review aspects of transcriptional regulation in response to the plant hormone gibberellic acid (GA) and its second messenger guanosine 3\\',5\\'-cyclic monophosphate (cGMP) in Arabidopsis thaliana, both wild type and selected mutants. Evidence suggests enrichment of GA-responsive (GARE) elements in promoters of genes that are transcriptionally upregulated in response to cGMP but downregulated in a GA insensitive mutant (ga1-3). In contrast, in the genes upregulated in the mutant, no enrichment in the GARE is observed suggesting that GARE motifs are diagnostic for GA-induced and cGMP-dependent transcriptional upregulation. Further, we review how expression studies of GA-dependent transcription factors and transcriptional networks based on common promoter signatures derived from ab initio analyses can contribute to our understanding of plant responses at the systems level. © 2010 Landes Bioscience.

  4. Simulation of an Aspheric Glass Lens Forming Behavior in Progressive GMP Process

    International Nuclear Information System (INIS)

    Chang, Sung Ho; Lee, Young Min; Kang, Jeong Jin; Hong, Seok Kwan; Shin, Gwang Ho; Heo, Young Moo; Jung, Tae Sung

    2007-01-01

    Recently, GMP(Glass Molding Press) process is mainly used to produce aspheric glass lenses. Because glass lens is heated at high temperature above Tg (Transformation Temperature) for forming the glass, the quality of aspheric glass lens is deteriorated by residual stresses which are generated in a aspheric glass lens after forming. In this study, as a fundamental study to develop the mold for progressive GMP process, we conducted a aspheric glass lens forming simulation. Prior to a aspheric glass lens forming simulation, compression and thermal conductivity tests were carried out to obtain mechanical and thermal properties of K-PBK40 which is newly developed material for precision molding, and flow characteristics of K-PBK40 were obtained at high temperature. Then, using the flow characteristics obtained, compression simulation was carried out and compared with the experimental result for the purpose of verifying the obtained flow characteristics. Finally, a glass lens press simulation in progressive GMP process was carried out and we could forecast the shape of deformed glass lenses and residual stresses contribution in the structure of deformed glass lenses after forming

  5. Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium.

    Science.gov (United States)

    Jonas, Kristina; Edwards, Adrianne N; Ahmad, Irfan; Romeo, Tony; Römling, Ute; Melefors, Ojar

    2010-02-01

    Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3'-5')-cyclic-diguanosine monophosphate (c-di-GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA-binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF-EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post-transcriptionally. The c-di-GMP-specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c-di-GMP-inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility-sessility switch in S. Typhimurium at multiple levels.

  6. A proposed impact assessment method for genetically modified plants (AS-GMP Method)

    International Nuclear Information System (INIS)

    Jesus-Hitzschky, Katia Regina Evaristo de; Silveira, Jose Maria F.J. da

    2009-01-01

    An essential step in the development of products based on biotechnology is an assessment of their potential economic impacts and safety, including an evaluation of the potential impact of transgenic crops and practices related to their cultivation on the environment and human or animal health. The purpose of this paper is to provide an assessment method to evaluate the impact of biotechnologies that uses quantifiable parameters and allows a comparative analysis between conventional technology and technologies using GMOs. This paper introduces a method to perform an impact analysis associated with the commercial release and use of genetically modified plants, the Assessment System GMP Method. The assessment is performed through indicators that are arranged according to their dimension criterion likewise: environmental, economic, social, capability and institutional approach. To perform an accurate evaluation of the GMP specific indicators related to genetic modification are grouped in common fields: genetic insert features, GM plant features, gene flow, food/feed field, introduction of the GMP, unexpected occurrences and specific indicators. The novelty is the possibility to include specific parameters to the biotechnology under assessment. In this case by case analysis the factors of moderation and the indexes are parameterized to perform an available assessment.

  7. Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

    Directory of Open Access Journals (Sweden)

    Louisa McRobert

    2008-06-01

    Full Text Available Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA, can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+ is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.

  8. Good manufacturing practice (GMP) compliance in the biologics sector: plasma fractionation.

    Science.gov (United States)

    Ways, J P; Preston, M S; Baker, D; Huxsoll, J; Bablak, J

    1999-12-01

    The U.S. blood supply is the safest it has ever been. Due to blood safety and the introduction of viral inactivation/clearance technologies, protein therapies derived from human blood have also in recent years had a history of product safety. Nevertheless, since 1995, the plasma-fractionation industry has experienced increased compliance-related actions by the Food and Drug Administration (FDA), as shown by a substantive increase in the number of FDA 483 inspectional observations, FDA warning letters and other FDA regulatory action. An evaluation of these trends shows that they reflect the implementation by the FDA of increased inspectional interest in the plasma-fractionation industry and an evolution of inspectional practices and standards of current good manufacturing practice (cGMP). Plasma fractionators have responded to FDA actions by carefully evaluating and addressing each inspectional observation, assessing impact to product and taking appropriate actions, including corrective actions to prevent future occurrence. They have made major investments in facilities, quality systems, personnel and training to meet the evolving standards of cGMP and in an effort to implement these standards systemically. Through industry associations, manufacturers have further enhanced product safety by adopting additional voluntary standards for plasma to prevent the entry of potentially unsuitable plasma into the production process. The industry remains committed to application of cGMP and to working with the FDA in further evolution of these standards while striving to assure a continued supply of safe, pure and effective plasma-derived therapies.

  9. Role of parking in the hotel supply chain management

    Directory of Open Access Journals (Sweden)

    Robert Maršanić

    2015-12-01

    Full Text Available Background: Supply chain management in tourism has only recently become the topic of the scientific research. The hotel product as a tourist product presents a specific mix of services and products The focus of this study has been placed on the hotel company, that, in order to create such a product, builds its own network of partners (companies, co-workers, to bring together and coordinate activities intended to result in the desired features of the hotel product. This study was evaluated as a scientifically relevant because until now the position of parking services in the hotel product has not been analyzed from the perspective of the hotel efforts and abilities to provide parking places for their guests by analyzing to which extent a good and available parking space really affects the quality of the hotel product. The aim of the study was to define the framework in which the supply chain management acts with reference to the parking service and stakeholders in the network. Methods: The method of interviewing hotel managers was used to obtain necessary data. Through the simple numerical calculations including the number of parking spaces and the capacity of the hotel accommodation we tried to identify the interrelationship, i.e. the degree of alignment of the respective sizes. Results: It turned out that towns of Rijeka and Opatija are faced with a shortage of parking spaces, especially during the tourist season. The trend of providing parking services for guests in hotel-owned garages or car parks is typical for the everyday hotel operation and the shortage of such an option, is resolved through the lease of a certain number of parking spaces in public garages and car parks. These parking spaces are away from the hotel, the guests' dissatisfaction is a normal consequence of such a decision and it is mitigated through the commercial measures. Hotel management considers a provided parking space an important element of the hotel product quality

  10. The today nuclear park

    International Nuclear Information System (INIS)

    Girard, Ph.; Marignac, Y.; Tassart, J.

    2000-03-01

    This economic analysis of the nuclear industry, takes stock on the french nuclear park, the nuclear materials flux, the operating and in construction from 1970 to 1998 reactors, the storage and the wastes reprocessing. The second part proposes many scenario in function of the reactors lifetime and the industrial policy of fuel reprocessing. This analysis shows the interest of extending the power plants lifetime and evaluates the consequences of a reprocessing-recycling policy facing the stop of such a policy in 2010. (A.L.B.)

  11. Orlice Nature Park - environmental themes

    International Nuclear Information System (INIS)

    Hanus, L.

    2002-01-01

    The aim of this abstract is to outline the main characteristics of Orlice Nature Park and of the procedure of Environmental Impact Assessment (EIA), and to evaluate public interest in the nature park and in nature protection in general. Orlice Nature Park was instituted in 1996. The function of the park is to protect the character of the area of landscape around the River Orlice. Orlice Natural Park covers an area of 115 sq. km. The main environmental risks to the park are: intensive agriculture, forest mono-culture, industry, transport, channel improvement, the building of holiday cottages, sport, and recreation. Among the conflicts of interest in the park are: nature protection, water management, building constrictions, business, fishery, water sports and recreation. During the process of Environmental Impact Assessment in Hradec Kralove, the public voiced its opinion against the building of a supermarket within the grounds of of the nature park. In this case the public showed its interest in the value of nature and landscape, the value of human health and the value of plant species. In general, the public and the local media show an interest in the park only in exceptional circumstances. (author)

  12. Parking Spoorzone Delft : Addressing expected parking challenges 2015-2017

    NARCIS (Netherlands)

    Piccot, C.; Groenendijk, L.; Rot, M.; Van der Meijs, P.; Rakers, T.; Negenborn, R.R.; Annema, J.A.; Pel, A.; Vleugel, J.

    2014-01-01

    This project is carried out on request of the BVOW, the interest group of the neighbourhoods Olofsbuurt and Westerkwartier in Delft, in order to propose solutions for the parking issue of Spoorzone Delft expected between 2015 and 2017. They are worried that parking disturbances will emerge in their

  13. Identification, activity and disulfide connectivity of C-di-GMP regulating proteins in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2010-11-01

    Full Text Available C-di-GMP, a bacterial second messenger plays a key role in survival and adaptation of bacteria under different environmental conditions. The level of c-di-GMP is regulated by two opposing activities, namely diguanylate cyclase (DGC and phosphodiesterase (PDE-A exhibited by GGDEF and EAL domain, respectively in the same protein. Previously, we reported a bifunctional GGDEF-EAL domain protein, MSDGC-1 from Mycobacterium smegmatis showing both these activities (Kumar and Chatterji, 2008. In this current report, we have identified and characterized the homologous protein from Mycobacterium tuberculosis (Rv 1354c named as MtbDGC. MtbDGC is also a bifunctional protein, which can synthesize and degrade c-di-GMP in vitro. Further we expressed Mtbdgc in M. smegmatis and it was able to complement the MSDGC-1 knock out strain by restoring the long term survival of M. smegmatis. Another protein Rv 1357c, named as MtbPDE, is an EAL domain protein and degrades c-di-GMP to pGpG in vitro. Rv1354c and 1357c have seven cysteine amino acids in their sequence, distributed along the full length of the protein. Disulfide bonds play an important role in stabilizing protein structure and regulating protein function. By proteolytic digestion and mass spectrometric analysis of MtbDGC, connectivity between cysteine pairs Cys94-Cys584, Cys2-Cys479 and Cys429-Cys614 was determined, whereas the third cysteine (Cys406 from N terminal was found to be free in MtbDGC protein, which was further confirmed by alkylation with iodoacetamide labeling. Bioinformatics modeling investigations also supported the pattern of disulfide connectivity obtained by Mass spectrometric analysis. Cys406 was mutated to serine by site directed mutagenesis and the mutant MtbC406S was not found to be active and was not able to synthesize or degrade c-di-GMP. The disulfide connectivity established here would help further in understanding the structure - function relationship in MtbDGC.

  14. Landscape ecology: a concept for protecting park resources

    Science.gov (United States)

    Allen, Craig D.; Lissoway, John; Yarborough, Keith

    1990-01-01

    The Southwest Region has been supporting Resource Basic Inventory (RBI) efforts to establish baseline data for comparisons with long-term monitoring results to be conducted in the future. This “pulse taking” is a part of the Servicewide initiative being fostered so that resource managers, scientists, and park managers will be able to track the health of park resources by determining changes and trends. The RBI work is being linked with the development of Geographic Information Systems (GIS) at Bandelier, Big Thicket, Big Bend, Padre Island, and Guadalupe Mountains. Many of the parks in the southwest Region have only partially completed RBIs. This informational shortcoming is a pervasive threat to the parks because without detailed knowledge of the parks’ respective resources the Service cannot protect them adequately. To overcome this deficiency, the SWRO’s Division of Natural Resources Management and Science has fostered at Bandelier a pilot research effort, which started in FY ’87 and utilizes a landscape ecology paradigm. This concept links the RBI, GIS, and research activities in a park to present an overall picture of the park in its regional ecosystem setting. The flowchart diagrams this project’s concept. The results have been encouraging. A final report was recently completed (Allen 1989). This concept may now be applied to other Southwest Region parks.

  15. Consistents of car’s parking in Lithuanian towns

    Directory of Open Access Journals (Sweden)

    M. Burinskienė

    2003-08-01

    Full Text Available Large towns of Lithuania should especially focus on the solution of the parked cars; and modern technologies should be employed for that. The research methods have been substantiated and the recommendations for the technical regulations of the short-term and long-term car parking near different objects of attraction have been worked out on the basis of selective natural research, which is significant when issuing technical specifications to investors on the way the surroundings of the objects being built should be arranged and on what rearrangement of the urban streets is necessary. With a high level of motorization, the organization of the car parking process is a complicated problem of urban planning. The accumulated experience and the carried out analysis show that car parking problems can be positively solved even with a high level of motorization by: making use of the urban area as reasonably as possible so that the spaces could take the greatest possible number of cars; limiting the duration of parking so that the greater number of cars could use the same parking space; promoting car sharing; differentiating the entrance possibilities for different vehicles with regard of time, space and fee size. Solutions related to the determination of the parking space should be achieved in the context of the strategy of total urban development, area and traffic planning, traffic safety improvement and preservation of unique environment.

  16. Survey report 1998. Survey on actual condition of science parks and similar facilities in Asian countries; 1998 nendo chosa hokokusho. Asia shokoku chiiki ni okeru science park nado no jittai chosa

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    Implemented at NEDO, on such technical development issues peculiar to developing nations as are difficult to solve by their research and development ability alone, has been a consistent research cooperation with countries in question, such as installation of plants and research facilities, joint research operation, and training of researchers, while Japanese technological skill and research and development know how are utilized, as the international cooperation projects. In this survey, an actual condition was investigated including potential of science parks and similar facilities in Asian countries (Thailand, Indonesia, Malaysia and India), for the purpose of unearthing the needs, seeds, etc., of the future international research cooperation projects. The parks and facilities selected for the survey are as follows. The Thai technology/science parks are the Thai Science Park and four other parks; the Indonesian technology parks are Bukit Indah Industrial City and eleven other parks; the major Malaysian technology parks are Technology Park Malaysia and fourteen other parks; the major Indian technology parks are Electronics City and fifteen other parks. (NEDO)

  17. Redesign of Denggung Park as Sleman Urban Park based on Local Wisdom in Yogyakarta

    Science.gov (United States)

    Sanjaya, I.; Fatimah, IS

    2017-10-01

    Sleman Regency is one of the administrative area in Special Region of Yogyakarta Province which has increased the pace of infrastructure development activities that undertaken by the central government affects another surrounding area. The pace of infrastructure development impacts such problems in Sleman Regency such as, increasingly limited public spaces and changes in understanding the value of local wisdom. Sleman Regency has a park located in central government which is Denggung Park. This park has low visitors and less of aesthetic value which require re-design to improve the quality as public space for cultural identity space. The base concept of Urban Park adopted the philosophy that connects to four components in Javanese mythology. The four components in Javanese mythology symbolize the journey of human life in the Javanese cosmological theory, there are Mount Merapi, Keraton, Krapyak Stage, and South seas. The design concept inspired from pattern of Yogyakarta traditional clothing namely, Batik Kawung which describe of Philosophy “Four of Brotherhood and Five of Central itself” by means synergize four items creating world nature and human as life catalyzer. This study uses descriptive and spatial analysis method. The result of this research is expected to be a design recommendation for Sleman Regency governance in the urban park development.

  18. Globalisation of commercial theme parks: the walt Disney Company

    OpenAIRE

    DE GROOTE, Patrick

    2009-01-01

    The Economics Research Associates (ERA) defines a theme park as ‘A gated attraction that contains rides and/or shows in a themed environment, offers a pay-one-price ticket for its guests and attracts at least 500,000 annual visits’ (ERA, 2007). A more detailed description for theme parks is given by Philip L. Pearce (in Jafar Jafari, 2000, 124-5): ‘Theme parks are capital intensive, highly developed, self-contained recreational spaces which invariably charge admission. The entertainment, ride...

  19. Self-evaluation System for Low carbon Industrial Park--A Case Study of TEDA Industrial Park in Tianjin

    Science.gov (United States)

    Wenyan, W.; Fanghua, H.; Ying, C.; Ouyang, W.; Yuan, Q.

    2013-12-01

    Massive fossil fuel burning caused by industrialization development is one major reason of global climate change. After Copenhagen climate summit, the studies of low-carbon city gain attentions from many countries. On 25th Nov. 2009, the State Council executive meeting announced that by 2020 China will reduce the carbon dioxide emissions per unit of GDP by 40% to 45% compared with the level of 2005. Industrial Park as an important part of city, has developed rapidly in recent years, and turns into a key element and an alternative mechanism to achieve emission reduction target. Thus, establishing a low carbon development model for industrial park is one of the most effective ways to build sustainable low carbon cities. By adopting the self-evaluation system of low carbon industrial park, this research aims to summarize the low carbon concept in industrial park practice. According to The Guide for Low Carbon Industrial Development Zones, the quantitative evaluation system is divided into 4 separate categories with 23 different quantitative indicators. The 4 categories include: 1) energy and GHG management (weigh 60%), 2) circular economy and environmental protection (weigh 15%), 3) administration and incentive mechanisms of industrial parks (weigh 15%), and 4) planning and urban forms (weigh 10%). By going through the necessary stages and by leading continuous improvements low carbon development goals can be achieved. Tianjin TEDA industrial park is selected as one case study to conduct an assessment on TEDA low-carbon development condition. Tianjin TEDA Industrial Park is already an ecological demonstration industrial park in China, with good foundations on environmental protection, resource recycling, etc. Based on the self-evaluation system, the indicators, such as the energy using efficiency and the degree of land intensive utilization, are also analyzed and assessed. Through field survey and data collection, in accordance with the quantitative self

  20. Molecular properties of mammalian proteins that interact with cGMP: protein kinases, cation channels, phosphodiesterases, and multi-drug anion transporters.

    Science.gov (United States)

    Francis, Sharron H; Blount, Mitsi A; Zoraghi, Roya; Corbin, Jackie D

    2005-09-01

    Cyclic GMP is a critical second messenger signaling molecule in many mammalian cell types. It is synthesized by a family of guanylyl cyclases that is activated in response to stimuli from hormones such as natriuretic peptides, members of the guanylin family, and chemical stimuli including nitric oxide and carbon monoxide. The resulting elevation of cGMP modulates myriad physiological processes. Three major groups of cellular proteins bind cGMP specifically at allosteric sites; interaction of cGMP with these sites modulates the activities and functions of other domains within these protein groups to bring about physiological effects. These proteins include the cyclic nucleotide (cN)-dependent protein kinases, cN-gated cation channels, and cGMP-binding phosphodiesterases (PDE). Cyclic GMP also interacts with the catalytic sites of many cN PDEs and with some members of the multi-drug anion transporter family (MRPs) which can extrude nucleotides from cells. The allosteric cN-binding sites in the kinases and the cN-gated channels are evolutionarily and biochemically related, whereas the allosteric cGMP-binding sites in PDEs (also known as GAF domains), the catalytic sites of PDEs , and the ligand-binding sites in the MRPs are evolutionarily and biochemically distinct from each other and from those in the kinase and channel families. The sites that interact with cGMP within each of these groups of proteins have unique properties that provide for cGMP binding. Within a given cell, cGMP can potentially interact with members of all these groups of proteins if they are present. The relative abundance and affinities of these various cGMP-binding sites in conjunction with their subcellular compartmentation, proximity to cyclases and PDEs, and post-translational modification contribute importantly in determining the impact of these respective proteins to cGMP signaling within a particular cell.

  1. Parking taxes : evaluating options and impacts

    International Nuclear Information System (INIS)

    Litman, T.A.

    2006-01-01

    In addition to encouraging the use of alternative modes of transport, parking taxes can help to reduce congestion, air pollution, and urban sprawl. Various types of parking taxes were evaluated in this paper, as well as their impacts on parking supply, prices and travel patterns. Examples of various parking tax programs in major cities in Canada, Europe, the United States and Australia were presented. Parking tax programs were divided into 2 main categories: (1) per-space parking levies which distribute cost burdens and encourage property owners to manage parking supply more efficiently and (2) commercial parking taxes on parking rental transactions which discourage the pricing of parking and concentrate impacts in limited areas. Worksite parking levies were discussed, as well stormwater fees and employee parking as a taxable benefit. Typical parking facility financial costs were reviewed and best practices for structuring and implementing parking taxes to increase public acceptability were outlined. It was suggested that the tax base should be broad and well-defined. Local governments should increase parking prices to market rates before imposing special parking taxes, and taxes and fees should be structured to avoid undesirable land use. Parking tax reforms should be part of an overall parking and mobility management program. Stakeholders should be consulted to insure that regulations, administrative procedures and enforcement policies are efficient and fair. The establishment of an evaluation program to determine tax impacts on parking supply and pricing, economic activity, traffic and spillover problems was also recommended. 42 refs., 4 tabs., 1 fig

  2. The perception of visitors towards the level of satisfaction on park (Case study: Singha Merjosari Park Malang)

    Science.gov (United States)

    Priadaniswari, R.

    2017-06-01

    Park is one of the public spaces which is used by people to get happiness and comfort. Singha Merjosari Park is one of the parks in Malang that is functioned as a recreational and educational park for the citizen. In weekends and national holidays Singha Merjosari park get visited by so many visitors. But if we see the reality, there are still some problems regarding visitor satisfaction. Also, there are attributes that has performance levels decrease that will become another new problem. The purpose of this study is to analyze the perception of visitors about the level of visitor satisfaction and what attributes that need to be improved and developed by managers in the future. The approach method in this research is descriptive quantitative. Primary data is based on measurement and observation. The number of samples used is 100 respondents referring to the number of samples determination by Slovin formula with the sample selection used is accidental sampling technique. The analysis technique used is Importance Performance Analysis (IPA) and Costumer Satisfaction Index (CSI). Based on the results of IPA analysis, the things that should get important attention and should be improved is the aesthetics of lighting, cleanliness of parking area and toilet, shade in park area, and availability of clean water. While the result of CSI value analysis is 65,30%. This means visitors are satisfied, but visitors are still not satisfied overall. Implications or changes that should be given is the aesthetics of lighting should be more creative and become the identity of the park (for example, lamp lanterns should be suitable with the concept of the park). Also, the change of toilet look so that visitors can enjoy the look and it can be iconic (toilet concept according to local culture of Malang) and the prevalence of lighting in the park area at night.

  3. California Community Colleges Parking Survey.

    Science.gov (United States)

    McIntyre, Chuck

    In 1990, a representative sample of 25 California community colleges was contacted by telephone to determine their parking policies and practices. The colleges were sampled on the basis of location and size. Study findings included the following: (1) 17 of the colleges reported that they had insufficient numbers of on-campus parking spaces; (2)…

  4. Smart parking management and navigation system

    KAUST Repository

    Saadeldin, Mohamed

    2017-01-01

    Various examples are provided for smart parking management, which can include navigation. In one example, a system includes a base station controller configured to: receive a wireless signal from a parking controller located at a parking space

  5. Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway.

    Science.gov (United States)

    Pose, Inés; Silveira, Valentina; Morales, Francisco R

    2011-06-01

    Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Magnesium Lithospermate B, an Active Extract of Salvia miltiorrhiza, Mediates sGC/cGMP/PKG Translocation in Experimental Vasospasm

    Directory of Open Access Journals (Sweden)

    Chih-Zen Chang

    2014-01-01

    Full Text Available Background. Soluble guanylyl cyclases (sGCs and Ras homolog gene family, member A (rhoA/Ras homolog gene family kinase(rho-kinase plays a role in vascular smooth muscle relaxation in subarachnoid hemorrhage (SAH. It is of interest to examine the effect of MLB on rhoA/ROCK and sGC/cGMP/PKG expression. Methods. A rodent SAH model was employed. Tissue samples were for sGCα1, sGCβ1, PKG, rhoA, ROCK (Western blot, and cGMP (ELISA measurement. Results. MLB morphologically improved convolution of the internal elastic lamina, distortion of endothelial wall, and necrosis of the smooth muscle in the SAH rats. Expressed cGMP, sGCα1, sGCβ1, and PKG in the SAH groups were reduced (P<0.01, and MLB precondition significantly induced cGMP, sGCα1, sGCβ1, and PKG. L-NAME reversed the vasodilation effect of MLB, reduced the bioexpression of PKG and cGMP (P<0.01, and tends to reduce sGCα1 level and induce rhoA, ROCK level in MLB precondition + SAH groups. Conclusion. These results demonstrate that sGC/cGMP/PKG and NO/ET pathways play pivotal roles in SAH-induced vasospasm. Through activating sGC/cGMP/PKG pathway and partially by inactivating rho-kinase in a NO-dependent mechanism, MLB shows promise to be an effective strategy for the treatment of this disease entity.

  7. GMP-140 binds to a glycoprotein receptor on human neutrophils: Evidence for a lectin-like interaction

    International Nuclear Information System (INIS)

    Moore, K.L.; Varki, A.; McEver, R.P.

    1991-01-01

    GMP-140 is a rapidly inducible receptor for neutrophils and monocytes expressed on activated platelets and endothelial cells. It is a member of the selectin family of lectin-like cell surface molecules that mediate leukocyte adhesion. We used a radioligand binding assay to characterize the interaction of purified GMP-140 with human neutrophils. Unstimulated neutrophils rapidly bound [125I]GMP-140 at 4 degrees C, reaching equilibrium in 10-15 min. Binding was Ca2+ dependent, reversible, and saturable at 3-6 nM free GMP-140 with half-maximal binding at approximately 1.5 nM. Receptor density and apparent affinity were not altered when neutrophils were stimulated with 4 beta-phorbol 12-myristate 13-acetate. Treatment of neutrophils with proteases abolished specific binding of [125I]GMP-140. Binding was also diminished when neutrophils were treated with neuraminidase from Vibrio cholerae, which cleaves alpha 2-3-, alpha 2-6-, and alpha 2-8-linked sialic acids, or from Newcastle disease virus, which cleaves only alpha 2-3- and alpha 2-8-linked sialic acids. Binding was not inhibited by an mAb to the abundant myeloid oligosaccharide, Lex (CD15), or by the neoglycoproteins Lex-BSA and sialyl-Lex-BSA. We conclude that neutrophils constitutively express a glycoprotein receptor for GMP-140, which contains sialic acid residues that are essential for function. These findings support the concept that GMP-140 interacts with leukocytes by a lectin-like mechanism

  8. Current and Future Dynamics of the Red-Cockaded Woodpecker Population Inhabiting the Savannah River National Environmental Research Park: Managing For Population Growth

    International Nuclear Information System (INIS)

    Walters, J.R.; Taylor, T.B.; Daniels, S.J.; Crowder, L.B.; Pridd, J.A.

    2001-01-01

    Research aimed to study the dynamics of the SRS population of Red-Cockaded woodpecker and compare to those of other populations to identify factors limiting population growth; recruitment clusters were evaluated to determine what properties of individual cavity trees, surrounding habitat and the surrounding landscape might limit occupancy through natural dispersal. A spatial simulation model was used to project expected dispersal rates and population growth under current conditions and compare those estimates to observed dispersal and population growth. Red cockaded woodpecker populations at SRS are stable considering size. Research reveals that closer placement of recruitment clusters to active territories would produce higher growth rates while decreasing management intensity

  9. Current and Future Dynamics of the Red-Cockaded Woodpecker Population Inhabiting the Savannah River National Environmental Research Park: Managing For Population Growth

    Energy Technology Data Exchange (ETDEWEB)

    Walters, J.R.; Taylor, T.B.; Daniels, S.J.; Crowder, L.B.; Pridd, J.A.

    2001-01-01

    Research aimed to study the dynamics of the SRS population of Red-Cockaded woodpecker and compare to those of other populations to identify factors limiting population growth; recruitment clusters were evaluated to determine what properties of individual cavity trees, surrounding habitat and the surrounding landscape might limit occupancy through natural dispersal. A spatial simulation model was used to project expected dispersal rates and population growth under current conditions and compare those estimates to observed dispersal and population growth. Red cockaded woodpecker populations at SRS are stable considering size. Research reveals that closer placement of recruitment clusters to active territories would produce higher growth rates while decreasing management intensity.

  10. CERN in the park

    CERN Multimedia

    2002-01-01

    CERN will be the centre of debate at a 'Café scientifique' on Monday 29 April. The aim of the Cafés scientifiques, which are organised by the association of Bancs Publics, is to kindle discussion between ordinary people and specialists in a scientific field. This Monday, Maurice Bourquin, President of the CERN Council, Hans Hoffmann, Director of Technology Transfer and Scientific Computing at CERN, Gilbert Guignard, a physicist at CERN, and Ruhal Floris, who teaches mathematical didactics at the University of Geneva, will explain the usefulness and contributions to science of the world's biggest laboratory for particle physics. What is CERN for? Monday 29 April at 18.30 Musée d'histoire des sciences, Geneva (in the park Perle du Lac) Entry free Wine and buffet after the discussion

  11. Yellowcake National Park

    International Nuclear Information System (INIS)

    Dagget, D.

    1985-01-01

    Exploration for and mining of uranium ore is going on within 10 miles of the Grand Canyon National Park. The current rush started in 1980, when a Denver-based company, Energy Fuels Nuclear, took over a claim in Hack Canyon and uncovered a very rich deposit of uranium ore. Recent explorations have resulted in some 1300 claims in the area around the Grand Canyon, many of them in the Arizona Strip, the land between the Canyon and Utah. The center of current controversy is the 1872 Mining Law. Replacement of the law with a leasing system similar to that used for leasable minerals such as coal, oil shale, oil and gas, potash, and phosphate is advocated. 1 figure

  12. Sensor-guided parking system for a carlike robot

    Science.gov (United States)

    Jiang, Kaichum; Seneviratne, L. D.

    1998-07-01

    This paper presents an automated parking strategy for a car- like mobile robot. The study considers general parking manoeuvre cases for a rectangular robot, including parallel parking. The robot is constructed simulating a conventional car, which is subject to non-holonomic constraints and thus only has two degrees of freedom. The parking space is considered as rectangular, and detected by ultrasonic sensors mounted on the robot. A motion planning algorithm develops a collision-free path for parking, taking into account the non- holonomic constraints acting on the car-like robot. A research into general car maneuvers has been conducted and useful results have been achieved. The motion planning algorithm uses these results, combined with configuration space method, to produce a collision-free path for parallel parking, depending on the parking space detected. A control program in the form of a graphical user interface has been developed for users to operate the system with ease. The strategy is implemented on a modified B12 mobile robot. The strategy presented has the potential for application in automobiles.

  13. Parking Space Occupancy at Rail Stations in Klang Valley

    Directory of Open Access Journals (Sweden)

    Ho Phooi Wai

    2017-01-01

    Full Text Available The development of Klang Valley Integrated Rapid Transit system in Klang Valley, Malaysia has been quickly gaining momentum during the recent years. There will be two new MRT lines (MRT Line 1 and MRT Line 2 and one new LRT line (LRT Line 3 extended from the current integrated rail transit system by year 2020 with more than 90 new rail stations. With the substantial addition of potential rail passengers, there are doubts whether the existing Park and Ride facilities in Klang Valley are able to accommodate the future parking space demand at rail stations. This research studies the parking occupancy at various Park and Ride facilities in Klang Valley namely Taman Jaya, Asia Jaya, Taman Paramount, Taman Bahagia and Kelana Jaya by applying the non-conventional method utilizing Google Earth imageries. Results showed that the parking occupancy rate at these LRT stations were 100% or more before the commencement of LRT extension (Kelana Jaya and Ampang Lines in 2016 and in the range of 36% to 100% after the commencement of LRT extension due to the additionally built car parks and changes in parking pattern with dispersed passenger traffic.

  14. In Vivo Biochemistry: Single-Cell Dynamics of Cyclic Di-GMP in Escherichia coli in Response to Zinc Overload.

    Science.gov (United States)

    Yeo, Jongchan; Dippel, Andrew B; Wang, Xin C; Hammond, Ming C

    2018-01-09

    Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities in vivo remain highly challenging to study in real time and for individual cells. Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP. Specifically, we demonstrate that intracellular levels of cyclic di-GMP in Escherichia coli are repressed with excess zinc, but not with other divalent metals. Furthermore, in both flow cytometry and fluorescence microscopy setups, we monitor the dynamic increase in cellular cyclic di-GMP levels upon zinc depletion and show that this response is due to de-repression of the endogenous diguanylate cyclase DgcZ. In the presence of zinc, cells exhibit enhanced cell motility and increased sensitivity to antibiotics due to inhibited biofilm formation. Taken together, these results showcase the application of RBF biosensors in visualizing single-cell dynamic changes in cyclic di-GMP signaling in direct response to environmental cues such as zinc and highlight our ability to assess whether observed phenotypes are related to specific signaling enzymes and pathways.

  15. Differential regulation of c-di-GMP metabolic enzymes by environmental signals modulates biofilm formation in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Gai-Xian eRen

    2016-06-01

    Full Text Available Cyclic diguanylate (c-di-GMP is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs, HmsT and HmsD and one phosphodiesterase (PDE, HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD and HmsP in Y. pestis. Biofilm formation was higher in the presence of nonlethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfonate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulates their DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments.

  16. Understanding parking habits at CERN

    CERN Multimedia

    Anaïs Schaeffer

    2016-01-01

    The SMB department is setting up a monitoring system in certain CERN car parks in order to evaluate their occupancy rates and subsequently make them easier to use.    Vehicle registration plate readers (red triangles) are now installed at the entrances and exits of the Le Cèdres car park (in orange) and of the Building 4 and 5 one (in blue). The 2 other car parks (Building 40 in violet and “high-voltage” in green) will be equipped at a later stage. Vehicle registration plate readers are now installed at the entrances and exits of the Les Cèdres car park and of the Building 4 and 5 car park, both on the Meyrin site. The information collected by these readers will allow the occupancy levels of these car parks to be analysed throughout the day, establishing periods of peak usage and the pattern of vehicle movements. “We have been experiencing parking problems at CERN for several years n...

  17. Aftermath of Griffith Park Fire

    Science.gov (United States)

    2007-01-01

    In mid-May 2007, wind-driven flames raced through Griffith Park in Los Angeles, forcing hasty evacuations and threatening numerous famous landmarks and tourist spots, such as the Los Angeles Zoo and the Hollywood Sign. Ultimately, no one was injured in the fire, which may have been started by a cigarette. About 800 acres burned in the urban park, which is itself a Hollywood landmark, having been the location for several movies, including Rebel Without A Cause. This image of the park was captured by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite on June 6, 2007, about a month after the fire. ASTER detects both visible and infrared wavelengths of light, and both kinds have been used to make this image. Vegetation appears in various shades of red, while the burned areas appear charcoal. Roads and dense urban areas appear purplish-gray or white. Water is dark blue. Large burned areas are evident in the northwest and southeast parts of the park, with scattered smaller patches along the southern margin. Some botanical gardens and parts of a bird sanctuary, as well as some park structures like restrooms, were destroyed. The park's unburned, natural vegetation appears brick red, while the irrigated golf courses adjacent to the park are bright red. NASA image created by Jesse Allen, using data provided courtesy of the NASA/GSFC/MITI/ERSDAC/JAROS, and U.S./Japan ASTER Science Team.

  18. Role of cyclic di-GMP in Xylella fastidiosa biofilm formation, plant virulence, and insect transmission.

    Science.gov (United States)

    Chatterjee, Subhadeep; Killiny, Nabil; Almeida, Rodrigo P P; Lindow, Steven E

    2010-10-01

    Xylella fastidiosa must coordinately regulate a variety of traits contributing to biofilm formation, host plant and vector colonization, and transmission between plants. Traits such as production of extracellular polysaccharides (EPS), adhesins, extracellular enzymes, and pili are expressed in a cell-density-dependent fashion mediated by a cell-to-cell signaling system involving a fatty acid diffusible signaling factor (DSF). The expression of gene PD0279 (which has a GGDEF domain) is downregulated in the presence of DSF and may be involved in intracellular signaling by modulating the levels of cyclic di-GMP. PD0279, designated cyclic di-GMP synthase A (cgsA), is required for biofilm formation, plant virulence, and vector transmission. cgsA mutants exhibited a hyperadhesive phenotype in vitro and overexpressed gumJ, hxfA, hxfB, xadA, and fimA, which promote attachment of cells to surfaces and, hence, biofilm formation. The mutants were greatly reduced in virulence to grape albeit still transmissible by insect vectors, although at a reduced level compared with transmission rates of the wild-type strain, despite the fact that similar numbers of cells of the cgsA mutant were acquired by the insects from infected plants. High levels of EPS were measured in cgsA mutants compared with wild-type strains, and scanning electron microscopy analysis also revealed a thicker amorphous layer surrounding the mutants. Overexpression of cgsA in a cgsA-complemented mutant conferred the opposite phenotypes in vitro. These results suggest that decreases of cyclic di-GMP result from the accumulation of DSF as cell density increases, leading to a phenotypic transition from a planktonic state capable of colonizing host plants to an adhesive state that is insect transmissible.

  19. Thrombin has biphasic effects on the nitric oxide-cGMP pathway in endothelial cells and contributes to experimental pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Katrin F Nickel

    Full Text Available BACKGROUND: A potential role for coagulation factors in pulmonary arterial hypertension has been recently described, but the mechanism of action is currently not known. Here, we investigated the interactions between thrombin and the nitric oxide-cGMP pathway in pulmonary endothelial cells and experimental pulmonary hypertension. PRINCIPAL FINDINGS: Chronic treatment with the selective thrombin inhibitor melagatran (0.9 mg/kg daily via implanted minipumps reduced right ventricular hypertrophy in the rat monocrotaline model of experimental pulmonary hypertension. In vitro, thrombin was found to have biphasic effects on key regulators of the nitric oxide-cGMP pathway in endothelial cells (HUVECs. Acute thrombin stimulation led to increased expression of the cGMP-elevating factors endothelial nitric oxide synthase (eNOS and soluble guanylate cyclase (sGC subunits, leading to increased cGMP levels. By contrast, prolonged exposition of pulmonary endothelial cells to thrombin revealed a characteristic pattern of differential expression of the key regulators of the nitric oxide-cGMP pathway, in which specifically the factors contributing to cGMP elevation (eNOS and sGC were reduced and the cGMP-hydrolyzing PDE5 was elevated (qPCR and Western blot. In line with the differential expression of key regulators of the nitric oxide-cGMP pathway, a reduction of cGMP by prolonged thrombin stimulation was found. The effects of prolonged thrombin exposure were confirmed in endothelial cells of pulmonary origin (HPAECs and HPMECs. Similar effects could be induced by activation of protease-activated receptor-1 (PAR-1. CONCLUSION: These findings suggest a link between thrombin generation and cGMP depletion in lung endothelial cells through negative regulation of the nitric oxide-cGMP pathway, possibly mediated via PAR-1, which could be of relevance in pulmonary arterial hypertension.

  20. Analysis of Parking Reliability Guidance of Urban Parking Variable Message Sign System

    OpenAIRE

    Zhenyu Mei; Ye Tian; Dongping Li

    2012-01-01

    Operators of parking guidance and information systems (PGIS) often encounter difficulty in determining when and how to provide reliable car park availability information to drivers. Reliability has become a key factor to ensure the benefits of urban PGIS. The present paper is the first to define the guiding parking reliability of urban parking variable message signs (VMSs). By analyzing the parking choice under guiding and optional parking lots, a guiding parking reliability model was constru...

  1. A Scientific Calculator for Exact Real Number Computation Based on LRT, GMP and FC++

    Directory of Open Access Journals (Sweden)

    J. A. Hernández

    2012-03-01

    Full Text Available Language for Redundant Test (LRT is a programming language for exact real number computation. Its lazy evaluation mechanism (also called call-by-need and its infinite list requirement, make the language appropriate to be implemented in a functional programming language such as Haskell. However, a direction translation of the operational semantics of LRT into Haskell as well as the algorithms to implement basic operations (addition subtraction, multiplication, division and trigonometric functions (sin, cosine, tangent, etc. makes the resulting scientific calculator time consuming and so inefficient. In this paper, we present an alternative implementation of the scientific calculator using FC++ and GMP. FC++ is a functional C++ library while GMP is a GNU multiple presicion library. We show that a direct translation of LRT in FC++ results in a faster scientific calculator than the one presented in Haskell.El lenguaje de verificación redundante (LRT, por sus siglas en inglés es un lenguaje de programación para el cómputo con números reales exactos. Su método de evaluación lazy (o mejor conocido como llamada por necesidad y el manejo de listas infinitas requerido, hace que el lenguaje sea apropiado para su implementación en un lenguaje funcional como Haskell. Sin embargo, la implementación directa de la semántica operacional de LRT en Haskell así como los algoritmos para funciones básicas (suma, resta, multiplicación y división y funciones trigonométricas (seno, coseno, tangente, etc hace que la calculadora científica resultante sea ineficiente. En este artículo, presentamos una implementación alternativa de la calculadora científica usando FC++ y GMP. FC++ es una librería que utiliza el paradigma Funcional en C++ mientras que GMP es una librería GNU de múltiple precisión. En el artículo mostramos que la implementación directa de LRT en FC++ resulta en una librería más eficiente que la implementada en Haskell.

  2. Cyclic GMP-AMP Synthase is Activated by Double-stranded DNA-Induced Oligomerization

    OpenAIRE

    Li, Xin; Shu, Chang; Yi, Guanghui; Chaton, Catherine T.; Shelton, Catherine L.; Diao, Jiasheng; Zuo, Xiaobing; Kao, C Cheng; Herr, Andrew B.; Li, Pingwei

    2013-01-01

    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide 2′,5′ cGAMP that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-β gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and ...

  3. GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats.

    Science.gov (United States)

    Rubin, M A; Jurach, A; da Costa Júnior, E M; Lima, T T; Jiménez-Bernal, R E; Begnini, J; Souza, D O; de Mello, C F

    1996-09-02

    Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.

  4. Contributions of non-urban state parks to youth physical activity: A case study in northern Georgia

    Science.gov (United States)

    Lincoln R. Larson; Jason W. Whiting; Gary T. Green; J.M. Bowker

    2015-01-01

    A growing body of research has documented positive relationships among youth physical activity levels and park use. However, most investigations to date have focused on municipal parks, and relatively little is known about the physical activity levels of racially and ethnically diverse populations of youth using different types of parks in non-urban settings. This...

  5. From an eco-industrial park towards an eco-city : a case study in Suzhou, China

    NARCIS (Netherlands)

    Yu, Chang; Dijkema, Gerard P. J.; de Jong, Martin; Shi, Han

    2015-01-01

    As eco-industrial park policies have been in place for years, many mature eco-industrial parks tend to acquire more than just industrial functions and become new urban districts. We investigated this development and conducted empirical research in Suzhou Industrial Park, to obtain insight in how a

  6. Public Parks and Wellbeing in Urban Areas of the United States.

    Directory of Open Access Journals (Sweden)

    Lincoln R Larson

    Full Text Available Sustainable development efforts in urban areas often focus on understanding and managing factors that influence all aspects of health and wellbeing. Research has shown that public parks and green space provide a variety of physical, psychological, and social benefits to urban residents, but few studies have examined the influence of parks on comprehensive measures of subjective wellbeing at the city level. Using 2014 data from 44 U.S. cities, we evaluated the relationship between urban park quantity, quality, and accessibility and aggregate self-reported scores on the Gallup-Healthways Wellbeing Index (WBI, which considers five different domains of wellbeing (e.g., physical, community, social, financial, and purpose. In addition to park-related variables, our best-fitting OLS regression models selected using an information theory approach controlled for a variety of other typical geographic and socio-demographic correlates of wellbeing. Park quantity (measured as the percentage of city area covered by public parks was among the strongest predictors of overall wellbeing, and the strength of this relationship appeared to be driven by parks' contributions to physical and community wellbeing. Park quality (measured as per capita spending on parks and accessibility (measured as the overall percentage of a city's population within ½ mile of parks were also positively associated with wellbeing, though these relationships were not significant. Results suggest that expansive park networks are linked to multiple aspects of health and wellbeing in cities and positively impact urban quality of life.

  7. An Interpretive Study of Yosemite National Park Visitors' Perspectives Toward Alternative Transportation in Yosemite Valley

    Science.gov (United States)

    White, Dave D.

    2007-01-01

    The National Park Service (NPS) is increasingly focusing on alternative transportation systems in national parks to address environmental and social problems arising from a historical reliance on personal automobiles as the primary means of visitor access. Despite the potential advantages, alternative transportation may require a reorientation in the way that Americans have experienced national parks since the advent of auto-tourism in the early twentieth century. Little research exists, however, on visitor perspectives towards alternative transportation or the rationale underlying their perspectives. It remains unclear how transportation systems affect visitors’ experiences of the park landscape or the factors influencing their travel behavior in the parks. This report presents an interpretive study of visitor perspectives toward transportation management in the Yosemite Valley area of Yosemite National Park, California. Qualitative analysis of 160 semi-structured interviews identified individual psychological factors as well as situational influences that affect visitors’ behavior and perspectives. Individual psychological factors include perceived freedom, environmental values and beliefs, prior experience with Yosemite National Park and other national parks, prior experience with alternative transportation in national parks, and sensitivity to subjective perceptions of crowding. Situational factors included convenience, access, and flexibility of travel modes, as well as type of visit, type of group, and park use level. Interpretive communication designed to encourage voluntary visitor use of alternative transportation should focus on these psychological and situational factors. Although challenges remain, the results of this study suggest approaches for shaping the way Americans visit and experience their national parks to encourage environmental sustainability.

  8. Motor-park people shift gear.

    Science.gov (United States)

    Nnoli, C

    1992-01-01

    White, U.S. homosexual males were primarily affected in the early stages of the AIDS pandemic. Some Western researchers argued, however, that the syndrome originated in Africa. Strong political and social response to this notion resulted in only an anemic response to the growing AIDS epidemic in Nigeria. Nonetheless, the Stop AIDS Organization finally launched the Motor Park AIDS Education Program (MPAEP) in 1988, for health and education outreach to populations at risk of STDs and HIV infection. Specifically targeted are long-distance truck drivers, their young male assistants known as motor boys, and the barmaids, prostitutes, and homeless juveniles who frequent motor parks where these drivers rest while on the road. Many of these long-haul drivers have unprotected casual and commercial sex, both homosexual and heterosexual, take drugs, and suffer high rates of STDs. Marginalized, 75% illiterate, and speaking a variety of languages, these populations tend to be largely ignorant of the incurable nature of AIDS. Over 45% of motor park populations are estimated to be infected with an STD, or to have a future re-infection. These drivers are optimal vectors for the spread of HIV both internationally and within Nigeria. MPAEP workers work 6 days/week in the larger interstate motor parks to reach out to their predominantly male customers. They meet a host of primary health needs, and refer STD clients for testing and treatment. Drug use and homosexuality are 2 topics of discussion especially taboo in African society which have nonetheless been vigorously researched by MPAEP. Many drivers are unacknowledged bisexuals who have sex with their motor boys. Workers therefore explain the need to use condoms in same-sex activity without specifically mentioning homosexuality. Many Nigerians deny the existence of HIV and AIDS, are reluctant to speak about sex, and consider MPAEP workers to be intruders. Despite opposition in Muslim- dominated Northern Nigeria, however, program

  9. Influence of Parking Price on Parking Garage Users’ Behaviour

    Directory of Open Access Journals (Sweden)

    Jelena Simićević

    2012-09-01

    Full Text Available Parking charge is a powerful tool for solving parking and traffic congestion problems. In order to achieve the expected effects without any adverse impact it is necessary to understand well the users’ responses to this policy. This paper, based on a sample of interviewed parking garage users, has developed binary logit model for identification and quantification of characteristics of users and trips, on which the acceptance of parking price is dependent. In addition, multinomial logit model has been made in order to predict what the users will opt for when faced with an increase in parking price. For the first time the parameter “shorten duration” has been introduced which has shown to be the most significant in making behaviour-related decisions. The results show that the users with the purpose work are the most sensitive to an increase in parking charge, what can be deemed positive for policy makers. However, great sensitivity of the users with the purpose shopping should cause their concern. The results of the multinomial model show that they would not discontinue coming into the area after all.

  10. A concise discussion of the regulatory role of cGMP kinase I in cardiac physiology and pathology.

    Science.gov (United States)

    Hofmann, Franz

    2018-06-22

    The underlying cause of cardiac hypertrophy, fibrosis, and heart failure has been investigated in great detail using different mouse models. These studies indicated that cGMP and cGMP-dependent protein kinase type I (cGKI) may ameliorate these negative phenotypes in the adult heart. Recently, evidence has been published that cardiac mitochondrial BKCa channels are a target for cGKI and that activation of mitoBKCa channels may cause some of the positive effects of conditioning in ischemia/reperfusion injury. It will be pointed out that most studies could not present convincing evidence that it is the cGMP level and the activity cGKI in specific cardiac cells that reduces hypertrophy or heart failure. However, anti-fibrotic compounds stimulating nitric oxide-sensitive guanylyl cyclase may be an upcoming therapy for abnormal cardiac remodeling.

  11. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

    Science.gov (United States)

    Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

    2017-09-19

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. IMPORTANCE Bacterial cells have evolved several

  12. Exercise training improves blood flow to contracting skeletal muscle of older men via enhanced cGMP signaling

    DEFF Research Database (Denmark)

    Piil, Peter Bergmann; Smith Jørgensen, Tue; Egelund, Jon

    2018-01-01

    Physical activity has the potential to offset age-related impairments in the regulation of blood flow and O2 delivery to the exercising muscles; however, the mechanisms underlying this effect of physical activity remain poorly understood. The present study examined the role of cGMP in training...... a period of aerobic high-intensity exercise training. To determine the role of cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Before training, inhibition of PDE5 increased (P... group; however, these effects of PDE5 inhibition were not detected after training. These findings suggest a role for enhanced cGMP signaling in the training-induced improvement of regulation of blood flow in contracting skeletal muscle of older men....

  13. Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

    Science.gov (United States)

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

    2017-05-01

    The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

  14. Multinational underground nuclear parks

    Energy Technology Data Exchange (ETDEWEB)

    Myers, C.W. [Nuclear Engineering and Nonproliferation Division, Los Alamos National Laboratory, MS F650, Los Alamos, NM 87544 (United States); Giraud, K.M. [Wolf Creek Nuclear Operating Corporation, 1550 Oxen Lane NE, P.O. Box 411, Burlington, KS 66839-0411 (United States)

    2013-07-01

    Newcomer countries expected to develop new nuclear power programs by 2030 are being encouraged by the International Atomic Energy Agency to explore the use of shared facilities for spent fuel storage and geologic disposal. Multinational underground nuclear parks (M-UNPs) are an option for sharing such facilities. Newcomer countries with suitable bedrock conditions could volunteer to host M-UNPs. M-UNPs would include back-end fuel cycle facilities, in open or closed fuel cycle configurations, with sufficient capacity to enable M-UNP host countries to provide for-fee waste management services to partner countries, and to manage waste from the M-UNP power reactors. M-UNP potential advantages include: the option for decades of spent fuel storage; fuel-cycle policy flexibility; increased proliferation resistance; high margin of physical security against attack; and high margin of containment capability in the event of beyond-design-basis accidents, thereby reducing the risk of Fukushima-like radiological contamination of surface lands. A hypothetical M-UNP in crystalline rock with facilities for small modular reactors, spent fuel storage, reprocessing, and geologic disposal is described using a room-and-pillar reference-design cavern. Underground construction cost is judged tractable through use of modern excavation technology and careful site selection. (authors)

  15. cGMP and nitric oxide modulate thrombin-induced endothelial permeability : Regulation via different pathways in human aortic and umbilical vein endothelial cells

    NARCIS (Netherlands)

    Draijer, R.; Atsma, D.E.; Laarse, A. van der; Hinsbergh, V.W.M. van

    1995-01-01

    Previous studies have demonstrated that cGMP and cAMP reduce the endothelial permeability for fluids and macromolecules when the endothelial permeability is increased by thrombin. In this study, we have investigated the mechanism by which cGMP improves the endothelial barrier function and examined

  16. Interactions in the aqueous phase and adsorption at the air-water interface of caseinoglycomacropeptide (GMP) and beta-lactoglobulin mixed systems.

    Science.gov (United States)

    Martinez, María J; Sánchez, Cecilio Carrera; Patino, Juan M Rodríguez; Pilosof, Ana M R

    2009-01-01

    The aim of this work was to study the interactions and adsorption of caseinoglycomacropeptide (GMP) and GMP:beta-lactoglobulin (beta-lg) mixed system in the aqueous phase and at the air-water interface. The existence of associative interactions between GMP and beta-lg in the aqueous phase was investigated by dynamic light scattering, differential scanning calorimetry (DSC), fluorometry and native PAGE-electrophoresis. The surface pressure isotherm and the static and dynamic surface pressure were determined by tensiometry and surface dilatational properties. The results showed that GMP presented higher surface activity than beta-lg at a concentration of 4%wt but beta-lg showed higher film forming ability. In the mixed systems beta-lg dominated the static and dynamic surface pressure and the rheological properties of interfacial films suggesting that beta-lg hinders GMP adsorption because, in simple competition, GMP should dominate because of its higher surface activity. The surface predominance of beta-lg can be attributed to binding of GMP to beta-lg in the aqueous phase that prevents GMP adsorption on its own.

  17. The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa

    DEFF Research Database (Denmark)

    Riess, O; Noerremoelle, A; Weber, B

    1992-01-01

    The finding of a mutation in the beta subunit of the cyclic GMP (cGMP) phosphodiesterase gene causing retinal degeneration in mice (the Pdeb gene) prompted a search for disease-causing mutations in the human phosphodiesterase gene (PDEB gene) in patients with retinitis pigmentosa. All 22 exons...

  18. Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2012-02-01

    Full Text Available Nitric oxide (NO is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP and the cGMP-dependent kinase (PKG are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ were used. We observed that long-term exposure to the NO donor (24 h, NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.

  19. Architectural heritage or theme park

    Directory of Open Access Journals (Sweden)

    Ignasi Solà-Morales

    1998-04-01

    Full Text Available The growing parallelism between the perception and the consumer use of theme parks and architectural heritage gives rise to a reflection about the fact that the architectural object has been turned into a museum piece, stripped  of its original value and its initial cultural substance to become images exposed to multiple gazes, thus producing what the author calis the "Theme Park effect", with consequences on protected architecture.

  20. Vision-Based Parking-Slot Detection: A Benchmark and A Learning-Based Approach

    Directory of Open Access Journals (Sweden)

    Lin Zhang

    2018-03-01

    Full Text Available Recent years have witnessed a growing interest in developing automatic parking systems in the field of intelligent vehicles. However, how to effectively and efficiently locating parking-slots using a vision-based system is still an unresolved issue. Even more seriously, there is no publicly available labeled benchmark dataset for tuning and testing parking-slot detection algorithms. In this paper, we attempt to fill the above-mentioned research gaps to some extent and our contributions are twofold. Firstly, to facilitate the study of vision-based parking-slot detection, a large-scale parking-slot image database is established. This database comprises 8600 surround-view images collected from typical indoor and outdoor parking sites. For each image in this database, the marking-points and parking-slots are carefully labeled. Such a database can serve as a benchmark to design and validate parking-slot detection algorithms. Secondly, a learning-based parking-slot detection approach, namely P S D L , is proposed. Using P S D L , given a surround-view image, the marking-points will be detected first and then the valid parking-slots can be inferred. The efficacy and efficiency of P S D L have been corroborated on our database. It is expected that P S D L can serve as a baseline when the other researchers develop more sophisticated methods.

  1. Concept of Lunar Energy Park

    Science.gov (United States)

    Niino, Masayuki; Kisara, Katsuto; Chen, Lidong

    1993-10-01

    This paper presents a new concept of energy supply system named Lunar Energy Park (LEP) as one of the next-generation clean energy sources. In this concept, electricity is generated by nuclear power plants built on the moon and then transmitted to receiving stations on the earth by laser beam through transporting systems situated in geostationary orbit. The lunar nuclear power plants use a high-efficiency composite energy conversion system consisting of thermionic and thermoelectric generators to change nuclear thermal energy into electricity directly. The nuclear resources are considered to be available from the moon, and nuclear fuel transport from earth to moon is not necessary. Because direct energy conversion systems are employed, the lunar nuclear plants can be operated and controlled by robots and are maintenance-free, and so will cause no pollution to humans. The key technologies for LEP include improvements of conversion efficiency of both thermionic and thermoelectric converters, and developments of laser-beam power transmission technology as well. The details, including the construction of lunar nuclear plants, energy conversion and energy transmission systems, as well as the research plan strategies for this concept are reviewed.

  2. cGMP-dependent protein kinase I, the circadian clock, sleep and learning.

    Science.gov (United States)

    Feil, Robert; Hölter, Sabine M; Weindl, Karin; Wurst, Wolfgang; Langmesser, Sonja; Gerling, Andrea; Feil, Susanne; Albrecht, Urs

    2009-07-01

    The second messenger cGMP controls cardiovascular and gastrointestinal homeostasis in mammals. However, its physiological relevance in the nervous system is poorly understood.1 Now, we have reported that the cGMP-dependent protein kinase type I (PRKG1) is implicated in the regulation of the timing and quality of sleep and wakefulness.2Prkg1 mutant mice showed altered distribution of sleep and wakefulness as well as reduction in rapid-eye-movement sleep (REMS) duration and in non-REMS consolidation. Furthermore, the ability to sustain waking episodes was compromised. These observations were also reflected in wheel-running and drinking activity. A decrease in electroencephalogram power in the delta frequency range (1-4 Hz) under baseline conditions was observed, which was normalized after sleep deprivation. Together with the finding that circadian clock amplitude is reduced in Prkg1 mutants these results indicate a decrease of the wake-promoting output of the circadian system affecting sleep. Because quality of sleep might affect learning we tested Prkg1 mutants in several learning tasks and find normal spatial learning but impaired object recognition memory in these animals. Our findings indicate that Prkg1 impinges on circadian rhythms, sleep and distinct aspects of learning.

  3. Developing a tool for the preparation of GMP audit of pharmaceutical contract manufacturer.

    Science.gov (United States)

    Linna, Anu; Korhonen, Mirka; Mannermaa, Jukka-Pekka; Airaksinen, Marja; Juppo, Anne Mari

    2008-06-01

    Outsourcing is rapidly growing in the pharmaceutical industry. When the manufacturing activities are outsourced, control of the product's quality has to be maintained. One way to confirm contract manufacturer's GMP (Good Manufacturing Practice) compliance is auditing. Audits can be supported for instance by using GMP questionnaires. The objective of this study was to develop a tool for the audit preparation of pharmaceutical contract manufacturers and to validate its contents by using Delphi method. At this phase of the study the tool was developed for non-sterile finished product contract manufacturers. A modified Delphi method was used with expert panel consisting of 14 experts from pharmaceutical industry, authorities and university. The content validity of the developed tool was assessed by a Delphi questionnaire round. The response rate in Delphi questionnaire round was 86%. The tool consisted of 103 quality items, from which 90 (87%) achieved the pre-defined agreement rate level (75%). Thirteen quality items which did not achieve the pre-defined agreement rate were excluded from the tool. The expert panel suggested only minor changes to the tool. The results show that the content validity of the developed audit preparation tool was good.

  4. Spatiotemporal and functional characterisation of the Plasmodium falciparum cGMP-dependent protein kinase.

    Directory of Open Access Journals (Sweden)

    Christine S Hopp

    Full Text Available Signalling by 3'-5'-cyclic guanosine monophosphate (cGMP exists in virtually all eukaryotes. In the apicomplexan parasite Plasmodium, the cGMP-dependent protein kinase (PKG has previously been reported to play a critical role in four key stages of the life cycle. The Plasmodium falciparum isoform (PfPKG is essential for the initiation of gametogenesis and for blood stage schizont rupture and work on the orthologue from the rodent malaria parasite P. berghei (PbPKG has shown additional roles in ookinete differentiation and motility as well as liver stage schizont development. In the present study, PfPKG expression and subcellular location in asexual blood stages was investigated using transgenic epitope-tagged PfPKG-expressing P. falciparum parasites. In Western blotting experiments and immunofluorescence analysis (IFA, maximal PfPKG expression was detected at the late schizont stage. While IFA suggested a cytosolic location, a degree of overlap with markers of the endoplasmic reticulum (ER was found and subcellular fractionation showed some association with the peripheral membrane fraction. This broad localisation is consistent with the notion that PfPKG, as with the mammalian orthologue, has numerous cellular substrates. This idea is further supported by the global protein phosphorylation pattern of schizonts which was substantially changed following PfPKG inhibition, suggesting a complex role for PfPKG during schizogony.

  5. Phenotypic stability and plasticity in GMP-derived cells as determined by their underlying regulatory network.

    Science.gov (United States)

    Ramírez, Carlos; Mendoza, Luis

    2018-04-01

    Blood cell formation has been recognized as a suitable system to study celular differentiation mainly because of its experimental accessibility, and because it shows characteristics such as hierarchical and gradual bifurcated patterns of commitment, which are present in several developmental processes. Although hematopoiesis has been extensively studied and there is a wealth of molecular and cellular data about it, it is not clear how the underlying molecular regulatory networks define or restrict cellular differentiation processes. Here, we infer the molecular regulatory network that controls the differentiation of a blood cell subpopulation derived from the granulocyte-monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils, basophils and mast cells. We integrate published qualitative experimental data into a model to describe temporal expression patterns observed in GMP-derived cells. The model is implemented as a Boolean network, and its dynamical behavior is studied. Steady states of the network can be clearly identified with the expression profiles of monocytes, mast cells, neutrophils, basophils, and eosinophils, under wild-type and mutant backgrounds. All scripts are publicly available at https://github.com/caramirezal/RegulatoryNetworkGMPModel. lmendoza@biomedicas.unam.mx. Supplementary data are available at Bioinformatics online.

  6. Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production

    DEFF Research Database (Denmark)

    You, J P; Wang, Qian; Zhang, W

    1994-01-01

    this relaxation by 54% and 70%, respectively. The effect of L-NOARG was completely reversed by L-arginine. Blockade of nerve excitation with tetrodotoxin (TTX) had no affect on the 15% CO2 elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response...... to hypercapnia. L-NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 M HCl resulted in relaxation identical...... elicits vasodilatation of isolated rat basilar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels by L-NOARG and MB suggest that there exists a basal NO formation in the cerebral vessel wall....

  7. The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia

    DEFF Research Database (Denmark)

    Fazli, Mustafa; O'Connell, Aileen; Nilsson, Martin

    2011-01-01

    Burkholderia cenocepacia is an opportunistic respiratory pathogen that can cause severe infections in immune-compromised individuals and is associated with poor prognosis for patients suffering from cystic fibrosis. The second messenger cyclic diguanosine monophosphate (c-di-GMP) has been shown...... to control a wide range of functions in bacteria, but little is known about these regulatory mechanisms in B. cenocepacia. Here we investigated the role that c-di-GMP plays in the regulation of biofilm formation and virulence in B. cenocepacia. Elevated intracellular levels of c-di-GMP promoted wrinkly...... colony, pellicle and biofilm formation in B. cenocepacia. A screen for transposon mutants unable to respond to elevated levels of c-di-GMP led to the identification of the mutant bcam1349 that did not display increased biofilm and pellicle formation with excessive c-di-GMP levels, and displayed a biofilm...

  8. Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Larsen, Per; Bouzinova, Elena V.

    2008-01-01

    have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously...... known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP......-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small...

  9. Protecting national parks from air pollution effects: Making sausage from science and policy

    Science.gov (United States)

    Baron, Jill S.; Blett, Tamara; Malm, William C.; Alexander, Ruth; Doremus, Holly

    2016-01-01

    The story of air pollution research, policy development, and management in national parks is a fascinating blend of cultural change, vision, interdisciplinary and interagency collaboration, and science-policy-management-stakeholder collaborations. Unable to ignore the loss of iconic vistas from regional haze and loss of fish from acid rain in the 1980s, the National Park Service (NPS) embraced an obligation to protect resources from threats originating outside park boundaries. Upholding the Organic Act requirement for parks to remain "unimpaired" for the enjoyment of future generations, and using the Clean Air Act statement that NPS has an “affirmative responsibility” to protect park resources, NPS has supported, and effectively used, research as a means to protect lands, waters, and vistas from a mostly unseen threat. Using visibility and atmospheric nitrogen deposition as examples, we will illustrate some success stories where NPS led the way to benefit not only parks, but the Nation.

  10. Wireless based Smart Parking System using Zigbee

    OpenAIRE

    Hamzah Asyrani Bin Sulaiman; Mohd Fareez Bin Mohd Afif; Mohd Azlishah Bin Othman; Mohamad Harris Bin Misran; Maizatul Alice Binti Meor Said

    2013-01-01

    One of main issues of developing big parking space for shopping complexes, office complexes and other types of building that requires large parking space is to notify the visitors of occupied and nonoccupied parking space. Most of the visitors might spending up to 30 to 45 minutes just to find an empty parking space. In most recent technology, some parking lot system offered a system that could automatically count when the car entering the empty car space and blocking an infrared signal thus ...

  11. Attitudes of Citizens towards Urban Parks and Green Spaces for Urban Sustainability: The Case of Gyeongsan City, Republic of Korea

    Directory of Open Access Journals (Sweden)

    Young-Chang Lee

    2015-06-01

    Full Text Available Urban parks and green spaces support a wide array of species and play an important role in long-term sustainability. This study analyzed the needs and attitudes of citizens towards urban parks and green spaces in order to provide information for setting the future direction of urban sustainability to maximize quality of life. A questionnaire survey was conducted to analyze the general characteristics of respondents and their awareness of parks and spaces. First, the results indicate that the main purpose of visiting parks was relaxation and walking. Second, the type of parks visited most frequently by the respondents was pocket parks around home. Third, the main reason for going to the frequently visited parks was “close to home”. Fourth, the major reason for visiting parks infrequently was “improper park management”. Fifth, the desired types of urban parks were relaxation parks close to natural rivers. Sixth, citizens wanted to participate in the expansion projects of parks and green spaces through non-profit civic organizations or volunteer activities. Further research with a comparative analysis among different cities will be necessary to generalize Korean attitudes to urban parks and green spaces for urban sustainability.

  12. Public parks as urban tourism in Jakarta

    Science.gov (United States)

    Adiati, M. P.; Lestari, N. S.; Wiastuti, R. D.

    2018-03-01

    Sustainable urban tourism development should provide better places for people to live in and for people to visit. Jakarta as the capital city has a potential for its urban tourism. Thus, urban tourism attribute such as Public Park should be in high- quality to cope with the needs of urban people and outside visitors. The purpose of this study is to investigate Public Park attributes and to analyze its compliance refer to Public Park that eventually supports sustainable urban tourism. This paper used a qualitative approach. Primary data obtain from direct field observation in seven Public Parks in Jakarta; Menteng Park, Suropati Park, Situ Lembang Park, Ayodhya Park, Cattleya Park, Kodok Park, and Langsat Park. Observation checks list use as guidance. The result provides an assessment of Public Park based on four categories; the accessibility, park activities, safety, and user. The implication of this study offers recommendations to enhance Public Park so that it complies with good public park design- attributes and with the obligations of sustainable urban tourism in Jakarta.

  13. Parking management : strategies, evaluation and planning

    International Nuclear Information System (INIS)

    Litman, T.A.

    2006-01-01

    Parking facilities are a major cost to society. Current planning practices are based on the assumption that parking should be abundant and provided free, with costs borne indirectly. This report examined parking management strategies related to integrated parking plans. Problems with current parking planning practices were reviewed. The costs of parking facilities were examined, as well as the savings that can accrue from improved management techniques. Strategies included shared parking; remote parking and shuttle services; walking and cycling improvements; improved enforcement and control; and increasing the capacity of existing parking facilities. Parking pricing methods, financial incentives and parking tax reforms were reviewed. Issues concerning user information and marketing were examined. Overflow parking plans were evaluated. Three illustrative examples of parking management programs were outlined, along with details of implementation, planning and evaluation procedures. It was concluded that cost-effective parking management programs can often reduce parking requirements by 20 to 40 per cent compared with conventional planning requirements, in addition to providing economic, social and environmental benefits. 32 refs., 7 tabs., 3 figs

  14. Informal and formal trail monitoring protocols and baseline conditions: Acadia National Park

    Science.gov (United States)

    Marion, Jeffrey L.; Wimpey, Jeremy F.; Park, L.

    2011-01-01

    At Acadia National Park, changing visitor use levels and patterns have contributed to an increasing degree of visitor use impacts to natural and cultural resources. To better understand the extent and severity of these resource impacts and identify effective management techniques, the park sponsored this research to develop monitoring protocols, collect baseline data, and identify suggestions for management strategies. Formal and informal trails were surveyed and their resource conditions were assessed and characterized to support park planning and management decision-making.

  15. Impacts of Eco-tourism on Ethnic People: A study on Lawachara National Park, Sylhet, Bangladesh

    OpenAIRE

    Md. Moniruzzaman Muzib

    2014-01-01

    This research work seeks the impacts of Ecotourism on ethnic people of Lawachara National Park, Kamalganja, Moulvibazar, Sylhet. Empirical data has been collected through survey & FGDs from the residents of two villages called Khasi Punji and Dulahajra of this park.Observed evidences show that foremost influence of Ecotourism fall on economic aspects of ethnic life. Income level has been increased compare then before after establishing eco-park in this forest. People become involve with vario...

  16. Skate Parks as a Context for Adolescent Development

    Science.gov (United States)

    Bradley, Graham L.

    2010-01-01

    All people influence, and are influenced by, the contexts they inhabit. Leisure contexts are no exception. The current research comprised three studies investigating the links between one leisure context, skate parks, and adolescent development. Using interview, observation, and questionnaire methods, the research shed light on several of the…

  17. INVESTIGATION AND EVALUATION OF SPATIAL PATTERNS IN TABRIZ PARKS USING LANDSCAPE METRICS

    Directory of Open Access Journals (Sweden)

    Ali Majnouni Toutakhane

    2016-01-01

    Full Text Available Nowadays, the green spaces in cities and especially metropolises have adopted a variety of functions. In addition to improving the environmental conditions, they are suitable places for spending free times and mitigating nervous pressures of the machinery life based on their distribution and dispersion in the cities. In this research, in order to study the spatial distribution and composition of the parks and green spaces in Tabriz metropolis, the map of Parks prepared using the digital atlas of Tabriz parks and Arc Map and IDRISI softwares. Then, quantitative information of spatial patterns of Tabriz parks provided using Fragstats software and a selection of landscape metrics including: the area of class, patch density, percentage of landscape, average patch size, average patch area, largest patch index, landscape shape index, average Euclidean distance of the nearest neighborhood and average index of patch shape. Then the spatial distribution, composition, extent and continuity of the parks was evaluated. Overall, only 8.5 percent of the landscape is assigned to the parks, and they are studied in three classes of neighborhood, district and regional parks. Neighborhood parks and green spaces have a better spatial distribution pattern compared to the other classes and the studied metrics showed better results for this class. In contrast, the quantitative results of the metrics calculated for regional parks, showed the most unfavorable spatial status for this class of parks among the three classes studied in Tabriz city.

  18. Smart parking management and navigation system

    KAUST Repository

    Saadeldin, Mohamed

    2017-11-09

    Various examples are provided for smart parking management, which can include navigation. In one example, a system includes a base station controller configured to: receive a wireless signal from a parking controller located at a parking space; determine a received signal strength indicator (RSSI) from the wireless signal; and identify a presence of a vehicle located at the parking space based at least in part on the RSSI. In another example, a method includes receiving a wireless signals from a base station controller and a parking controller located at a parking space; determining RSSIs from the wireless signals; and determining a location of the mobile computing device in a parking facility based at least in part on the RSSIs. In another example, a RSSI can be received, a parking occupancy can be determined using the RSSI, and an electronic record can be updated based on the parking occupancy.

  19. Application of halophilic nuclease H of Micrococcus varians subsp. halophilus to commercial production of flavoring agent 5'-GMP.

    Science.gov (United States)

    Kamekura, M; Hamakawa, T; Onishi, H

    1982-01-01

    RNA was degraded at 60 degrees C for 24 h by halophilic nuclease H in supernatants from broth cultures of Micrococcus varians subsp. halophilus containing 12% NaCl. Since contaminating 5'-nucleotidase exhibited almost no activity under these conditions, the 5'-GMP formed could be recovered from the reaction mixture, and the yield was 805 mg from 5 g of RNA. PMID:6184020

  20. Brain Region-Specific Effects of cGMP-Dependent Kinase II Knockout on AMPA Receptor Trafficking and Animal Behavior

    Science.gov (United States)

    Kim, Seonil; Pick, Joseph E.; Abera, Sinedu; Khatri, Latika; Ferreira, Danielle D. P.; Sathler, Matheus F.; Morison, Sage L.; Hofmann, Franz; Ziff, Edward B.

    2016-01-01

    Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO…

  1. Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic GMP-AMP Synthase.

    Science.gov (United States)

    Kato, Kazuki; Ishii, Ryohei; Hirano, Seiichi; Ishitani, Ryuichiro; Nureki, Osamu

    2015-05-05

    Cyclic dinucleotides (CDNs) play key roles as second messengers and signaling molecules in bacteria and metazoans. The newly identified dinucleotide cyclase in Vibrio cholerae (DncV) produces three different CDNs containing two 3'-5' phosphodiester bonds, and its predominant product is cyclic GMP-AMP, whereas mammalian cyclic GMP-AMP synthase (cGAS) produces only cyclic GMP-AMP containing mixed 2'-5' phosphodiester bonds. We report the crystal structures of V. cholerae and Escherichia coli DncV in complex with various nucleotides in the pre-reaction states. The high-resolution structures revealed that DncV preferably recognizes ATP and GTP as acceptor and donor nucleotides, respectively, in the first nucleotidyl transfer reaction. Considering the recently reported intermediate structures, our pre-reaction state structures provide the precise mechanism of 3'-5' linked cyclic AMP-GMP production in bacteria. A comparison with cGAS in the pre-reaction states suggests that the orientation of the acceptor nucleotide primarily determines the distinct linkage specificities between DncV and cGAS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate

    NARCIS (Netherlands)

    Uckert, Stefan; Oelke, Matthias; Stief, Christian G.; Andersson, K.-E.; Jonas, Udo; Hedlund, Petter

    2006-01-01

    With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate.

  3. A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission

    NARCIS (Netherlands)

    Baker, D.A.; Stewart, L.B.; Large, J.M.; Bowyer, P.W.; Ansell, K.H.; Jimenez-Diaz, M.B.; Bakkouri, M. El; Birchall, K.; Dechering, K.J.; Bouloc, N.S.; Coombs, P.J.; Whalley, D.; Harding, D.J.; Smiljanic-Hurley, E.; Wheldon, M.C.; Walker, E.M.; Dessens, J.T.; Lafuente, M.J.; Sanz, L.M.; Gamo, F.J.; Ferrer, S.B.; Hui, R.; Bousema, T.; Angulo-Barturen, I.; Merritt, A.T.; Croft, S.L.; Gutteridge, W.E.; Kettleborough, C.A.; Osborne, S.A.

    2017-01-01

    To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase

  4. The Oxidative Stress Agent Hypochlorite Stimulates c-di-GMP Synthesis and Biofilm Formation in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Nikola Strempel

    2017-11-01

    Full Text Available The opportunistic human pathogen Pseudomonas aeruginosa is able to survive under a variety of often harmful environmental conditions due to a multitude of intrinsic and adaptive resistance mechanisms, including biofilm formation as one important survival strategy. Here, we investigated the adaptation of P. aeruginosa PAO1 to hypochlorite (HClO, a phagocyte-derived host defense compound and frequently used disinfectant. In static biofilm assays, we observed a significant enhancement in initial cell attachment in the presence of sublethal HClO concentrations. Subsequent LC-MS analyses revealed a strong increase in cyclic-di-GMP (c-di-GMP levels suggesting a key role of this second messenger in HClO-induced biofilm development. Using DNA microarrays, we identified a 26-fold upregulation of ORF PA3177 coding for a putative diguanylate cyclase (DGC, which catalyzes the synthesis of the second messenger c-di-GMP – an important regulator of bacterial motility, sessility and persistence. This DGC PA3177 was further characterized in more detail demonstrating its impact on P. aeruginosa motility and biofilm formation. In addition, cell culture assays attested a role for PA3177 in the response of P. aeruginosa to human phagocytes. Using a subset of different mutants, we were able to show that both Pel and Psl exopolysaccharides are effectors in the PA3177-dependent c-di-GMP network.

  5. Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels

    DEFF Research Database (Denmark)

    Chua, Song Lin; Ding, Yichen; Liu, Yang

    2016-01-01

    . Comparative genomic analysis of the RSCVs revealed that mutations in the wspF gene, which encodes for a repressor of WspR diguanylate cyclase (DGC), were responsible for increased intracellular cyclic-di-GMP content and production of Psl exopolysaccharide. Psl provides the first line of defence against ROS...

  6. Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex.

    Directory of Open Access Journals (Sweden)

    Yan Hao

    2011-05-01

    Full Text Available Elevation of the second messenger cGMP by nitric oxide (NO activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarrays revealed >40 genes that are sensitive to EGL-4 activity in a SAEG-1-dependent manner. We present evidence that EGL-4 controls egg laying via one of these genes, Y45F10C.2, which encodes a novel protein that is expressed exclusively in the uterine epithelium. Our results indicate that, in addition to cytoplasmic functions, active EGL-4/PKG acts in the nucleus via a conserved Class I histone deacetylase complex to regulate gene expression pertinent to behavioral and physiological responses to cGMP. We also identify transcriptional targets of EGL-4 that carry out discrete components of the physiological response.

  7. Strategic Management of Tourism in the National Parks (Case: National Park Skadar Lake

    Directory of Open Access Journals (Sweden)

    Iva Bulatović

    2015-07-01

    Full Text Available In this paper we will try to prepare strategic analysis in order to give right guidelines for national park’s management. We are going to analyze National Park Skadar Lake as a tourist destination. We will use different strategic tools for proper analysis such as Life Cycle Concept, Boston Consulting Group Matrix, Ansoff Matrix, and McKinsey matrix. A strategy that involves penetration of the market would be desirable in the case of developing excursion, cultural – religious tourism, event tourism, hunting and fishing tourism, and wine tourism. Furthermore, market diversification is essential when it comes to new tourist products such as eco-tourism, rural tourism, scientific research, MICE tourism, golf and camping tourism, while the transformation of existing and introduction of new tourist products is expected within the sport - recreational, health, culture, excursions, wine tourism, etc.The paper will provide a framework for future research in the field of strategic management of tourism development in national parks. This topic has not yet been thoroughly analyzed and it is expected to serve as the basis of a strategic plan for managing tourism in the National Park Skadar Lake and / or as an incentive for researchers to enter more deeply into the issue

  8. Learning from Millennium Park, Chicago

    Energy Technology Data Exchange (ETDEWEB)

    Guen, T. [American Society of Landscape Architects, Washington, DC (United States)]|[Terry Guen Design Associates, Chicago, IL (United States)

    2006-07-01

    This paper identified the value of creating green space for public use in an urban area in support of a sustainable environment. The inauguration of Chicago's Millennium Park in July 2004 marked a landmark civic achievement in greening an industrial urban centre. The Park was constructed on a 25-acre, previously vacant 100 year old rail property. In 2001, the first phase of the Park opened with the construction of the garages, train bridge, and infrastructure for future sculptural pieces. The green roof landscaping involved soil and drainage pathways, planting 11 acres of lawn and trees, and building a skating rink and restaurants. Phase 2 included new construction of donor enhancements. Among many benefits, this project stimulated investment in adjacent private development. This paper outlined the historic motivation for the park as a cultural and aesthetic benefit for the public. It reviewed the construction costs, the multiple sources of funding, and the multidisciplinary effort involving public agencies and private supporters. The landscape team included experts in soil, irrigation, planting, design and plant selection. Millennium Park has proven that current design and construction industries have the technical and physical ability to create cultural spaces of interest. 6 figs.

  9. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

    Science.gov (United States)

    Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

    2006-03-01

    Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

  10. Protected natural resources: Media representations of national parks

    Directory of Open Access Journals (Sweden)

    Simeunović-Bajić Nataša

    2011-01-01

    Full Text Available This paper attempts to set trends of reporting about national parks as exquisite units of national importance through the research of online editions of dominant media in Serbia. Since 2009 the entire set of “green laws“ was adopted, the great progress has been made in this area, and the research will refer to the next year of 2010 so it can be detected how much is the public informed by the means of communication about ambient, ecologic, aesthetic and recreational potentials of the national parks in Serbia.

  11. The Diversity of Ecotourism Potentials in Kelimutu National Park of Ende Regency

    Directory of Open Access Journals (Sweden)

    Josef A. Gadi Djou

    2016-10-01

    Full Text Available Natural tourist destination management plays a crucial role in materializing three important aspects, namely conservation, participation, and education. As a tourist destination, Kelimutu National Park, possessing a big ecosystem potential, tourist and cultural potentials, is expected to provide economy, culture, and conservation impacts on the society surrounding Kelimutu National Park. The problem of this study is how the variety of ecotourism potential in Kelimutu National Park is able to prosper the surrounding society. To answer this question, the definition of ecotourism, national park, national park ecotourism, and ecotourism potential need to be understood. Several methods used in answering the problems of the study are finding out the location of Kelimutu National Park, collecting qualitative data by conducting library research and participatory observation. The results were conceptually described, supported by tables and pictures.

  12. A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle.

    Science.gov (United States)

    Koltes, James E; Mishra, Bishnu P; Kumar, Dinesh; Kataria, Ranjit S; Totir, Liviu R; Fernando, Rohan L; Cobbold, Rowland; Steffen, David; Coppieters, Wouter; Georges, Michel; Reecy, James M

    2009-11-17

    Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle.

  13. Science parks as knowledge organizations

    DEFF Research Database (Denmark)

    Hansson, Finn

    gained agrowing importance in the new economy. If we shift focus to organizationtheory discussions on new knowledge and innovation has specialized in relationto the process of creation, managing, organizing, sharing, transferring etc. ofknowledge. The evaluation of science parks has to relate......Recent studies of the impact of science parks have questioned traditionalassumption about the effect of the parks on innovation and economic growth.Most studies tend to measure the effect by rather traditional measures, revenue,survival of new firms, without taking into account, that knowledge has...... to the changed role ofknowledge in the creation of economic growth. With the help of the concept ofthe ba from Nonanka, the article discuss if or how traditional organized scienceparks can become central actors in the new knowledge production or has to beviewed as an outdated institution from the industrial...

  14. Identification of the gamma subunit-interacting residues on photoreceptor cGMP phosphodiesterase, PDE6alpha '.

    Science.gov (United States)

    Granovsky, A E; Artemyev, N O

    2000-12-29

    Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory gamma subunit (Pgamma). Chimeric proteins between cone PDE6alpha' and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pgamma. Substitution of the segment PDE5-(773-820) by the corresponding PDE6alpha'-(737-784) sequence in the wild-type PDE5 or in a PDE5/PDE6alpha' chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pgamma. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pgamma-binding region, PDE6alpha'-(750-760), revealed PDE6alpha' residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pgamma. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met(758) and Gln(752) directly bind Pgamma. A model of the PDE6 catalytic site shows that PDE6alpha'-(750-760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pgamma to Met(758) would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.

  15. Physiological and Molecular Effects of the Cyclic Nucleotides cAMP and cGMP on Arabidopsis thaliana

    KAUST Repository

    Herrera, Natalia M.

    2012-12-01

    The cyclic nucleotide monophosphates (CNs), cAMP and cGMP, are second messengers that participate in the regulation of development, metabolism and adaptive responses. In plants, CNs are associated with the control of pathogen responses, pollen tube orientation, abiotic stress response, membrane transport regulation, stomatal movement and light perception. In this study, we hypothesize that cAMP and cGMP promote changes in the transcription level of genes related to photosynthesis, high light and membrane transport in Arabidopsis thaliana leaves and, that these changes at the molecular level can have functional biological consequences. For this reason we tested if CNs modulate the photosynthetic rate, responses to high light and root ion transport. Real time quantitative PCR was used to assess transcription levels of selected genes and infrared gas analyzers coupled to fluorescence sensors were used to measure the photosynthetic parameters. We present evidence that both cAMP and cGMP modulate foliar mRNA levels early after stimulation. The two CNs trigger different responses indicating that the signals have specificity. A comparison of proteomic and transcriptional changes suggest that both transcriptional and post-transcriptional mechanisms are modulated by CNs. cGMP up-regulates the mRNA levels of components of the photosynthesis and carbon metabolism. However, neither cAMP nor cGMP trigger differences in the rate of carbon assimilation, maximum efficiency of the photosystem II (PSII), or PSII operating efficiency. It was also demonstrated that CN regulate the expression of its own targets, the cyclic nucleotide gated channels - CNGC. Further studies are needed to identify the components of the signaling transduction pathway that mediate cellular changes and their respective regulatory and/or signaling roles.

  16. cGMP-phosphodiesterase inhibition enhances photic responses and synchronization of the biological circadian clock in rodents.

    Directory of Open Access Journals (Sweden)

    Santiago A Plano

    Full Text Available The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN and is synchronized by several environmental stimuli, mainly the light-dark (LD cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2. The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC, cGMP and its related protein kinase (PKG. Pharmacological manipulation of cGMP by phosphodiesterase (PDE inhibition (e.g., sildenafil increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions.

  17. GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP 'Fluorodopa F 18 Injection'

    International Nuclear Information System (INIS)

    Kao, C.K.; Hsu Wenlin; Xie Hengli; Lin Mingchi; Lan Wenchun; Chao Haoyu

    2011-01-01

    Lately, 6-[ 18 F]fluoro-L-DOPA (FDOPA) has found increase in its clinical demand for whole-body positron emission tomography (PET) scans, and two key issues in fulfilling this demand are the difficulties in producing FDOPA under the recently imposed PET drug good manufacturing practice (GMP) regulations and in providing it in the quality meeting the terms of major compendia. This paper describes the approaches for the GMP production of FDOPA and for the product testing to meet the standard of United States Pharmacopeia (USP) 'Fluorodopa F 18 Injection.' FDOPA was produced by the carrier-added electrophilic aromatic substitution reaction in the facility complying Pharmaceutical Inspection Cooperation Scheme clean room standard. The special aseptic handling technique was applied to minimize the bioburden. The product quality control followed all testing items and procedures, including three different settings of high performance liquid chromatography (HPLC). The process yielded FDOPA average 2.60±0.26 GBq (N=22) in every batch. All qualities of the product were within the specifications described in the USP 'Fluorodopa F 18 Injection.' The entire production was audited by the government authority and certified to comply with the latest PET drug GMP regulation. Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests. (author)

  18. Genetic Dissection of the Regulatory Network Associated with High C-di-GMP Levels in Pseudomonas putida KT2440

    Directory of Open Access Journals (Sweden)

    María Isabel Ramos-González

    2016-07-01

    Full Text Available Most bacteria grow in nature forming multicellular structures named biofilms. The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP is a key player in the regulation of the transition from planktonic to sessile lifestyles and this regulation is crucial in the development of biofilms. In Pseudomonas putida KT2440, Rup4959, a multidomain response regulator with diguanylate cyclase activity, when overexpressed causes an increment in the intracellular levels of c-di-GMP that gives rise to a pleiotropic phenotype consisting of increased biofilm formation and crinkly colony morphology. In a broad genomic screen we have isolated mutant derivatives that lose the crinkly morphology, designed as cfc (crinkle free colony. A total of nineteen different genes have been identified as being related with the emergence of the cfc phenotype either because the expression or functionality of Rup4959 is compromised, or due to a lack of transduction of the c-di-GMP signal to downstream elements involved in the acquisition of the phenotype. Discernment between these possibilities was investigated by using a c-di-GMP biosensor and by HPLC-MS quantification of the second messenger. Interestingly five of the identified genes encode proteins with AAA+ ATPase domain. Among the bacterial determinants found in this screen are the global transcriptional regulators GacA, AlgU and FleQ and two enzymes involved in the arginine biosynthesis pathway. We present evidences that this pathway seems to be an important element to both the availability of the free pool of the second messenger c-di-GMP and to its further transduction as a signal for biosynthesis of biopolimers. In addition we have identified an uncharacterized hybrid sensor histidine kinase whose phosphoaceptor conserved histidine residue has been shown in this work to be required for in vivo activation of the orphan response regulator Rup4959, which suggests these two elements constitute a two

  19. Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.

    Science.gov (United States)

    Otari, K V; Upasani, C D

    2015-08-01

    The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

  20. Smart parking management system with decal electronics system

    KAUST Repository

    Hussain, Muhammad Mustafa; Wicaksono, Irmandy

    2017-01-01

    Various examples are related to parking management, including identifying and reserving empty parking spaces. In one example, a smart parking space system includes a parking controller located at a parking space. The parking controller can identify a vehicle located at the parking space via an input sensor or a transceiver that initiates wireless communication with an electronic tag associated with the vehicle; and communicate a parking vacancy associated with the parking space to a remote computing device based at least in part on the identification of the vehicle. In another example, a computing device can receive parking vacancy data associated with a parking space from a parking controller; determine a parking vacancy associated with the parking space using the parking vacancy data; and encode for display on a client device a network page that includes an indication of the parking vacancy associated with the parking space.

  1. Smart parking management system with decal electronics system

    KAUST Repository

    Hussain, Muhammad Mustafa

    2017-09-21

    Various examples are related to parking management, including identifying and reserving empty parking spaces. In one example, a smart parking space system includes a parking controller located at a parking space. The parking controller can identify a vehicle located at the parking space via an input sensor or a transceiver that initiates wireless communication with an electronic tag associated with the vehicle; and communicate a parking vacancy associated with the parking space to a remote computing device based at least in part on the identification of the vehicle. In another example, a computing device can receive parking vacancy data associated with a parking space from a parking controller; determine a parking vacancy associated with the parking space using the parking vacancy data; and encode for display on a client device a network page that includes an indication of the parking vacancy associated with the parking space.

  2. 3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation

    International Nuclear Information System (INIS)

    Karaolis, David K.R.; Cheng, Kunrong; Lipsky, Michael; Elnabawi, Ahmed; Catalano, Jennifer; Hyodo, Mamoru; Hayakawa, Yoshihiro; Raufman, Jean-Pierre

    2005-01-01

    The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is a naturally occurring small molecule that regulates important signaling mechanisms in prokaryotes. Recently, we showed that c-di-GMP has 'drug-like' properties and that c-di-GMP treatment might be a useful antimicrobial approach to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent or treat infection. In the present communication, we report that c-di-GMP (≤50 μM) has striking properties regarding inhibition of cancer cell proliferation in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and epidermal growth factor)-induced cell proliferation of human colon cancer (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP at biologically relevant doses showed no lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an attractive and novel 'drug-platform technology' that can be used not only to develop new antimicrobial agents, but also to develop novel therapeutic agents to prevent or treat cancer

  3. Structural and functional characteristics of cGMP-dependent methionine oxidation in Arabidopsis thaliana proteins

    KAUST Repository

    Marondedze, Claudius

    2013-01-05

    Background: Increasing structural and biochemical evidence suggests that post-translational methionine oxidation of proteins is not just a result of cellular damage but may provide the cell with information on the cellular oxidative status. In addition, oxidation of methionine residues in key regulatory proteins, such as calmodulin, does influence cellular homeostasis. Previous findings also indicate that oxidation of methionine residues in signaling molecules may have a role in stress responses since these specific structural modifications can in turn change biological activities of proteins. Findings. Here we use tandem mass spectrometry-based proteomics to show that treatment of Arabidopsis thaliana cells with a non-oxidative signaling molecule, the cell-permeant second messenger analogue, 8-bromo-3,5-cyclic guanosine monophosphate (8-Br-cGMP), results in a time-dependent increase in the content of oxidised methionine residues. Interestingly, the group of proteins affected by cGMP-dependent methionine oxidation is functionally enriched for stress response proteins. Furthermore, we also noted distinct signatures in the frequency of amino acids flanking oxidised and un-oxidised methionine residues on both the C- and N-terminus. Conclusions: Given both a structural and functional bias in methionine oxidation events in response to a signaling molecule, we propose that these are indicative of a specific role of such post-translational modifications in the direct or indirect regulation of cellular responses. The mechanisms that determine the specificity of the modifications remain to be elucidated. 2013 Marondedze et al.; licensee BioMed Central Ltd.

  4. A visitor motivational typology at Mapungubwe National Park and World Heritage Site

    Directory of Open Access Journals (Sweden)

    Uwe P. Hermann

    2016-05-01

    Research purpose: This study aimed to develop a general visitor profile and to describe the motivational factors for visiting the park in order to support the development of tourism at MNP. Motivation of the study: A tourism management plan is required for the park; however, any planning associated planning requires an assessment of tourist behaviour and needs. Research design, approach and method: An online questionnaire was distributed to a database of visitors to MNP during March−April 2013. A total of 486 responses were received. Data were analysed using descriptive statistics through frequencies and means. Motivator constructs were analysed through a factor analysis. Main findings: The study both confirmed and contradicted previous findings from other national parks in terms of visitor profiles and motivations. Most crucially, this study identified a new motivational factor for visiting national parks, which advances the need to manage the heritage aspect of world heritage sites distinctly from national parks. Managerial implications: The results indicated that visitors to MNP were older and better educated compared to visitors at other national parks. These visitors included predominantly first-time visitors. In addition these visitors are mainly motivated by the need for a nature experience, although the park is not a Big 5 reserve, findings also identified heritage and education as a unique motivational factor for this park. Contribution added: The study promotes the requirement of a unique park-specific tourism management strategy for MNP as the market base of this park is demographically distinct. In addition, the park should improve the promotion of its status as a World Heritage asset in relation to its natural attributes in order to attract greater numbers of heritage tourists. Although the park features exceptional natural features, the reserve is not a Big 5 reserve and this may result in dissatisfaction with the major group of visitors seeking a

  5. cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

    Science.gov (United States)

    De Jonge, Hugo R.; Tilly, Ben C.; Hogema, Boris M.; Pfau, Daniel J.; Kelley, Catherine A.; Kelley, Megan H.; Melita, August M.; Morris, Montana T.; Viola, Ryan M.

    2013-01-01

    The in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride secretion. CNP binds to natriuretic receptors in the basolateral membrane, elevates cellular cGMP, and opens cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in the apical membrane. CNP-provoked chloride secretion was completely inhibitable by the nonspecific protein kinase inhibitor staurosporine and the PKA inhibitor H89 but insensitive to H8, an inhibitor of type I and II isoforms of cGMP-dependent protein kinase (cGKI and cGKII). CNP-induced secretion could not be mimicked by nonhydrolyzable cGMP analogs added alone or in combination with the protein kinase C activator phorbolester, arguing against a role for cGK or for cGMP-induced PKC signaling. We failed to detect a dogfish ortholog of cGKII by molecular cloning and affinity chromatography. However, inhibitors of the cGMP-inhibitable isoform of phosphodiesterase (PDE3) including milrinone, amrinone, and cilostamide but not inhibitors of other PDE isoenzymes mimicked the effect of CNP on chloride secretion in perfused glands and monolayers. CNP raised cGMP and cAMP levels in the SRG epithelial cells. This rise in cAMP as well as the CNP and amrinone-provoked chloride secretion, but not the rise in cGMP, was almost completely blocked by the Gαi-coupled adenylyl cyclase inhibitor somatostatin, arguing against a role for cGMP cross-activation of PKA in CNP action. These data provide molecular, functional, and pharmacological evidence for a CNP/cGMP/PDE3/cAMP/PKA signaling cascade coupled to CFTR in the SRG. PMID:24259420

  6. Parks and recreation employment status: implications from a civil service perspective

    Science.gov (United States)

    Joel Frater; Arthur Graham

    2002-01-01

    Current research on the credentialing process in parks, recreation and leisure services has focused primarily on accreditation and certification and has largely ignored the civil service exam as a credentialing toll or condition of employment in many state and municipal parks and recreation departments.

  7. Physical activity levels and preferences of ethnically diverse visitors to Georgia State Parks

    Science.gov (United States)

    Lincoln Larson; Jason W. Whiting; Gary T. Green; Michael Bowker

    2014-01-01

    Parks provide many outdoor recreation opportunities that encourage physical activity and healthy lifestyles, and research has recently begun to explore the demographic, social, and environmental factors associated with park-based activity levels, particularly outside of urban areas. This study used a mixed methods approach to investigate physical activity levels and...

  8. In vitro and in vivo generation and characterization of Pseudomonas aeruginosa biofilm-dispersed cells via c-di-GMP manipulation

    DEFF Research Database (Denmark)

    Chua, Song Lin; Hultqvist, Louise D; Yuan, Mingjun

    2015-01-01

    Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a global secondary bacterial messenger that controls the formation of drug-resistant multicellular biofilms. Lowering the intracellular c-di-GMP content can disperse biofilms, and it is proposed as a biofilm eradication strategy...... biofilms by reducing the intracellular c-di-GMP content through modulation of phosphodiesterases (PDEs). Unlike conventional protocols that demonstrate biofilm dispersal by biomass quantification, our protocols enable physiological characterization of the dispersed cells. Biomarkers of dispersed cells...

  9. San Francisco SFpark and parking information systems.

    Science.gov (United States)

    2011-01-01

    SFpark is a demonstration of a new approach to parking management that : will evaluate the effectiveness of demand-responsive pricing and real-time : information on parking availability for reducing congestion and greenhouse gas : emissions and provi...

  10. Assessment of climate change effects on Canada's National Park system.

    Science.gov (United States)

    Suffling, Roger; Scott, Daniel

    2002-03-01

    To estimate the magnitude of climate change anticipated for Canada's 38 National Parks (NPs) and Park Reserves, seasonal temperature and precipitation scenarios were constructed for 2050 and 2090 using the Canadian Centre for Climate Modelling and Analysis (CCCma) coupled model (CGCM1). For each park, we assessed impacts on physical systems, species, ecosystems and people. Important, widespread changes relate to marine and freshwater hydrology, glacial balance, waning permafrost, increased natural disturbance, shorter ice season, northern and upward altitudinal species and biome shifts, and changed visitation patterns. Other changes are regional (e.g., combined East coast subsidence and sea level rise increase coastal erosion and deposition, whereas, on the Pacific coast, tectonic uplift negates sea level rise). Further predictions concern individual parks (e.g., Unique fens of Bruce Peninsular NP will migrate lakewards with lowered water levels, but structural regulation of Lake Huron for navigation and power generation would destroy the fens). Knowledge gaps are the most important findings. For example: we could not form conclusions about glacial mass balance, or its effects on rivers and fjords. Likewise, for the East Coast Labrador Current we could neither estimate temperature and salinity effects of extra iceberg formation, nor the further effects on marine food chains, and breeding park seabirds. We recommend 1) Research on specific large knowledge gaps; 2) Climate change information exchange with protected area agencies in other northern countries; and 3) incorporating climate uncertainty into park plans and management. We discuss options for a new park management philosophy in the face of massive change and uncertainty.

  11. Protect Czech park from development

    Czech Academy of Sciences Publication Activity Database

    Kindlmann, Pavel; Křenová, Zdeňka

    2016-01-01

    Roč. 531, č. 7595 (2016), s. 448-448 ISSN 0028-0836 Institutional support: RVO:86652079 Keywords : Protect Czech park Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sci ences (social aspects to be 5.7) Impact factor: 40.137, year: 2016

  12. 'Shockley park' stirs racism row

    Science.gov (United States)

    Gwynne, Peter

    2009-07-01

    A local authority in Northern California has encountered unexpected resistance to its decision to name a park after the Nobel-prize-winning physicist William Shockley, with a coalition of churches and civic groups preparing to petition against the name at a meeting scheduled for 23 July.

  13. PLC Based Automatic Multistoried Car Parking System

    OpenAIRE

    Swanand S .Vaze; Rohan S. Mithari

    2014-01-01

    This project work presents the study and design of PLC based Automatic Multistoried Car Parking System. Multistoried car parking is an arrangement which is used to park a large number of vehicles in least possible place. For making this arrangement in a real plan very high technological instruments are required. In this project a prototype of such a model is made. This prototype model is made for accommodating twelve cars at a time. Availability of the space for parking is detecte...

  14. Evaluating urban parking policies with agent-based model of driver parking behavior

    NARCIS (Netherlands)

    Martens, C.J.C.M.; Benenson, I.

    2008-01-01

    This paper presents an explicit agent-based model of parking search in a city. In the model, “drivers” drive toward their destination, search for parking, park, remain at the parking place, and leave. The city’s infrastructure is represented by a high-resolution geographic information system (GIS)

  15. The on-street parking premium and car drivers' choice between street and garage parking

    NARCIS (Netherlands)

    Kobus, M.B.W.; Gutierrez Puigarnau, E.; Rietveld, P.; van Ommeren, J.N.

    2013-01-01

    We introduce a methodology to estimate the effect of parking prices on car drivers' choice between street and garage parking. Our key identifying assumption is that the marginal benefit of parking duration does not depend on this choice. The endogeneity of parking duration is acknowledged in the

  16. What's Ahead for our National Parks?

    Science.gov (United States)

    George, Jean Craighead

    1972-01-01

    To insure the future of our National Parks, sweeping changes must be made. Encroaching civilization at the expense of nature has forced National Park officials to consider alternatives to future development - limiting number of visitors, facilities outside the parks and curtailing vehicular traffic. (BL)

  17. SmartPark Technology Demonstration Project

    Science.gov (United States)

    2013-11-01

    The purpose of FMCSAs SmartPark initiative is to determine the feasibility of a technology for providing truck parking space availability in real time to truckers on the road. SmartPark consists of two phases. Phase I was a field operational test ...

  18. 32 CFR 634.31 - Parking.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Parking. 634.31 Section 634.31 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Traffic Supervision § 634.31 Parking. (a) The most efficient use of existing on- and off-street parking...

  19. The comparative analyses of selected aspects of conservation and management of Vietnam’s national parks

    Directory of Open Access Journals (Sweden)

    Le Thanh An

    2018-01-01

    policy makers and researchers in seeking solutions for the sustainable management of natural resources in national parks.

  20. Research Article

    African Journals Online (AJOL)

    2016-05-15

    May 15, 2016 ... Architecture, energy, technology and architecture research, a member of ... Keywords: Building Automation, Intelligent Management, ..... Ability to set activate lighting and ventilation systems in smart entry and exit car parking.

  1. Field Guide to the Plant Community Types of Voyageurs National Park

    Science.gov (United States)

    Faber-Langendoen, Don; Aaseng, Norman; Hop, Kevin; Lew-Smith, Michael

    2007-01-01

    INTRODUCTION The objective of the U.S. Geological Survey-National Park Service Vegetation Mapping Program is to classify, describe, and map vegetation for most of the park units within the National Park Service (NPS). The program was created in response to the NPS Natural Resources Inventory and Monitoring Guidelines issued in 1992. Products for each park include digital files of the vegetation map and field data, keys and descriptions to the plant communities, reports, metadata, map accuracy verification summaries, and aerial photographs. Interagency teams work in each park and, following standardized mapping and field sampling protocols, develop products and vegetation classification standards that document the various vegetation types found in a given park. The use of a standard national vegetation classification system and mapping protocol facilitate effective resource stewardship by ensuring compatibility and widespread use of the information throughout the NPS as well as by other Federal and state agencies. These vegetation classifications and maps and associated information support a wide variety of resource assessment, park management, and planning needs, and provide a structure for framing and answering critical scientific questions about plant communities and their relation to environmental processes across the landscape. This field guide is intended to make the classification accessible to park visitors and researchers at Voyageurs National Park, allowing them to identify any stand of natural vegetation and showing how the classification can be used in conjunction with the vegetation map (Hop and others, 2001).

  2. CRP-Cyclic AMP Regulates the Expression of Type 3 Fimbriae via Cyclic di-GMP in Klebsiella pneumoniae.

    Directory of Open Access Journals (Sweden)

    Ching-Ting Lin

    Full Text Available Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of PmrkA were increased in Δcrp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of PmrkHI and PmrkJ were decreased in ΔlacZΔcrp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Δcrp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of PmrkHI in the ΔlacZΔcrp strain was diminished in ΔlacZΔcrpΔmrkHI, but increased in the ΔlacZΔcrpΔmrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Δcrp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP

  3. Why travel motivations and socio-demographics matter in managing a National Park

    Directory of Open Access Journals (Sweden)

    Melville Saayman

    2009-06-01

    Full Text Available The Addo Elephant National Park is one of only a few national parks in the world that offers the Big 7 experience and is therefore one of South Africa’s prime tourism destinations. The park plays an important role in the regional economy and has become a hub for tourism development. The aim of this article is to determine the extent to which socio-demographic and behavioural and motivational indicators influence the spending of tourists to the park. A better understanding of the latter could help marketers and planners to increase the economic impact of the park. Since 2001, surveys have been conducted among tourists to the park and have included a number of socio-demographic, behavioural and motivational questions. In this analysis, 537 questionnaires were used. The methodology used includes factor analysis, cross-sectional regression analysis and pseudo-panel data analysis to determine and compare possible influences on spending. The research identifies six motives for tourists travelling to the Addo Elephant National Park; these are nature, activities, family and socialisation, escape, attractions and photography. The research found that a combination of socio-demographic and motivational factors influences visitor spending decisions. Added to this, the research confi rms that tourist attractions, including national parks, differ from one another and that the variables that influence spending therefore also differ.

  4. The Internet Marketing of Disney Theme Parks

    Directory of Open Access Journals (Sweden)

    Carol J. Auster

    2013-03-01

    Full Text Available The purpose of this study was to analyze the portrayal of gender and race in the images on the official Disney websites used to market five theme parks: the Disneyland Parks in California, Paris, Tokyo, and Hong Kong, and the Magic Kingdom in Florida. This is important because of the growth of e-commerce, Disney’s global influence, and the potential impact on those who view the images. The 452 images that had Disney human characters, human-like characters, animals, cast members, or guests were coded for gender. The main gender hypothesis, that the percentage of male-dominated images would exceed the percentage of female-dominated images, was tested using gender disparity values, which measured the gap between the percentage of male-dominated and female-dominated images. The hypothesis tended to be supported overall, and for most of the resorts (e.g., Florida, lands (e.g., Adventureland, and activities (attractions, entertainment, dining for human characters, human-like characters, animals, and cast members, but not for guests. Furthermore, the hypotheses that gender disparity values would be highest for images of animals and lowest for images of guests was supported for all five resorts, six of eight lands, and all three activities. Additional analysis also revealed the preponderance of same-sex pairings in parent–child combinations in the images. With regard to race, while the images of some theme parks displayed more racial diversity among their guests than others, in some images, individuals of different races were shown interacting whereas in others they were not. Explanations for these findings and suggestions for future research are discussed.

  5. Which age group spends the most in a national park?

    Directory of Open Access Journals (Sweden)

    Francesca Cini

    2014-06-01

    Full Text Available Age (and its changing structure amongst the wider population is one of the most relevant aspects required to better understand and forecast the needs, interests and associated consumption behaviours of tourists. This research used age to investigate the expenditure patterns amongst a sample of visitors to the Table Mountain National Park (TMNP, South Africa. In March 2010, visitors to the TMNP were found to differ significantly from those at other parks, as they were younger and most of them were foreigners. This study found that younger visitors (18–29 years were higher spenders when compared to those aged 30–49 years. As parks are generally visited by older people, this study showed the economic importance of the younger market. The research also made clear implications and recommendations for park management as to how to address these findings. Conservation implications: Conservation is dependent on funding. One of the main sources of income is tourism and tourism related activities. This research can assist marketers and managers to target the right markets in order to be more sustainable. This research also shows the importance of environmental education at an early age in order to grow awareness and to target the right markets.

  6. Parking in the city

    Czech Academy of Sciences Publication Activity Database

    Šeba, Petr

    2007-01-01

    Roč. 112, č. 4 (2007), s. 981-690W ISSN 0587-4246. [Workshop on Quantum Chaos and Localisation /3./. Warsaw, 25.05.2007-27.05.2007] R&D Projects: GA AV ČR(CZ) IAA100480501 Grant - others:GAMŠk(CZ) LC06002 Institutional research plan: CEZ:AV0Z10100521 Keywords : solvable models of nanosystems * Markov process Subject RIV: BE - Theoretical Physics Impact factor: 0.340, year: 2007

  7. Metal assessment in urban park soils in Sao Paulo 4. Alfredo Volpi (Morumbi Park)

    International Nuclear Information System (INIS)

    Camargo, Sonia P.; Figueiredo, Ana Maria G.; Pavese, Arthur C.; Gumiero, Felipe C.; Enzweiler, Jacinta

    2007-01-01

    The presence of elevated metal concentrations in soils of the urban environment has been recognized as an important source of metal intake to humans, particularly to children, which are more susceptible to the adverse effects of soil ingestion than adults. There has been little research on urban soils in Sao Paulo, a very populated city with severe pollution problems, and there is little information about metal concentration levels in public parks of Sao Paulo. As part of a project which aims metal assessment in urban park soils from Sao Paulo, in the present paper the concentration of the elements As, Ba, Cr, Sb and Zn were determined in topsoil samples (0- 5 cm and 0-20 cm) from Alfredo Volpi (Morumbi) park of Sao Paulo. Instrumental Neutron Activation Analysis (INAA) was used for metal analysis. Preliminary results showed higher concentrations of As, Ba and Sb compared with the values considered as reference for soils in Sao Paulo, according to Environmental Protection Agency of the State of Sao Paulo (CETESB). In some samples Ba showed concentration levels higher than the Prevention values reported by CETESB. (author)

  8. Marketization trajectories in the Danish road and park sectors

    DEFF Research Database (Denmark)

    Lindholst, Andrej Christian; Hansen, Morten Balle; Petersen, Ole Helby

    2016-01-01

    (as providers of maintenance services) in the municipal road and park sectors in Denmark over the past 30 years. The study draws theoretically on historical institutionalism as an interpretive framework and empirically on findings from earlier research, register data from municipal accounts as well...... as new survey data. Findings – Marketization within the road and park sectors has historically taken place through gradual changes, in particular by processes of layering and displacement, which has added up to substantial transformations in both sectors. Transformations relate to the levels of private...... sector involvement, the purpose of using private contractors, the extent of competition and the design of contractual arrangements. The road sector has been a frontrunner in this marketization process, while the park sector increasingly has been “catching up.” Originality/value – The paper contributes...

  9. 36 CFR 7.25 - Hawaii Volcanoes National Park.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Hawaii Volcanoes National Park. 7.25 Section 7.25 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.25 Hawaii Volcanoes National Park. (a...

  10. Clearance of Pseudomonas aeruginosa Foreign-Body Biofilm Infections through Reduction of the Cyclic Di-GMP Level in the Bacteria

    DEFF Research Database (Denmark)

    Christensen, Louise D.; van Gennip, Maria; Rybtke, Morten Theil

    2013-01-01

    Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections....... It has recently been established that the secondary messenger cyclic diguanosine monophosphate (c-di-GMP) functions as a positive regulator of biofilm formation in several different bacteria. In the present study we investigated whether manipulation of the c-di-GMP level in bacteria potentially can...... be used for biofilm control in vivo. We constructed a Pseudomonas aeruginosa strain in which a reduction in the c-di-GMP level can be achieved via induction of the Escherichia coli YhjH c-di-GMP phosphodiesterase. Initial experiments showed that induction of yhjH expression led to dispersal...

  11. Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

    2015-01-01

    regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed...... to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal...... in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age....

  12. The exopolysaccharide gene cluster Bcam1330-Bcam1341 is involved in Burkholderia cenocepacia biofilm formation, and its expression is regulated by c-di-GMP and Bcam1349

    DEFF Research Database (Denmark)

    Fazli, Mustafa; McCarthy, Yvonne; Givskov, Michael

    2013-01-01

    In Burkholderia cenocepacia, the second messenger cyclic diguanosine monophosphate (c-di-GMP) has previously been shown to positively regulate biofilm formation and the expression of cellulose and type-I fimbriae genes through binding to the transcriptional regulator Bcam1349. Here, we provide...... evidence that cellulose and type-I fimbriae are not involved in B. cenocepacia biofilm formation in flow chambers, and we identify a novel Bcam1349/c-di-GMP-regulated exopolysaccharide gene cluster which is essential for B. cenocepacia biofilm formation. Overproduction of Bcam1349 in trans promotes wrinkly...... matrix exopolysaccharide and to be essential for flow-chamber biofilm formation. We demonstrate that Bcam1349 binds to the promoter region of genes in the Bcam1330-Bcam1341 cluster and that this binding is enhanced by the presence of c-di-GMP. Furthermore, we demonstrate that overproduction of both c-di-GMP...

  13. Nitric oxide increases cyclic GMP levels, AMP-activated protein kinase (AMPK)alpha1-specific activity and glucose transport in human skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A S; Long, Y C; de Castro Barbosa, T

    2010-01-01

    -nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) would increase intracellular cyclic GMP (cGMP) levels and promote glucose transport. METHODS: Skeletal muscle strips were prepared from vastus lateralis muscle biopsies obtained from seven healthy men. Muscle strips were incubated in the absence or presence...... of 5 mmol/l spermine NONOate or 120 nmol/l insulin. The L6 muscle cells were treated with spermine NONOate (20 micromol/l) and incubated in the absence or presence of insulin (120 nmol/l). The direct effect of spermine NONOate and insulin on glucose transport, cGMP levels and signal transduction...... was determined. RESULTS: In human skeletal muscle, spermine NONOate increased glucose transport 2.4-fold (p GMP levels (80-fold, p

  14. Terror Park: A future theme park in 2100

    OpenAIRE

    Wright, Daniel

    2017-01-01

    In the future, tourism and entertainment could be displayed as spectacles of horror, where consumers are offered and opportunity to revisit the tragedies of the past. Current displays of death where the past is exhibited and consumed as fun, scary and as entertainment productions are widespread. The movie industry provides horror to all ages, children can be exposed to the goulash past in various forms, such as the popular book series ‘Horrible Histories’. Theme parks, rides and roller-coaste...

  15. Rural Latino youth park use: characteristics, park amenities, and physical activity.

    Science.gov (United States)

    Perry, Cynthia K; Saelens, Brain E; Thompson, Beti

    2011-06-01

    Less than half of youth engage in sufficient physical activity to achieve health benefits. Key environmental factors of park and recreation spaces may influence youth physical activity. We sought to ascertain youth characteristics and behaviors that attract youth to parks with specific amenities and encourage physical activity while at the parks in a rural, predominantly Latino community. We examined the quality of amenities in the 13 parks and recreation spaces that middle school aged youth have access to in their community using the Environmental Assessment of Parks and Recreation Spaces (EAPRS) tool. Middle school students completed surveys in the school classroom (n = 1,102) regarding park use, physical activity, and intrapersonal characteristics (e.g., motivators). We used logistic regression to identify correlates of any park use, use of higher quality field and court parks, and active and sedentary park use. Younger age, participation in an after school activity, and identification of a team as a motivator were positively associated with any park use. Use of higher quality court and field parks was associated with participation in an after school activity and being Latino. The odds of being active in the parks were greater for boys and Latinos. Older age and alcohol use are correlated with being sedentary at the park, while odds of being sedentary at the park were lower for boys and youth who met physical activity guidelines. Organized team activities may encourage active use of higher quality fields and courts parks by Latino youth; thereby, increasing their level of physical activity.

  16. THE CHARACTER CONTEXT IN THE DEVELOPMENT OF JAYENGRONO PARK

    Directory of Open Access Journals (Sweden)

    Aldrin Yusuf Firmansyah

    2009-07-01

    Full Text Available The aim of the research is to examine the context of the Willemsplein development. Willemsplein was a public urban-square in Dutch c¬o¬lonial era (plein at Jembatan Merah area. Willemsplein, which in the following time became Surabaya urban heritage, changes into a private me¬¬mo¬rial park which is known as Taman Jayeng¬rono (Jayengrono Park. The context of this park is the most important aspect in the urban-square de¬¬velopment be¬cause the attainment of the suitability and continuity of the visual-formal, memory, and meaning of the urban-square arrangement implicitely shows certain character. The research method is a qualitative des¬crip¬tive method which is implied to analyze the comparation of the arrangement of Jayengrono Park in the past and at present in three phases. The first phase is the identification of the chronological formation of Jayengrono Park by using the analysis technique of the historical period suitability (diachronic reading towards the phy¬sical arrangement (synchronic reading. The second phase is the identification of the proportion of Jayengrono Park by using the analysis technique of the measurement of the square-proportion ratio. The last phase is the iden¬tification of the place by using the analysis technique of simulation. The research shows that the Willems¬ple¬in arrangement combines the classical European open-square arrangement of the two development centers in Italy and France through the usage of the sequences of streets, rivers and bridges and the usage of the street axes as the mathematical result of the square proportion. The deletion of the intagible identitiy in Willemsplein shows that the character context cannot be attained; or it can be interpreted as the loss of the identity of the cu¬l¬tural reservation in the development of Jayengrono Park. Concurrently, it means that the development of Ja¬yeng¬rono Park is merely as an urban green open-square.

  17. Critical Role of Nitric Oxide-cGMP Cascade in the Formation of cAMP-Dependent Long-Term Memory

    Science.gov (United States)

    Aonuma, Hitoshi; Mizunami, Makoto; Matsumoto, Yukihisa; Unoki, Sae

    2006-01-01

    Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. Here we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP pathway to induce LTM. We have…

  18. Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

    Science.gov (United States)

    Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

    2014-01-01

    Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

  19. CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob disease but not Parkinson's disease and amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Patrick Oeckl

    Full Text Available BACKGROUND: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP and cyclic guanosine-3',5'-monophosphate (cGMP are important second messengers and are potential biomarkers for Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS and Creutzfeldt-Jakob disease (CJD. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS the cerebrospinal fluid (CSF concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15 had lower cAMP (-70% and cGMP (-55% concentrations in CSF compared with controls (n = 11. There was no difference in PD, PD dementia (PDD and ALS cases. Receiver operating characteristic (ROC curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC of 0.86 (cAMP and 0.85 (cGMP. We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92 and to 93% and 100% for the ratio tau/cAMP (AUC 0.99. CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.

  20. Construction and expression of a functional monoclonal antibody SZ-51 specific for GMP-140 chimeric fab fragment in Escherichia coli

    International Nuclear Information System (INIS)

    Gu Jianming; Zhang Xiaomin; Xia Lijun; Wan Haiying; Liu Yue; Li Peixia; Ruan Changgeng

    1996-04-01

    The variable region cDNAs of a monoclonal antibody SZ-51 specific for α-granule membrane protein (GMP-140) on the surface of activated human platelets were spliced with the constant region cDNA of the heavy chain CH1 and light chain k of human Ig G by means of the gene recombination techniques. The above recombinant gene was amplified by the polymerase chain reaction (PCR). The expression vector of phage plasmid pHEN1 SZ-51 Fab/Hu was constructed. The pHEN1-51 Fab/Hu was introduced into non-suppressor E. coli HB2151. The amount of expression of SZ-51 chimeric Fab/Hu measured by quantitative ELISA was about 500 μg/L. Western blot demonstrated that the SZ-51 chimeric Fab fragment could specifically bind to GMP-140. (2 figs.)

  1. Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus.

    Science.gov (United States)

    An, Jie; Durcan, Laura; Karr, Reynold M; Briggs, Tracy A; Rice, Gillian I; Teal, Thomas H; Woodward, Joshua J; Elkon, Keith B

    2017-04-01

    Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi-Goutières syndrome. A recently discovered DNA-activated type I IFN pathway, cyclic GMP-AMP synthase (cGAS), has been linked to Aicardi-Goutières syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN-stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP-AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra-performance liquid chromatography tandem mass spectrometry. Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15% of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression. © 2016, American College of Rheumatology.

  2. The effects of nitric oxide-cGMP pathway stimulation on dopamine in the medial preoptic area and copulation in DHT-treated castrated male rats.

    Science.gov (United States)

    Sato, Satoru M; Wersinger, Scott R; Hull, Elaine M

    2007-08-01

    Dopamine (DA) in the medial preoptic area (MPOA) provides important facilitative influence on male rat copulation. We have shown that the nitric oxide-cGMP (NO-cGMP) pathway modulates MPOA DA levels and copulation. We have also shown that systemic estradiol (E(2)) maintains neuronal NO synthase (nNOS) immunoreactivity in the MPOA of castrates, as well as relatively normal DA levels. This effect of E(2) on nNOS probably accounts for at least some of the previously demonstrated behavioral facilitation by intra-MPOA E(2) administration in castrates. Therefore, we hypothesized that stimulation of the MPOA NO-cGMP pathway in dihydrotestosterone (DHT)-treated castrates should restore DA levels and copulatory behaviors. Reverse-dialysis of a NO donor, sodium nitroprusside (SNP), increased extracellular DA in the MPOA of DHT-treated castrates and restored the ability to copulate to ejaculation in half of the animals. A cGMP analog, 8-Br-cGMP, also increased extracellular DA, though not as robustly, but did not restore copulatory ability. The effectiveness of the NO donor in restoring copulation and MPOA DA levels is consistent with our hypothesis. However, the lack of behavioral effects of 8-Br-cGMP, despite its increase in MPOA DA, suggests that NO may have additional mediators in the MPOA in the regulation of copulation. Furthermore, the suboptimal copulation seen in the NO donor-treated animals suggests the importance of extra-MPOA systems in the regulation of copulation.

  3. Clinical application of combined detection of serum hs-CRP, GMP-140 and cTnI in patients with coronary heart diseases

    International Nuclear Information System (INIS)

    Qin Jibao; Wu Zhaozeng

    2010-01-01

    Objective: To explore the clinical significance of changes of serum hs-CRP, GMP-140 and cTnI levels in patients with coronary heart diseases. Methods: Serum GMP-140 (with RIA), cTnI (with ELISA) and hs-CRP (with immuno turbidity method) levels were determined in 91 patients with coronary heart diseases (42 SAP, 34UAP, 15AMI) and 35 controls. Results: Serum hs-CRP, GMP-140, cTnI levels in patients with coronary heart diseases were significantly higher than those in controls (P <0.01). Among the patients with of coronary heart diseases, the magnitude of changes of the levels of serum hs-CRP, GMP-140 and cTnI levels in AMI and UAP groups were significantly larger than those in SAP group (P < 0.05). Serum hs-CRP levels were positively correlated with serum GMP-140 and cTnI levels (r = 0.6214, 0.6023, P < 0.01). Conclusion: Serum hs-CRP, GMP140 and cTnI levels were closely related to the diseases process of coronary heart diseases and were of great clinical importance for assessment of the disease and outcome prediction. (authors)

  4. The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons

    Directory of Open Access Journals (Sweden)

    Marina ePolito

    2013-11-01

    Full Text Available The NO-cGMP signaling plays an important role in the regulation of striatal function although the mechanisms of action of cGMP specifically in medium spiny neurons (MSNs remain unclear. Using genetically encoded fluorescent biosensors, including a novel Epac-based sensor (EPAC-SH150 with increased sensitivity for cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO donors in both striatonigral and striatopallidal MSNs, and this cGMP signal was controlled partially by PDE2. At the level of cAMP brief forskolin stimulations produced transient cAMP signals which differed between D1 and D2 medium spiny neurons. NO inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect that was translated and magnified downstream of cAMP, at the level of PKA. PDE2 thus appears as a critical effector of NO which modulates the post-synaptic response of MSNs to dopaminergic transmission.

  5. High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with evasion of plant immunity.

    Science.gov (United States)

    Pfeilmeier, Sebastian; Saur, Isabel Marie-Luise; Rathjen, John Paul; Zipfel, Cyril; Malone, Jacob George

    2016-05-01

    The plant innate immune system employs plasma membrane-localized receptors that specifically perceive pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')-cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic-di-GMP signalling on bacterial behaviour. © 2015 THE AUTHORS MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

  6. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

    Science.gov (United States)

    Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

    2012-05-01

    Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

  7. Lake Turkana National Parks Kenya.

    OpenAIRE

    2005-01-01

    Lake Turkana is the largest, most northerly and most saline of Africa's Rift Valley lakes and an outstanding laboratory for the study of plant and animal communities. The three National Parks are a stopover for migrant waterfowl and are major breeding grounds for the Nile crocodile and hippopotamus. The Koobi Fora deposits are rich in pre-human, mammalian, molluscan and other fossil remains and have contributed more to the understanding of Quaternary palaeoenvironments than any other site on ...

  8. Sovremennoje iskusstvo v angliskom parke

    Index Scriptorium Estoniae

    2003-01-01

    Performance-kunsti rühmituse Virus (Alan Holligan, Stewart Bennett ja Ewan Robertson Edinburghist) projekt "Sekkumine - kaasaegne kunst inglise pargis" toimub Väliskunsti muuseumis, Mikkeli muuseumis ja selle ümbruses. Inspiratsiooniks on Kadrioru park ning parginäitused Mikkeli ja Väliskunsti muuseumis. Radical Loyalty projektist, millele pani aluse Chris Evans (Glasgow) 2002. a. ja mille raames plaanitakse skulptuuripargi rajamist Järvakandisse. Evansi projekt presentatsiooni formaadis toimub Mikkeli muuseumis video ja fotode abil

  9. Feasibility of Wind Energy Parks

    International Nuclear Information System (INIS)

    Villar, Jose

    2000-01-01

    The paper discuss the feasibility of wind energy parks including aspects of supply and demand of energy, costs of generation and risks of investment associated. The paper introduce to the situation of wind energy in the word and specifically in Spain, describes the legal framework in promotion of renewables in Spain, the analysis of revenues and the risk of this business in the european market

  10. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING.

    Science.gov (United States)

    Zhang, Xu; Shi, Heping; Wu, Jiaxi; Zhang, Xuewu; Sun, Lijun; Chen, Chuo; Chen, Zhijian J

    2013-07-25

    The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2'-OH of GMP and 5'-phosphate of AMP, and the other between 3'-OH of AMP and 5'-phosphate of GMP. This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages. The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Procedures development and methodology of control for application of good manufacture practices (GMP) on human blood irradiation

    International Nuclear Information System (INIS)

    Boghi, Claudio

    2008-01-01

    The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of leukocytes. The implementation of the procedures will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies of the procedures in order to establish a GMP (Good Manufacturing Practices) were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaS0 4 :Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, traceability and calibration. The PMMA and Gafchromic dosimetric systems have shown a better performance and were adopted on studies of irradiators qualification that are necessary to implementation of GMP. The irradiation tests have been done in a Gammacell 220 irradiator. The developed procedures can be adapted for different kinds of gamma irradiators, allowing implanting a quality assurance program and a GMP for blood irradiation. (author)

  12. Role of cyclic GMP in cells with the properties of smooth muscle cultured from the rat myometrium

    International Nuclear Information System (INIS)

    Krall, J.F.; Morin, A.

    1986-01-01

    Cells growing in culture with previously described properties of rat uterine smooth muscle accumulated 45 Ca 2+ from the medium. Ca 2+ uptake by these cells was stimulated by the addition to the medium of 8-bromo-cGMP but not by 8-bromo-cAMP. Ca 2+ uptake was also stimulated by carbachol and by the nitro-vasodilator nitroprusside. Although cholinergic agonists have been shown previously to stimulate contraction but not cGMP synthesis in the rat myometrium, both carbachol and nitroprusside stimulated cGMP production by the cultured cells. These results suggested the cells had cholinergic receptor-medicated functions that reflected some neurotransmitter-sensitive properties of uterine smooth muscle in situ. When determined by a specific radioligand binding assay, subcellular fractions of the cultured cells bound muscarinic cholinergic agonists and antagonists with affinities expected of the muscarinic receptor. The cells were also sensitive to the β-adrenergic catecholamine agonist isoproterenol, which stimulated cAMP production but not Ca 2+ uptake. Carbachol failed to inhibit isoproterenol-dependent cAMP production, which is an important property of the cholinergic receptor in uterine smooth muscle in situ. These results suggest some but not all acetylcholine-sensitive properties of uterine smooth muscle may be retained in cell culture

  13. Islet isolation and GMP, ISO 9001:2000: what do we need--a 3-year experience.

    Science.gov (United States)

    Hengster, P; Hermann, M; Pirkebner, D; Draxl, A; Margreiter, R

    2005-10-01

    Pancreatic islet cell isolation and transplantation has been performed for many years at several institutions. Although all institutions aim to produce high-quality islets, applied standards widely deviate from standards in the pharmaceutical industry. The legal situation within the European Union has changed requirements for setting up and running such a laboratory. The process is now clearly defined as a production of a pharmaceutical and therefore must be licensed by federal authorities. Analysis of workload for establishing an islet isolation program that fulfil GMP and ISO 9001 criteria including an estimation of costs and the impact of such a system on the isolation process. The definition of quality parameters and documentation is a central issue of all islet isolation laboratories. Therefore, GMP and ISO 9001:2000 do not add additional work per se. On the other hand, clear guidelines, a clear policy, working place descriptions, forms, checklists, and, particularly standard operating procedures, are instrumental for smooth functioning within the department. Collection of data such as errors, improvement measures, and preventive measures reduces subsequent costs. A clear definition of responsibilities minimizes organizational problems. Steering of inspection devices prevents bias errors and validating the processes clearly points out incorrect assumptions. Documentation helps to prove the correctness of the production at any time and is of use also for scientific evaluations. We strongly feel that GMP criteria are mandatory and together with an ISO 9001:2000 quality management system offers significant advantages for the process of islet isolation and a continuous improvement process.

  14. A Practical Application of Statistical Gap Analysis in National Park Management in Costa Rica

    Directory of Open Access Journals (Sweden)

    Aguirre González, Juan Antonio

    2009-04-01

    Full Text Available If the tourism growth predicted materialized as tourism for Costa Rica protected areas would see major increases. A study conducted in Volcan Poas National Park and Volcan Turrialba National Park two of Costa Rica leading volcanic crater parks was undertaken to make available to national parks and protected areas managers, a procedure, that could be use: to measure using an adapted form of the expectations disconfirmation theory the satisfaction of visitors to Costa Rica national parks, and to evaluate if the results could be used for establishing the areas of the park infrastructure, services and recreational options that needed improvement and management decisions to enhance visitor's satisfaction. The sample included 1414 surveys The findings indicates that the procedure adapted base on the expectations-disconfirmation model was proven helpful in: a getting the information to help “zero in”, the man-agement decisions in the short and medium term and for the development of the Tourist Management Plans that is to say being developed in the 2 sites, b guiding park managers in the resource allocation process, under the conditions of scarcity that are so common in developing countries, c facilitating regular monitoring of the conditions, with a simple and quick methodology that can be used for “day to day” decisions and more sophisticated statistical analysis d identifying the areas in the management of protected areas that need further analysis and in that way is contributing to the development of the long term socio-economic research programs in national parks, e the “real” importance of the information and education activities in national parks, combination of activities that seems to be critical to enhance “consumer satisfaction” among the visitors to national parks everywhere and particularly as a means of understanding whether visitors needs and expectations are met, whether they receive what they should and as a context for

  15. Urban Heat Islands (UHI) and the influence of city parks within the urban environment.

    Science.gov (United States)

    Garcia, W.; Shandas, V.; Voelkel, J.; Espinoza, D.

    2016-12-01

    Urban Heat Islands (UHI) and the influence of city parks within the urban environment.As cities grow outward and their populations increase the Urban Heat Island (UHI) phenomena becomes an ever more important topic to reducing environmental stressors. When UHI combines with human sensitivities such as pre-existing health conditions, and other vulnerabilities, finding an effective way to cool our cities is a matter of life and death. One way to cool an area is to introduce vegetation; which is abundant is in city parks. This study measures the cooling effect and temperature gradient of city parks; characterizing the relationship between the cooling effects within parks and surrounding neighborhoods. Past studies of the UHI are largely based on satellite images and, more recently, car traverses across that describe the ambient temperatures. The present project aims to understand the effects of parks on the UHI by asking two research questions: (1) how do the physical characteristics and designs of city parks impact the variation in ambient temperatures? And (2) what effect does the park have on cooling the surrounding neighborhoods? We address these questions by using a bicycle mounted with a temperature probe, and a series of geospatial analytics. The bicycle collects temperature data every one second, and the traverse intervals are an hour long to prevent normal fluctuations of daily temperature. Preliminary analysis shows that there is a temperature gradient within the parks (Figure 1). Further, the average temperature of the urban park could cool the surrounding area by upwards of 2°C, depending on the physical characteristics of then park and neighborhood. Our results suggest that the role of smaller parks and their design can reduce heat stress particularly among the vulnerable populations. These results can help urban planners make informed decisions when developing future city infrastructure.

  16. Visitation in island parks: indicators as a tool for management

    Directory of Open Access Journals (Sweden)

    Ginessa Corrêa Lemos

    2013-12-01

    Full Text Available Park visitation has been increasing every year; however, the majority of the protected areas have no satisfactory and qualified administrative structure to control visitation, especially when island ecosystems are considered. The State Park of Ilhabela (PEIb is a good example of this, and was therefore selected for this study, which hoped to identify indicators for better management of park visitation. In order to select indicators to be used as a reference for this purpose, this study employed the Bountîle – Base of observation for nautical and terrestrial purposes within islands - developed by French researchers for the National Park of Port-Cros, and complemented this with guidelines from the Brazilian Ministry of Environment and other authors. These led to the selection of the following indicators: a opportunities of recreation for a diverse public; b visitation security; c satisfaction with the experience; d minimal environmental impact; e spinoff of socioeconomic development of the surrounding community. Based on the PEIb analyses, 20 management indicators were identified using the following criteria: uses and users; climatic conditions; well-being of the residents; security; profile of the visitor; well-being of the visitors; behavior of the visitors; certification, management, and institutional integration. The criteria of the indicators is greatly diversified, as it is believed that such diversity is essential to encompass the varied aspects that must be considered by a visitation management system in a conservation area. The indicators are flexible, and can be changed anytime, so that they will always be in harmony with the goals of the park management plan. In order to be efficient, they should be feasible economically, technically, and operationally. It is essential that indicators and protocols be discussed and tested with park workers and local actors, ensuring active management and continuous monitoring.

  17. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization.

    Science.gov (United States)

    Li, Xin; Shu, Chang; Yi, Guanghui; Chaton, Catherine T; Shelton, Catherine L; Diao, Jiasheng; Zuo, Xiaobing; Kao, C Cheng; Herr, Andrew B; Li, Pingwei

    2013-12-12

    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-β gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and IFN-β reporter assays of cGAS mutants demonstrated that interactions at both DNA binding sites are essential for cGAS activation. Mutagenesis and DNA binding studies showed that the two sites bind dsDNA cooperatively and that site B plays a critical role in DNA binding. The structure of mouse cGAS bound to dsDNA and 2',5' cGAMP provided insight into the catalytic mechanism of cGAS. These results demonstrated that cGAS is activated by dsDNA-induced oligomerization. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

    Directory of Open Access Journals (Sweden)

    Geneviève Pèépin

    2017-10-01

    Full Text Available Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1 by low-dose camptothecin (CPT can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40 large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development.

  19. Molecular cloning and functional characterization of porcine cyclic GMP-AMP synthase.

    Science.gov (United States)

    Wang, Jiang; Chu, Beibei; Du, Lili; Han, Yingqian; Zhang, Xuemei; Fan, Shuangshuang; Wang, Yueying; Yang, Guoyu

    2015-06-01

    Cyclic GMP-AMP synthase (cGAS), which belongs to the nucleotidyltransferase family, recognizes cytosolic DNA and induces the type I interferon (IFN) pathway through the synthesis of the second messenger cGAMP. In this study, porcine cGAS (p-cGAS) was identified and its tissue distribution, subcellular localization, and functions in innate immunity were characterized. The coding sequence of p-cGAS is 1494 bp long, encodes 497 amino acids, and is most similar (74%) to Bos taurus cGAS. p-cGAS mRNA is abundant in the spleen, duodenum, jejunum, and ileum. The subcellular distribution of p-cGAS is not only in the cytosol, but also on the endoplasmic reticulum (ER) membrane. The overexpression of wild-type p-cGAS in porcine kidney epithelial cells, but not its catalytically inactive mutants, induced IFN-β expression, which was dependent on STING and IRF3. However, the downregulation of p-cGAS by RNA interference markedly reduced IFN-β expression after pseudorabies virus (PRV) infection or poly(dA:dT) transfection. These results demonstrate that p-cGAS is an important DNA sensor, required for IFN-β activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Maintenance of cyclic GMP-AMP homeostasis by ENPP1 is involved in pseudorabies virus infection.

    Science.gov (United States)

    Wang, Jiang; Lu, Shao-Fang; Wan, Bo; Ming, Sheng-Li; Li, Guo-Li; Su, Bing-Qian; Liu, Jiao-Yang; Wei, Yu-Shuang; Yang, Guo-Yu; Chu, Bei-Bei

    2018-03-01

    In a previous study, we demonstrated that porcine cyclic GMP-AMP (cGAMP) synthase (cGAS) catalyzes cGAMP production and is an important DNA sensor for the pseudorabies virus (PRV)-induced activation of interferon β (IFN-β). Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) has recently been identified as the hydrolase of cGAMP in rodents, but its role in porcine cells is not clear. Our recent study demonstrated that porcine ENPP1 is responsible for the homeostasis of cGAMP and is critical for PRV infection. Porcine ENPP1 mRNA is predominantly expressed in muscle. PRV infection was enhanced by ENPP1 overexpression and attenuated by silencing of ENPP1. During PRV infection, the activation of IFN-β and NF-κB was reduced in ENPP1 overexpressed cells and promoted in ENPP1 knockdown cells. Investigation of the molecular mechanisms of ENPP1 during PRV infection showed that ENPP1 hydrolyzed cGAMP in PRV-infected or cGAMP-transfected cells and inhibited IRF3 phosphorylation, reducing IFN-β secretion. These results, combined with those for porcine cGAS, demonstrate that ENPP1 acts coordinately with cGAS to maintain the reservoir of cGAMP and participates in PRV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. cGMP-Dependent Protein Kinase Inhibitors in Health and Disease

    Directory of Open Access Journals (Sweden)

    Jens Schlossmann

    2013-02-01

    Full Text Available cGMP-dependent protein kinases (PKG exhibit diverse physiological functions in the mammalian system e.g., in vascular and gastrointestinal smooth muscles, in platelets, in kidney, in bone growth, nociception and in the central nervous system. Furthermore, PKG were found in insects and in the malaria parasite Plasmodium falciparum. Two different genes of PKG exist: a the PKG-I gene that is expressed as cytosolic PKG-Iα or PKG-Iβ isoform, and b the PKG-II gene, which expresses the membrane associated PKG-II protein. The enzyme kinetics, the localization and the substrates of these PKG enzymes differ utilizing different physiological functions. Various inhibitors of PKG were developed directed against diverse functional regions of the kinase. These inhibitors of PKG have been used to analyse the specific functions of these enzymes. The review article will summarize these different inhibitors regarding their specificity and their present applications in vitro and in vivo. Furthermore, it will be discussed that the distinct inhibition of the PKG enzymes could be used as a valuable pharmacological target e.g., in the treatment of cardiovascular diseases, diarrhea, cancer or malaria.

  2. GMP-grade platelet lysate enhances proliferation and migration of tenon fibroblasts.

    Science.gov (United States)

    Carducci, Augusto; Scafetta, Gaia; Siciliano, Camilla; Carnevale, Roberto; Rosa, Paolo; Coccia, Andrea; Mangino, Giorgio; Bordin, Antonella; Vingolo, Enzo Maria; Pierelli, Luca; Lendaro, Eugenio; Ragona, Giuseppe; Frati, Giacomo; De Falco, Elena

    2016-01-01

    Tenon's fibroblasts (TFs), widely employed as in vitro model for many ophthalmological studies, are routinely cultured with FBS. Platelet Lysate (PL), a hemoderivate enriched with growth factors and cytokines has been largely tested in several clinical applications and as substitute of FBS in culture. Here, we investigate whether PL can exert biological effects on TF populations similarly to other cell types. Results show that PL significantly enhances cell proliferation and migration vs. FBS, without influencing cell size/granularity. Upregulation of EGF, VEGF, KDR, MMP2-9, FAK mRNA levels also occurs and phosphorylation of AKT but not of ERK1/2 is significantly enhanced. The inhibition of the PI3kinase/AKT pathway with the specific inhibitor wortmannin, decreases PL-induced cell migration but not proliferation. Condition supernatants containing PL show increased bioavailability of Nitric Oxide and reduced levels of 8-Iso-PGF2-alpha, correlating with cell proliferation and migration. Pro-angiogenic/inflammatory soluble factors (GRO, Angiogenin, EGF, I-309, PARC) are exclusively or greater expressed in media containing PL than FBS. GMP-grade PL preparations positively influence in vitro biological effects of TFs representing a suitable and safer alternative to FBS.

  3. An ant-plant mutualism through the lens of cGMP-dependent kinase genes.

    Science.gov (United States)

    Malé, Pierre-Jean G; Turner, Kyle M; Doha, Manjima; Anreiter, Ina; Allen, Aaron M; Sokolowski, Marla B; Frederickson, Megan E

    2017-09-13

    In plant-animal mutualisms, how an animal forages often determines how much benefit its plant partner receives. In many animals, foraging behaviour changes in response to foraging gene expression or activation of the cGMP-dependent protein kinase (PKG) that foraging encodes. Here, we show that this highly conserved molecular mechanism affects the outcome of a plant-animal mutualism. We studied the two PKG genes of Allomerus octoarticulatus, an Amazonian ant that defends the ant-plant Cordia nodosa against herbivores. Some ant colonies are better 'bodyguards' than others. Working in the field in Peru, we found that colonies fed with a PKG activator recruited more workers to attack herbivores than control colonies. This resulted in less herbivore damage. PKG gene expression in ant workers correlated with whether an ant colony discovered an herbivore and how much damage herbivores inflicted on leaves in a complex way; natural variation in expression levels of the two genes had significant interaction effects on ant behaviour and herbivory. Our results suggest a molecular basis for ant protection of plants in this mutualism. © 2017 The Author(s).

  4. Configuration study of large wind parks

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Stefan

    2003-07-01

    In this thesis, layouts of various large-scale wind parks, using both AC as well as DC, are investigated. Loss modelling of the wind park components as well as calculations of the energy capture of the turbines using various electrical systems are performed, and the energy production cost of the various park configurations is determined. The most interesting candidate for a DC transmission based wind park was investigated more in detail, the series DC wind park. Finally, the power quality impact in the PCC (point of common coupling) was studied. It was found that from an energy capture point of view, the difference in energy production between various wind turbine systems is very small. Of all the investigated wind park configurations, the wind park with the series connected DC wind turbines seems to have the best potential to give the lowest energy production cost, if the transmission distance is longer then 10-20 km. Regarding the series DC wind park it was found that it is the most difficult one to control. However, a control algorithm for the series park and its turbines was derived and successfully tested. Still, several more details regarding the control of the series wind park has to be dealt with.

  5. Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.

    Science.gov (United States)

    Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

    2015-01-01

    Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 μmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  6. The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.

    Directory of Open Access Journals (Sweden)

    Kátia R L Schwarz

    Full Text Available This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP and cGMP-dependent kinase (PKG during in vitro maturation (IVM on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs, and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII, cGMP levels, lipid content in oocytes (OO, transcript abundance for genes involved in lipolysis (ATGL and lipid droplets (PLIN2 in cumulus cells (CC and OO, and presence of phosphorylated (active hormone sensitive lipase (HSLser563 in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme with 10-5M sildenafil (SDF during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05 and did not affect on maturation rate (84.3±6.4% MII. Fetal calf serum (FCS in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05. FCS increased lipid content in OO (40.1 FI, p<0.05 compared to BSA (34.6 FI, while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05. PKG inhibitor (KT5823 reversed this effect (38.9 FI, p<0.05. ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI compared to its use in either or none of the culture periods (34.2 FI, p<0.05. Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.

  7. Barrier Free Park Design for the Disabled Persons: A Case Study of the KLCC Park

    Directory of Open Access Journals (Sweden)

    Hazreena Hussein

    2006-12-01

    Full Text Available Making green spaces accessible to as many people as possible is now mainstream thinking in planning, design and management. Green spaces call be internal or external, integrated or separated with building. The purpose of this paper is to investigate and identify the characteristics in creating green spaces for the disabled persons' to enjoy. This research is dedicated specially for those with sensory disabilities, i.e. visually impaired' persons.The research will focus on issues and constraints that seem to impede their basic necessity, which is a barrier to them in enjoying the green spaces alongside their sighted peers. However, this research can also be applied to other users such as children, elderly people, pregnant women and parent with strollers. An example of a case study selected is the Kuala Lumpur City Centre (KLCC Park, where the author will explore the objectives and design principles of the Park. The findings are intended to provide recommendation on appropriate design criteria for the visually impaired persons in helping to maintain and manage green spaces. This is also to provide general information on different type of plants, highlighting their value and use in design as advised by landscape architects.

  8. Analysis of Parking Reliability Guidance of Urban Parking Variable Message Sign System

    Directory of Open Access Journals (Sweden)

    Zhenyu Mei

    2012-01-01

    Full Text Available Operators of parking guidance and information systems (PGIS often encounter difficulty in determining when and how to provide reliable car park availability information to drivers. Reliability has become a key factor to ensure the benefits of urban PGIS. The present paper is the first to define the guiding parking reliability of urban parking variable message signs (VMSs. By analyzing the parking choice under guiding and optional parking lots, a guiding parking reliability model was constructed. A mathematical program was formulated to determine the guiding parking reliability of VMS. The procedures were applied to a numerical example, and the factors that affect guiding reliability were analyzed. The quantitative changes of the parking berths and the display conditions of VMS were found to be the most important factors influencing guiding reliability. The parking guiding VMS achieved the best benefit when the parking supply was close to or was less than the demand. The combination of a guiding parking reliability model and parking choice behavior offers potential for PGIS operators to reduce traffic congestion in central city areas.

  9. Denali Park wolf studies: Implications for Yellowstone

    Science.gov (United States)

    Mech, L. David; Meier, Thomas J.; Burch, John W.

    1991-01-01

    The Northern Rocky Mountain Wolf Recovery Plan approved by the U.S. Fish and Wildlife Service (1987) recommends re-establishment of wolves (Canis lupus) in Yellowstone National Park. Bills proposing wolf re-establishment in the Park have been introduced into the U.S. House and Senate. However, several questions have been raised about the possible effects of wolf re-establishment on other Yellowstone Park fauna, on human use of the Park and on human use of surrounding areas. Thus the proposed wolf re-establishment remains controversial.Information pertinent to some of the above questions is available from a current study of wolf ecology in Denali National Park and Preserve, Alaska, which we began in 1986. Although Denali Park differs from Yellowstone in several ways, it is also similar enough in important respects to provide insight into questions raised about wolf re-establishment in Yellowstone.

  10. Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

    Directory of Open Access Journals (Sweden)

    Matías Castro

    Full Text Available An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs and degraded by phosphodiesterases (PDEs. We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319 that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process.

  11. Decreased levels of guanosine 3', 5'-monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease.

    Science.gov (United States)

    Ugarte, Ana; Gil-Bea, Francisco; García-Barroso, Carolina; Cedazo-Minguez, Ángel; Ramírez, M Javier; Franco, Rafael; García-Osta, Ana; Oyarzabal, Julen; Cuadrado-Tejedor, Mar

    2015-06-01

    Levels of the cyclic nucleotides guanosine 3', 5'-monophosphate (cGMP) or adenosine 3', 5'-monophosphate (cAMP) that play important roles in memory processes are not characterized in Alzheimer's disease (AD). The aim of this study was to analyse the levels of these nucleotides in cerebrospinal fluid (CSF) samples from patients diagnosed with clinical and prodromal stages of AD and study the expression level of the enzymes that hydrolyzed them [phosphodiesterases (PDEs)] in the brain of AD patients vs. For cGMP and cAMP CSF analysis, the cohort (n = 79) included cognitively normal participants (subjective cognitive impairment), individuals with stable mild cognitive impairment or AD converters (sMCI and cMCI), and mild AD patients. A high throughput liquid chromatography-tandem mass spectrometry method was used. Interactions between CSF cGMP or cAMP with mini-mental state examination (MMSE) score, CSF Aβ(1-42) and CSF p-tau were analysed. For PDE4, 5, 9 and 10 expression analysis, brains of AD patients vs. controls (n = 7 and n = 8) were used. cGMP, and not cAMP levels, were significantly lower in the CSF of patients diagnosed with mild AD when compared with nondemented controls. CSF levels of cGMP showed a significant association with MMSE-diagnosed clinical dementia and with CSF biomarker Aβ42 in AD patients. Significant increase in PDE5 expression was detected in temporal cortex of AD patients compared with that of age-matched healthy control subjects. No changes in the expression of others PDEs were detected. These results support the potential involvement of cGMP in the pathological and clinical development of AD. The cGMP reduction in early stages of AD might participate in the aggravation of amyloid pathology and cognitive decline. © 2014 British Neuropathological Society.

  12. Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

    Science.gov (United States)

    Kulesekara, Hemantha; Lee, Vincent; Brencic, Anja; Liberati, Nicole; Urbach, Jonathan; Miyata, Sachiko; Lee, Daniel G.; Neely, Alice N.; Hyodo, Mamoru; Hayakawa, Yoshihiro; Ausubel, Frederick M.; Lory, Stephen

    2006-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action. PMID:16477007

  13. CAR SECURITY ENHANCEMENT IN PARKING AREAS

    OpenAIRE

    NANYONGA BERINDA; AYESIGA LINDSEY PATRA; BYEKWASO FAISAL; NATULINDA LADAN

    2017-01-01

    Over time, car thefts have been reported within Kampala parking areas. This has been majorly due to inefficient security measures of the available parking systems which focus mainly on the car and not the driver, making parking management a challenge. The focus of this survey was to explore the requirements of a new system called Car to Driver Matching Security System to enhance security of cars in Kampala, in particular, from the experience of 15 people. The data collected was then analyzed ...

  14. Open Days: information on CERN parking

    CERN Document Server

    2013-01-01

    The organising team for the Open Days (28-29 September) would like to inform you that some parking sites in Meyrin and Prévessin will have to be kept free as of 18 September for the installation of tents and marquees.   Next week, CERN Management will address parking concerns and give you more information on other parking possibilities. The Open Day organising team thanks you for your cooperation and apologises for any inconvenience.

  15. Advanced parking management systems : a cross-cutting study : taking the stress out of parking

    Science.gov (United States)

    2007-01-01

    This study examines advanced parking management systems (APMSs) in three venues: airports, central business districts, and transit park-and-ride locations. Specifically, the systems examined in this study provide directional and space availability in...

  16. Amphibians of Olympic National Park

    Science.gov (United States)

    ,

    2000-01-01

    Amphibians evolved from fishes about 360 million years ago and were the first vertebrates adapted to life on land. The word amphibian means "double life." It refers to the life history of many amphibians, which spend part of their life in water and part on land. There are three major groups of amphibians: salamanders, frogs, and toads, and caecilians. Salamanders, frogs, and toads can be found in Olympic National Park (ONP), but caecilians live only in tropical regions. Many amphibians are generalist predators, eating almost any prey they can fit into their mouths.

  17. Ecological Resilience of Small Urban Parks

    DEFF Research Database (Denmark)

    JasmaniI, Zanariah Binti

    consists of several sub-variables or attributes. The attributes of physical characteristics include park size, land use, park shape, proximity to a road and the presence of a water element. Elements relating to vegetation diversity, such as the presence and share of native and exotic species, presence....... Birds and butterflies react differently to various park maintenance practices (e.g. mowing). Based on the overall results, findings and discussion of the key features for bird and butterfly richness and abundance, study IV proposes nine recommendations for small urban parks to improve their ecological...

  18. Mode choice and shopping mall parking

    OpenAIRE

    Ersoy, Fulya Yüksel; Ersoy, Fulya Yuksel

    2012-01-01

    In this thesis, I analyze individuals' mode choice decisions and shopping mall's parking space pricing behavior. Individuals have three choices: first they may come to the mall by car in which case they have to park, second they may come by public transportation, or they do not visit the mall and go for their outside option. The mall determines the price of the good and the parking fee after the government sets public transportation fare. I find that the equilibrium parking fees are always le...

  19. Park Accessibility Impacts Housing Prices in Seoul

    Directory of Open Access Journals (Sweden)

    Jin Han Park

    2017-01-01

    Full Text Available Housing prices are determined by a variety of factors, including the features of the building and the neighborhood environment, and a potential buyer decides to buy a house after reviewing these factors and concluding that it is worth the price. We used Hedonic Price Methods to find the relationship between monetary value of house and access conditions to urban parks. Two meaningful results were discovered in this study: first, as the distance from the park increases, the value of the park inherent in the housing price decreases; second, the greater walking accessibility, to the park, the higher the park value inherent in housing prices. Despite presenting shorter distances to walk and more entrances, poorly accessible zones were deemed as such due to the necessity of crossing an arterial road. This indicates that the results can define accessibility not as the Euclidian distance but as the shortest walking distance while considering crossroads and park entrances. The results of this study have significant implications for urban park economic impact analyses in Seoul. Also, the increase in housing prices closer to parks supports the idea that access is dependent on the residents’ socioeconomic status. Lastly, the results of this study can improve walking accessibility to the park.

  20. iParking: An Intelligent Indoor Location-Based Smartphone Parking Service

    OpenAIRE

    Liu, Jingbin; Chen, Ruizhi; Chen, Yuwei; Pei, Ling; Chen, Liang

    2012-01-01

    Indoor positioning technologies have been widely studied with a number of solutions being proposed, yet substantial applications and services are still fairly primitive. Taking advantage of the emerging concept of the connected car, the popularity of smartphones and mobile Internet, and precise indoor locations, this study presents the development of a novel intelligent parking service called iParking. With the iParking service, multiple parties such as users, parking facilities and service p...

  1. Smart Parking Management Pilot Project: A Bay Area Rapid Transit (BART) District Parking Demonstration

    OpenAIRE

    Shaheen, Susan; Rodier, Caroline; Eaken, Amanda M.

    2005-01-01

    This report presents early findings from an application of advanced parking technologies to maximize existing parking capacity at the Rockridge BART station, which was launched in December 2004 in the East San Francisco Bay Area. The smart parking system includes traffic sensors that count the number of vehicles entering and exiting the parking lots at the station. A reservation system allows travelers to reserve spaces by Internet, personal digital assistant (PDA), phone, and cell phone. The...

  2. Omora Ethnobotanical Park and the UNESCO Cape Horn Biosphere Reserve

    Directory of Open Access Journals (Sweden)

    Eugene C. Hargrove

    2008-12-01

    Full Text Available The biocultural conservation and research initiative of Omora Ethnobotanical Park and the UNESCO Cape Horn Biosphere Reserve was born in a remote part of South America and has rapidly expanded to attain regional, national, and international relevance. The park and the biosphere reserve, led by Ricardo Rozzi and his team, have made significant progress in demonstrating the way academic research supports local cultures, social processes, decision making, and conservation. It is a dynamic hive of investigators, artists, writers, students, volunteers, and friends, all exploring ways to better integrate academia and society. The initiative involves an informal consortium of institutions and organizations; in Chile, these include the University of Magallanes, the Omora Foundation, and the Institute of Ecology and Biodiversity, and in the United States, the University of North Texas, the Omora Sub-Antarctic Research Alliance, and the Center for Environmental Philosophy at the University of North Texas. The consortium intends to function as a hub through which other institutions and organizations can be involved in research, education, and biocultural conservation. The park constitutes one of three long-term socio-ecological research sites in Chile of the Institute of Ecology and Biodiversity.

  3. Key Features of Governance in Brazilian Science and Technology Parks

    Directory of Open Access Journals (Sweden)

    Milton Correia Sampaio Filho

    2017-09-01

    Full Text Available The situation of Brazilian Science and Technology Parks (STPs operation led to the field research. Even with the public policy of stimulus and support of associations, nothing has been mapped on the dissemination of results (economic growth and regional development. This scenario instigates the question: What are the governance characteristics of Brazilian Science and Technology Parks? A empirical field research was developed, taking into consideration the possibility of replication trought the registration of the choice criteria in the multiple cases and trought research detalhes and data colection. Eight STPs (TECNOPUC - Porto Alegre, Valetec - Novo Hamburgo, Tecnosinos - Sao Leopoldo, Unicamp, CIATEC and TECHNOPARK - Campinas, Rio Park - Rio de Janeiro and SergipeTec participated in research. The results and considerations about the research question allows to infer the little effectiveness of governance (without qualitative or quantitative performance indicators is possibly caused by tensions characterized by elements such as heterogeneity in characteristics of organizations that are part of STPs, lack of consensus on common goals, pressure forces and influences affecting trusts, nonconformity standards and personal and organizational preferences. Leadership relations championed by the government and / or companies can negatively influence the STP's performance as a whole.

  4. 36 CFR 7.39 - Mesa Verde National Park.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Mesa Verde National Park. 7... SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.39 Mesa Verde National Park. (a) Visiting of... the admission of commercial automobiles and buses to Mesa Verde National Park, contained in § 5.4 of...

  5. A city park on top of shops and a dike

    NARCIS (Netherlands)

    van Veelen, P.C.; Voorendt, M.Z.; van der Zwet, C; Kothuis, Baukje; Kok, Matthijs

    2017-01-01

    The Roof Park ('Dakpark’) is an elevated park on a former railway yard in the Delfshaven quarter in Rotterdam. The park is located on top of the roof of a new shopping centre, which includes a parking garage (hence its name, ‘dak’ means ‘roof’). The park is the

  6. Preferences, benefits, and park visits: a latent class segmentation analysis

    NARCIS (Netherlands)

    Kemperman, A.D.A.M.; Timmermans, H.J.P.

    2006-01-01

    This study describes and predicts segments of urban park visitors to support park planning and policy making. A latent class analysis is used to identify segments of park users who differ regarding their preferences for park characteristics, benefits sought in park visits, and sociodemographics.

  7. Characterization of the cGMP-dependent protein kinase SmcGK1 of Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Silke Leutner

    2011-06-01

    Full Text Available Schistosomes are trematode parasites and of worldwide medical importance for humans and animals. Growth and development of these parasites require a specific host environment, but also permanent communication processes between the two genders. Accumulating molecular evidence indicates that the responsible interactions are mediated by signal transduction processes. Conserved signaling molecules were identified, and first approaches made for their characterization. However, no representative of the conserved family of cGMP-dependent protein kinases (cGKs has been described in this parasite yet. Within the Schistosoma mansoni genome data-set we identified cGK homologs, of which one was investigated in more detail in this study. We present the cloning of SmcGK1, whose sequence shows homology to cGKs of higher eukaryotes. SmcGK1 was found to be gender-independently transcribed in adult schistosomes. The occurrence of SmcGK1 sense and antisense transcripts suggests that the expression of this gene is controlled at the post-transcriptional level. In situ hybridization experiments demonstrated a gonad-preferential expression profile in both genders indicating a role of SmcGK1, at least during sexual development of schistosomes. Using a cGK-specific inhibitor to treat adult schistosomes in vitro finally resulted in a multifaceted phenotype including slow motion, oocyte congestion, and reduced egg production.Esquistossomos são parasitas trematodos de importância médica em todo o mundo para o homem e os animais. O crescimento e o desenvolvimento destes parasitas requerem um ambiente específico do hospedeiro, mas também um processo de comunicação permanente entre parasitas dos dois sexos. Evidência molecular tem se acumulado e indica que as interações são mediadas por processos de transdução de sinal. Moléculas sinalizadoras conservadas foram identificadas, e as primeiras abordagens têm sido feitas para sua caracterização. Contudo, não foi

  8. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses.

    Science.gov (United States)

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J; Stunden, H James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R; Cain, Jason E; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

    2017-10-03

    Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40) large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development. IMPORTANCE Recent studies suggest that low-dose DNA-damaging compounds traditionally used in cancer therapy can have opposite effects on antiviral responses, either suppressing (with the example of CPT) or potentiating (with the example of doxorubicin) them. Our work demonstrates that the minor DNA damage promoted by low-dose CPT can also trigger strong antiviral responses, dependent on the presence of viral oncogenes. Taken together, these results call for caution in the therapeutic use of low-dose chemotherapy agents to modulate antiviral responses in humans. Copyright © 2017 Pépin et al.

  9. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases.

    Science.gov (United States)

    Gao, Daxing; Li, Tuo; Li, Xiao-Dong; Chen, Xiang; Li, Quan-Zhen; Wight-Carter, Mary; Chen, Zhijian J

    2015-10-20

    TREX1 is an exonuclease that digests DNA in the cytoplasm. Loss-of-function mutations of TREX1 are linked to Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE) in humans. Trex1(-/-) mice exhibit autoimmune and inflammatory phenotypes that are associated with elevated expression of interferon (IFN)-induced genes (ISGs). Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates the IFN pathway. Upon binding to DNA, cGAS is activated to catalyze the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce IFNs and other cytokines. Here we show that genetic ablation of cGas in Trex1(-/-) mice eliminated all detectable pathological and molecular phenotypes, including ISG induction, autoantibody production, aberrant T-cell activation, and lethality. Even deletion of just one allele of cGas largely rescued the phenotypes of Trex1(-/-) mice. Similarly, deletion of cGas in mice lacking DNaseII, a lysosomal enzyme that digests DNA, rescued the lethal autoimmune phenotypes of the DNaseII(-/-) mice. Through quantitative mass spectrometry, we found that cGAMP accumulated in mouse tissues deficient in Trex1 or DNaseII and that this accumulation was dependent on cGAS. These results demonstrate that cGAS activation causes the autoimmune diseases in Trex1(-/-) and DNaseII(-/-) mice and suggest that inhibition of cGAS may lead to prevention and treatment of some human autoimmune diseases caused by self-DNA.

  10. The impact of cGMP compliance on consumer confidence in dietary supplement products

    International Nuclear Information System (INIS)

    Crowley, Richard; FitzGerald, Libby Harvey

    2006-01-01

    The FDA estimates that US citizens spend more than $ 8.5 billion a year on dietary supplements and world wide the market is estimated at more than $ 60 billion. However, although a majority of consumers express confidence in the safety of these products, 74% believe the government should be more involved in ensuring that these products are safe and efficacious. Recent regulatory initiatives such as the imminent adoption of cGMPs for dietary supplements in the US, implementation of cGMPs in Canada and the recent EU dietary supplement initiative represent legislative and industry response to public clamor for more comprehensive oversight of dietary supplements. Regardless of mandated practices, the majority of dietary supplement manufacturers have done an excellent job of protecting the safety and quality of their products. The promulgation of these cGMPs will help ensure consumers that equal standards are followed throughout the industry. For some companies with established processes based on existing food or pharmaceutical cGMP regulations, the transition will be relatively painless while, for many, it will represent a significant increase in the level of documentation and testing. However, consumers deserve and demand that products meet standards for safety and quality and the implementation of cGMPs for these products are an important first step. Although the cGMPs are designed to ensure products are safe from a standpoint of identity, purity, quality, strength and composition, they do not address preclinical or clinical testing of ingredients for safety or efficacy. This would involve ingredients meeting the requirements of Generally Recognized as Safe (GRAS) status or going through the New Dietary Ingredient (NDI) process

  11. GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC.

    Directory of Open Access Journals (Sweden)

    Natalie Fekete

    Full Text Available BACKGROUND: Mesenchymal stromal cells (MSC have gained importance in tissue repair, tissue engineering and in immunosupressive therapy during the last years. Due to the limited availability of MSC in the bone marrow, ex vivo amplification prior to clinical application is requisite to obtain therapeutic applicable cell doses. Translation of preclinical into clinical-grade large-scale MSC expansion necessitates precise definition and standardization of all procedural parameters including cell seeding density, culture medium and cultivation devices. While xenogeneic additives such as fetal calf serum are still widely used for cell culture, its use in the clinical context is associated with many risks, such as prion and viral transmission or adverse immunological reactions against xenogeneic components. METHODS AND FINDINGS: We established animal-free expansion protocols using platelet lysate as medium supplement and thereby could confirm its safety and feasibility for large-scale MSC isolation and expansion. Five different GMP-compliant standardized protocols designed for the safe, reliable, efficient and economical isolation and expansion of MSC was performed and MSC obtained were analyzed for differentiation capacity by qPCR and histochemistry. Expression of standard MSC markers as defined by the International Society for Cellular Therapy as well as expression of additional MSC markers and of various chemokine and cytokine receptors was analysed by flow cytometry. Changes of metabolic markers and cytokines in the medium were addressed using the LUMINEX platform. CONCLUSIONS: The five different systems for isolation and expansion of MSC described in this study are all suitable to produce at least 100 millions of MSC, which is commonly regarded as a single clinical dose. Final products are equal according to the minimal criteria for MSC defined by the ISCT. We showed that chemokine and integrin receptors analyzed had the same expression pattern

  12. Impacts of national parks on tourism: a case study from a prominent alpine national park

    International Nuclear Information System (INIS)

    Getzner, M.

    2008-01-01

    National parks and other categories of protected areas are often assumed to enhance regional economic development due to park tourism. The current study attempts to estimate the impact of the Hohe Tauern national park (Austria) on tourism by exploring whether and to what extent the national park may have had an influence on tourism development. For most national park communities, the results suggest that the establishment of the national park had some impact by enforcing an already positive trend or by weakening or reversing a negative trend of tourism. However, breakpoint tests exhibit turning points up to several years after the establishment of the park, indicating that taking a national park as the basis for tourism development is a medium to long term development strategy. In the short term, the impact of a national park on tourism is not measurable. Tourism increased by 1 to 3% annually after the breakpoint, indicating that the establishment of a national park has to be incorporated into the tourism and development strategy of a region right from the start. The causal relationship between the establishment of the national park and tourism development may be weak, in particular in communities where the difference between the actual and the forecast numbers of overnight stays is small. Marketing national park tourism and building up a brand or distinctive label may therefore contribute to regional development particularly in the long term. [it

  13. Mammal inventories for eight National Parks in the Southern Colorado Plateau Network

    Science.gov (United States)

    Bogan, Michael A.; Geluso, Keith; Haymond, Shauna; Valdez, Ernest W.

    2007-01-01

    Historically, the Colorado Plateau has been the subject of many geological and biological explorations. J. W. Powell explored and mapped the canyon country of the Colorado River in 1869 (Powell 1961). C. H. Merriam, V. Bailey, M. Cary, and other employees of the Bureau of Biological Survey conducted biological explorations of the area in the late 1800s. In recent times, researchers such as S. D. Durrant (1952), Durrant and Robinson (1962), D. M. Armstrong (1972), J. S. Findley et al. (1975), D. F. Hoff meister (1986), and J. Fitzgerald et al. (1994) have made considerable contributions to our understanding of the fauna of the Colorado Plateau. Despite earlier efforts, biological details on many regions of the plateau have remained insufficiently explored. In an effort to gather valuable biological information, the National Park Service (NPS) initiated a nationwide program to inventory vascular plants and vertebrates on NPS lands (Stuart 2000). The U.S. Geological Survey, Fort Collins Science Center, Arid Lands Field Station became a cooperator on this effort in 2001, when we began mammalian inventories on five parks within the NPS Southern Colorado Plateau Network (SCPN): Aztec Ruins National Monument (AZRU), El Morro National Monument (ELMO), Petroglyph National Monument (PETR), Salinas Pueblo Missions National Monument (SAPU), and Yucca House National Monument (YUHO). Existing baseline data on mammalian occurrences in these parks varied from very sparse to moderate, with little information available for most parks. In most cases, information was insufficient to assess the status of species of local concern. A final report on inventory efforts on these five parks was submitted in February 2004 (Bogan et al. 2004). In 2003, biologists from the Arid Lands Field Station began work on three additional parks in the SCPN: Bandelier National Monument (BAND), Chaco Culture National Historical Park (CHCU), and El Malpaís National Monument (ELMA). The primary emphasis at

  14. Development of Science and Technology Parks in Poland: Opportunities for New Modes of Cooperation in the Biopharmaceutical Industry

    Directory of Open Access Journals (Sweden)

    Michal Staszkow

    2017-03-01

    Full Text Available The aim of the article is to verify the development of science and technology parks in Poland as well as the opportunities of development of new forms of cooperation with the use of science and technology parks in the bio pharmaceutical industry in Poland. The first section reviews the origins and definitions of science and technology parks in order to clarify and systematize the concepts used in existing research and practice. Subsequently, the ensuing sections discuss the evolution of science and technology parks and different organizational models of STPS. Further, the analysis centres on science and technology parks in Poland. Then the importance of science and technology parks for the development of new modes of cooperation in the bio pharmaceutical industry is elaborated upon. The paper ends with a set of implications and conclusions.

  15. Radiological safety and GMP in the bulk batch manufacturing, formulation and dispensing of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Thulasidhasan, A.; Tiwary, Bikash; Kumar, Uma Sheri; Kale, Pooja; Tiwary, Richa; Gaurav, Ananad; Shah, B.K.; Topale, P.D.; Prabhakar, G.; Sachdev, S.S.

    2010-01-01

    Full text: Radiopharmaceutical Program of BRIT is involved in the manufacturing of ready to use radiopharmaceuticals for therapy for the last three decades. Ready to use Radiopharmaceutical products include, 131 I-Sodium iodide solution and capsules for thyroid carcinoma and metastatic lesions, 131 I MIBG injection for diagnosis and therapy of adrenal medullae tumors and their mets, 153 Sm-EDTMP injection and 32 P- Sodium orthophosphate injection for bone pain palliative treatment. BRIT's radiopharmaceutical production facility is a radioisotope laboratory classified as Type-III facility for handling radioisotopes of Group-II, Group-III and Group-IV approved by AERB. This facility meets all the radiological safety requirements as per AERB guidelines. Production of above mentioned radiopharmaceuticals is carried out in Production Plants (PP), β, γ Glove boxes (GB) and Fume hoods (FH). Typical production procedure involves bulk processing, formulation, sterilization and dispensing of doses. Production Plants (PP) are exclusively designed facilities to carry out the production in a radiologically safe manner, at the same time maintaining aseptic conditions required for injectables as per the current GMP. Each production plant has a leak tight Isolator box, made up of high quality SS which has provisions for remote handling devices like, Tongs, dispensing systems, service points for vacuum, gas, compressed air, water and electric power. This Isolator box is shielded from all sides by required amount of lead (2 inch or 4 inch), and has an access port called 'Transport Port Box' with double door transport lock and is equipped with a trolley. Two filter unit systems are fitted at the top of the plant and each unit comprises of activated Charcoal filter and HEPA filter in tandem, this in turn is connected to special exhaust meant for radioactive gases. Similarly, the designs of β, γ Glove boxes (GB) and Fume hoods (FH) also incorporate all radiological safety features

  16. How do New York City’s Recent Rezonings Align With its Goals for Park Accessibility?

    Directory of Open Access Journals (Sweden)

    Vicki Been

    2010-01-01

    Full Text Available In 2007, New York City adopted a long-term sustainability plan that announced a goal of ensuring that almost every New Yorker lives within a ten minute walk of a park of substantial size. At the same time, policymakers are rewriting the City’s land use map through an unprecedented series of neighborhood level rezonings that involve changing the use type and residential capacity of affected lots or groups of lots. Despite the confluence of these interventions, no research has analyzed how the rezonings interact with the City’s park infrastructure, and specifically, whether residential capacity changes in areas close to parks differ from those in areas further away. In this research, we employ a database of every tax lot in New York City to investigate how well the City-initiated rezonings correlate with the goal of providing New Yorkers with good access to the City’s parks. Our results indicate a mixed picture; while most ‘upzoned’ lots (lots where residential capacity was added were near parks, we also find that the majority of ‘downzoned’ lots (lots where residential capacity was reduced were also close to parks. The net impact of these rezonings was a modest increase in residential capacity for the City as a whole, but the increases were disproportionately focused in areas further from parks.

  17. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

    International Nuclear Information System (INIS)

    Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M.; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

    2014-01-01

    Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation

  18. Free and total GMP (glycomacropeptide contents of milk during bovine lactation Variação dos teores de GMP (glicomacropeptídeo livre e total no leite bovino durante a lactação

    Directory of Open Access Journals (Sweden)

    Andréa Maria Furlanetti

    2003-12-01

    Full Text Available Individual milk samples taken every two weeks from parturition to the end of lactation from 34 animals of three different herds and breeds were analyzed for free-GMP. A milk pool of each herd was analyzed for free and total GMP (released from k-casein by the action of rennin and the data were correlated with sanitary conditions of animal and udder, phase of lactation and milk production. Most udder problems were concentrated near parturition, with few and spaced occurrences of clinical mastitis. The Californian Mastitis Test (CMT results showed oscillations compatible with the phases of lactation period and environmental conditions. The widest variations in free-GMP occurred as a function of lactation period and as a consequence of clinical or subclinical mastitis. Higher levels were observed at the beginning of lactation (5.87mg L-1 of sialic acid, becoming normal with mean values of about 3.30mg L-1 at the end of the second month, and increasing again during the final third of lactation. On average, the same trends were observed for total GMP released by commercial rennet, beginning with slightly high values (35.59mg L-1, becoming normal by the sixth month with values close to 27.15mg L-1, and rising gradually up to the end of lactation, with 58.35mg L-1 of sialic acid. These results prove to be useful for the correct interpretation of tests applied to milk selection with respect to proteolytic status or even to restrain frauds by the addition of whey to milk.Amostras quinzenais, desde o parto até o final do período de lactação, obtidas de 34 vacas de três diferentes raças e propriedades, foram analisadas quanto à presença de GMP livre. Um "pool" das amostras quinzenais de cada rebanho foi analisada tanto para o conteúdo de GMP livre quanto para o GMP total (liberado da k-caseína pela ação da renina, correlacionando-os com as condições sanitárias do animal e do úbere, à fase da lactação e à produção de leite. A maioria

  19. Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

    Science.gov (United States)

    Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

    2002-03-26

    Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

  20. Nitric oxide-soluble guanylyl cyclase-cyclic GMP signaling in the striatum: New targets for the treatment of Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Anthony R West

    2011-06-01

    Full Text Available Striatal nitric oxide (NO-producing interneurons play an important role in the regulation of corticostriatal synaptic transmission and motor behavior. Striatal NO synthesis is driven by concurrent activation of NMDA and dopamine (DA D1 receptors. NO diffuses into the dendrites of medium-sized spiny neurons (MSNs which contain high levels of NO receptors called soluble guanylyl cyclases (sGC. NO-mediated activation of sGC leads to the synthesis of the second messenger cGMP. In the intact striatum, transient elevations in intracellular cGMP primarily act to increase neuronal excitability and to facilitate glutamatergic corticostriatal transmission. NO-cGMP signaling also functionally opposes the inhibitory effects of DA D2 receptor activation on corticostriatal transmission. Not surprisingly, abnormal striatal NO-sGC-cGMP signaling becomes apparent following striatal DA depletion, an alteration thought to contribute to pathophysiological changes observed in basal ganglia circuits in Parkinson’s disease (PD. Here, we discuss recent developments in the field which have shed light on the role of NO-sGC-cGMP signaling pathways in basal ganglia dysfunction and motor symptoms associated with PD and L-DOPA-induced dyskinesias.

  1. Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp.

    Science.gov (United States)

    Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

    2015-09-08

    Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s(-1)). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals.

  2. Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB

    DEFF Research Database (Denmark)

    Fazli, Mustafa; Rybtke, Morten Levin; Steiner, Elisabeth

    2017-01-01

    Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm...... formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm......-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high...

  3. Determining service improvement priority in a zoological park

    Directory of Open Access Journals (Sweden)

    Ronald Sukwadi

    2014-01-01

    Full Text Available Purpose: The objective of this research is to determine the service improvement priority based on tourist judgements and experiences on service quality in a zoological park. Design/methodology/approach: A powerful integrated model was developed to acquire accurate critical service attributes and their priority ranks that can promote tourist satisfaction and tourist loyalty. Drawing on relevant literature, a model was proposed based on tourists’ perspective by integrating structural equation model (SEM with SERVQUAL and refined Kano models. Findings and Originality/value: Based on the analysis of data through some quantitative tools, the study helped in prioritizing the critical service attributes, which, if adopted, improved, and implemented, could lead to satisfaction of tourists. This will help a zoological park to propose more efficient and value-added improvement policies of the service Research limitations/implications: The primary limitation in the scope its sample. Because the study involved only one Zoological Park in Indonesia, the results cannot be generalized across a national wide spectrum. Originality/value: The study was the first to successfully apply an integrated model in tourism sector, which has previously not been used. The study has hopefully opened up an area of research and methodology that could provide considerable further benefits for researchers interested in this topic. Moreover, the integrated model has proven to be useful in determining the priority rank of critical service quality attributes.

  4. ARCHITECTURAL PLACEMAKING OF TECHNOLOGY PARKS: ENCOURAGEMENT OF CREATIVE THINKING

    Directory of Open Access Journals (Sweden)

    Rykov Kirill Nikolaevich

    2012-10-01

    Full Text Available The present-day postindustrial or information-oriented society features an ever growing role of creative and intellectual abilities. This trend facilitates transformation of the workforce, as the portion of manual labor is reduced, while the one of intellectual labor goes up. As a result, architectural placemaking has to meet the new requirements driven by the specific nature of social and physiological constituents of the headwork. The aim of the article is the identification of new challenges that the high-quality architecture has to meet in its efforts to service the intellectual labour environment. For illustrative purposes, the author has chosen research and technology parks as the most typical postindustrial facilities. According to the author, intellectual constituents of the architectural practice represent systematic and research components. This division is the result of the analysis of research and technology parks. The author has made an attempt to identify special conditions of effective creativity in architectural practice. They include comfort, availability, information system development, calm, sociality, significance and variability. The list of conditions and general methods of their implementation presented by the author can be used in a wide range of project goals connected with the architectural design of research and technology parks and stimulation of creative potential of the people involved.

  5. Contrary to Common Observations in the West, Urban Park Access Is Only Weakly Related to Neighborhood Socioeconomic Conditions in Beijing, China

    Directory of Open Access Journals (Sweden)

    Xingyue Tu

    2018-04-01

    Full Text Available Parks provide critical ecosystem services to urban residents. Park access critically determines how parks are used by residents. Many existing studies, which mostly have been conducted in developed countries, reported that park access disproportionately benefits the socioeconomically advantaged groups. To test if this observation also holds true in developing countries, we examined the park access and its relationship with socioeconomic conditions in Beijing, China. We used a buffering method and a road network-based analysis to calculate the park access of 130 neighborhoods, and applied the Pearson correlation to examine how neighborhood park access is related to socioeconomic conditions. Our results showed that (1 the park access decreased from 76% in the downtown areas to 24% in the suburbs; (2 the correlation coefficients (r between socioeconomic conditions and park access were all smaller than 0.3 (p < 0.05—that is, explaining less than 8% of the variability. Our study indicated that neighborhood socioeconomic conditions were only weakly associated with park access in Beijing and did not support the common phenomenon in western countries. Such a contradiction might be explained by the fact that park planning in Beijing is funded and administered by the city government and influenced by the central government’s policy, whereas in most developed countries market sectors play a critical role in park planning. Our research suggested that urban planning funded by governments, when aimed at improving the wellbeing of all urban residents, may effectively reduce potential environmental inequalities.

  6. Exploring Attitudes, Perceived Norms, and Personal Agency: Insights Into Theory-Based Messages to Encourage Park-Based Physical Activity in Low-Income Urban Neighborhoods.

    Science.gov (United States)

    Groshong, Lisa; Stanis, Sonja A Wilhelm; Kaczynski, Andrew T; Hipp, J Aaron; Besenyi, Gina M

    2017-02-01

    Public parks hold promise for promoting population-level PA, but studies show a significant portion of park use is sedentary. Past research has documented the effectiveness of message-based strategies for influencing diverse behaviors in park settings and for increasing PA in nonpark contexts. Therefore, to inform message-based interventions (eg, point-ofdecision prompts) to increase park-based PA, the purpose of this study was to elicit insights about key attitudes, perceived norms, and personal agency that affect park use and park-based PA in low-income urban neighborhoods. This study used 6 focus groups with youth and adults (n = 41) from low-income urban areas in Kansas City, MO, to examine perceptions of key attitudinal outcomes and motivations, perceived norms, key referents, and personal agency facilitators and constraints that affect park use and park-based PA. Participant attitudes reflected the importance of parks for mental and physical health, with social interaction and solitude cited as key motivations. Of 10 themes regarding perceived norms, influential others reflected participants' ethnic makeup but little consensus emerged among groups. Social and safety themes were cited as both facilitators and constraints, along with park offerings and setting. Information about attitudes, perceived norms, and personal agency can increase understanding of theoretically derived factors that influence park-based PA and help park and health professionals create communication strategies to promote PA.

  7. Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

    International Nuclear Information System (INIS)

    Barbosa, A.L.R.; Pinheiro, C.A.; Oliveira, G.J.; Torres, J.N.L.; Moraes, M.O.; Ribeiro, R.A.; Vale, M.L.; Souza, M.H.L.P.

    2012-01-01

    Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K + ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K + ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E 2 - (PGE 2 , 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE 2 ) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE 2 ) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE 2 ; 8 µg/paw) and the ATP-sensitive K + channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE 2 ; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels

  8. The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-β during Chlamydia trachomatis infection.

    Science.gov (United States)

    Zhang, Yugen; Yeruva, Laxmi; Marinov, Anthony; Prantner, Daniel; Wyrick, Priscilla B; Lupashin, Vladimir; Nagarajan, Uma M

    2014-09-01

    IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-β expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3' to 5' exonuclease, reduced IFN-β expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP-AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-β expression. We determined that cGAS is required for IFN-β expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-β, coculture of cells depleted for either STING or cGAS rescued IFN-β expression. These data demonstrate that cyclic GMP-AMP produced in infected cGAS(+)STING(-) cells can migrate into adjacent cells via gap junctions to function in trans in cGAS(-)STING(+) cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-β expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-β expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis. Copyright © 2014 by The American Association of Immunologists, Inc.

  9. Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience.

    Science.gov (United States)

    Becherucci, Valentina; Piccini, Luisa; Casamassima, Serena; Bisin, Silvia; Gori, Valentina; Gentile, Francesca; Ceccantini, Riccardo; De Rienzo, Elena; Bindi, Barbara; Pavan, Paola; Cunial, Vanessa; Allegro, Elisa; Ermini, Stefano; Brugnolo, Francesca; Astori, Giuseppe; Bambi, Franco

    2018-05-02

    The use of platelet lysate (PL) for the ex-vivo expansion of mesenchymal stromal/stem cells (MSCs) was initially proposed by Doucet et al. in 2005, as an alternative to animal serum. Moreover, regulatory authorities discourage the use of fetal bovine serum (FBS) or other animal derivatives, to avoid risk of zoonoses and xenogeneic immune reactions. Even if many studies investigated PL composition, there still are some open issues related to its use in ex-vivo MSC expansion, especially according to good manufacturing practice (GMP) grade protocols. As an authorized cell factory, we report our experience using standardized PL produced by Azienda Ospedaliero Universitaria Meyer Transfusion Service for MSC expansion according to a GMP grade clinical protocol. As suggested by other authors, we performed an in-vitro test on MSCs versus MSCs cultured with FBS that still represents the best way to test PL batches. We compared 12 MSC batches cultured with DMEM 5% PL with similar batches cultured with DMEM 10% FBS, focusing on the MSC proliferation rate, MSC surface marker expression, MSC immunomodulatory and differentiation potential, and finally MSC relative telomere length. Results confirmed the literature data as PL increases cell proliferation without affecting the MSC immunophenotype, immunomodulatory potential, differentiation potential and relative telomere length. PL can be considered a safe alternative to FBS for ex-vivo expansion of MSC according to a GMP grade protocol. Our experience confirms the literature data: a large number of MSCs for clinical applications can be obtained by expansion with PL, without affecting the MSC main features. Our experience underlines the benefits of a close collaboration between the PL producers (transfusion service) and the end users (cell factory) in a synergy of skills and experiences that can lead to standardized PL production.

  10. The Role of Aquaporin 1 Activated by cGMP in Myocardial Edema Caused by Cardiopulmonary Bypass in Sheep

    Directory of Open Access Journals (Sweden)

    Fang-bao Ding

    2013-11-01

    Full Text Available Background/Aims: Most cardiac procedures involve the use of cardiopulmonary bypass (CPB, which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB. Methods: ODQ, a specific inhibitor of soluble guanylate cyclase (sGC, was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA. mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively. Results: The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (pin vitro experiments showed the same changing trends as in vivo. Conclusion: cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.

  11. Salvinorin A preserves cerebral pial artery autoregulation after forebrain ischemia via the PI3K/AKT/cGMP pathway

    Directory of Open Access Journals (Sweden)

    H.P. Dong

    2018-03-01

    Full Text Available This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR control group received DMSO (1 µL/kg immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg and LY294002 (10 µM, L-NAME (10 μM, or norbinaltorphimine (norBIN, 1 μM after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF were also measured. The phosphorylation of AKT (p-AKT was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.

  12. 45 CFR 3.23 - Parking.

    Science.gov (United States)

    2010-10-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE Traffic Regulations § 3.23 Parking. (a) A person may not stand (vehicle... sign, crosswalk, or traffic control signal; (5) In a double-parked position; (6) At a curb painted...

  13. Parking guidance - modelling, simulation and impact assessment

    NARCIS (Netherlands)

    Jonkers, E.; Noort, M. van; Veen, J.L. van der

    2011-01-01

    Intelligent parking services that help drivers with reservation of a parking spot, navigation and automated payment have reached the deployment phase. These services may provide significant benefits to drivers and municipalities. Drivers may experience an increase in comfort and lower and more

  14. Parking regulations on the CERN sites

    CERN Multimedia

    General Infrastructure Services Department

    2010-01-01

    The site surveillance service is also responsible for supervising compliance with the parking regulations on the CERN site. In that context, it ensures that the following rules are complied with on the CERN car park: Vehicles may not be left on a CERN car park for longer than 5 consecutive working days. However, CERN users are entitled to leave their vehicles parked at CERN for a longer period in the car park near Building 588 , subject to completing the application form "Demande d'autorisation pour un stationnement de longue durée" (application for a long-term parking permit) and sending it to the Reception and Access Control Service (access.surveillance@cern.ch) prior to departure.   Parking spaces, which are in short supply in many crowded areas of the CERN site, must not be occupied by abandoned vehicles/wrecks. The service organizes the disposal of such vehicles. Any CERN users wishing to get rid of a private vehicle parked on one of the CERN car pa...

  15. Private Sector Thinking Saves Park U.

    Science.gov (United States)

    Breckon, Donald; Gibb, John

    2000-01-01

    Recounts the restructuring and resulting survival of Park University (Missouri) over the last decade. A process of evaluating the university's competitive strategy resulted in changes in tuition pricing; development of the Park School of Distance Learning, which serves primarily military installations; minority student marketing; and development…

  16. The external cruising costs of parking

    NARCIS (Netherlands)

    Inci, E.; van Ommeren, J.N.; Kobus, Martijn

    2017-01-01

    Existing work emphasizes the importance of traffic congestion externalities, but typically ignores cruising-for-parking externalities. We estimate the marginal external cruising costs of parking—that is, the time costs that an additional parked car imposes on drivers by inducing them to cruise for

  17. Full-Automatic Parking registration and payment

    DEFF Research Database (Denmark)

    Agerholm, Niels; Lahrmann, Harry; Jørgensen, Brian

    2014-01-01

    As part of ITS Platform North Denmark, a full-automatic GNSS-based parking payment (PP) system was developed (PP app). On the basis of the parking position and parking time, the PP app can determine the price of parking and collect the amount from the car owner’s bank account. The driver...... is informed about any initiation of PP via SMS message. If the driver finds the payment erroneous, it can be cancelled via SMS message. Parking attendants can check if the car in question has an ongoing payment for parking. To handle the problems with GNSS-based positioning in densely built-up areas......, an advanced map matching algorithm was integrated in the PP app. 24 of the participating vehicles used the PP app, and 58 parking payments were carried out without errors. In a few cases, the wrong parking area was selected. This was due to lack of information in the map rather than errors in the map matching...

  18. Modelling of fire spread in car parks

    NARCIS (Netherlands)

    Noordijk, L.M.; Lemaire, A.D.

    2005-01-01

    Currently, design codes assume that in a car park fire at most 3-4 vehicles are on fire at the same time. Recent incidents in car parks have drawn international attention to such assumptions and have raised questions as to the fire spreading mechanism and the resulting fire load on the structure.

  19. Markov chain of distances between parked cars

    International Nuclear Information System (INIS)

    Seba, Petr

    2008-01-01

    We describe the distribution of distances between parked cars as a solution of certain Markov processes and show that its solution is obtained with the help of a distributional fixed point equation. Under certain conditions the process is solved explicitly. The resulting probability density is compared with the actual parking data measured in the city. (fast track communication)

  20. Mapping wilderness character in Olympic National Park

    Science.gov (United States)

    James Tricker; Peter Landres; Jennifer Chenoweth; Roger Hoffman; Scott Ruth

    2013-01-01

    The Olympic Wilderness was established November 16, 1988 when President Ronald Reagan signed the Washington Park Wilderness Act. A total of 876,447 acres or 95% of Olympic National Park (OLYM) was designated as wilderness and became a part of the National Wilderness Preservation System, wherein wilderness character would be preserved. The purpose of this project was to...

  1. Tourists' motivations for visiting Kakum National Park, Ghana ...

    African Journals Online (AJOL)

    Tourists' motivations for visiting Kakum National Park, Ghana. ... four main motivations of tourists who visited the park, namely adventure, education, ... Park were influenced by varied combinations of intrinsic and extrinsic motivational factors.

  2. The Tankwa Karoo National Park feral goat population: A unique ...

    African Journals Online (AJOL)

    The Tankwa Karoo National Park feral goat population: A unique genetic ... The feral goats from Tankwa Karoo National Park in the Northern Cape, South Africa, ... Park and former Tankwa goats, now kept on a private farm were genotyped, ...

  3. Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes

    OpenAIRE

    Wang, Yan; Su, Guo-Hua; Zhang, Fang; Chu, Jing-Xue; Wang, Yun-Shan

    2015-01-01

    Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdow...

  4. Evaluation of fisher restoration in Olympic National Park and the Olympic Recovery Area: 2013 Annual Progress Report

    Science.gov (United States)

    Patricia J. Happe; Kurt J. Jenkins; Michael K. Schwartz; Jeffrey C. Lewis; Keith B. Aubry

    2014-01-01

    With the translocation and release of 90 fishers [Pekania pennanti (formerly Martes pennanti)] from British Columbia to Olympic National Park during 2008-2010, the National Park Service and Washington Department of Fish and Wildlife accomplished the first phase of fisher restoration in Washington State. Beginning in 2013, we initiated a new research project to...

  5. The relationship of volunteerism to the physical activity and health of older adults in a metropolitan park setting

    Science.gov (United States)

    Julie S. Son; Andrew J. Mowen; Deborah L. Kerstetter

    2007-01-01

    Volunteers are an important resource to park districts. However, it is less clear how well park districts benefit the health and well-being of their volunteers. The objectives of the current study were: 1) to try to replicate findings of positive relationships of volunteering to physical health and physical activity, and 2) to extend previous research to examine the...

  6. Estimating Areas of Vulnerability: Sea Level Rise and Storm Surge Hazards in the National Parks

    Science.gov (United States)

    Caffrey, M.; Beavers, R. L.; Slayton, I. A.

    2013-12-01

    The University of Colorado Boulder in collaboration with the National Park Service has undertaken the task of compiling sea level change and storm surge data for 105 coastal parks. The aim of our research is to highlight areas of the park system that are at increased risk of rapid inundation as well as periodic flooding due to sea level rise and storms. This research will assist park managers and planners in adapting to climate change. The National Park Service incorporates climate change data into many of their planning documents and is willing to implement innovative coastal adaptation strategies. Events such as Hurricane Sandy highlight how impacts of coastal hazards will continue to challenge management of natural and cultural resources and infrastructure along our coastlines. This poster will discuss the current status of this project. We discuss the impacts of Hurricane Sandy as well as the latest sea level rise and storm surge modeling being employed in this project. In addition to evaluating various drivers of relative sea-level change, we discuss how park planners and managers also need to consider projected storm surge values added to sea-level rise magnitudes, which could further complicate the management of coastal lands. Storm surges occurring at coastal parks will continue to change the land and seascapes of these areas, with the potential to completely submerge them. The likelihood of increased storm intensity added to increasing rates of sea-level rise make predicting the reach of future storm surges essential for planning and adaptation purposes. The National Park Service plays a leading role in developing innovative strategies for coastal parks to adapt to sea-level rise and storm surge, whilst coastal storms are opportunities to apply highly focused responses.

  7. Identifying features of pocket parks that may be related to health promoting use

    DEFF Research Database (Denmark)

    Peschardt, Karin Kragsig; Stigsdotter, Ulrika K.; Schipperijn, Jasper

    2016-01-01

    . The results show that ‘green features’ do not seem to be of crucial importance for ‘socialising’ whereas, as expected, features promoting gathering should be prioritised. For ‘rest and restitution’, the main results show that ‘green ground cover’ and ‘enclosed green niches’ are important, while ‘disturbing......Urban green spaces have been shown to promote health and well-being and recent research indicates that the two primary potentially health promoting uses of pocket parks are ‘rest and restitution’ and ‘socialising’. The aim of this study is to identify features in pocket parks that may support...... features’ (playground, view outside park) should be avoided. The results add knowledge about the features which support the health promoting use of pocket parks to the existing body of research....

  8. iParking: an intelligent indoor location-based smartphone parking service.

    Science.gov (United States)

    Liu, Jingbin; Chen, Ruizhi; Chen, Yuwei; Pei, Ling; Chen, Liang

    2012-10-31

    Indoor positioning technologies have been widely studied with a number of solutions being proposed, yet substantial applications and services are still fairly primitive. Taking advantage of the emerging concept of the connected car, the popularity of smartphones and mobile Internet, and precise indoor locations, this study presents the development of a novel intelligent parking service called iParking. With the iParking service, multiple parties such as users, parking facilities and service providers are connected through Internet in a distributed architecture. The client software is a light-weight application running on a smartphone, and it works essentially based on a precise indoor positioning solution, which fuses Wireless Local Area Network (WLAN) signals and the measurements of the built-in sensors of the smartphones. The positioning accuracy, availability and reliability of the proposed positioning solution are adequate for facilitating the novel parking service. An iParking prototype has been developed and demonstrated in a real parking environment at a shopping mall. The demonstration showed how the iParking service could improve the parking experience and increase the efficiency of parking facilities. The iParking is a novel service in terms of cost- and energy-efficient solution.

  9. iParking: An Intelligent Indoor Location-Based Smartphone Parking Service

    Directory of Open Access Journals (Sweden)

    Liang Chen

    2012-10-01

    Full Text Available Indoor positioning technologies have been widely studied with a number of solutions being proposed, yet substantial applications and services are still fairly primitive. Taking advantage of the emerging concept of the connected car, the popularity of smartphones and mobile Internet, and precise indoor locations, this study presents the development of a novel intelligent parking service called iParking. With the iParking service, multiple parties such as users, parking facilities and service providers are connected through Internet in a distributed architecture. The client software is a light-weight application running on a smartphone, and it works essentially based on a precise indoor positioning solution, which fuses Wireless Local Area Network (WLAN signals and the measurements of the built-in sensors of the smartphones. The positioning accuracy, availability and reliability of the proposed positioning solution are adequate for facilitating the novel parking service. An iParking prototype has been developed and demonstrated in a real parking environment at a shopping mall. The demonstration showed how the iParking service could improve the parking experience and increase the efficiency of parking facilities. The iParking is a novel service in terms of cost- and energy-efficient solution.

  10. iParking: An Intelligent Indoor Location-Based Smartphone Parking Service

    Science.gov (United States)

    Liu, Jingbin; Chen, Ruizhi; Chen, Yuwei; Pei, Ling; Chen, Liang

    2012-01-01

    Indoor positioning technologies have been widely studied with a number of solutions being proposed, yet substantial applications and services are still fairly primitive. Taking advantage of the emerging concept of the connected car, the popularity of smartphones and mobile Internet, and precise indoor locations, this study presents the development of a novel intelligent parking service called iParking. With the iParking service, multiple parties such as users, parking facilities and service providers are connected through Internet in a distributed architecture. The client software is a light-weight application running on a smartphone, and it works essentially based on a precise indoor positioning solution, which fuses Wireless Local Area Network (WLAN) signals and the measurements of the built-in sensors of the smartphones. The positioning accuracy, availability and reliability of the proposed positioning solution are adequate for facilitating the novel parking service. An iParking prototype has been developed and demonstrated in a real parking environment at a shopping mall. The demonstration showed how the iParking service could improve the parking experience and increase the efficiency of parking facilities. The iParking is a novel service in terms of cost- and energy-efficient solution. PMID:23202179

  11. Event detection for car park entries by video-surveillance

    Science.gov (United States)

    Coquin, Didier; Tailland, Johan; Cintract, Michel

    2007-10-01

    Intelligent surveillance has become an important research issue due to the high cost and low efficiency of human supervisors, and machine intelligence is required to provide a solution for automated event detection. In this paper we describe a real-time system that has been used for detecting car park entries, using an adaptive background learning algorithm and two indicators representing activity and identity to overcome the difficulty of tracking objects.

  12. Conversion of waste dump into a recreation and leisure park

    International Nuclear Information System (INIS)

    Petit, E.; Martens, P.N.

    1997-01-01

    In a two year strategy-project Aachen University investigated possibilities for postmining activities for a German coal mine. All research work was based on existing infrastructure and mine related potentials. One of the potentials is the waste dump with a height of 90 m above surface and 40 ha in size. This paper deals with the idea of converting the dump into a recreation and leisure park with greater than regional significance. 3 refs., 4 figs

  13. Fear of crime in urban parks

    DEFF Research Database (Denmark)

    Maruthaveeran, Sreetheran; Konijnendijk, Cecil Cornelis

    2015-01-01

    This study was conducted to determine the attributes which evoke ‘fear of crime’ and to determine the defensive behaviour among the urban park users. Findings are based on qualitative studies undertaken in the city of Kuala Lumpur among the park and non-park users (N = 19) by means of semi......-structured in-depth interviews. The interview consists of respondents from various age, gender and race. The results revealed universal similarities to other cultures on fear of crime in urban green spaces. This study has highlighted eight themes on the attributes which evoke fear among the residents of Kuala...... behaviour towards crime in urban parks but this was only observed among the women. This paper has also highlighted the implications on park planning and management from the comments given by the respondents. Though the aspect of fear towards crime in urban green spaces is not a major focus in Malaysia...

  14. Conditions for the management of carrying capacity in the parks of Parks&Benefits

    DEFF Research Database (Denmark)

    Brandt, Jesper; Holmes, Esbern

    2011-01-01

    Growth in the number of visitors is an upcoming problem in nature parks. Nature parks are at the same time facing increasing demand, falling public appropriations and receding focus on their conservation functions. To ensure a balancing of nature protection and economic utilization the concept...... stakeholders, balancing use and protection preferably based on scientific and/or experiential cognition. The conditions for the management of carrying capacity for the 8 nature parks in the EC Baltic Project Parks&Benefits are analysed in the report. 1. Part focus on the methodology, concentrated...... on the comparison of the common conditions related to the international nature protection obligations in the parks, primarily expressed through the management under the EU Natura2000-program. In part 2, a comparison of the 8 parks concerning extent, land use composition, population in and around the park...

  15. IMPLEMENTATION OF IMAGE PROCESSING IN REAL TIME CAR PARKING SYSTEM

    OpenAIRE

    SAYANTI BANERJEE,; PALLAVI CHOUDEKAR,; M.K.MUJU

    2011-01-01

    Car parking lots are an important object class in many traffic and civilian applications. With the problems of increasing urban trafficcongestion and the ever increasing shortage of space, these car parking lots are needed to be well equipped with automatic parkingInformation and Guidance systems. Goals of intelligent parking lot management include counting the number of parked cars, and identifyingthe available location. This work proposes a new system for providing parking information and g...

  16. Crystallization and preliminary X-ray analysis of the flagellar motor `brake' molecule YcgR with c-di-GMP from Escherichia coli.

    Science.gov (United States)

    Hou, Yanjie; Li, De Feng; Wang, Da Cheng

    2013-06-01

    In Escherichia coli and Salmonella enterica, bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), a ubiquitous bacterial second-messenger molecule that participates in many cellular processes, can regulate flagellar motor speed and reduce cell swimming velocity by binding to the PilZ-containing protein YcgR. Here, the crystallization and preliminary X-ray crystallographic analysis of YcgR with c-di-GMP are reported. The crystals diffracted to 2.3 Å resolution and belonged to space group R3:H, with unit-cell parameters a = b = 93.96, c = 109.61 Å. The asymmetric unit appeared to contain one subunit with a Matthews coefficient of 3.21 Å(3) Da(-1). The results reported here provide a sound basis for solving the crystal structure of YcgR with c-di-GMP and revealing its structure-function relationship based on the three-dimensional structure.

  17. Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole-cell oscillations in smooth muscle cells

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian; Aalkjær, Christian; Nilsson, Holger

    2007-01-01

    waves sweeping through the cytoplasm when the SR is stimulated to release calcium. A rise in cyclic guanosine monophosphate (cGMP) leads to the experimentally observed transition from waves to whole-cell calcium oscillations. At the same time membrane potential starts to oscillate and the frequency...... approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes uniform opening of L-type calcium...... onset of oscillations in membrane potential within the individual cell may underlie sudden intercellular synchronization and the appearance of vasomotion. Key words: Vasomotion, Chloride channel, cGMP, Mathematical model, Calcium waves....

  18. GMP-compliant automated synthesis of [{sup 18}F]AV-45 (Florbetapir F 18) for imaging {beta}-amyloid plaques in human brain

    Energy Technology Data Exchange (ETDEWEB)

    Yao, C.-H. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Lin, K.-J. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Weng, C.-C. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Hsiao, I.-T. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Ting, Y.-S. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Yen, T.-C. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Jan, T.-R. [Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Skovronsky, Daniel [Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104 (United States); Kung, M.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Wey, S.-P., E-mail: spwey@mail.cgu.edu.t [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China)

    2010-12-15

    We report herein the Good Manufacturing Practice (GMP)-compliant automated synthesis of {sup 18}F-labeled styrylpyridine, AV-45 (Florbetapir), a novel tracer for positron emission tomography (PET) imaging of {beta}-amyloid (A{beta}) plaques in the brain of Alzheimer's disease patients. [{sup 18}F]AV-45 was prepared in 105 min using a tosylate precursor with Sumitomo modules for radiosynthesis under GMP-compliant conditions. The overall yield was 25.4{+-}7.7% with a final radiochemical purity of 95.3{+-}2.2% (n=19). The specific activity of [{sup 18}F]AV-45 reached as high as 470{+-}135 TBq/mmol (n=19). The present studies show that [{sup 18}F]AV-45 can be manufactured under GMP-compliant conditions and could be widely available for routine clinical use.

  19. Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

    Science.gov (United States)

    Roccatello, D; Mengozzi, G; Ferro, M; Cesano, G; Polloni, R; Mosso, R; Bonetti, G; Inconis, T; Paradisi, L; Sena, L M

    1995-09-01

    An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p effective renal plasma flow (p counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

  20. Sustainable urban spaces: Ecological parks

    Directory of Open Access Journals (Sweden)

    Burçak Erdoğan Onur

    2016-01-01

    Full Text Available Rapidly depleted resources with technological and economic developments which increased in recent years has led to deterioration of the natural balance in the world. Urban ecosystems is considerably changed, especially with population growth and intensive construction in the city. This situation, as such in all other areas, urban ecosystems are also increasing their sustainability concerns. More compatible solution with the natural process in landscape design and management have to be brought. This article describes the conceptual structure of ecological park that has become a tool for sustainable urban target in community that matured of environmental awareness. Also planning, design and management principles are explained by supporting with application examples. The obtained results within the framework, it is aimed to create a source for similar applications that will lead to spread in our country. In addition, it is put forward suggestions for dissemination of such practices.

  1. The Upper Danube Nature Park

    International Nuclear Information System (INIS)

    Dosedla, H.C.

    1997-01-01

    When in 1980 the Upper Danube Nature Park was founded as one of 65 nature sanctuaries in Germany there was great diversity of opinions concerning its intended character. The protected region consisting of a geologically outstanding landscape within central Europe is covering the first 80 km the upper Danube where the young river shortly after it's source in the Black Forest is breaking through the narrow canyons of the Jurassic rock plateau of the so-called Suebian Alps and also locates the subterranean passage where the stream is submerging from the surface for nearly ten miles. Since the purpose of nature preservation according to German las is closely combined with the rather contradicting aim of offering an attractive recreation area thus facing the immense impacts of modern mass tourism there are numerous problems which in the course of years have resulted in an intricate patterns of subtle management methods coping with the growing awareness of the ecological balance. (author)

  2. Photovoltaics at Point Pelee Park

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    Case study of an Ontario Hydro-installed photovoltaic system at Point Pelee Park, a bird sanctuary located on Lake Erie, is described. The system consists of a 1080 W photovoltaic array used to supply electricity to one of the washrooms. The cost for installing the system was $30,000 which was considerably cheaper than the $100,000 estimate for an underground power line. The independent system is the only source of energy for the washroom, therefore it was necessary to reduce the total electrical demand required by the facility. Electricity was used for the water pump, chlorinator and lighting. Motion sensors were installed to further reduce electrical demand. Washroom heaters were converted to propane. 2 figs.

  3. A DESIGN STUDY OF AN INNOVATIVE BARRIER SYSTEM FOR PERSONAL PARKING LOTS

    OpenAIRE

    BÖRKLÜ, Hüseyin; KALYON, Sadık

    2018-01-01

    The increase in the number of cars made it necessary to protectthe parking areas. This research includes a literature review aboutcommercially available barriers, which are arm barriers, rising bollards, chainbarriers, automatic and manual private barriers from the point of common andside-by-side parking lots. Their advantages and disadvantages are evaluated.After the literature review work, a design requirements list for a car parkprotector, which includes important and strong properties of ...

  4. Tuna Park Shopping Centre A comparative study of marketing communication tools

    OpenAIRE

    Wongrattanavichit, Teewin; Wang, Haiyan

    2008-01-01

    Date: 2008 June 08 Course: Master thesis Authors: Haiyan Wang, Teewin Wongrattanavichit Tutor: Jan Löwstedt Title: The study of marketing communication effectiveness and customer perception of Tuna Park shopping centre Introduction: The research about the effectiveness of marketing communication tool and customer perception was studied in Tuna Park shopping center, Eskilstuna. The marketing strategy and objective was to compare with the results from the questionnaire in order to measure the e...

  5. Public parks and wellbeing in urban areas of the United States

    Science.gov (United States)

    Lincoln R. Larson; Viniece Jennings; Scott A. Cloutier

    2016-01-01

    Sustainable development efforts in urban areas often focus on understanding and managing factors that influence all aspects of health and wellbeing. Research has shown that public parks and green space provide a variety of physical, psychological, and social benefits to urban residents, but few studies have examined the influence of parks on comprehensive measures of...

  6. Linear Parks along Urban Rivers: Perceptions of Thermal Comfort and Climate Change Adaptation in Cyprus

    Directory of Open Access Journals (Sweden)

    Elias Giannakis

    2016-10-01

    Full Text Available The development of green space along urban rivers could mitigate urban heat island effects, enhance the physical and mental well-being of city dwellers, and improve flood resilience. A linear park has been recently created along the ephemeral Pedieos River in the urban area of Nicosia, Cyprus. Questionnaire surveys and micrometeorological measurements were conducted to explore people’s perceptions and satisfaction regarding the services of the urban park. People’s main reasons to visit the park were physical activity and exercise (67%, nature (13%, and cooling (4%. The micrometeorological measurements in and near the park revealed a relatively low cooling effect (0.5 °C of the park. However, the majority of the visitors (84% were satisfied or very satisfied with the cooling effect of the park. Logistic regression analysis indicated that the odds of individuals feeling very comfortable under a projected 3 °C future increase in temperature would be 0.34 times lower than the odds of feeling less comfortable. The discrepancies between the observed thermal comfort index and people’s perceptions revealed that people in semi-arid environments are adapted to the hot climatic conditions; 63% of the park visitors did not feel uncomfortable at temperatures between 27 °C and 37 °C. Further research is needed to assess other key ecosystems services of this urban green river corridor, such as flood protection, air quality regulation, and biodiversity conservation, to contribute to integrated climate change adaptation planning.

  7. Tools of integration of innovation-oriented machine-building enterprises in industrial park environment

    Directory of Open Access Journals (Sweden)

    К.О. Boiarynova

    2017-08-01

    Full Text Available The research is devoted to the development of the tools for the integration of innovation-oriented mechanical engineering enterprises into the environment of industrial park as functional economic systems, which are capable on the own development basis to provide the development of resident enterprises. The article analyzes the opportunities for the development of mechanical engineering enterprises. The formed structure of the mechanism of integration of mechanical engineering enterprises as functional economic systems into the industrial park environment is based on: 1 the development of participation programs in the industrial park of the mechanical engineering enterprises as an innovation-oriented partner, which foresees the development of the enterprise immediately and the development of other residents; 2 the provision of high-tech equipment of resident enterprises of industrial parks; 3 the creation of subsidiary-spin-out enterprises of large mechanical engineering enterprises for high-tech production in the industrial park. The author proposes the road map that reveals the procedures for the integration and functioning the investigated enterprises through interaction as well as in the ecosystem of the industrial park and in the general ecosystem of functioning, and the tools for providing economic functionality through economic and organizational proceedings at preventive, partner and resident phases of integration. The tools allow the innovation-oriented mechanical engineering enterprises to integrate into such territorial structures as industrial parks, this in complex will allow carrying out their purposes in the development of the real sector of the economy.

  8. Cost benefit of investment on quality in pharmaceutical manufacturing: WHO GMP pre- and post-certification of a Nigerian pharmaceutical manufacturer.

    Science.gov (United States)

    Anyakora, Chimezie; Ekwunife, Obinna; Alozie, Faith; Esuga, Mopa; Ukwuru, Jonathan; Onya, Steve; Nwokike, Jude

    2017-09-18

    Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study. This paper also discusses how to drive more local manufacturers to invest in quality to attain GMP compliance; and proffers practical recommendations for local manufacturers who would want to invest in quality to meet ethical and regulatory obligations. The cost benefit of improving the quality of Chi Pharmaceuticals Limited's facilities and system to attain WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was calculated by dividing the annual benefits derived from quality improvement interventions by the annual costs of implementing quality improvement interventions, referred to as a benefit-cost ratio (BCR). Cost benefit of obtaining WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was 5.3 (95% confidence interval of 5.0-5.5). Investment in quality improvement intervention is cost-beneficial for local manufacturing companies. Governments and regulators in African countries should support pharmaceutical companies striving to invest in quality. Collaboration of local manufacturing companies with global companies will further improve quality. Local pharmaceutical companies should be encouraged to key into development opportunities available for pharmaceutical companies in Africa.

  9. Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway.

    Science.gov (United States)

    Kim, Hye Yoom; Oh, Hyuncheol; Li, Xiang; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

    2011-01-27

    The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined. Changes in vascular tension, guanosine 3',5'-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at -70°C. ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca(2+)-free but not L-typed Ca(2+) channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate, modulators of store-operated Ca(2+) entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K(+) channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation. Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

    KAUST Repository

    Qia, Zhi; Verma, Rajeev K.; Gehring, Christoph A; Yamaguchi, Yube; Zhao, Yichen; Ryan, Clarence A.; Berkowitz, Gerald A.

    2010-01-01

    receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33

  11. URBAN COMMUNITY RESPONSES TO VISUAL APPROPRIATE THEMATIC DESIGN, SUPER HERO PARK BANDUNG

    Directory of Open Access Journals (Sweden)

    Dian Duhita

    2017-06-01

    Full Text Available Parks is one of city public area that serves as a communal place for city community. On another perspective, parks is an architectural design that is designed with an aesthetic element to attract. Bandung, since a few years was to make improvements in various sectors, especially in the public space. Through the slogan Creative City, Bandung City Government revived communities part of the citizens by providing place for a activities, creation and production. Thematic Parks became one of the alternative approaches responsive design as part of creative cities development. Object of research study object is Super Hero park. The purpose of research is to analyzing the response of communities to design a thematic park. The study was conducted with a qualitative approach through participation observation method. The scope of the research includes visual appropriate and city community response. The conclussion obtain that visual appropriate are in accordance with the theme. Urban Community was able to respond well the identity of Super Hero park with visual appropriate design.

  12. Implementation Of Conservation Policy Through The Protection Of Life Support System In The Karimunjawa National Park

    Science.gov (United States)

    Ariyani, Nur Anisa Eka; Kismartini

    2018-02-01

    The Karimunjawa National Park as the only one marine protected area in Central Java, managed by zonation system has decreased natural resources in the form of decreasing mangrove forest area, coral cover, sea biota population such as clams and sea cucumbers. Conservation has been done by Karimunjawa National Park Authority through protection of life support system activities in order to protect the area from degradation. The objective of the research is to know the implementation of protection and security activities of Karimunjawa National Park Authority for the period of 2012 - 2016. The research was conducted by qualitative method, processing secondary data from Karimunjawa National Park Authority and interview with key informants. The results showed that protection and security activities in The Karimunjawa National Park were held with three activities: pre-emptive activities, preventive activities and repressive activities. Implementation of conservation policy through protection of life support system is influenced by factors of policy characteristic, resource factor and environmental policy factor. Implementation of conservation policy need support from various parties, not only Karimunjawa National Park Authority as the manager of the area, but also need participation of Jepara Regency, Central Java Provinces, communities, NGOs, researchers, developers and tourism actors to maintain and preserve existing biodiversity. Improving the quality of implementors through education and training activities, the availability of the state budget annually and the support of stakeholders is essential for conservation.

  13. cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

    Directory of Open Access Journals (Sweden)

    Steiner Jennifer A

    2009-08-01

    Full Text Available Abstract Background The Na+/Cl--dependent serotonin (5-hydroxytryptamine, 5-HT transporter (SERT is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport in vitro and an increased rate of SERT-mediated 5-HT clearance in vivo. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear. Results In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting

  14. The phytosulfokine (PSK) receptor is capable of guanylate cyclase activity and enabling cyclic GMP-dependent signaling in plants

    KAUST Repository

    Kwezi, Lusisizwe; Ruzvidzo, Oziniel; Wheeler, Janet I.; Govender, Kershini; Iacuone, Sylvana; Thompson, Philip E.; Gehring, Christoph A; Irving, Helen R.

    2011-01-01

    Phytosulfokines (PSKs) are sulfated pentapeptides that stimulate plant growth and differentiation mediated by the PSK receptor (PSKR1), which is a leucine-rich repeat receptor-like kinase. We identified a putative guanylate cyclase (GC) catalytic center in PSKR1 that is embedded within the kinase domain and hypothesized that the GC works in conjunction with the kinase in downstream PSK signaling. We expressed the recombinant complete kinase (cytoplasmic) domain of AtPSKR1 and show that it has serine/threonine kinase activity using the Ser/Thr peptide 1 as a substrate with an approximate Km of 7.5 μM and Vmax of 1800 nmol min-1 mg-1 of protein. This same recombinant protein also has GC activity in vitro that is dependent on the presence of either Mg2+ or Mn2+. Overexpression of the full-length AtPSKR1 receptor in Arabidopsis leaf protoplasts raised the endogenous basal cGMP levels over 20-fold, indicating that the receptor has GC activity in vivo. In addition, PSK-α itself, but not the non-sulfated backbone, induces rapid increases in cGMP levels in protoplasts. Together these results indicate that the PSKR1 contains dual GC and kinase catalytic activities that operate in vivo and that this receptor constitutes a novel class of enzymes with overlapping catalytic domains. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Evaluation of Tissue Homogenization to Support the Generation of GMP-Compliant Mesenchymal Stromal Cells from the Umbilical Cord

    Directory of Open Access Journals (Sweden)

    Ryan J. Emnett

    2016-01-01

    Full Text Available Recent studies have demonstrated that the umbilical cord (UC is an excellent source of mesenchymal stromal cells (MSCs. However, current protocols for extracting and culturing UC-MSCs do not meet current good manufacturing practice (cGMP standards, in part due to the use of xenogeneic reagents. To support the development of a cGMP-compliant method, we have examined an enzyme-free isolation method utilizing tissue homogenization (t-H followed by culture in human platelet lysate (PL supplemented media. The yield and viability of cells after t-H were comparable to those obtained after collagenase digestion (Col-D. Importantly, kinetic analysis of cultured cells showed logarithmic growth over 10 tested passages, although the rate of cell division was lower for t-H as compared to Col-D. This slower growth of t-H-derived cells was also reflected in their longer population doubling time. Interestingly, there was no difference in the expression of mesenchymal markers and trilineage differentiation potential of cells generated using either method. Finally, t-H-derived cells had greater clonogenic potential compared to Col-D/FBS but not Col-D/PL and were able to maintain CFU-F capacity through P7. This bench scale study demonstrates the possibility of generating therapeutic doses of good quality UC-MSCs within a reasonable length of time using t-H and PL.

  16. Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications.

    Directory of Open Access Journals (Sweden)

    Shelly E Tannenbaum

    Full Text Available Clinically compliant human embryonic stem cells (hESCs should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs.

  17. Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy

    Directory of Open Access Journals (Sweden)

    Howard R. Seay

    2017-03-01

    Full Text Available Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR. Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

  18. Effects of Tang Niao Ning decoction on ET-1, GMP-140 and TXB2 in diabetic rats

    International Nuclear Information System (INIS)

    Song Jumin; Wang Lifen; Liao Han; Wang Wei; Hua Weiguo

    2003-01-01

    To investigate the effects of Tang Niao Ning decoction on fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), endothelin (ET-1), platelet granule membrane protein (GMP-140), thromboxane B 2 (TXB 2 ), 6-keto-prostaglandin F 1α (6-keto-PGF 1α ), the selected female Wistar rats were modeled by streptozotocin (STZ) and high fat diets, and were randomly divided into two groups as Tang Niao Ning and model group, while the normal control group was set up. The Tang Niao Ning group started to supply decoctions after these rats had been fed one week with high fat diets. The rats were killed after six weeks. Above items were examed. The results showed that the model group displayed marked difference when the experiment finished compared with the normal group. The contents of fasting blood glucose and blood lipid were increased, accompanied with the phenomena of hoisting ET-1, enhancing GMP-140, increasing TXB 2 and droping 6-Keto-PGF 1α . After treatment in time with Tang Niao Ning decoction, all kinds of items were adjusted to normal level gradually. It suggested that the treatment with Tang Niao Ning decoction might decrease FBG and blood lipid. In some ways, the decoction could improve the signs of blood stasis. The regulation mechanisms of the decoction was characteristic of wholism through many channels

  19. The phytosulfokine (PSK) receptor is capable of guanylate cyclase activity and enabling cyclic GMP-dependent signaling in plants

    KAUST Repository

    Kwezi, Lusisizwe

    2011-04-19

    Phytosulfokines (PSKs) are sulfated pentapeptides that stimulate plant growth and differentiation mediated by the PSK receptor (PSKR1), which is a leucine-rich repeat receptor-like kinase. We identified a putative guanylate cyclase (GC) catalytic center in PSKR1 that is embedded within the kinase domain and hypothesized that the GC works in conjunction with the kinase in downstream PSK signaling. We expressed the recombinant complete kinase (cytoplasmic) domain of AtPSKR1 and show that it has serine/threonine kinase activity using the Ser/Thr peptide 1 as a substrate with an approximate Km of 7.5 μM and Vmax of 1800 nmol min-1 mg-1 of protein. This same recombinant protein also has GC activity in vitro that is dependent on the presence of either Mg2+ or Mn2+. Overexpression of the full-length AtPSKR1 receptor in Arabidopsis leaf protoplasts raised the endogenous basal cGMP levels over 20-fold, indicating that the receptor has GC activity in vivo. In addition, PSK-α itself, but not the non-sulfated backbone, induces rapid increases in cGMP levels in protoplasts. Together these results indicate that the PSKR1 contains dual GC and kinase catalytic activities that operate in vivo and that this receptor constitutes a novel class of enzymes with overlapping catalytic domains. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Mutation of the cyclic di-GMP phosphodiesterase gene in Burkholderia lata SK875 attenuates virulence and enhances biofilm formation.

    Science.gov (United States)

    Jung, Hae-In; Kim, Yun-Jung; Lee, Yun-Jung; Lee, Hee-Soo; Lee, Jung-Kee; Kim, Soo-Ki

    2017-10-01

    Burkholderia sp. is a gram-negative bacterium that commonly exists in the environment, and can cause diseases in plants, animals, and humans. Here, a transposon mutant library of a Burkholderia lata isolate from a pig with swine respiratory disease in Korea was screened for strains showing attenuated virulence in Caenorhabditis elegans. One such mutant was obtained, and the Tn5 insertion junction was mapped to rpfR, a gene encoding a cyclic di-GMP phosphodiesterase that functions as a receptor. Mutation of rpfR caused a reduction in growth on CPG agar and swimming motility as well as a rough colony morphology on Congo red agar. TLC analysis showed reduced AHL secretion, which was in agreement with the results from plate-based and bioluminescence assays. The mutant strain produced significantly more biofilm detected by crystal violet staining than the parent strain. SEM of the mutant strain clearly showed that the overproduced biofilm contained a filamentous structure. These results suggest that the cyclic di-GMP phosphodiesterase RpfR plays an important role in quorum sensing modulation of the bacterial virulence and biofilm formation.