WorldWideScience

Sample records for range 1-17 years

  1. Earliest hominin cancer: 1.7-million-year-old osteosarcoma from Swartkrans Cave, South Africa

    Directory of Open Access Journals (Sweden)

    Edward J. Odes

    2016-07-01

    Full Text Available The reported incidence of neoplasia in the extinct human lineage is rare, with only a few confirmed cases of Middle or Later Pleistocene dates reported. It has generally been assumed that pre-modern incidence of neoplastic disease of any kind is rare and limited to benign conditions, but new fossil evidence suggests otherwise. We here present the earliest identifiable case of malignant neoplastic disease from an early human ancestor dated to 1.8-1.6 million years old. The diagnosis has been made possible only by advances in 3D imaging methods as diagnostic aids. We present a case report based on re-analysis of a hominin metatarsal specimen (SK 7923 from the cave site of Swartkrans in the Cradle of Humankind, South Africa. The expression of malignant osteosarcoma in the Swartkrans specimen indicates that whilst the upsurge in malignancy incidence is correlated with modern lifestyles, there is no reason to suspect that primary bone tumours would have been any less frequent in ancient specimens. Such tumours are not related to lifestyle and often occur in younger individuals. As such, malignancy has a considerable antiquity in the fossil record, as evidenced by this specimen.

  2. The Unknown Oldowan: ~1.7-Million-Year-Old Standardized Obsidian Small Tools from Garba IV, Melka Kunture, Ethiopia.

    Science.gov (United States)

    Gallotti, Rosalia; Mussi, Margherita

    2015-01-01

    The Oldowan Industrial Complex has long been thought to have been static, with limited internal variability, embracing techno-complexes essentially focused on small-to-medium flake production. The flakes were rarely modified by retouch to produce small tools, which do not show any standardized pattern. Usually, the manufacture of small standardized tools has been interpreted as a more complex behavior emerging with the Acheulean technology. Here we report on the ~1.7 Ma Oldowan assemblages from Garba IVE-F at Melka Kunture in the Ethiopian highland. This industry is structured by technical criteria shared by the other East African Oldowan assemblages. However, there is also evidence of a specific technical process never recorded before, i.e. the systematic production of standardized small pointed tools strictly linked to the obsidian exploitation. Standardization and raw material selection in the manufacture of small tools disappear at Melka Kunture during the Lower Pleistocene Acheulean. This proves that 1) the emergence of a certain degree of standardization in tool-kits does not reflect in itself a major step in cultural evolution; and that 2) the Oldowan knappers, when driven by functional needs and supported by a highly suitable raw material, were occasionally able to develop specific technical solutions. The small tool production at ~1.7 Ma, at a time when the Acheulean was already emerging elsewhere in East Africa, adds to the growing amount of evidence of Oldowan techno-economic variability and flexibility, further challenging the view that early stone knapping was static over hundreds of thousands of years.

  3. [Relationship between dietary behaviors and growth-development of 1-7 years old children from seven provinces in Chinese rural areas].

    Science.gov (United States)

    Zhang, Huan; Luo, Miyang; Wang, Zhihui; Luo, Jiayou; Shi, Yanling

    2013-05-01

    To explore the status of dietary behaviors of 1-7 years old children and its relationship with growth-development in Chinese rural areas and to provide 13,692 1-7 years old scientific evidences for corresponding intervention. children from seven provinces in Chinese rural areas were randomly identified by multistage stratified cluster sampling. The ascertainment methods included face to face questionnaires and anthropometric measurements. Chi-square test and non-conditional logistic regression analysis were used to assess the relationship between dietary behaviors and growth-development. Among the respondents, 53.1% occasionally/never drank milk/soymilk, 48.1% ate snacks almost everyday, 22.5% were picky eaters, 7.3% were breakfast-skippers, 1.9% couldn't dine on time. Multivariate nonconditional logistic regression analysis showed that occasionally/never have breakfast, occasionally/never drink milk or soymilk, occasionally/never eat snacks were associated with stunting. Occasionally/never have breakfast or eat snacks were associated with underweight. The five dietary behaviors were not associated with wasting, overweight and obesity in our study. The incidence of children's poor dietary behaviors was relatively high in Chinese rural areas, which had a close association with children stunting and underweight.

  4. [A retrospective study on HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B aged 1-7 years].

    Science.gov (United States)

    Zhu, S S; Dong, Y; Xu, Z Q; Wang, L M; Chen, D W; Gan, Y; Wang, F C; Yan, J G; Cao, L L; Wang, P; Zhang, H F

    2016-10-20

    Objective: To investigate the HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B (CHB) aged 1-7 years. Methods: A retrospective analysis was performed for the HBsAg clearance rate in 293 children who were hospitalized in 302 Hospital of PLA from June 2006 to December 2013, met the inclusion criteria, received antiviral therapy, and were followed up for at least 6 months after the withdrawal of antiviral therapy. The t-test or the rank sum test was applied according to the distribution of continuous data, and the chi-square test was used for comparison of categorical data. Results: The HBsAg positive rate of children's mothers was 91.1%. In the age groups of >1-≤2 years, >2-≤3 years, >3-≤4 years, >4-≤5 years, >5-≤6 years, and >6-≤7 years, the HBsAg clearance rates were 66.1%, 65.5%, 45.7%, 41.3%, 20.6%, and 27.6%, respectively. There were significant differences in HBsAg clearance rate between the age groups of >1-≤3 years and >3-≤5 years, >1-≤3 years and >5-≤7 years, and >3-≤5 years and >5-≤7 years (P = 0.001, 0.000, and 0.008). Of all children, 64.8% were boys, among whom 41.1% achieved HBsAg clearance, and 35.2% were girls, among whom 61.2% achieved HBsAg clearance; there was a significant difference in HBsAg clearance rate between boys and girls (P = 0.001). The children with pretreatment alanine aminotransferase (ALT) levels of ≤80 IU/L, > 80 IU/L, ≤200 IU/L, and > 200 IU/L had HBsAg clearance rates of 40.7%, 51.2%, 47.6%, and 49.4%, respectively; there were no significant differences in HBsAg clearance rate between the ALT ≤80 IU/L and ALT > 80 IU/L groups and the ALT ≤200 IU/L and ALT > 200 IU/L groups (P = 0.101 and 0.778). There was no significant difference in HBsAg clearance rate between the pretreatment HBV DNA load < 1×10(7) IU/ml and ≥1×10(7) IU/ml groups (54.9% vs 46.7%, P = 0.286). Of all children, 14.2% had genotype B and an HBsAg clearance rate of 57.1%, and 85% had

  5. [Injuries among children and adolescents (1-17 years) and implementation of safety measures. Results of the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS)].

    Science.gov (United States)

    Kahl, H; Dortschy, R; Ellsässer, G

    2007-01-01

    Parent interviews with regard to their children's accidents and to accident protective measures in the Health Interview and Examination Survey for Children and Adolescents (KiGGS) aimed at extending our knowledge of age- and gender-specific injuries and to identify risk groups and risk factors for injury prevention. The parents of 16,706 children (aged 1-17 years) were asked about their children's injuries within the last 12 months which were medically treated, and about accident mechanisms, consequences of injuries, and ambulatory and hospital treatment. In addition, parents and children aged 11 to 17 years (n = 6813) were asked to give information on protective measures. According to the parents 15.9 % of the children had at least one injury within the last 12 months, 15.2 % because of an accident and 0.8 % because of assault. In the age group 1-17 boys have been injured significantly more often than girls (17.9 % vs. 14,0 %). Overall, 13.3 % of 2,410 injured children and adolescents were hospitalized. Two thirds of the accidents among toddlers were domestic accidents (60 %) whereas leisure and sport accidents were most prevalent in children and adolescents aged 5-14 years and 15-17 years (32.1 % and 38.9 %). The proportion of accidents in child care facilities and educational institutions tripled from infancy to school age (age 5-14 years) (10.9-28.7 %), as did traffic accidents (5.6-16.7 %). The three most frequent injury mechanisms in the age range 1-17 years were falls on level ground (35.2 %), falls from heights (25.2 %) and collisions with objects or persons (20.6 %). Falls from heights showed the highest risk in toddlers (35.8 %). Contusions, sprains and strains increased to a highest level of 50.9 % in adolescents; likewise, bone fractures increased from 10.7 % in toddlers to 21.8 % in adolescents aged 15-17 years. An influence of socioeconomic status on injuries overall and on consequences of injuries was not seen. For traffic accidents in children aged

  6. To reactivate or not to reactivate: nature and varied behavior of structural inheritance in the Proterozoic basement of the Eastern Colorado mineral belt over 1.7 billion years of earth history

    Science.gov (United States)

    Caine, Jonathan S.; Ridley, John; Wessel, Zachary R.

    2010-01-01

    The eastern central Front Range of the Rocky Mountains in Colorado has long been a region of geologic interest because of Laramide-age hydrothermal polymetallic vein-related ores. The region is characterized by a well-exposed array of geologic structures associated with ductile and brittle deformation, which record crustal strain over 1.7 billion years of continental growth and evolution. The mineralized areas lie along a broad linear zone termed the Colorado Mineral Belt. This lineament has commonly been interpreted as following a fundamental boundary, such as a suture zone, in the North American Proterozoic crust that acted as a persistent zone of weakness localizing the emplacement of magmas and associated hydrothermal fluid flow. However, the details on the controls of the location, orientation, kinematics, density, permeability, and relative strength of various geological structures and their specific relationships to mineral deposit formation are not related to Proterozoic ancestry in a simple manner. The objectives of this field trip are to show key localities typical of the various types of structures present, show recently compiled and new data, offer alternative conceptual models, and foster dialogue. Topics to be discussed include: (1) structural history of the eastern Front Range; (2) characteristics, kinematics, orientations, and age of ductile and brittle structures and how they may or may not relate to one another and mineral deposit permeability; and (3) characteristics, localization, and evolution of the metal and non–metal-bearing hydrothermal systems in the eastern Colorado Mineral Belt.

  7. Kenai National Moose Range : Annual narrative report : Calendar year 1966

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Kenai National Moose Range outlines Refuge accomplishments during the 1966 calendar year. The report begins by summarizing the...

  8. Kenai National Moose Range : Annual narrative report : Calendar year 1965

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Kenai National Moose Range outlines Refuge accomplishments during the 1965 calendar year. The report begins by summarizing the...

  9. National Bison Range Annual narrative report: Calendar year 1991

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1991 calendar year. The report begins with an introduction to the...

  10. National Bison Range: Annual narrative report: Calendar year 1993

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1993 calendar year. The report begins with an introduction to the...

  11. National Bison Range Annual narrative report: Calendar year 1984

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1984 calendar year. The report begins with an introduction to the...

  12. National Bison Range : Annual narrative report: Calendar year 1985

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1985 calendar year. The report begins with an introduction to the...

  13. National Bison Range: Annual narrative report: Calendar year 1992

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1992 calendar year. The report begins with an introduction to the...

  14. National Bison Range Annual narrative report: Calendar year 1983

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1983 calendar year. The report begins with an introduction to the...

  15. National Bison Range Annual narrative report: Calendar year 1982

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1982 calendar year. The report begins with an introduction to the...

  16. National Bison Range Annual narrative report: Calendar year 1990

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1990 calendar year. The report begins with an introduction to the...

  17. National Bison Range Annual narrative report: Calendar year 1988

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1988 calendar year. The report begins with an introduction to the...

  18. National Bison Range Annual narrative report: Calendar year: 1978

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1978 calendar year. The report begins with an introduction to the...

  19. National Bison Range: Refuge narrative report: Calendar year 1966

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for National Bison Range outlines Refuge accomplishments during the 1966 calendar year. The report begins by summarizing the weather...

  20. National Bison Range: Annual narrative report: Calendar year 1977

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for the National Bison Range outlines Refuge accomplishments for the 1977 calendar year. The report begins with an introduction to the...

  1. Tonopah Test Range Post-Closure Inspection Annual Report, Tonopah Test Range, Nevada, Calendar Year 2003

    Energy Technology Data Exchange (ETDEWEB)

    U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office; Bechtel Nevada

    2004-04-01

    This post-closure inspection report provides documentation of the semiannual inspection activities, maintenance and repair activities, and conclusions and recommendations for calendar year 2003 for eight corrective action units located on the Tonopah Test Range, Nevada.

  2. Consumer testing of the preliminary paediatric food-based dietary guidelines for healthy children aged 1-7 years, among English- and Afrikaans-speaking mothers in the city of Cape Town, South Africa.

    Science.gov (United States)

    Scott, Lesley Dalene; Marais, Debbi; Bourne, Lesley

    2009-07-01

    The aim of this qualitative study was to test the comprehensibility of the preliminary food-based dietary guidelines (FBDG) for healthy South African children aged 1-7 years. Objectives included assessing exposure to FBDG, comprehension of the proposed paediatric FBDG (PFBDG) and whether the guidelines can be used in meal planning. Focus group discussions were used to collect data. Discussions were facilitated by the investigator in either English or Afrikaans, according to a predetermined discussion schedule. Focus groups were formed on the basis of language and socio-economic status (SES). Areas within the City of Cape Town representing lower, middle and upper SES groups. A total of seventy-six English- and Afrikaans-speaking mothers were contacted via randomly selected consenting preschool groups to participate voluntarily. Most mothers reported that they do not use guidelines. They had a good grasp of the concepts of and need for PFBDG. They suggested slight alterations to wording/phrasing of the guidelines. The most problematic guidelines were those regarding starch, milk and sweet treats/drinks. No substantial differences were found between English and Afrikaans data. Differences were found between SES groups, with the upper SES groups comprehending the guidelines better. The proposed PFBDG were well received. The target population that would benefit the most from these guidelines would be the less educated, lower SES groups. The present study shows that once the guidelines have been modified, they may be used as a comprehensive guide for nutritional education.

  3. Tonopah Test Range Post-Closure Inspection Annual Report, Tonopah Test Range, Nevada, Calendar Year 2002

    Energy Technology Data Exchange (ETDEWEB)

    R. B. Jackson

    2003-08-01

    This Post-Closure Inspection Annual Report provides documentation of the semiannual inspections conducted at the following Corrective Action Units (CAU)s: CAU 400: Bomblet Pit and Five Points Landfill; CAU 404: Roller Coaster Lagoons and Trench; CAU 407: Roller Coaster RadSafe Area; CAU 424: Area 3 Landfill Complexes; CAU 426: Cactus Spring Waste Trenches; CAU 427: Septic Waste Systems 2, 6; and CAU 453: Area 9 UXO Landfill, all located at the Tonopah Test Range, Nevada. Post-closure inspections are not required at CAU 400 but are conducted to monitor vegetation and fencing at the site. Site inspections were conducted in May and November 2002. All site inspections were made after Nevada Division of Environmental Protection (NDEP) approval of the appropriate Closure Report (CR), excluding CAU 400 which did not require a CR, and were conducted in accordance with the Post-Closure Inspection Plans in the NDEP-approved CRs. Post-closure inspections conducted during 2002 identified several areas requiring maintenance/repairs. Maintenance work and proposed additional monitoring are included in the appropriate section for each CAU. This report includes copies of the Post-Closure Inspection Plans, Post-Closure Inspection Checklists, copies of the field notes, photographs, and the Post-Closure Vegetative Monitoring Report. The Post-Closure Inspection Plan for each CAU is located in Attachment A. Post-Closure Inspection Checklists are in Attachment B. Copies of the field notes from each inspection are included in Attachment C. Attachment D consists of the photographic logs and photographs of the sites. The post-closure vegetative monitoring report for calendar year 2002 is included in Attachment E.

  4. Experimental forests and ranges : 100 years of research success stories

    Science.gov (United States)

    Gail Wells; Deborah Hayes; Katrina Krause; Ann Bartuska; Susan LeVan-Green; Jim Anderson; Tivoli Gough; Mary Adams; Thomas Schuler; Randy Kolka; Steve Sebestyen; Laura Kenefic; John Brissette; Susan Stout; Keith Kanoti; Fred Swanson; Sarah Greene; Margaret Herring; Martin Ritchie; Carl Skinner; Tom Lisle; Elizabeth Keppeler; Leslie Reid; Peter Wohlegemuth; Stanley Kitchen; Ward McCaughey; Jim Guldin; Don Bragg; Michael Shelton; David Loftis; Cathryn Greenberg; Julia Murphy

    2009-01-01

    In 2008, Forest Service Research and Development celebrated the Centennial Anniversary of these Experimental Forests and Ranges. This publication celebrates the many scientists who over the course of decades conducted the long-term studies that began and are continuing to shed light on important natural resource issues. Story suggestions were solicited from the...

  5. Immersion francaise precoce: Sciences humaines 1-7 (Early French Immersion: Social Sciences 1-7).

    Science.gov (United States)

    Burt, Andy; And Others

    This curriculum guide for the human sciences or social studies is intended for use in grades 1-7 in the early French immersion program. The program is organized around key concepts, generalizations, and themes derived from the social sciences, and allows the teacher a wide choice of content. The guide presents the following topics: (1) the…

  6. Immersion francaise precoce: Mathematique 1-7 (Early French Immersion: Mathematics 1-7).

    Science.gov (United States)

    Burt, Andy; And Others

    This mathematics curriculum guide is intended for use in grades 1-7 in the early French immersion program. After an initial listing of textbooks in French for teachers and students, it presents: (1) a general overview of the theory of modern mathematics and a suggested sequence of activities; (2) some notes on the application of the theory and a…

  7. Middle infrared (wavelength range: 8 μm-14 μm) 2-dimensional spectroscopy (total weight with electrical controller: 1.7 kg, total cost: less than 10,000 USD) so-called hyperspectral camera for unmanned air vehicles like drones

    Science.gov (United States)

    Yamamoto, Naoyuki; Saito, Tsubasa; Ogawa, Satoru; Ishimaru, Ichiro

    2016-05-01

    We developed the palm size (optical unit: 73[mm]×102[mm]×66[mm]) and light weight (total weight with electrical controller: 1.7[kg]) middle infrared (wavelength range: 8[μm]-14[μm]) 2-dimensional spectroscopy for UAV (Unmanned Air Vehicle) like drone. And we successfully demonstrated the flights with the developed hyperspectral camera mounted on the multi-copter so-called drone in 15/Sep./2015 at Kagawa prefecture in Japan. We had proposed 2 dimensional imaging type Fourier spectroscopy that was the near-common path temporal phase-shift interferometer. We install the variable phase shifter onto optical Fourier transform plane of infinity corrected imaging optical systems. The variable phase shifter was configured with a movable mirror and a fixed mirror. The movable mirror was actuated by the impact drive piezo-electric device (stroke: 4.5[mm], resolution: 0.01[μm], maker: Technohands Co.,Ltd., type:XDT50-45, price: around 1,000USD). We realized the wavefront division type and near common path interferometry that has strong robustness against mechanical vibrations. Without anti-mechanical vibration systems, the palm-size Fourier spectroscopy was realized. And we were able to utilize the small and low-cost middle infrared camera that was the micro borometer array (un-cooled VOxMicroborometer, pixel array: 336×256, pixel pitch: 17[μm], frame rate 60[Hz], maker: FLIR, type: Quark 336, price: around 5,000USD). And this apparatus was able to be operated by single board computer (Raspberry Pi.). Thus, total cost was less than 10,000 USD. We joined with KAMOME-PJ (Kanagawa Advanced MOdule for Material Evaluation Project) with DRONE FACTORY Corp., KUUSATSU Corp., Fuji Imvac Inc. And we successfully obtained the middle infrared spectroscopic imaging with multi-copter drone.

  8. Development of Workbench Programs for CUPID1.7 Code

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yun Je; Park, Ik Kyu; Lee, Jae Ryong; Lee Seung Jun; Yoon, Han Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    The CUPID1.7 code input is based on the text mode and not only needs pre-processing for grid generation but also post-processing for visualization of calculation results. Therefore, the integrated platform is required to deal with a series of work from pre-processing to post-processing in the manner of a graphical user interface (GUI). With the upgraded of CUPID1.6 to CUPID1.7, the workbench program was developed. Using the CUPID1.7 workbench, users conveniently perform a series of work for CUPID1.7 calculation from the pre-process to the post-process. Because the current version of CUPID1.7 workbench has some functional restrictions according to the hardware, OS, and problems, continuous updates will be conducted through the feedback from users groups. A component-scale thermal hydraulic analysis code, CUPID 1.7 (Component Unstructured Program for Interfacial Dynamics 1.7), was recently distributed in an upgraded version. The most noticeable change of the CUPID1.7 compared to CUPID1.6 is that a parallel calculation based on the Message Passing Interface (MPI) is supported. In addition, the workbench program for the CUPID1.7 (CUPID1.7 workbench) was developed.

  9. Angiotensin-(1-7-Mediated Signaling in Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Enéas R. M. Gomes

    2012-01-01

    Full Text Available The Renin-Angiotensin System (RAS acts at multiple targets and has its synthesis machinery present in different tissues, including the heart. Actually, it is well known that besides Ang II, the RAS has other active peptides. Of particular interest is the heptapeptide Ang-(1-7 that has been shown to exert cardioprotective effects. In this way, great compilations about Ang-(1-7 actions in the heart have been presented in the literature. However, much less information is available concerning the Ang-(1-7 actions directly in cardiomyocytes. In this paper, we show the actual knowledge about Ang-(1-7-mediated signaling in cardiac cells more specifically we provide a brief overview of ACE2/Ang-(1-7/Mas axis; and highlight the discoveries made in cardiomyocyte physiology through the use of genetic approaches. Finally, we discuss the protective signaling induced by Ang-(1-7 in cardiomyocytes and point molecular determinants of these effects.

  10. National Bison Range National Wildlife Refuge : Annual Narrative : Calendar Year 1995

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for National Bison Range outlines Refuge accomplishments during the 1995 calendar year. The report begins with a summary of the year's...

  11. National Bison Range National Wildlife Refuge : Annual Narrative : Calendar Year 1996

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for National Bison Range outlines Refuge accomplishments during the 1996 calendar year. The report begins with a summary of the year's...

  12. National Bison Range National Wildlife Refuge : Annual Narrative : Calendar Year 1997

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for National Bison Range outlines Refuge accomplishments during the 1997 calendar year. The report begins with a summary of the year's...

  13. National Bison Range National Wildlife Refuge : Annual Narrative : Calendar Year 1994

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for National Bison Range outlines Refuge accomplishments during the 1994 calendar year. The report begins with a summary of the year's...

  14. Pain without Nociceptors? Nav1.7-Independent Pain Mechanisms

    Science.gov (United States)

    Minett, Michael S.; Falk, Sarah; Santana-Varela, Sonia; Bogdanov, Yury D.; Nassar, Mohammed A.; Heegaard, Anne-Marie; Wood, John N.

    2014-01-01

    Summary Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain and olfaction in mice and humans. We examined the role of Nav1.7 as well as Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain. Constriction-injury-dependent neuropathic pain is abolished when Nav1.7 is deleted in sensory neurons, unlike nerve-transection-related pain, which requires the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief. Sympathetic sprouting that develops in parallel with nerve-transection pain depends on the presence of Nav1.7 in sympathetic neurons. Mechanical and cold allodynia required distinct sets of neurons and different repertoires of sodium channels depending on the nerve injury model. Surprisingly, pain induced by the chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require the presence of Nav1.7 sodium channels or Nav1.8-positive nociceptors. Thus, similar pain phenotypes arise through distinct cellular and molecular mechanisms. Therefore, rational analgesic drug therapy requires patient stratification in terms of mechanisms and not just phenotype. PMID:24440715

  15. Pain without Nociceptors? Nav1.7-Independent Pain Mechanisms

    Directory of Open Access Journals (Sweden)

    Michael S. Minett

    2014-01-01

    Full Text Available Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain and olfaction in mice and humans. We examined the role of Nav1.7 as well as Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain. Constriction-injury-dependent neuropathic pain is abolished when Nav1.7 is deleted in sensory neurons, unlike nerve-transection-related pain, which requires the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief. Sympathetic sprouting that develops in parallel with nerve-transection pain depends on the presence of Nav1.7 in sympathetic neurons. Mechanical and cold allodynia required distinct sets of neurons and different repertoires of sodium channels depending on the nerve injury model. Surprisingly, pain induced by the chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require the presence of Nav1.7 sodium channels or Nav1.8-positive nociceptors. Thus, similar pain phenotypes arise through distinct cellular and molecular mechanisms. Therefore, rational analgesic drug therapy requires patient stratification in terms of mechanisms and not just phenotype.

  16. Stable renal function in insulin-dependent diabetes mellitus 10 years after nephrotic range proteinuria.

    Science.gov (United States)

    Gault, M H; Fernandez, D

    1996-01-01

    It has been considered unlikely that patients with insulin-dependent diabetes and diabetic nephropathy with nephrotic range proteinuria can substantially reduce proteinuria and continue for many years without further loss of renal function. We present a patient who had the diagnosis of insulin-dependent diabetes made at age 15, had his first of 6 laser treatments for proliferative and hemorrhagic retinopathy at age 27 and was found to have nephrotic range proteinuria and edema with hypertension at age 29, when results of a renal biopsy were typical of diabetic nephropathy. Ten years later, with the last 5.5 years on ACE inhibitors, proteinuria has been neprotic range is very rare in reports, if not unique.

  17. Recognizing history in range ecology: 100 years of science and management on the Santa Rita Experimental Range

    Science.gov (United States)

    Nathan F. Sayre

    2003-01-01

    At the centennial of the Santa Rita Experimental Range, historical analysis is called for on two levels. First, as a major site in the history of range ecology, the Santa Rita illuminates past successes and failures in science and management and the ways in which larger social, economic, and political factors have shaped scientific research. Second, with the turn away...

  18. Angiotensin-(1-7) : Pharmacological properties and pharmacotherapeutic perspectives

    NARCIS (Netherlands)

    Iusuf, Dilek; Henning, Robert H.; van Gilst, Wiek H.; Roks, Anton J. M.

    2008-01-01

    Therapeutic modulation of the renin-angiotensin system is not complete without taking into consideration the beneficial effects of angiotensin-(1-7) in cardiovascular pathology. Various pharmacological pathways are already exploited to involve this heptapeptide in therapy as both inhibitors of

  19. Evaluation of mental foramen location in the 10–70 years age range ...

    African Journals Online (AJOL)

    Evaluation of mental foramen location in the 10–70 years age range using ... limit from the lower edge of the mandible, and vertical size of the MF were measured. ... Conclusions: Knowing both the position and the distance of the MF from the ...

  20. Normal range of thoracic kyphosis in 13 to 18 years old healthy schoolboys in Kermanshah (2008

    Directory of Open Access Journals (Sweden)

    Farid Najafi

    2011-11-01

    Full Text Available Background: Increased thoracic kyphosis more than normal ranges are assessed as abnormal. But normal ranges of thoracic kyphosis in deferent age groups have not been identified in our country yet. The aim of present study was investigation of normal ranges of thoracic kyphosis to use as a diagnosis tool in school aged children in Kermanshah, Western-Iran.Methods: A descriptive research designed and ethical approval was obtained. 582 student boys 13 - 18 years old were cluster sampled randomly from two guidance and two high schools. Each age group included 97 students. Dorsal curves were measured using flexicurve method. Normal range of boy student’s kyphosis was determined using descriptive statistics of mean and two standard deviations.Results: The mean thoracic kyphosis values ranged from 18.29 to 52.50 degrees. It was 34.41±7.47 for age 13 and 35.55±7.07 degree for age 18. It increased gradually from 13 to 16 and then there was a little decrease to 18 years. Conclusion: Our results showed a little difference with other similar studies, which may be related to different measurement methods or personal characteristics. These can be used as normal values for local schools and these normal values need to be determined for all age groups in different population.

  1. Immersion francaise precoce: Education physique 1-7 (Early French Immersion: Physical Education for Grades 1-7).

    Science.gov (United States)

    Burt, Andy; And Others

    This curriculum guide for physical education is intended for use in grades 1-7 in the early French immersion program. It is a translation of the regular physical education program and a compilation of references and supplementary teaching material. It is noted that because of the comparative lack of references in French, much of the reference…

  2. Kuppuswamy’s Socio-economic Status Scale: Updating Income Ranges for the Year 2015

    Directory of Open Access Journals (Sweden)

    Hema Thakkar

    2015-12-01

    Full Text Available Community and hospital based studies require assessment of socio-economic status of an individual/family. Socioeconomic status (SES is an important determinant of the health, nutritional status, mortality, and morbidity of an individual. SES also influences the accessibility, affordability, acceptability, and actual utilization of available health facilities. (1There are many different scales to measure the SES of a family: Rahudkar scale 1960, Udai Parikh scale 1964, Jalota Scale 1970, Kulshrestha scale 1972, Kuppuswamy scale 1976, Shrivastava scale 1978, Bharadwaj scale 2001. (2,3,4,5,6,7,8 However, social transition and fast growing economy have reduced these scales effectiveness in measuring the SES over the years.Kuppuswamy’s socio-economic status scale is an important tool to measure socioeconomic status of families in urban areas. It was first proposed by Kuppuswamy in the in the year 1976. (6 (Table-1 This scale takes into account education, occupation of the head of the family and total income of the family per month from all the sources to categorise families into 5 groups; namely upper, upper middle, lower middle, upper lower and lower socioeconomic status. It is used by students and researchers in India for hospital and community based research. Mishra D and Singh HP (9 in their article on revision of Kuppuswamy’s Socio-economic status scale have pointed that an income scale usually has relevance only for the period under study. They further clarified that due to the steady inflation and consequent fall in the value of the rupee, the income criteria in the scale lose their relevance. There is an unprecedented demand from researchers for the updated version of this because changes in inflation rate change the monetary values of the monthly income range scores. Attempts to revise the original scale to bring the income subscale up to date are done by various authors.The year wise reference indices are shown in Table -2. It tell us

  3. Normative voice range profiles in vocally trained and untrained children aged between 7 and 10 years.

    Science.gov (United States)

    Schneider, Berit; Zumtobel, Michaela; Prettenhofer, Walter; Aichstill, Birgitta; Jocher, Werner

    2010-03-01

    Only limited data on normal vocal constitution and vocal capabilities in school-aged children are available. To take better care of children's voices, it might be helpful to know voice ranges and limits of not only vocally trained but also vocally untrained children. Goal of this study was the evaluation of singing voice capabilities of vocally healthy children with different social and vocal/musical backgrounds using voice range profile measurements (VRP). VRP percentiles that reflect constitutional aspects were suggested. In this cross-sectional study, 186 children (aged between seven and 10 years), attending five schools, were included. VRP measurements were performed under field conditions. Interviews and questionnaires regarding vocal strain and vocal training were applied; the answers were used for classification of singing activity and vocal training (KLASAK). All children reached a mean singing voice range of at least two octaves. By using the answers of interviews and questionnaires, the children could be classified according to vocal strain and vocal training. The groups showed no significant differences regarding VRP measurements. In the following step, percentiles were calculated. Twenty-five percent of all children (P25) reached a minimum voice range of almost two octaves, namely, 22 semitones (ST) from 220 to 784 Hz with soft and loud singing. Half of the children (P50) had a voice range of 24 ST (2 octaves), while soft singing and a larger voice range of 26 ST while loud singing. The measurements of third quartile (P75) revealed that 25% of children have even a larger voice range than 29 dB (from 196 Hz/g to 1047 Hz/c3) and can sing at most frequencies louder than 90 dB. P90 demonstrated that 10% of the children can sing even lower or higher than the frequency range between 196 Hz/g and 1319 Hz/e3 analyzed. The voice range seems not to be constrained by social but by voice/musical background: children of vocally/musically encouraged schools had wider

  4. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2012

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environmental Restoration

    2013-01-28

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2012 and includes inspection and repair activities completed at the following CAUs: · CAU 400: Bomblet Pit and Five Points Landfill (TTR) · CAU 407: Roller Coaster RadSafe Area (TTR) · CAU 424: Area 3 Landfill Complexes (TTR) · CAU 453: Area 9 UXO Landfill (TTR) · CAU 487: Thunderwell Site (TTR)

  5. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, For Calendar Year 2010

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environmental Restoration

    2011-03-30

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2010 and includes inspection and repair activities completed at the following seven CAUs: · CAU 400: Bomblet Pit and Five Points Landfill (TTR) · CAU 407: Roller Coaster RadSafe Area (TTR) · CAU 424: Area 3 Landfill Complexes (TTR) · CAU 426: Cactus Spring Waste Trenches (TTR) · CAU 453: Area 9 UXO Landfill (TTR) · CAU 484: Surface Debris, Waste Sites, and Burn Area (TTR) · CAU 487: Thunderwell Site (TTR)

  6. Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study.

    Science.gov (United States)

    Leal, R; Pinto, H; Galvão, A; Santos, L; Romãozinho, C; Macário, F; Alves, R; Pratas, J; Sousa, V; Marinho, C; Prado E Castro, L; Campos, M; Mota, A; Figueiredo, A

    2017-05-01

    There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Diurnal Temperature Range in Relation to Daily Mortality and Years of Life Lost in Wuhan, China.

    Science.gov (United States)

    Zhang, Yunquan; Yu, Chuanhua; Yang, Jin; Zhang, Lan; Cui, Fangfang

    2017-08-08

    Diurnal temperature range (DTR) is an important meteorological indicator associated with global climate change, and has been linked with mortality and morbidity in previous studies. To date, however, little evidence has been available regarding the association of DTR with years of life lost (YLL). This study aimed to evaluate the DTR-related burden on both YLL and mortality. We collected individual records of all registered deaths and daily meteorological data in Wuhan, central China, between 2009 and 2012. For the whole population, every 1 °C increase in DTR at a lag of 0-1 days was associated with an increase of 0.65% (95% CI: 0.08-1.23) and 1.42 years (-0.88-3.72) for mortality and YLL due to non-accidental deaths, respectively. Relatively stronger DTR-mortality/YLL associations were found for cardiovascular deaths. Subgroup analyses (stratified by gender, age, and education level) showed that females, the elderly (75+ years old), and those with higher education attainment (7+ years) suffered more significantly from both increased YLL and mortality due to large DTR. Our study added additional evidence that short-term exposure to large DTR was associated with increased burden of premature death using both mortality incidence and YLL.

  8. Demographic effects of canine parvovirus on a free-ranging wolf population over 30 years

    Science.gov (United States)

    Mech, L.D.; Goyal, S.M.; Paul, W.J.; Newton, W.E.

    2008-01-01

    We followed the course of canine parvovinis (CPV) antibody prevalence in a subpopulation of wolves (Canis 1upus) in northeastern Minnesota from 1973, when antibodies were first detected, through 2004. Annual early pup survival was reduced by 70%, and wolf population change was related to CPV antibody prevalence. In the greater Minnesota population of 3,000 wolves, pup survival was reduced by 40-60%. This reduction limited the Minnesota wolf population rate of increase to about 4% per year compared with increases of 16-58% in other populations. Because it is young wolves that disperse, reduced pup survival may have caused reduced dispersal and reduced recolonization of new range in Minnesota. ?? Wildlife Disease Association 2008.

  9. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, For Calendar Year 2008

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environmental Restoration

    2009-03-19

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Unit (CAU) sites located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2008 and includes inspection and repair activities completed at the following ten CAUs: CAU 400: Bomblet Pit and Five Points Landfill (TTR) CAU 404: Roller Coaster Lagoons and Trench (TTR) CAU 407: Roller Coaster RadSafe Area (TTR) CAU 423: Area 3 Underground Discharge Point, Building 0360 (TTR) CAU 424: Area 3 Landfill Complexes (TTR) CAU 426: Cactus Spring Waste Trenches (TTR) CAU 427: Area 3 Septic Waste Systems 2, 6 (TTR) CAU 453: Area 9 UXO Landfill (TTR) CAU 484: Surface Debris, Waste Sites, and Burn Area (TTR) CAU 487: Thunderwell Site (TTR)

  10. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2014

    Energy Technology Data Exchange (ETDEWEB)

    Silvas, A. J. [National Security Technologies, LLC, Las Vegas, NV (United States). Nevada Test Site; Lantow, Tiffany A. [National Security Technologies, LLC, Las Vegas, NV (United States). Nevada Test Site

    2015-03-25

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2014 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports and subsequent correspondence with the Nevada Division of Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Photographs taken during inspections are included in Appendix D. The annual post-closure inspections were conducted on May 28, 2014. Maintenance was required at CAU 407. Animal burrows were backfilled and erosion repairs were performed. Vegetation monitoring was performed at CAU 407 in June 2014. The vegetation monitoring report is included in Appendix E.

  11. Calendar Year 2004 annual site environmental report : Tonopah Test Range, Nevada & Kauai Test Facility, Hawaii.

    Energy Technology Data Exchange (ETDEWEB)

    Montoya, Amber L.; Wagner, Katrina; Goering, Teresa Lynn; Koss, Susan I.; Salinas, Stephanie A.

    2005-09-01

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2004. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2005) and DOE Order 231.1A, Environment, Safety, and Health Reporting (DOE 2004b).

  12. Association of plasma angiotensin-(1-7 level and left ventricular function in patients with type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Pan-Pan Hao

    Full Text Available We recently found that overexpression of angiotensin (Ang-converting enzyme 2, which metabolizes Ang-II to Ang-(1-7 and Ang-I to Ang-(1-9, may prevent diabetes-induced left ventricular remodeling and dysfunction in rats. Our objective was to evaluate the association of plasma Ang-(1-7 level and left ventricular function in patients with type 2 diabetes mellitus.We measured the left ventricular ejection fraction (EF, ratio of early to late left ventricular filling velocity (E/A and ratio of early diastolic mitral inflow to annular velocity (E/Ea by ultrasonography in 110 patients with type 2 diabetes mellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7 level in patients with a poor EF (15 was significantly lower than that in patients with E/Ea ≤15. Ang-(1-7 level was negatively correlated with E/Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1-7, hemoglobin A1c and Ang-II levels as well as duration of diabetes predicted EF; Ang-(1-7 level, fasting blood glucose, low-density lipoprotein cholesterol level and duration of diabetes predicted E/A; and Ang-(1-7 and hemoglobin A1c levels predicted E/Ea.Plasma Ang-(1-7 level is independently associated with left ventricular function in patients with type 2 diabetes mellitus and may be a biomarker for assessing cardiac function in such patients.

  13. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2013

    Energy Technology Data Exchange (ETDEWEB)

    Silvas, A. J.

    2014-03-03

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2013 and includes inspection and repair activities completed at the following CAUs: • CAU 400: Bomblet Pit and Five Points Landfill (TTR) • CAU 407: Roller Coaster RadSafe Area (TTR) • CAU 424: Area 3 Landfill Complexes (TTR) • CAU 453: Area 9 UXO Landfill (TTR) • CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports and subsequent correspondence with the Nevada Division of Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Field notes are included in Appendix D. Photographs taken during inspections are included in Appendix E. The annual post-closure inspections were conducted on May 14, 2013. Maintenance was performed at CAU 400, CAU 424, and CAU 453. At CAU 400, animal burrows were backfilled. At CAU 424, erosion repairs were completed at Landfill Cell A3-3, subsidence was repaired at Landfill Cell A3-4, and additional lava rock was placed in high-traffic areas to mark the locations of the surface grade monuments at Landfill Cell A3-3 and Landfill Cell A3-8. At CAU 453, two areas of subsidence were repaired and animal burrows were backfilled. Vegetation monitoring was performed at the CAU 400 Five Points Landfill and CAU 407 in June 2013. The vegetation monitoring report is included in Appendix F.

  14. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, For Calendar Year 2011

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environmental Restoration

    2012-02-21

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2011 and includes inspection and repair activities completed at the following CAUs: (1) CAU 400: Bomblet Pit and Five Points Landfill (TTR); (2) CAU 407: Roller Coaster RadSafe Area (TTR); (3) CAU 424: Area 3 Landfill Complexes (TTR); (4) CAU 453: Area 9 UXO Landfill (TTR); and (5) CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports. The post-closure inspection plan for each CAU is included in Appendix B. The inspection checklists are included in Appendix C, field notes are included in Appendix D, and photographs taken during inspections are included in Appendix E. The annual post-closure inspections were conducted May 3 and 4, 2011. Maintenance was performed at CAU 424, CAU 453, and CAU 487. At CAU 424, two surface grade monuments at Landfill Cell A3-3 could not be located during the inspection. The two monuments were located and marked with lava rock on July 13, 2011. At CAU 453, there was evidence of animal burrowing. Animal burrows were backfilled on July 13, 2011. At CAU 487, one use restriction warning sign was missing, and wording was faded on the remaining signs. A large animal burrow was also present. The signs were replaced, and the animal burrow was backfilled on July 12, 2011. As a best management practice, the use restriction warning signs at CAU 407 were replaced with standard Federal Facility Agreement and Consent Order signs on July 13, 2011. Vegetation monitoring was performed at the CAU 400 Five Points Landfill and CAU 407 in June 2011, and the vegetation monitoring report is included in Appendix F.

  15. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, For Calendar Year 2007

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environmental Restoration

    2008-06-01

    This report provides the results of the semiannual post-closure inspections conducted at the closed Corrective Action Unit (CAU) sites located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2007 and includes inspection and repair activities completed at the following nine CAUs: (1) CAU 400: Bomblet Pit and Five Points Landfill (TTR); (2) CAU 404: Roller Coaster Lagoons and Trench (TTR); (3) CAU 407: Roller Coaster RadSafe Area (TTR); (4) CAU 423: Area 3 Underground Discharge Point, Building 0360 (TTR); (5) CAU 424: Area 3 Landfill Complexes (TTR); (6) CAU 426: Cactus Spring Waste Trenches (TTR); (7) CAU 427: Area 3 Septic Waste Systems 2, 6 (TTR); (8) CAU 453: Area 9 UXO Landfill (TTR); and (9) CAU 487: Thunderwell Site (TTR). In a letter from the Nevada Division of Environmental Protection (NDEP) dated December 5, 2006, NDEP concurred with the request to reduce the frequency of post-closure inspections of CAUs at TTR to an annual frequency. This letter is included in Attachment B. Post-closure inspections were conducted on May 15-16, 2007. All inspections were conducted according to the post-closure plans in the approved Closure Reports. The post-closure inspection plan for each CAU is included in Attachment B, with the exception of CAU 400. CAU 400 does not require post-closure inspections, but inspections of the vegetation and fencing are conducted as a best management practice. The inspection checklists for each site inspection are included in Attachment C, the field notes are included in Attachment D, and the site photographs are included in Attachment E. Vegetation monitoring of CAU 400, CAU 404, CAU 407, and CAU 426 was performed in May 2007, and the vegetation monitoring report is included in Attachment F. Maintenance and/or repairs were performed at CAU 453. Animal burrows observed during the annual inspection at CAU 453 were backfilled on August 1, 2007. At this time, the TTR post-closure site inspections should continue as

  16. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2009

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environmental Restoration

    2010-05-28

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Unit (CAU) sites located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2009 and includes inspection and repair activities completed at the following seven CAUs: · CAU 400: Bomblet Pit and Five Points Landfill (TTR) · CAU 407: Roller Coaster RadSafe Area (TTR) · CAU 424: Area 3 Landfill Complexes (TTR) · CAU 426: Cactus Spring Waste Trenches (TTR) · CAU 453: Area 9 UXO Landfill (TTR) · CAU 484: Surface Debris, Waste Sites, and Burn Area (TTR) · CAU 487: Thunderwell Site (TTR) The annual post-closure inspections were conducted May 5–6, 2009. All inspections were conducted according to the post-closure plans in the approved Closure Reports. The post-closure inspection plan for each CAU is included in Attachment B, with the exception of CAU 400. CAU 400 does not require post-closure inspections, but inspections of the vegetation and fencing are conducted as a best management practice. The inspection checklists for each site inspection are included in Attachment C, the field notes are included in Attachment D, and the site photographs are included in Attachment E. Vegetation monitoring of CAU 400, CAU 404, CAU 407, and CAU 426 was performed in June 2009, and the vegetation monitoring report is included in Attachment F. Maintenance was performed at CAU 453. Animal burrows observed during the annual inspection were backfilled, and a depression was restored to grade on June 25, 2009. Post-closure site inspections should continue as scheduled. Vegetation survey inspections have been conducted annually at CAUs 400, 404, 407, and 426. Discontinuation of vegetation surveys is recommended at the CAU 400 Bomblet Pit and CAU 426, which have been successfully revegetated. Discontinuation of vegetation surveys is also recommended at CAU 404, which has been changed to an administrative closure with no inspections required. Vegetation

  17. Angiotensin-(1-7) Is an Endogenous Ligand for the G Protein-Coupled Receptor Mas

    National Research Council Canada - National Science Library

    Robson A. S. Santos; Ana C. Simoes e Silva; Christine Maric; Denise M. R. Silva; Raquel Pillar Machado; Insa de Buhr; Silvia Heringer-Walther; Sergio Veloso B. Pinheiro; Myriam Teresa Lopes; Michael Bader; Elizabeth P. Mendes; Virgina Soares Lemos; Maria Jose Campagnole-Santos; Heinz-Peter Schultheiss; Robert Speth; Thomas Walther

    2003-01-01

    ...) antagonist indicated the existence of a distinct Ang-(1-7) receptor. We demonstrate that genetic deletion of the G protein-coupled receptor encoded by the Mas protooncogene abolishes the binding of Ang-(1-7) to mouse kidneys...

  18. Paracin 1.7, a bacteriocin produced by Lactobacillus paracasei HD1.7 isolated from Chinese cabbage sauerkraut, a traditional Chinese fermented vegetable food.

    Science.gov (United States)

    Ge, Jingping; Ping, Wenxiang; Song, Gang; Du, Chunmei; Ling, Hongzhi; Sun, Xin; Gao, Ying

    2009-05-01

    To purify and characterize bacteriocin produced by L. paracasei HD1.7. Paracin 1.7 was purified by chromatography and its molecular weight was measured by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Antibacterial activity was measured by using the agar-well diffusion method. The bacterial strain for the fermentation was identified as Lactobacillus subsp. paracasei. Paracin 1.7 had the activity of inhibiting the growth of other bacteria. Maximum production of Paracin 1.7 was in the stationary phase. Paracin 1.7 can be well purified with Cation exchange chromatography, Sephedex (G50, G25, G10) gel chromatography and high performance liquid chromatography (HPLC) on C18 column and its determined molecular weight was about 11 kDa by Tricine-SDS-PAGE. Paracin 1.7 shows a broad spectrum of activities against various strains in the genera of Proteus, Bacillus, Enterobacter, Staphylococcus, Escherichia, Lactobacillus, Microccus, Pseudomonas, Salmonella and Saccharomyces, some of which belong to food borne pathogenic bacteria. Although Paracin 1.7 displayed stability toward heat and acidic pH, it was sensitive to several proteolytic enzymes. The inhibitory activities remain well after stored at 4 degrees C for 4 months; the inhibitory activity declined only 4.19%. Paracin 1.7 can be a potential food preservative on the basis of its antibacterial characters.

  19. 38 CFR 1.17 - Evaluation of studies relating to health effects of radiation exposure.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Evaluation of studies relating to health effects of radiation exposure. 1.17 Section 1.17 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS GENERAL PROVISIONS Program Evaluation § 1.17 Evaluation of studies relating to health effects of radiation...

  20. Clarence Rhode National Wildlife Range : Annual Narrative Report : Calendar Year 1976

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Clarence Rhode National Wildlife Refuge outlines Refuge accomplishments during the 1976 calendar year. The report begins with an...

  1. Clarence Rhode National Wildlife Range : Annual Narrative Report : Calendar Year 1977

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Clarence Rhode National Wildlife Refuge outlines Refuge accomplishments during the 1977 calendar year. The report begins with an...

  2. Comparative study of joint range of motion in children between 7 and 12 years of age from different gender

    Directory of Open Access Journals (Sweden)

    S.I.L. Melo

    2011-01-01

    Full Text Available The aim of the study was to evaluate and compare active and passive joint range of motion in children in relation to gender and age. This study involved 103 children (43 boys and 60 girls categorized into two groups: G1 (7 to 9 years old and G2 (10 to 12 years old. The flexitest protocol, active and passive, and the SAPO® were used to evaluate joint range of motion. A paired t test was applied to compare active and passive joint range of motion and an independent t test (p < .05 was used to compare active and passive range of motion between gender and age. Results showed that the passive joint ranges of motion of the lower limbs are higher than active motion (p < .001. Girls presented greater passive ankle flexion than boys did (p = .002. Children between 7 and 12 years of age presented similar standards of joint range of motion of low limb. Significant differences were found between passive and active angular range of motion in the hip, knee and ankle. There were no differences between boys and girls in the joint range of motion as well as among age groups.

  3. Ultrasonic attenuation in human calcaneus from 0.2 to 1.7 MHz.

    Science.gov (United States)

    Wear, K A

    2001-03-01

    Ultrasonic attenuation has been demonstrated to be a useful measurement in the diagnosis of osteoporosis. Most studies have employed ultrasound in a range of frequencies from about 200 kHz-300 kHz to 600 kHz-1 MHz, and many have assumed a linear dependence of attenuation on frequency. In order to investigate the attenuation properties of human calcaneus at higher frequencies, 16 defatted human calcanea were interrogated in vitro using two matched pairs of transducers with center frequencies of 500 kHz and 2.25 MHz. The linear dependence of attenuation on frequency seems to extend up to at least 1.7 MHz. The correlation between attenuation coefficient and frequency from 400 kHz to 1.7 MHz was r = 0.999 (95% confidence interval, CI, = 0.998-1.00). The measurements suggest that some deviations from linear frequency dependence of attenuation may occur at lower frequencies (below 400 kHz), however.

  4. Life after INF (Intermediate-Range Nuclear Forces): West Germany in the Year 2000.

    Science.gov (United States)

    1988-03-14

    1960 will be the principal leaders of Germany in 2000. Most matured during or after the " Wirtschaftswunder ," or economic reconstruction of the 1950’s...years had more pro-military and pro-NATO sentiments than those in their late twenties.1 2 THE ECONOMY " Wirtschaftswunder " was a fundamental matter of

  5. Ten Years of Change in Sierran Stringer Meadows: An Evaluation of Range Condition Models

    Science.gov (United States)

    Barbara H. Allen

    1989-01-01

    Grazed Sierra Nevada stringer meadow systems were sampled on Blodgett Forest Research Station in northern California between 1977 and 1987 to determine cattle use, and to examine changes in production and species composition over time. Utilization of meadow species averaged 61 percent over the 10 years, but use increased to more than 80 percent utilization after 1985....

  6. Angiotensin-(1-7): Beyond the Cardio-Renal Actions

    DEFF Research Database (Denmark)

    Passos-Silva, Danielle G; Verano-Braga, Thiago; Santos, Robson AS

    2013-01-01

    It is well known that the renin-angiotensin system (RAS) plays a key role in the modulation of many functions in the body. Angiotensin (Ang) II acting on AT1R has a central role in mediating most of the actions of the RAS. However, over the past 10 years, several studies presented evidence for th...

  7. Oak Ridge National Laboratory Health and Safety Long-Range Plan: Fiscal years 1989--1995

    Energy Technology Data Exchange (ETDEWEB)

    1989-06-01

    The health and safety of its personnel is the first concern of ORNL and its management. The ORNL Health and Safety Program has the responsibility for ensuring the health and safety of all individuals assigned to ORNL activities. This document outlines the principal aspects of the ORNL Health and Safety Long-Range Plan and provides a framework for management use in the future development of the health and safety program. Each section of this document is dedicated to one of the health and safety functions (i.e., health physics, industrial hygiene, occupational medicine, industrial safety, nuclear criticality safety, nuclear facility safety, transportation safety, fire protection, and emergency preparedness). Each section includes functional mission and objectives, program requirements and status, a summary of program needs, and program data and funding summary. Highlights of FY 1988 are included.

  8. Accelerated ice-sheet mass loss in Antarctica from 18-year satellite laser ranging measurements

    Directory of Open Access Journals (Sweden)

    Shuanggen Jin

    2016-02-01

    Full Text Available Accurate estimate of the ice-sheet mass balance in Antarctic is very difficult due to complex ice sheet condition and sparse in situ measurements. In this paper, the low-degree gravity field coefficients of up to degree and order 5 derived from Satellite Laser Ranging (SLR measurements are used to determine the ice mass variations in Antarctica for the period 1993–2011. Results show that the ice mass is losing with -36±13 Gt/y in Antarctica, -42±11 Gt/y in the West Antarctica and 6±10 Gt/y in the East Antarctica from 1993 to 2011. The ice mass variations from the SLR 5×5 have a good agreement with the GRACE 5×5, GRACE 5×5 (1&2 and GRACE (60×60 for the entire continent since 2003, but degree 5 from SLR is not sufficient to quantify ice losses in West and East Antarctica, respectively. The rate of ice loss in Antarctica is -28±17 Gt/y for 1993-2002 and -55±17 Gt/y for 2003-2011, indicating significant accelerated ice mass losses since 2003. Furthermore, the results from SLR are comparable with GRACE measurements.

  9. National semen analysis reference range reporting: adherence to the 1999 World Health Organization guidelines 10 years later.

    Science.gov (United States)

    Penn, Heidi A; Windsperger, Andrew; Smith, Zachary; Parekattil, Sijo J; Kuang, Wayne W; Kolettis, Peter N; Nangia, Ajay K

    2011-06-01

    To determine the adherence by laboratories across the United States to the standard semen analysis guidelines and parameter reference ranges 10 years after being set by the World Health Organization (WHO) in 1999 and to compare compliance between regional laboratories vs. specialty assisted reproductive technology (ART) laboratories. Observational study. Regional clinical and reproductive endocrinology andrology laboratories. Blank or deidentified semen analysis reports were collected from laboratories through direct contact or from reports received as part of clinical care for male infertility. Adherence to semen analysis reference range reporting as recommended by the 1999 WHO guidelines. Semen analyses reports were collected from 111 laboratories from 31 different states. Of 111 laboratories, 26 (23%) reported all reference range parameters in accordance with the guidelines. Of 65 ART laboratories, 21 (32%) complied with all reference range parameters as outlined by the guidelines, vs. 5 of 46 non-ART laboratories (11%). Seventy percent of laboratories that did not report 1999 WHO parameters did so because of differences in reference values for normal morphology. Adherence to WHO 1999 semen analysis reference range guidelines has not been achieved by ART and non-ART laboratories 10 years after being introduced. Non-ART laboratories report reference ranges less accurately than ART laboratories. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. "I Was in Year 5 and I Failed Maths": Identifying the Range and Causes of Maths Anxiety in First Year Pre-Service Teachers

    Science.gov (United States)

    Wilson, Sue

    2015-01-01

    Mathematics anxiety affects primary pre-service teachers' engagement with and future teaching of mathematics. The study aimed to assess the level and range of mathematics anxiety in first year pre-service teachers entering their teacher education course, and to investigate the sources of this anxiety as perceived and identified by them. Data…

  11. Vascular Actions of Angiotensin 1-7 in the Human Microcirculation: Novel Role for Telomerase.

    Science.gov (United States)

    Durand, Matthew J; Zinkevich, Natalya S; Riedel, Michael; Gutterman, David D; Nasci, Victoria L; Salato, Valerie K; Hijjawi, John B; Reuben, Charles F; North, Paula E; Beyer, Andreas M

    2016-06-01

    This study examined vascular actions of angiotensin 1-7 (ANG 1-7) in human atrial and adipose arterioles. The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1-7, we tested the hypothesis that overnight ANG 1-7 treatment restores the NO component of FMD in arterioles from patients with CAD. Endothelial telomerase activity is essential for preserving the NO component of vasodilation in the human microcirculation; thus, we also tested whether telomerase activity was necessary for ANG 1-7-mediated vasoprotection by treating separate arterioles with ANG 1-7±the telomerase inhibitor 2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid. ANG 1-7 dilated arterioles from patients without CAD, whereas dilation was significantly reduced in arterioles from patients with CAD. In atrial arterioles from patients with CAD incubated with ANG 1-7 overnight, the NO synthase inhibitor NG-nitro-l-arginine methyl ester abolished FMD, whereas the hydrogen peroxide scavenger polyethylene glycol catalase had no effect. Conversely, in vessels incubated with ANG 1-7+2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid, NG-nitro-l-arginine methyl ester had no effect on FMD, but polyethylene glycol catalase abolished dilation. In cultured human coronary artery endothelial cells, ANG 1-7 significantly increased telomerase activity. These results indicate that ANG 1-7 dilates human microvessels, and dilation is abrogated in the presence of CAD. Furthermore, ANG 1-7 treatment is sufficient to restore the NO component of FMD in arterioles from patients with CAD in a telomerase-dependent manner. ANG 1-7 exerts vasoprotection in the human microvasculature via modulation of telomerase activity. © 2016 American Heart Association, Inc.

  12. Angiotensin-(1-7) regulates Angiotensin II-induced VCAM-1 expression on vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Feng [Department of Cardiology, Peking University People' s Hospital, Beijing (China); William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (United Kingdom); Ren, Jingyi [Department of Cardiology, Peking University People' s Hospital, Beijing (China); Chan, Kenneth [William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (United Kingdom); Chen, Hong, E-mail: chenhongbj@medmail.com.cn [Department of Cardiology, Peking University People' s Hospital, Beijing (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer We for the first time found that Ang-(1-7) inhibits Ang II-induced VCAM-1 expression. Black-Right-Pointing-Pointer The inhibitory effect of Ang-(1-7) on VCAM-1 is mediated by MAS receptor. Black-Right-Pointing-Pointer The effect of Ang-(1-7) is due to the suppression of NF-kappaB translocation. -- Abstract: Angiotensin II (Ang II) and Angiotensin-(1-7) (Ang-(1-7)) are key effector peptides in the renin-angiotensin system. Increased circulatory Ang II level is associated with the development of hypertension and atherosclerosis, whereas Ang-(1-7) is a counter-regulatory mediator of Ang II which appears to be protective against cardiovascular disease. However, whether Ang-(1-7) regulates the action of Ang II on vascular endothelial cells (EC) remains unclear. We investigated the effects of Ang II and Ang-(1-7) in the context of atherogenesis, specifically endothelial cell VCAM-1 expression that is implicated in early plaque formation. The results show that Ang II increased VCAM-1 mRNA expression and protein displayed on EC surface, while Ang-(1-7) alone exerted no effects. However, Ang-(1-7) significantly suppressed Ang II-induced VCAM-1 expression. Ang-(1-7) also inhibited the Ang II-induced VCAM-1 promoter activity driven by transcription factor NF-KappaB. Furthermore, immunofluorescence assay and ELISA showed that Ang II facilitated the nuclear translocation of NF-kappaB in ECs, and this was attenuated by the presence of Ang-(1-7). The inhibitory effects of Ang-(1-7) on Ang II-induced VCAM-1 promoter activity and NF-kappaB nuclear translocation were all reversed by the competitive antagonist of Ang-(1-7) at the Mas receptor. Our results suggest that Ang-(1-7) mediates its affects on ECs through the Mas receptor, and negatively regulates Ang II-induced VCAM-1 expression by attenuating nuclear translocation of NF-kappaB.

  13. AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium.

    Science.gov (United States)

    Wiemer, Gabriele; Dobrucki, Lawrence W; Louka, Febee R; Malinski, Tadeusz; Heitsch, Holger

    2002-12-01

    Recently, we demonstrated that the heptapeptide angiotensin-(1-7) (Ang-[1-7]) exhibits a favorable kinetic of nitric oxide (NO) release accompanied by extremely low superoxide (O2-) production. In this report we describe AVE 0991, a novel nonpeptide compound that evoked effects similar to Ang-(1-7) on the endothelium. AVE 0991 and unlabeled Ang-(1-7) competed for high-affinity binding of [125I]-Ang-(1-7) to bovine aortic endothelial cell membranes with IC50 values of 21+/-35 and 220+/-280 nmol/L, respectively. Stimulated NO and O2- release from bovine aortic endothelial cells was directly and simultaneously measured on the cell surface by selective electrochemical nanosensors. Peak concentrations of NO and O2- release by AVE 0991 and Ang-(1-7) (both 10 micromol/L) were not significantly different (NO: 295+/-20 and 270+/-25 nmol/L; O2-: 18+/-2 and 20+/-4 nmol/L). However, the released amount of bioactive NO was approximately 5 times higher for AVE 0991 in comparison to Ang-(1-7). The selective Ang-(1-7) antagonist [D-Ala(7)]-Ang-(1-7) inhibited the AVE 0991-induced NO and O2- production by approximately 50%. A similar inhibition level was observed for the Ang II AT1 receptor antagonist EXP 3174. In contrast, the Ang II AT2 receptor antagonist PD 123,177 inhibited the AVE 0991-stimulated NO production by approximately 90% but without any inhibitory effect on O2- production. Both NO and O2- production were inhibited by NO synthase inhibition ( approximately 70%) and by bradykinin B2 receptor blockade (approximately 80%). AVE 0991 efficiently mimics the effects of Ang-(1-7) on the endothelium, most probably through stimulation of a specific, endothelial Ang-(1-7)-sensitive binding site causing kinin-mediated activation of endothelial NO synthase.

  14. Panel mounted time code reader. [Day of year, hour, minute, second from standard Inter Range Instrumentation Group time codes

    Energy Technology Data Exchange (ETDEWEB)

    Shaum, R. L.

    1978-02-01

    The time code reader described is composed of an assembly of commonly available electronic components logically arranged to minimize component count while reliably achieving the basic function of decoding and displaying the time of year information which is available in each of several standard Inter Range Instrumentation Group (IRIG) time codes. The time code reader omits all subsidiary functions of the code except that of retrieving a readable time of year (day, hour, minute, second). The reader can be mounted on any equipment panel having an available flat surface that is 2 by 6 inches in dimensions. IRIG time codes A, B, E, and G can be read without the necessity of switching, and a relatively wide range of input voltages is accommodated.

  15. Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory.

    Science.gov (United States)

    Lazaroni, Thiago L N; Raslan, Ana Cláudia S; Fontes, Walkiria R P; de Oliveira, Marilene L; Bader, Michael; Alenina, Natalia; Moraes, Márcio F D; Dos Santos, Robson A; Pereira, Grace S

    2012-01-01

    It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. 37 CFR 1.17 - Patent application and reexamination processing fees.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Patent application and reexamination processing fees. 1.17 Section 1.17 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES General Provisions Fees...

  17. The role of angiotensin(1-7) in renal vasculature of the rat

    NARCIS (Netherlands)

    van der Wouden, Els A.; Ochodnický, Peter; van Dokkum, Richard Pe; Roks, Anton Jm; Deelman, Leo E.; de Zeeuw, Dick; Henning, Robert H.

    2006-01-01

    Angiotensin(1-7) is an active component of the renin-angiotensin-aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1-7) on the renal vasculature in vitro and in vivo. Isolated small renal arteries were studied in an arteriograph

  18. The role of angiotensin(1-7) in renal vasculature of the rat

    NARCIS (Netherlands)

    van der Wouden, Els A.; Ochodnicky, Peter; van Dokkum, Richard P. E.; Roks, Anton J. M.; Deelman, Leo E.; de Zeeuw, Dick; Henning, Robert H.

    2006-01-01

    Objective Angiotensin(1-7) is an active component of the renin-angiotensin-aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1-7) on the renal vasculature in vitro and in vivo. Methods Isolated small renal arteries were studied

  19. Angiotensin-(1-7) attenuates hyposmolarity-induced ANP secretion via the Na+-K+ pump.

    Science.gov (United States)

    Shah, Amin; Oh, Young-Bin; Shan, Gao; Song, Chang Ho; Park, Byung-Hyun; Kim, Suhn Hee

    2010-09-01

    The alteration in osmolarity challenges cell volume regulation, a vital element for cell survival. Hyposmolarity causes an increase in cell volume. Recently, it has been reported that the renin-angiotensin system (RAS) plays a role in cell volume regulation. We investigated the effect of angiotensin-(1-7) [Ang-(1-7)] on hyposmolarity-induced atrial natriuretic peptide (ANP) secretion in normal and diabetic (DM) rat atria and modulation of the effect of Ang-(1-7) by the Na(+)-K(+) pump. Using isolated control rat atria, we observed that perfusion of hyposmotic solution into the atria increased ANP secretion. When Ang-(1-7) [0.1 microM or 1 microM] was perfused in a hyposmolar solution, it decreased the hyposmolarity-induced ANP secretion in a dose-dependent manner. This effect of Ang-(1-7) could be mediated by the Na(+)-K(+) pump, since ouabain, an Na(+)-K(+) pump inhibitor, significantly decreased the effect of Ang-(1-7) on hyposmolarity-induced ANP secretion. In contrast, N(omega) Nitro-l-arginine methyl ester hydrochloride (l-NAME) did not modify the effect of Ang-(1-7) on the hyposmolarity-induced ANP secretion. Interestingly, the ANP secretion was increased robustly by the perfusion of the hyposmolar solution in the DM atria, as compared to the control atria. However, the inhibitory effect of Ang-(1-7) on the hyposmolarity-induced ANP secretion was not observed in the DM atria. In the DM atria, atrial contractility was significantly increased. Taken together, we concluded that Ang-(1-7) attenuated hyposmolarity-induced ANP secretion via the Na(+)-K(+) pump and a lack of Ang-(1-7) response in DM atria may partly relate to change in Na(+)-K(+) pump activity. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method.

    LENUS (Irish Health Repository)

    Murphy, S J

    2012-02-01

    BACKGROUND: Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described. AIM: To assess the effectiveness of a corticosteroid withdrawal method. METHODS: Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn\\'s disease), median age 53.5 years (range 29-75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean. RESULTS: Median durations for disease and corticosteroid dependency were 21 (range 3-45) and 14 (range 2-45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5-73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056). CONCLUSIONS: Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients.

  1. Elevation-Dependent Temperature Trends in the Rocky Mountain Front Range: Changes over a 56- and 20-Year Record

    Science.gov (United States)

    McGuire, Chris R.; Nufio, César R.; Bowers, M. Deane; Guralnick, Robert P.

    2012-01-01

    Determining the magnitude of climate change patterns across elevational gradients is essential for an improved understanding of broader climate change patterns and for predicting hydrologic and ecosystem changes. We present temperature trends from five long-term weather stations along a 2077-meter elevational transect in the Rocky Mountain Front Range of Colorado, USA. These trends were measured over two time periods: a full 56-year record (1953–2008) and a shorter 20-year (1989–2008) record representing a period of widely reported accelerating change. The rate of change of biological indicators, season length and accumulated growing-degree days, were also measured over the 56 and 20-year records. Finally, we compared how well interpolated Parameter-elevation Regression on Independent Slopes Model (PRISM) datasets match the quality controlled and weather data from each station. Our results show that warming signals were strongest at mid-elevations over both temporal scales. Over the 56-year record, most sites show warming occurring largely through increases in maximum temperatures, while the 20-year record documents warming associated with increases in maximum temperatures at lower elevations and increases in minimum temperatures at higher elevations. Recent decades have also shown a shift from warming during springtime to warming in July and November. Warming along the gradient has contributed to increases in growing-degree days, although to differing degrees, over both temporal scales. However, the length of the growing season has remained unchanged. Finally, the actual and the PRISM interpolated yearly rates rarely showed strong correlations and suggest different warming and cooling trends at most sites. Interpretation of climate trends and their seasonal biases in the Rocky Mountain Front Range are dependent on both elevation and the temporal scale of analysis. Given mismatches between interpolated data and the directly measured station data, we caution

  2. Elevation-dependent temperature trends in the Rocky Mountain Front Range: changes over a 56- and 20-year record.

    Directory of Open Access Journals (Sweden)

    Chris R McGuire

    Full Text Available Determining the magnitude of climate change patterns across elevational gradients is essential for an improved understanding of broader climate change patterns and for predicting hydrologic and ecosystem changes. We present temperature trends from five long-term weather stations along a 2077-meter elevational transect in the Rocky Mountain Front Range of Colorado, USA. These trends were measured over two time periods: a full 56-year record (1953-2008 and a shorter 20-year (1989-2008 record representing a period of widely reported accelerating change. The rate of change of biological indicators, season length and accumulated growing-degree days, were also measured over the 56 and 20-year records. Finally, we compared how well interpolated Parameter-elevation Regression on Independent Slopes Model (PRISM datasets match the quality controlled and weather data from each station. Our results show that warming signals were strongest at mid-elevations over both temporal scales. Over the 56-year record, most sites show warming occurring largely through increases in maximum temperatures, while the 20-year record documents warming associated with increases in maximum temperatures at lower elevations and increases in minimum temperatures at higher elevations. Recent decades have also shown a shift from warming during springtime to warming in July and November. Warming along the gradient has contributed to increases in growing-degree days, although to differing degrees, over both temporal scales. However, the length of the growing season has remained unchanged. Finally, the actual and the PRISM interpolated yearly rates rarely showed strong correlations and suggest different warming and cooling trends at most sites. Interpretation of climate trends and their seasonal biases in the Rocky Mountain Front Range are dependent on both elevation and the temporal scale of analysis. Given mismatches between interpolated data and the directly measured station data

  3. Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

    Directory of Open Access Journals (Sweden)

    Yiangou Yiangos

    2010-06-01

    Full Text Available Abstract Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS, considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5 and controls (n = 12, and the other patients with BMS (n = 7 and controls (n = 10. BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS. Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS.

  4. Characteristics of laser produced plasmas of hafnium and tantalum in the 1-7 nm region

    Science.gov (United States)

    Li, Bowen; Otsuka, Takamitsu; Sokell, Emma; Dunne, Padraig; O'Sullivan, Gerry; Hara, Hiroyuki; Arai, Goki; Tamura, Toshiki; Ono, Yuichi; Dinh, Thanh-Hung; Higashiguchi, Takeshi

    2017-11-01

    Soft X-ray (SXR) spectra from hafnium and tantalum laser produced plasmas were recorded in the 1-7 nm region using two Nd:YAG lasers with pulse lengths of 170 ps and 10 ns, respectively, operating at a range of power densities. The maximum focused peak power density was 2. 3 × 1014 W cm-2 for 170 ps pulses and 1. 8 × 1012 W cm-2 for 10 ns pulses, respectively. Two intense quasicontinuous intensity bands resulting from n = 4 - n = 4 and n = 4 - n = 5 unresolved transition arrays (UTAs) dominate both sets of experimental spectra. Comparison with calculations performed with the Cowan suite of atomic structure codes as well as consideration of previous experimental and theoretical results aided identification of the most prominent features in the spectra. For the 10 ns spectrum, the highest ion stage that could be identified from the n = 4 - n = 5 arrays were lower than silver-like Hf25+ and Ta26+ (which has a 4 d 104 f ground configuration) indicating that the plasma temperature attained was too low to produce ions with an outermost 4 d subshell, while for the 170 ps plasmas the presence of significantly higher stages was deduced and lines due to 4 d-5 p transitions were clearly evident. Furthermore, we show an enhancement of emission from tantalum using dual laser irradiation, and the effect of pre-pulse durations and delay times between two pulses are demonstrated.

  5. Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid.

    Science.gov (United States)

    Olivon, V C; Aires, R D; Santiago, L B; Ramalho, L Z N; Cortes, S F; Lemos, V S

    2015-09-01

    Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang-(1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1-7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang-(1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7)-vasorelaxant response. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Angiotensin-(1-7) recruits muscle microvasculature and enhances insulin's metabolic action via mas receptor.

    Science.gov (United States)

    Fu, Zhuo; Zhao, Lina; Aylor, Kevin W; Carey, Robert M; Barrett, Eugene J; Liu, Zhenqi

    2014-06-01

    Angiotensin-(1-7) [Ang-(1-7)], an endogenous ligand for the G protein-coupled receptor Mas, exerts both vasodilatory and insulin-sensitizing effects. In skeletal muscle, relaxation of precapillary arterioles recruits microvasculature and increases the endothelial surface area available for nutrient and hormone exchanges. To assess whether Ang-(1-7) recruits microvasculature and enhances insulin action in muscle, overnight-fasted adult rats received an intravenous infusion of Ang-(1-7) (0, 10, or 100 ng/kg per minute) for 150 minutes with or without a simultaneous infusion of the Mas inhibitor A-779 and a superimposition of a euglycemic insulin clamp (3 mU/kg per minute) from 30 to 150 minutes. Hind limb muscle microvascular blood volume, microvascular flow velocity, and microvascular blood flow were determined. Myographic changes in tension were measured on preconstricted distal saphenous artery. Ang-(1-7) dose-dependently relaxed the saphenous artery (Pmicrovasculature and enhances the metabolic action of insulin. These effects may contribute to the cardiovascular protective responses associated with Mas activation and explain the insulin-sensitizing action of Ang-(1-7).

  7. Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma.

    Science.gov (United States)

    Savage, Paul D; Lovato, James; Brosnihan, K Bridget; Miller, Antonius A; Petty, W Jeffrey

    2016-01-01

    Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7), two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7) was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma) and 19 months (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.

  8. Phase II Trial of Angiotensin-(1-7 for the Treatment of Patients with Metastatic Sarcoma

    Directory of Open Access Journals (Sweden)

    Paul D. Savage

    2016-01-01

    Full Text Available Background. Angiotensin-(1-7 [Ang-(1-7] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7, two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7 was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7 was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months, and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months. Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma and 19 months (epithelioid hemangioendothelioma. Conclusions. Ang-(1-7 at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.

  9. Bilateral hand transplantation: Functional benefits assessment in five patients with a mean follow-up of 7.6 years (range 4-13 years).

    Science.gov (United States)

    Bernardon, Laurence; Gazarian, Aram; Petruzzo, Palmina; Packham, Tara; Guillot, Michel; Guigal, Vincent; Morelon, Emmanuel; Pan, Hua; Dubernard, Jean-Michel; Rizzo, Christophe; Feugier, Patrick; Streichenberger, Thibault; Bincaz, Ludovic; Urien, Jean-Pierre; Mezzadri, Guillaume; Rousselon, Thibault; Plotard, Franck; Seulin, Christian; Braye, Fabienne; Mojallal, Ali; Herzberg, Guillaume; Kanitakis, Jean; Abrahamyan, Davit; Kay, Simon; Badet, Lionel

    2015-09-01

    Between January 2000 and July 2009, five adults who had suffered bilateral traumatic below-elbow amputations, received bilateral hand-forearm allografts performed by the Lyon team. We report the functional benefits achieved over a mean follow-up period of 7.6 years (range 4-13 years), up to December 31st, 2013. Clinical measurement is hampered by the lack of specific validated assessment tools, obliging us to use non-specific standardized evaluation means. Our assessment shows that the restoration of motion, strength, and sensibility are fair. Functional results (Carroll upper extremity function test, 400-point test, Activities of daily living) are good, as well as quality of life evaluation (RAND-36). Subjective and overall results explored with questionnaires - Disabilities of the Arm Shoulder and Hand (DASH), Hand Transplantation Score System (HTSS), are very good. Improvement was seen to continue during the first three years, and then tend to become stable. Continued efforts should be directed at designing comprehensive, condition-specific, reliable outcome measurement tools. Continuous monitoring and evaluation of patients is required to assess the long-term risk-benefit balance. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Stellar imaging coronagraph an additional instrument for exoplanet exploration onboard the WSO-UV 1.7 meter orbital telescope

    Science.gov (United States)

    Shashkova, I.; Frolov, P.; Dzyuban, I.; Kiselev, A.; Tavrov, A.; Korablev, O.; Sachkov, M.; Nishikawa, J.; Kameda, S.

    2017-09-01

    The WSO-UV (World Space Observatory for Ultraviolet) is the orbital optical telescope with a 1.7 m diameter of primary mirror under construction. The WSO-UV is aimed for a 110-310 nm UV spectral range observations and it will have onboard science instruments: the spectrographs in UV and the imaging field cameras with filter wheels. Currently the WSO-UV project has the development up to a "C" phase and the telescope launch is optimistically scheduled to 2022. Recently, a new science instrument dedicated for exoplanets exploration has been proposed to the WSO-UV named SCEDI - Stellar Coronagraph for Exoplanet Direct Imaging.

  11. Effect of angiotensin-(1-7 on reperfusion arrhythmias in isolated rat hearts

    Directory of Open Access Journals (Sweden)

    L.A.A. Neves

    1997-06-01

    Full Text Available There is increasing evidence that angiotensin-(1-7 (Ang-(1-7 is an endogenous biologically active component of the renin-angiotensin system (RAS. In the present study, we investigated the effects of Ang-(1-7 on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2 and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2. In hearts perfused with Krebs-Ringer, Ang-(1-7 produced a concentration-dependent (27-210 nM reduction in coronary flow (25% reduction at highest concentration, while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM produced a significant reduction in coronary flow (39% and 48%, respectively associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7 or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang-(1-7 produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration. The facilitation of reperfusion arrhythmias by Ang-(1-7 was associated with an increase in the magnitude of the decreased force usually observed during the post-ischemic period. The effects of Ang-(1-7 were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM was similar but less pronounced than that of Ang-(1-7 at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7 and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS

  12. The tACE/Angiotensin (1-7)/Mas Axis Protects Against Testicular Ischemia Reperfusion Injury.

    Science.gov (United States)

    Al-Maghrebi, May; Renno, Waleed M

    2016-08-01

    To investigate whether exogenous angiotensin (Ang)-(1-7) administration can protect against the damaging consequences of testicular ischemia reperfusion (tIR) injury. Eighteen male Sprague-Dawley rats were divided equally among the following 3 groups: sham, unilateral tIR injury (1 hour of ischemic treatment and 4 hours of reperfusion), and tIR + Ang-(1-7) (0.3 mg/kg). Testicular tissues obtained from the rats were evaluated for the expression of testicular angiotensin-converting enzyme (tACE), Ang-(1-7), and the Ang-(1-7)-specific receptor Mas by immunohistochemistry and enzyme-linked immunosorbent assay. Reduced spermatogenesis, induction of the caspase-8 pathway, and nitric oxide (NO) generation were assessed. The effects of tIR and Ang-(1-7) treatment on the PI3K/Akt antiapoptosis pathway were also investigated. Testicular morphological changes and reduced spermatogenesis associated with decreased expression of the tACE/Ang-(1-7)/Mas axis were observed during tIR. These effects were also accompanied by increased activity of caspase-3 and -8, downregulation of the survivin and BAD transcripts, and decreased NO formation. During tIR, PTEN expression was increased, leading to inactivation of the PI3K/Akt pathway. Acute treatment with Ang-(1-7) prior to reperfusion attenuated the tIR-induced damage described above. Expression of the tACE/Ang-(1-7)/Mas axis was downregulated during tIR. Administration of exogenous Ang-(1-7) prior to reperfusion rescued tACE and Mas expression and protected against germ cell apoptosis and oxidative stress. Increased NO generation and activation of the PI3K/Akt signaling pathway may have partially contributed to these effects. The tACE/Ang-(1-7)/Mas axis likely plays a role in the maintenance of normal testis physiology and spermatogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Changes in hip and ankle range of motion and hip muscle strength in 8–11 year old novice female ballet dancers and controls: a 12 month follow up study

    Science.gov (United States)

    Bennell, K; Khan, K; Matthews, B; Singleton, C

    2001-01-01

    Objectives—To evaluate in a 12 month longitudinal study changes in hip and ankle range of motion and hip muscle strength in young female novice ballet dancers. Methods—Fifty three of the original 77 (69%) female dancers aged 8–11 years and 40 of the original 49 (82%) controls returned for follow up measurements one year later. Supine right active hip external (ER) and internal (IR) rotation were measured using an inclinometer. A turnout protractor was used to assess standing active turnout range. Range of right weight bearing ankle dorsiflexion and calf muscle length were measured in a standing lunge position using an inclinometer. A manual muscle tester was used to assess right hip flexor, IR, ER, abductor and adductor strength. Results—The mean (SD) 12 month change in hip ER did not differ between dancers (11.7 (11.3)°) and controls (8.1 (17.6)°). Dancers gained 12.5 (13.5)° hip IR which was significantly greater than controls (0.5 (13.9)°). Greater IR change was associated with improved IR strength (r = 0.34, pballet students and controls at this young age. However, ankle dorsiflexion did not, which is probably due to this movement being blocked by bony apposition, rather than soft tissue stretch. This has implications for ballet teachers, as it has long been accepted that this movement could be improved with training. Dancers had greater increases in hip strength after 12 months compared with controls in muscles specific for ballet, suggesting that hip strength can be trained at this young age. Whether these gains are permanent requires further study. Key Words: dance; ballet; range of motion; muscle strength PMID:11157464

  14. One year in the life of Bufo punctatus: annual patterns of body temperature in a free-ranging desert anuran

    Science.gov (United States)

    Rausch, Candice M.; Starkweather, Peter L.; van Breukelen, Frank

    2008-06-01

    The Mojave Desert is characterized by hot dry summers and cold winters. The red-spotted toad ( Bufo ( Anaxyrus) punctatus) is the predominant anuran species; yet little is known of their thermal histories and strategies to avoid temperature extremes. We measured body temperature ( T b) in free-ranging adult toads across all four seasons of a year using implanted data loggers. There is marked individual variation in the temperatures experienced by these toads. As expected, toads generally escape extreme seasonal and diel temperature fluctuations. However, our data demonstrate a much wider estimated T b range than was previously assumed. Though often for short periods, red-spotted toads do experience T b as low as 3.1°C and as high as 39.1°C. All animals showed periods of prolonged thermal stability in cooler months and wider diel oscillations in warmer months. Red-spotted toad thermal history is likely a function of site choice; the exploitation of different refuges results in diverse thermal experiences. These data represent the most complete record of thermal experiences for a desert anuran and reveal greater extremes in body temperature than previously suggested.

  15. Global Nav1.7 knockout mice recapitulate the phenotype of human congenital indifference to pain.

    Directory of Open Access Journals (Sweden)

    Jacinthe Gingras

    Full Text Available Clinical genetic studies have shown that loss of Nav1.7 function leads to the complete loss of acute pain perception. The global deletion is reported lethal in mice, however, and studies of mice with promoter-specific deletions of Nav1.7 have suggested that the role of Nav1.7 in pain transduction depends on the precise form of pain. We developed genetic and animal husbandry strategies that overcame the neonatal-lethal phenotype and enabled construction of a global Nav1.7 knockout mouse. Knockouts were anatomically normal, reached adulthood, and had phenotype wholly analogous to human congenital indifference to pain (CIP: compared to littermates, knockouts showed no defects in mechanical sensitivity or overall movement yet were completely insensitive to painful tactile, thermal, and chemical stimuli and were anosmic. Knockouts also showed no painful behaviors resulting from peripheral injection of nonselective sodium channel activators, did not develop complete Freund's adjuvant-induced thermal hyperalgesia, and were insensitive to intra-dermal histamine injection. Tetrodotoxin-sensitive sodium current recorded from cell bodies of isolated sensory neurons and the mechanically-evoked spiking of C-fibers in a skin-nerve preparation each were reduced but not eliminated in tissue from knockouts compared to littermates. Results support a role for Nav1.7 that is conserved between rodents and humans and suggest several possibly translatable biomarkers for the study of Nav1.7-targeted therapeutics. Results further suggest that Nav1.7 may retain its key role in persistent as well as acute forms of pain.

  16. Oribatid Mite Community Decline Two Years after Low-Intensity Burning in the Southern Cascade Range of California, USA

    Directory of Open Access Journals (Sweden)

    Nancy E. Gillette

    2012-10-01

    Full Text Available To assess effects of low-intensity fire, we combined two silvicultural prescriptions with prescribed fire in the California Cascade Range. In the first treatment, two 100-ha stands were thinned to reduce density while retaining old-growth structural characteristics, yielding residual stands with high structural diversity (HSD. Two other 100-ha plots were thinned to minimize old growth structure, producing even-aged stands of low structural diversity (LSD, and one 50-ha split-plot from each treatment was burned. In addition, two 50 ha old-growth Research Natural Areas (RNA were selected as untreated reference plots, one of which was also burned. Fire treatments profoundly altered mite assemblages in the short term, and forest structure modification likely exacerbated that response. Sampling conducted two years following treatment confirmed a continuing decline in oribatid mite abundance. Oribatid species richness and assemblage heterogeneity also declined, and community dominance patterns were disrupted. Oribatid responses to fire were either more intense or began earlier in the LSD treatments, suggesting that removal of old-growth structure exacerbated mite responses to fire. Prostigmatids recovered quickly, but their populations nonetheless diminished significantly in burned split-plots. Mite assemblage responses to prescribed fire were continuing nearly two years later, with no clear evidence of recovery.

  17. Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas.

    Science.gov (United States)

    Morales, María Gabriela; Abrigo, Johanna; Acuña, María José; Santos, Robson A; Bader, Michael; Brandan, Enrique; Simon, Felipe; Olguin, Hugo; Cabrera, Daniel; Cabello-Verrugio, Claudio

    2016-04-01

    Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophyin vivousing unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy. © 2016. Published by The Company of Biologists Ltd.

  18. Functionalized Fullerene Targeting Human Voltage-Gated Sodium Channel, hNav1.7.

    Science.gov (United States)

    Hilder, Tamsyn A; Robinson, Anna; Chung, Shin-Ho

    2017-08-16

    Mutations of hNa v 1.7 that cause its activities to be enhanced contribute to severe neuropathic pain. Only a small number of hNa v 1.7 specific inhibitors have been identified, most of which interact with the voltage-sensing domain of the voltage-activated sodium ion channel. In our previous computational study, we demonstrated that a [Lys 6 ]-C 84 fullerene binds tightly (affinity of 46 nM) to Na v Ab, the voltage-gated sodium channel from the bacterium Arcobacter butzleri. Here, we extend this work and, using molecular dynamics simulations, demonstrate that the same [Lys 6 ]-C 84 fullerene binds strongly (2.7 nM) to the pore of a modeled human sodium ion channel hNa v 1.7. In contrast, the fullerene binds only weakly to a mutated model of hNa v 1.7 (I1399D) (14.5 mM) and a model of the skeletal muscle hNa v 1.4 (3.7 mM). Comparison of one representative sequence from each of the nine human sodium channel isoforms shows that only hNa v 1.7 possesses residues that are critical for binding the fullerene derivative and blocking the channel pore.

  19. AVE 0991-angiotensin-(1-7) receptor agonist, inhibits atherogenesis in apoE-knockout mice.

    Science.gov (United States)

    Toton-Zuranska, J; Gajda, M; Pyka-Fosciak, G; Kus, K; Pawlowska, M; Niepsuj, A; Wolkow, P; Olszanecki, R; Jawien, J; Korbut, R

    2010-04-01

    Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. It was also proved that Ang II promotes atherogenesis. Angiotensin-(1-7) [Ang-(1-7)] opposites Ang II action. Therefore, we would like to find out whether Ang-(1-7) receptor agonist: AVE 0991, could ameliorate atherosclerosis progression in an experimental model of atherosclerosis: apolipoprotein E (apoE) - knockout mice. AVE 0991 inhibited atherogenesis, measured both by "en face" method (7.63+/-1.6% vs. 14.6+/-2.1%) and "cross-section" method (47 235+/-7 546 microm(2) vs. 91 416+/-8 357 microm(2)). This is the first report showing the effect of AVE 0991 on atherogenesis in gene-targeted mice.

  20. Downregulation of the ACE2/Ang-(1-7)/Mas axis in transgenic mice overexpressing GH.

    Science.gov (United States)

    Muñoz, Marina C; Burghi, Valeria; Miquet, Johanna G; Giani, Jorge F; Banegas, Ricardo D; Toblli, Jorge E; Fang, Yimin; Wang, Feiya; Bartke, Andrzej; Dominici, Fernando P

    2014-05-01

    The renin-angiotensin system (RAS) plays a crucial role in the regulation of physiological homeostasis and diseases such as hypertension, coronary artery disease, and chronic renal failure. In this cascade, the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/AT1 receptor axis induces pathological effects, such as vasoconstriction, cell proliferation, and fibrosis, while the ACE2/Ang-(1-7)/Mas receptor axis is protective for end-organ damage. The altered function of the RAS could be a contributing factor to the cardiac and renal alterations induced by GH excess. To further explore this issue, we evaluated the consequences of chronic GH exposure on the in vivo levels of Ang II, Ang-(1-7), ACE, ACE2, and Mas receptor in the heart and the kidney of GH-transgenic mice (bovine GH (bGH) mice). At the age of 7-8 months, female bGH mice displayed increased systolic blood pressure (SBP), a high degree of both cardiac and renal fibrosis, as well as increased levels of markers of tubular and glomerular damage. Angiotensinogen abundance was increased in the liver and the heart of bGH mice, along with a concomitant increase in cardiac Ang II levels. Importantly, the levels of ACE2, Ang-(1-7), and Mas receptor were markedly decreased in both tissues. In addition, Ang-(1-7) administration reduced SBP to control values in GH-transgenic mice, indicating that the ACE2/Ang-(1-7)/Mas axis is involved in GH-mediated hypertension. The data indicate that the altered expression profile of the ACE2/Ang-(1-7)/Mas axis in the heart and the kidney of bGH mice could contribute to the increased incidence of hypertension, cardiovascular, and renal alterations observed in these animals.

  1. Podocalyxin promotes glioblastoma multiforme cell invasion and proliferation by inhibiting angiotensin-(1-7)/Mas signaling.

    Science.gov (United States)

    Liu, Bo; Liu, Yu; Jiang, Yugang

    2015-05-01

    Podocalyxin (PODX) reportedly enhances invasion in many human cancers including glioblastoma multiforme (GBM). Recent studies have shown that the local renin-angiotensin system (RAS) in tumor environment contributes significantly to tumor progression. As a counter-regulatory axis in RAS, angiotensin (Ang)-(1-7)/Mas signaling has been shown to inhibit the growth and invasiveness of several human cancers including GBM. In the present study, we examined the crosstalk between PODX and Ang-(1-7)/Mas signaling in GBM cells, and assessed its impact on GBM cell invasion and proliferation. A strong negative correlation between the expression of PODX and Mas in GBM tumor tissues from 10 consecutive patients (r=-0.768, pMas at the mRNA and protein levels, which led to decreased density of Ang-(1-7)-binding Mas on the cell membrane. This effect was completely abolished by selective phosphatidylinositol 3-kinase (PI3K) inhibitor BKM120. By contrast, the stable knockdown of PODX in LN-229 and U-118 MG cells increased the expression of Mas and the density of Ang-(1-7)-binding Mas on the cell membrane. Overexpression and knockdown of PODX respectively reversed and enhanced the inhibitory effects of Ang-(1-7) on the expression/activity of matrix metalloproteinase-9 and cell invasion and proliferation in GBM cells. Although the overexpression of Mas showed no significant effect on the promoting effect of PODX on GBM cell invasion and proliferation in the absence of Ang-(1-7), it completely eliminated the effect of PODX in the presence of Ang-(1-7). In conclusion, to the best of our knowledge, the present study provided the first evidence that PODX inhibits Ang-(1-7)/Mas signaling by downregulating the expression of Mas through a PI3K-dependent mechanism in GBM cells. This effect led to enhanced GBM cell invasion and proliferation. The results of this study add new insight into the biological functions of PODX and the molecular mechanisms underlying GBM progression.

  2. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  3. The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Villalobos, Laura A; San Hipólito-Luengo, Álvaro; Ramos-González, Mariella; Cercas, Elena; Vallejo, Susana; Romero, Alejandra; Romacho, Tania; Carraro, Raffaele; Sánchez-Ferrer, Carlos F; Peiró, Concepción

    2016-01-01

    Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively. Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  4. Calendar year 2002 annual site environmental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie; Koss, Susan I.; Salinas, Stephanie A.

    2003-09-01

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, oversees TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2002. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 5400.1, General Environmental Protection Program (DOE 1990) and DOE Order 231.1, Environment, Safety, and Health Reporting (DOE 1996).

  5. Calendar year 2003 : annual site enviromental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie; Koss, Susan I.; Salinas, Stephanie A.

    2004-09-01

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2003. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2003) and DOE Order 231.1 Chg 2., Environment, Safety, and Health Reporting (DOE 1996).

  6. Concurrent validity of the wide range assessment of visual motor abilities in typically developing children ages 4 to 11 years.

    Science.gov (United States)

    Obler, Doris R; Avi-Itzhak, Tamara

    2011-10-01

    Pediatric clinicians working with school-age children use the Wide Range Assessment of Visual Motor Abilities (WRAVMA) as a method for evaluating visual perception and motor skills in children despite limited information on concurrent validity. Whether it may be substituted for the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) and has suitable estimates of concurrent validity were examined with a convenience sample of 91 typically developing children ages 4 to 11 years. No systematic concurrent validity between the WRAVMA and the VMI emerged. Only two subtests of the WRAVMA (Matching with Visual Perception, and Pegboard with Motor Coordination) gave scores statistically significantly correlated with those on the VMI, and these correlations were weak, accounting for very small amounts of the shared variance. As such, they have low clinical relevance. These findings do not provide evidence of concurrent validity to support the use of WRAVMA as an alternative method for the VMI for assessing children's visual perception and motor skills.

  7. Calendar year 2007 annual site environmental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii,

    Energy Technology Data Exchange (ETDEWEB)

    Agogino, Karen [Department of Energy, Albuquerque, NM (United States). National Nuclear Security Administration (NNSA); Sanchez, Rebecca [Sandia Corp., Albuquerque, NM (United States)

    2008-09-30

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE)/National Nuclear Security Administration (NNSA), through the Sandia Site Offi ce (SSO), in Albuquerque, NM, administers the contract and oversees contractor operations at TTR and KTF. Sandia manages and conducts operations at TTR in support of the DOE/NNSA’s Weapons Ordnance Program and has operated the site since 1957. Washington Group International subcontracts to Sandia in administering most of the environmental programs at TTR. Sandia operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2007. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia is responsible only for those environmental program activities related to its operations. The DOE/NNSA/Nevada Site Offi ce (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2007a) and DOE Manual 231.1-1A, Environment, Safety, and Health Reporting Manual (DOE 2007).

  8. Salmonella roggeveld 51 :-:1,7 A New Serotype | Brede | South ...

    African Journals Online (AJOL)

    A new Salmonella, S. roggeveld 51 : - : 1,7 is described. So far this Salmonella seems to be geographically restricted to the western Cape Province. A total of 18 different isolations, all performed at the Department of Medical Microbiology, University of Stellenbosch, between 1962 and 1969 gives some insight into the ...

  9. Assessment of Lexical and Non-Lexical Spelling in Students in Grades 1-7

    Science.gov (United States)

    Kohnen, Saskia; Colenbrander, Danielle; Krajenbrink, Trudy; Nickels, Lyndsey

    2015-01-01

    The main aim of this study was to develop standardised tests that assess some of the most important spelling skills for children in primary school: sound-letter mappings (non-lexical spelling) and word spelling accuracy (lexical spelling). We present normative comparison data for children in Grades 1-7 as well as measures of validity and…

  10. ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good

    National Research Council Canada - National Science Library

    Xu, Ping; Sriramula, Srinivas; Lazartigues, Eric

    2011-01-01

    ...). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1-7)/Mas axis...

  11. Angiotensin-(1-7) is a modulator of the human renin-angiotensin system

    NARCIS (Netherlands)

    Roks, AJM; van Geel, PP; Pinto, YM; Buikema, H; Henning, RH; de Zeeuw, D; van Gilst, WH

    The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1-7) to

  12. Angiotensin-(1-7) is a modulator of the human renin-angiotensin system

    NARCIS (Netherlands)

    Roks, A. J.; van Geel, P. P.; Pinto, Y. M.; Buikema, H.; Henning, R. H.; de Zeeuw, D.; van Gilst, W. H.

    1999-01-01

    The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1-7) to

  13. Nonpeptide AVE 0991 is an angiotensin-(1-7) receptor Mas agonist in the mouse kidney.

    Science.gov (United States)

    Pinheiro, Sérgio Veloso Brant; Simões e Silva, Ana Cristina; Sampaio, Walkyria Oliveira; de Paula, Renata Dutra; Mendes, Elizabeth Pereira; Bontempo, Elizabete Dias; Pesquero, João Bosco; Walther, Thomas; Alenina, Natalia; Bader, Michael; Bleich, Markus; Santos, Robson Augusto Souza

    2004-10-01

    It has been described recently that the nonpeptide AVE 0991 (AVE) mimics the effects of angiotensin-(1-7) [Ang-(1-7)] in bovine endothelial cells. In this study, we tested the possibility that AVE is an agonist of the Ang-(1-7) receptor Mas, in vitro and in vivo. In water-loaded C57BL/6 mice, AVE (0.58 nmol/g body weight) produced a significant reduction in urinary volume (0.06+/-0.03 mL/60 min [n=9] versus 0.27+/-0.05 [n=9]; PAVE. As observed previously for Ang-(1-7), the antidiuretic effect of AVE after water load was blunted in Mas-knockout mice (0.37+/-0.10 mL/60 min [n=9] versus 0.27+/-0.03 mL/60 min [n=11] AVE-treated mice). In vitro receptor autoradiography in C57BL/6 mice showed that the specific binding of 125I-Ang-(1-7) to mouse kidney slices was displaced by AVE, whereas no effects were observed in the binding of 125I-angiotensin II or 125I-angiotensin IV. Furthermore, AVE displaced the binding of 125I-Ang-(1-7) in Mas-transfected monkey kidney cells (COS) cells (IC50=4.75x10(-8) mol/L) and of rhodamine-Ang-(1-7) in Mas-transfected Chinese hamster ovary (CHO) cells. It also produced NO release in Mas-transfected CHO cells blocked by A-779 but not by angiotensin II type-1 (AT1) and AT2 antagonists. Contrasting with these data, the antidiuretic effect of AVE was totally blocked by AT2 antagonists and partially blocked (approximately 60%) by AT1 antagonists. The binding data, the results obtained in Mas-knockout mice and in Mas-transfected cells, show that AVE is a Mas receptor agonist. Our data also suggest the involvement of AT2/AT1-related mechanisms, including functional antagonism, oligomerization or cross-talk, in the renal responses to AVE.

  14. Year-round retrievals of trace gases in the Arctic using the Extended-range Atmospheric Emitted Radiance Interferometer

    Science.gov (United States)

    Mariani, Z.; Strong, K.; Palm, M.; Lindenmaier, R.; Adams, C.; Zhao, X.; Savastiouk, V.; McElroy, C. T.; Goutail, F.; Drummond, J. R.

    2013-06-01

    The Extended-range Atmospheric Emitted Radiance Interferometer (E-AERI) was installed at the Polar Environment Atmospheric Research Laboratory (PEARL) at Eureka, Nunavut, Canada in October 2008. Spectra from the E-AERI provide information about the radiative balance and budgets of trace gases in the Canadian high Arctic. Measurements are taken every 7 min year-round, including polar night when the solar-viewing spectrometers at PEARL are not operated. This allows E-AERI measurements to fill the gap in the PEARL dataset during the four months of polar night. Measurements were taken year-round in 2008-2009 at the PEARL Ridge Lab, which is 610 m a.s.l. (above sea-level), and from 2011 onwards at the Zero-Altitude PEARL Auxiliary Lab (0PAL), which is at sea level 15 km from the Ridge Lab. Total columns of O3, CO, CH4, and N2O have been retrieved using a modified version of the SFIT2 retrieval algorithm adapted for emission spectra. This provides the first ground-based nighttime measurements of these species at Eureka. Changes in the total columns driven by photochemistry and dynamics are observed. Analyses of E-AERI retrievals indicate accurate spectral fits (root-mean-square residuals consistent with noise) and a 10-15% uncertainty in the total column, depending on the trace gas. O3 comparisons between the E-AERI and a Bruker IFS 125HR Fourier transform infrared (FTIR) spectrometer, three Brewer spectrophotometers, two UV-visible ground-based spectrometers, and a System D'Analyse par Observations Zenithales (SAOZ) at PEARL are made from 2008-2009 and for 2011. 125HR CO, CH4, and N2O columns are also compared with the E-AERI measurements. Mean relative differences between the E-AERI and the other spectrometers are 1-10% (14% is for the un-smoothed profiles), which are less than the E-AERI's total column uncertainties. The E-AERI O3 and CO measurements are well correlated with the other spectrometers (r > 0.92 with the 125HR). The 24 h diurnal cycle and 365-day seasonal

  15. Environmental exposure of lead and iron deficit anemia in children age ranged 1-5 years: A cross sectional study

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Faheem; Kazi, Tasneem Gul; Afridi, Hassan Imran; Baig, Jameel Ahmed; Khan, Sumaira, E-mail: skhanzai@gmail.com; Kolachi, Nida Fatima; Wadhwa, Sham Kumar; Shah, Abdul Qadir, E-mail: shah_ceac@yahoo.com, E-mail: tgkazi@yahoo.com, E-mail: hassanimranafridi@yahoo.com, E-mail: jab_mughal@yahoo.com, E-mail: nidafatima6@gmail.com [National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro 76080 (Pakistan)

    2010-10-15

    Iron (Fe) deficiency is the most common nutritional problem among children and lead (Pb) toxicity is the most common environmental health threat to children all over the world. The objective of this study was to determine blood lead (BPb) levels and prevalence of Fe deficient anemia among 1 to 5 year old children attending day care clinic in pediatric ward of civil hospital Karachi, Pakistan. A total of 340 children of both genders participating in this study, were screened for anemia. Among them 215 were anemic and 125 non-anemic. The anemic group was further divided in two groups on the basis of % hemoglobin (Hb), mild (Hb < 10 g/dL) and severe anemic group (Hb < 8 g/dL), while non-anemic as referent children (Hb > 10 g/dL). The blood samples were analysed for Pb and Fe, along with hematological parameters. The result indicated that anemic children had a higher mean values of Pb in blood than referent children with Hb > 10 g/dL. The Pb levels < 100 {mu}g/L were detected in 40% referent children while 60% of them had > 10 {mu}g/dL. The BPb concentration in severe anemic children (53%) was found in the range of 100-200 {mu}g/L, whereas 47% had > 200 {mu}g/L. The significant negative correlations of BPb level with % Hb (r = -0.514 and r = -0.685) and Fe contents (r = -0.522, r = -0.762, p < 0.001) were observed in mild and severe anemic children respectively. While positive correlation was observed between BPb and age of both group and genders (r = 0.69, p < 0.01). The BPb levels were significantly associated with biochemical indices in the blood which have the potential to be used as biomarkers of Pb intoxication and Fe deficient anemia.

  16. Human-climate-environment interactions during the past 4000 years in the Taurus Mountain Range, SW Turkey

    Science.gov (United States)

    Verstraeten, Gert; Broothaerts, Nils; Van Loo, Maarten; Poblome, Jeroen; Degryse, Patrick

    2017-04-01

    The Eastern Mediterranean has been an area of intense human occupation since the early Neolithic. However, contrary to many temperate environments in NW Europe, human pressure on the landscape did not follow a linear trajectory from the Neolithic to the present, but is rather characterised by cycles of land cover expansion and contraction. Here, we provide a synthesis of human-climate-environment interactions in the region of the antique city of Sagalassos in the Taurus mountain range of SW Turkey. The combination of archaeological, palynological and geomorphological data, together with geochemical sediment provenancing and spatial modelling techniques, enabled to reconstruct the relative importance of anthropogenic pressure and climatic changes on the environment. The sensitivity of the landscape towards anthropogenic disturbance is strongly controlled by the geomorphic-tectonic setting, as well as by important feedback mechanisms in the soil system. The first major clearing of the landscape in the Iron Age led to a peak in soil erosion, but also to soil exhaustion limiting erosion rates in subsequent periods. Soil erosion and sediment delivery is more limited during the main occupation phases of the Roman Imperial Period. Periods with more favorable climate in the Roman and Mid-Byzantine periods resulted in the occupation of more isolated parts of the territory (i.e. higher up in the mountains), whilst a decrease in human pressure can be observed during the Early Byzantine and Ottoman periods related to less favorable conditions. Such smaller and short-lasting bursts of human occupation did not significanlty impact the environment. Only in the last two hundred years, human pressure reached similar values as those encountered in the classical period.

  17. Post-Closure Inspection Report for the Tonopah Test Range, Nevada. For Calendar Year 2015, Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, Patrick [Navarro, Las Vegas, NV (United States); Petrello, Jaclyn [Navarro, Las Vegas, NV (United States)

    2016-03-01

    This report provides the results of the annual post-closure inspections conducted at the closed corrective action units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2015 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved closure reports and subsequent correspondence with the Nevada Division of Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Field notes are included in Appendix D. The annual post-closure inspections were conducted on May 12, 2015. Maintenance was required at CAU 453. Cracking along the north trench was repaired. One monument is missing at CAU 424; it will be replaced in 2016. Postings at CAUs 407, 424, 453, and 487 contain contact information for TTR Security. It was noted that protocols may not be in place to ensure that the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) is notified if access is needed at these sites. NNSA/NFO is working with the U.S. Air Force and Sandia to determine whether more appropriate contact information or new protocols are warranted for each CAU. Based on these inspections, there has not been a significant change in vegetation, and vegetation monitoring was not recommended at CAU 400 or CAU 407 in 2015.

  18. Two year response of woody plants to LeTourneau tree crushers on the Kenai National Moose Range

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Evaluated the importance of disturbance by fire in providing moose forage on the Kenai National Moose Range. Discussed impacts of logging and fire and period of time...

  19. Narrative report: Calendar year 1976: Charles M. Russell National Wildlife Range and Hailstone, Halfbreed, Lake Mason & War Horse National Wildlife Refuges

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Charles M. Russell National Wildlife Range (including the satellite refuges) outlines Refuge accomplishments during the 1976 calendar year....

  20. Rare Nav1.7 variants associated with painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Blesneac, Iulia; Themistocleous, Andreas C; Fratter, Carl; Conrad, Linus J; Ramirez, Juan D; Cox, James J; Tesfaye, Solomon; Shillo, Pallai R; Rice, Andrew S C; Tucker, Stephen J; Bennett, David L H

    2017-11-22

    Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of DPN patients develop neuropathic pain for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis, for better patient stratification in clinical trials and to target therapy more appropriately. Here we examined the relationship between variants in the voltage gated sodium channel Nav1.7 and neuropathic pain in a deeply phenotyped cohort of patients with DPN. While no rare variants were found in 78 participants with painless DPN, we identified twelve rare Nav1.7 variants in ten (out of 111) study participants with painful DPN. Five of these variants had previously been described in the context of other neuropathic pain disorders and seven have not previously been linked to neuropathic pain. Those patients with rare variants reported more severe pain and greater sensitivity to pressure stimuli on quantitative sensory testing. Electrophysiological characterization of two of the novel variants (M1852T and T1596I) demonstrated gain of function changes as a consequence of markedly impaired channel fast inactivation. By using a structural model of Nav1.7 we were also able provide further insight into the structural mechanisms underlying fast activation and the role of the C-terminal domain in this process. Our observations suggest that rare Nav1.7 variants contribute to the development neuropathic pain in patients with diabetic peripheral neuropathy. Their identification should aid understanding of sensory phenotype, patient stratification and help target treatments effectively.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  1. Chronic allergic pulmonary inflammation is aggravated in angiotensin-(1-7) Mas receptor knockout mice.

    Science.gov (United States)

    Magalhães, Giselle S; Rodrigues-Machado, Maria Glória; Motta-Santos, Daisy; Alenina, Natalia; Bader, Michael; Santos, Robson A; Barcelos, Lucíola S; Campagnole-Santos, Maria José

    2016-12-01

    The angiotensin-(1-7) [ANG-(1-7)]/Mas receptor pathway is currently recognized as a counterbalancing mechanism of the renin-angiotensin system in different pathophysiological conditions. We have previously described that treatment with ANG-(1-7) attenuates lung inflammation and remodeling in an experimental model of asthma. In the present study, we investigated whether lack of the Mas receptor could alter the inflammatory response in a model of chronic allergic lung inflammation induced by ovalbumin (OVA). Mas receptor wild-type (MasWT) and knockout (MasKO) mice were subjected to four doses of OVA (20 μg/mice ip) with a 14-day interval. At the 21st day, nebulization with OVA (1%) was started, three times per week until the 46th day. Control groups received saline (0.9% ip) and were nebulized with saline (0.9%). MasWT-OVA developed a modest inflammatory response and minor pulmonary remodeling to OVA challenge. Strikingly, MasKO-OVA presented a significant increase in inflammatory cell infiltrate, increase in extracellular matrix deposition, increase in thickening of the alveolar parenchyma, increase in thickening of the smooth muscle layer of the pulmonary arterioles, increase in proinflammatory cytokine and chemokine levels in the lungs, characteristic of chronic asthma. Additionally, MasKO-OVA presented an increase in ERK1/2 phosphorylation compared with MasWT-OVA. Furthermore, MasKO-OVA showed a worse performance in a test of maximum physical exercise compared with MasWT-OVA. Our study shows that effects triggered by the Mas receptor are important to attenuate the inflammatory and remodeling processes in a model of allergic lung inflammation in mice. Our data indicate that impairment of the ANG-(1-7)/Mas receptor pathway may lead to worsening of the pathophysiological changes of asthma. Copyright © 2016 the American Physiological Society.

  2. Angiotensin 1-7 significantly reduces diabetes-induced leukocyte recruitment both in vivo and in vitro.

    Science.gov (United States)

    Bossi, Fleur; Bernardi, Stella; De Nardo, Daniele; Bramante, Alessandra; Candido, Riccardo; Carretta, Renzo; Fischetti, Fabio; Fabris, Bruno

    2016-01-01

    Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion. Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects. Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro. These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Voice training and changing weight--are they reflected in speaking fundamental frequency, voice range, and pitch breaks of 13-year-old girls? A longitudinal study.

    Science.gov (United States)

    Willis, Elizabeth C; Kenny, Dianna T

    2011-09-01

    Assessment of the voice-change progress of 20 girls (12-13 years) over 1 year by observing changes in speaking fundamental frequency (SFo), voice range, and register pitch breaks in the context of weight, height, voice training, and self-perception. One-year longitudinal collective case study. Twenty girls were recorded at the beginning and end of a year; nine girls were recorded another three times. SFo, vocal range, and characteristics were analyzed and interactions between these data assessed against weight and height to indicate pubertal development, and to test the hypothesis that changes in weight, height, SFo, and pitch breaks were related. Effects of training and the girls' self-perception of their voice use were also assessed. Vocal characteristics changed as the girls passed through different weight ranges. During 47.5-52.4 kg (called band 2) and 52.4-57.5 kg (band 3), there was progressive contraction of vocal range and in some girls a slight rise in SFo between recording times 1 and 5. Both high- and low-pitch breaks were present in 45% of girls' voices. Girls in band 4 (pitch breaks in vocal-range areas that indicated the development of adult vocal registers. In this study, voice-trained girls were heavier, had higher SFo, used wider speech-range inflection, had a higher vocal range, and greater voice-use confidence; all girls lost confidence in their voice use over the year. In this longitudinal study of twenty 13-year-old girls, voice changes in SFo, vocal range, and pitch-break frequency were synchronous with certain weight ranges. Girls with training registered higher maximum phonational frequency and were more confident in their voice use than girls without training. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  4. AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo.

    Science.gov (United States)

    Chen, Xinglu; Chen, Sansan; Pei, Nana; Mao, Yingying; Wang, Shengyao; Yan, Renhe; Bai, Na; Li, Andrew; Zhang, Yanling; Du, Hongyan; Chen, Baihong; Sumners, Colin; Li, Jinlong; Li, Hongwei

    2017-01-03

    Ang-(1-7) inhibits lung cancer cell growth both in vitro and in vivo. However, the molecular mechanism of action is unclear and also the rapid degradation of Ang-(1-7) in vivo limits its clinical application. Here, we have demonstrated that Ang- (1-7) inhibits lung cancer cell growth by interrupting pre-replicative complex assembly and restrains epithelial-mesenchymal transition via Cdc6 inhibition. Furthermore, we constructed a mutant adeno-associated viral vector AAV8 (Y733F) that produced stable and high efficient Ang-(1-7) expression in a xenograft tumor model. The results show that AAV8-mediated Ang-(1-7) over-expression can remarkably suppress tumor growth in vivo by down-regulating Cdc6 and anti-angiogenesis. Ang-(1-7) over-expression via the AAV8 method may be a promising strategy for lung cancer treatment.

  5. Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Louise M Burrell

    Full Text Available We previously reported that exogenous angiotensin (Ang 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE activity. This study investigated if the addition of an ACE inhibitor (ACEi to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day, Ang 1-7 (subcutaneous 24 μg/kg/h or dual therapy (all groups, n = 12. A control group (n = 10 of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.

  6. Interrelationships between Working Memory, Processing Speed, and Language Development in the Age Range 2-4 Years

    Science.gov (United States)

    Newbury, Jayne; Klee, Thomas; Stokes, Stephanie F.; Moran, Catherine

    2016-01-01

    Purpose: This study explored associations between working memory and language in children aged 2-4 years. Method: Seventy-seven children aged 24-30 months were assessed on tests measuring language, visual cognition, verbal working memory (VWM), phonological short-term memory (PSTM), and processing speed. A standardized test of receptive and…

  7. Using Quantum Mechanics to Facilitate the Introduction of a Broad Range of Chemical Concepts to First-Year Undergraduate Students

    Science.gov (United States)

    deSouza, Romualdo T.; Iyengar, Srinivasan S.

    2013-01-01

    A first-year undergraduate course that introduces students to chemistry through a conceptually detailed description of quantum mechanics is outlined. Quantization as arising from the confinement of a particle is presented and these ideas are used to introduce the reasons behind resonance, molecular orbital theory, degeneracy of electronic states,…

  8. Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

    Science.gov (United States)

    Lazaroni, Thiago Luiz do Nascimento; Bastos, Cristiane Perácio; Moraes, Márcio Flávio Dutra; Santos, Robson Souza; Pereira, Grace Schenatto

    2016-01-01

    Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD). Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 1.7 nm Platinum Nanoparticles: Synthesis with Glucose Starch, Characterization and Catalysis

    DEFF Research Database (Denmark)

    Engelbrekt, Christian; Sørensen, Karsten Holm; Lubcke, T.

    2010-01-01

    Monodisperse platinum nanoparticles (PtNPs) were synthesized by a green recipe. Glucose serves as a reducing agent and starch as a stabilization agent to protect the freshly formed PtNP cores in buffered aqueous solutions. Among the ten buffers studied, 2-(N-morpholino)ethanesulfonic acid (MES......), ammonium acetate and phosphate are the best media for PtNP size control and fast chemical preparation. The uniform sizes of the metal cores were determined by transmission electron microscopy (TEM) and found to be 1.8 +/- 0.5, 1.7 +/- 0.2 and 1.6 +/- 0.5 nm in phosphate, MES and ammonium acetate buffer...

  10. National Ignition Facility, subsystem design requirements beam control {ampersand} laser diagnostics SSDR 1.7

    Energy Technology Data Exchange (ETDEWEB)

    Bliss, E.

    1996-11-01

    This Subsystem Design Requirement document is a development specification that establishes the performance, design, development, and test requirements for the Alignment subsystem (WBS 1.7.1), Beam Diagnostics (WBS 1.7.2), and the Wavefront Control subsystem (WBS 1.7. 3) of the NIF Laser System (WBS 1.3). These three subsystems are collectively referred to as the Beam Control & Laser Diagnostics Subsystem. The NIF is a multi-pass, 192-beam, high-power, neodymium-glass laser that meets requirements set forth in the NIF SDR 002 (Laser System). 3 figs., 3 tabs.

  11. Effect of selective angiotensin antagonists on the antidiuresis produced by angiotensin-(1-7 in water-loaded rats

    Directory of Open Access Journals (Sweden)

    Baracho N.C.V.

    1998-01-01

    Full Text Available In the present study we evaluated the nature of angiotensin receptors involved in the antidiuretic effect of angiotensin-(1-7 (Ang-(1-7 in water-loaded rats. Water diuresis was induced in male Wistar rats weighing 280 to 320 g by water load (5 ml/100 g body weight by gavage. Immediately after water load the rats were treated subcutaneously with (doses are per 100 g body weight: 1 vehicle (0.05 ml 0.9% NaCl; 2 graded doses of 20, 40 or 80 pmol Ang-(1-7; 3 200 nmol Losartan; 4 200 nmol Losartan combined with 40 pmol Ang-(1-7; 5 1.1 or 4.4 nmol A-779; 6 1.1 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7; 7 4.4 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7; 8 95 nmol CGP 42112A, or 9 95 nmol CGP 42112A combined with 40 pmol Ang-(1-7. The antidiuretic effect of Ang-(1-7 was associated with an increase in urinary Na+ concentration, an increase in urinary osmolality and a reduction in creatinine clearance (CCr: 0.65 ± 0.04 ml/min vs 1.45 ± 0.18 ml/min in vehicle-treated rats, P<0.05. A-779 and Losartan completely blocked the effect of Ang-(1-7 on water diuresis (2.93 ± 0.34 ml/60 min and 3.39 ± 0.58 ml/60 min, respectively. CGP 42112A, at the dose used, did not modify the antidiuretic effect of Ang-(1-7. The blockade produced by Losartan was associated with an increase in CCr and with an increase in sodium and water excretion as compared with Ang-(1-7-treated rats. When Ang-(1-7 was combined with A-779 there was an increase in CCr and natriuresis and a reduction in urine osmolality compared with rats treated with Ang-(1-7 alone. The observation that both A-779, which does not bind to AT1 receptors, and Losartan blocked the effect of Ang-(1-7 suggests that the kidney effects of Ang-(1-7 are mediated by a non-AT1 angiotensin receptor that is recognized by Losartan.

  12. Angiotensin 1-7 ameliorates diabetic cardiomyopathy and diastolic dysfunction in db/db mice by reducing lipotoxicity and inflammation.

    Science.gov (United States)

    Mori, Jun; Patel, Vaibhav B; Abo Alrob, Osama; Basu, Ratnadeep; Altamimi, Tariq; Desaulniers, Jessica; Wagg, Cory S; Kassiri, Zamaneh; Lopaschuk, Gary D; Oudit, Gavin Y

    2014-03-01

    The angiotensin-converting enzyme 2 and angiotensin-(1-7) (Ang 1-7)/MasR (Mas receptor) axis are emerging as a key pathway that can modulate the development of diabetic cardiomyopathy. We studied the effects of Ang 1-7 on diabetic cardiomyopathy in db/db diabetic mice to elucidate the therapeutic effects and mechanism of action. Ang 1-7 was administered to 5-month-old male db/db mice for 28 days via implanted micro-osmotic pumps. Ang 1-7 treatment ameliorated myocardial hypertrophy and fibrosis with normalization of diastolic dysfunction assessed by pressure-volume loop analysis and echocardiography. The functional improvement by Ang 1-7 was accompanied by a reduction in myocardial lipid accumulation and systemic fat mass and inflammation and increased insulin-stimulated myocardial glucose oxidation. Increased myocardial protein kinase C levels and loss of phosphorylation of extracellular signal-regulated kinase 1/2 were prevented by Ang 1-7. Furthermore, Ang 1-7 treatment decreased cardiac triacylglycerol and ceramide levels in db/db mice, concomitantly with an increase in myocardial adipose triglyceride lipase expression. Changes in adipose triglyceride lipase expression correlated with increased SIRT1 (silent mating type information regulation 2 homolog 1) levels and deacetylation of FOXO1 (forkhead box O1). We identified a novel beneficial effect of Ang 1-7 on diabetic cardiomyopathy that involved a reduction in cardiac hypertrophy and lipotoxicity, adipose inflammation, and an upregulation of adipose triglyceride lipase. Ang 1-7 completely rescued the diastolic dysfunction in the db/db model. Ang 1-7 represents a promising therapy for diabetic cardiomyopathy associated with type 2 diabetes mellitus.

  13. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats.

    Science.gov (United States)

    Marques, Fúlvia D; Ferreira, Anderson J; Sinisterra, Rubén D M; Jacoby, Bruno A; Sousa, Frederico B; Caliari, Marcelo V; Silva, Gerluza A B; Melo, Marcos B; Nadu, Ana P; Souza, Leandro E; Irigoyen, Maria C C; Almeida, Alvair P; Santos, Robson A S

    2011-03-01

    In this study we evaluated the cardiac effects of a pharmaceutical formulation developed by including angiotensin (Ang)-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD), in normal, infarcted, and isoproterenol-treated rats. Myocardial infarction was produced by left coronary artery occlusion. Isoproterenol (2 mg/kg, IP) was administered daily for 7 days. Oral administration of HPβCD/Ang-(1-7) started immediately before infarction or associated with the first dose of isoproterenol. After 7 days of treatment, the rats were euthanized, and the Langendorff technique was used to analyze cardiac function. In addition, heart function was chronically (15, 30, 50 days) analyzed by echocardiography. Cardiac sections were stained with hematoxylin/eosin and Masson trichrome to evaluate cardiac hypertrophy and damage, respectively. Pharmacokinetic studies showed that oral HPβCD/Ang-(1-7) administration significantly increased Ang-(1-7) on plasma whereas with the free peptide it was without effect. Oral administration of HPβCD/Ang-(1-7) (30 μg/kg) significantly reduced the deleterious effects induced by myocardial infarction on systolic and diastolic tension, ±dT/dt, perfusion pressure, and heart rate. Strikingly, a 50% reduction of the infarcted area was observed in HPβCD/Ang-(1-7)-treated rats. Furthermore, HPβCD/Ang-(1-7) attenuated the heart function impairment and cardiac remodeling induced by isoproterenol. In infarcted rats chronically treated with HPβCD/Ang-(1-7), the reduction of ejection fraction and fractional shorting and the increase in systolic and diastolic left ventricular volumes observed in infarcted rats were attenuated. Altogether, these findings further confirm the cardioprotective effects of Ang-(1-7). More importantly, our data indicate that the HPβCD/Ang-(1-7) is a feasible formulation for oral administration of Ang-(1-7), which can be used as a cardioprotective drug.

  14. 78 FR 73880 - Proposal To Withdraw Spatial Data Transfer Standard, Parts 1-7

    Science.gov (United States)

    2013-12-09

    ...The Federal Geographic Data Committee (FGDC) proposes to withdraw the Spatial Data Transfer Standard (SDTS), Parts 1-7, http:// www.fgdc.gov/standards/projects/FGDC-standards-projects/SDTS/index-- html, as an FGDC-endorsed standard. FGDC maintenance authority agencies were asked to review the relevance of the SDTS, and they responded that the SDTS is no longer used by their agencies. The SDTS had provided a common mechanism for transferring digital geospatial data among different systems and for sharing and integrating data from many diverse sources. For more information about the SDTS, refer to the SUPPLEMENTARY INFORMATION section. The FGDC seeks comment from any organization that continues to provide data in the SDTS format and would prefer to retain the SDTS as an FGDC-endorsed standard. Alternatively, it seeks comment from any organization that supports withdrawal of the SDTS Parts 1-7 as an FGDC- endorsed standard. FGDC Standards Directive 9, Maintenance, http://www.fgdc.gov/standards/process/standards-directives/directive- 09, requires a 90-day public comment period for proposals to withdraw FGDC-endorsed standards.

  15. Stabilization of the angiotensin-(1-7) receptor Mas through interaction with PSD95.

    Science.gov (United States)

    Bian, Weihua; Sun, Licui; Yang, Longyan; Li, Ji-Feng; Hu, Jia; Zheng, Shuai; Guo, Ruihan; Feng, Duiping; Ma, Qian; Shi, Xiaocui; Xiong, Ying; Yang, Xiaomei; Song, Ran; Xu, Jianguo; Wang, Songlin; He, Junqi

    2013-08-01

    The functions and signalling mechanisms of the Ang-(1-7) [angiotensin-(1-7)] receptor Mas have been studied extensively. However, less attention has been paid to the intracellular regulation of Mas protein. In the present study, PSD95 (postsynaptic density 95), a novel binding protein of Mas receptor, was identified, and their association was characterized further. Mas specifically interacts with PDZ1-2, but not the PDZ3, domain of PSD95 via Mas-CT (Mas C-terminus), and the last four amino acids [ETVV (Glu-Thr-Val-Val)] of Mas-CT were determined to be essential for this interaction, as shown by GST pull-down, co-immunoprecipitation and confocal co-localization experiments. Gain-of-function and loss-of-function studies indicated that PSD95 enhanced Mas protein expression by increasing the stabilization of the receptor. Mas degradation was robustly inhibited by the proteasome inhibitor MG132 in time- and dose-dependent manners, and the expression of PSD95 impaired Mas ubiquitination, indicating that the PSD95-Mas association inhibits Mas receptor degradation via the ubiquitin-proteasome proteolytic pathway. These findings reveal a novel mechanism of Mas receptor regulation by which its expression is modulated at the post-translational level by ubiquitination, and clarify the role of PSD95, which binds directly to Mas, blocking the ubiquitination and subsequent degradation of the receptor via the ubiquitin-proteasome proteolytic pathway.

  16. Effect of a stable Angiotensin-(1-7) analogue on progenitor cell recruitment and cardiovascular function post myocardial infarction

    NARCIS (Netherlands)

    Sevá Pessôa, Bruno; Becher, Peter M oritz; Van Veghel, Richard; De Vries, René; Tempel, Dennie; Sneep, Stefan; Van Beusekom, Heleen; Van Der Velden, Vincent H J; Westermann, Dirk; Danser, A. H Jan; Roks, Anton J M

    2015-01-01

    BACKGROUND: Angiotensin-(1-7) improves cardiac function and remodeling after myocardial infarction (MI). This may involve recruitment of hematopoietic progenitor cells that support angiogenesis. However, angiotensin-(1-7) is rapidly metabolized in plasma and tissue. The authors investigated in mice

  17. Low sodium diet inhibits the local counter-regulator effect of angiotensin-(1-7) on angiotensin II

    NARCIS (Netherlands)

    Roks, Anton J M; Nijholt, Jeroen; van Buiten, Azuwerus; van Gilst, Wiek H; de Zeeuw, Dick; Henning, Robert H

    2004-01-01

    Objective The heptapeptide angiotensin-(1-7) [Ang-(1-7)] has been identified as a versatile, endogenous inhibitor of the renin-angiotensin system (RAS). As the therapeutic response to exogenous RAS inhibitors, such as AT, receptor antagonists, is altered by changes in salt intake, we investigated

  18. Angiotensin-converting enzyme 2, Angiotensin-(1-7) and Mas: new players of the Renin Angiotensin System

    DEFF Research Database (Denmark)

    Santos, Robson AS; Ferreira, Anderson J; Verano-Braga, Thiago

    2013-01-01

    . The discovery of the angiotensin-converting enzyme (ACE) homologue ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE....... In addition, it is now wellestablished that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counter regulatory pathway within the RAS the actions of which are in opposition to the vasoconstrictor...

  19. Angiotensin-(1-7 Promotes Resolution of Neutrophilic Inflammation in a Model of Antigen-Induced Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Lívia C. Barroso

    2017-11-01

    Full Text Available Defective resolution of inflammation may be crucial for the initiation and development of chronic inflammatory diseases, such as arthritis. Therefore, it has been suggested that therapeutic strategies based on molecules that facilitate inflammation resolution present great potential for the treatment of chronic inflammatory diseases. In this study, we investigated the effects and role of angiotensin-(1-7 [Ang-(1-7] in driving resolution of neutrophilic inflammation in a model of arthritis. For this purpose, male C57BL/6 mice were subjected to antigen-induced arthritis and treated with Ang-(1-7 at the peak of the inflammatory process. Analysis of the number of inflammatory cells, apoptosis, and immunofluorescence for NF-κB was performed in the exudate collected from the knee cavity. Neutrophil accumulation in periarticular tissue was measured by assaying myeloperoxidase activity. Apoptosis of human neutrophil after treatment with Ang-(1-7 was evaluated morphologically and by flow cytometry, and NF-κB phosphorylation by immunofluorescence. Efferocytosis was evaluated in vivo. Therapeutic treatment with Ang-(1-7 at the peak of inflammation promoted resolution, an effect associated with caspase-dependent neutrophils apoptosis and NF-κB inhibition. Importantly, Ang-(1-7 was also able to induce apoptosis of human neutrophils, an effect associated with NF-κB inhibition. The pro-resolving effects of Ang-(1-7 were inhibited by the Mas receptor antagonist A779. Finally, we showed that Ang-(1-7 increased the efferocytic ability of murine macrophages. Our results clearly demonstrate that Ang-(1-7 resolves neutrophilic inflammation in vivo acting in two key step of resolution: apoptosis of neutrophils and their removal by efferocytosis. Ang-(1-7 is a novel mediator of resolution of inflammation.

  20. Assessment of chemical and material contamination in waste wood fuels--A case study ranging over nine years.

    Science.gov (United States)

    Edo, Mar; Björn, Erik; Persson, Per-Erik; Jansson, Stina

    2016-03-01

    The increased demand for waste wood (WW) as fuel in Swedish co-combustion facilities during the last years has increased the import of this material. Each country has different laws governing the use of chemicals and therefore the composition of the fuel will likely change when combining WW from different origins. To cope with this, enhanced knowledge is needed on WW composition and the performance of pre-treatment techniques for reduction of its contaminants. In this study, the chemical and physical characteristics of 500 WW samples collected at a co-combustion facility in Sweden between 2004 and 2013 were investigated to determine the variation of contaminant content over time. Multivariate data analysis was used for the interpretation of the data. The concentrations of all the studied contaminants varied widely between sampling occasions, demonstrating the highly variable composition of WW fuels. The efficiency of sieving as a pre-treatment measure to reduce the levels of contaminants was not sufficient, revealing that sieving should be used in combination with other pre-treatment methods. The results from this case study provide knowledge on waste wood composition that may benefit its management. This knowledge can be applied for selection of the most suitable pre-treatments to obtain high quality sustainable WW fuels. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells.

    Directory of Open Access Journals (Sweden)

    Siti Sarah Fazalul Rahiman

    Full Text Available Dynorphin 1-17, (DYN 1-17 opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65 nuclear translocation and the release of interleukin-1beta (IL-1β and tumor necrosis factor-alpha (TNF-α from lipopolysaccharide (LPS-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM. Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11 on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM. These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.

  2. Improving Academic Achievement through Continuous Assessment Methods: In the Case of Year Two Students of Animal and Range Sciences Department in Wolaita Sodo University, Ethiopia

    Science.gov (United States)

    Sarka, Samuel; Lijalem, Tsegay; Shibiru, Tilaye

    2017-01-01

    The aim of this study was to assessing and implementing of continuous assessment to enhance academic performance of 2nd year Animal and Range Sciences department students in Wolaita sodo university; and to take action (train) to raise the academic performance to a desirable state. For the purpose of surveying the students' level of performance…

  3. Contribution of long-range transported aerosols to aerosol optical and physical properties: 3-year measurements at Gosan, Korea

    Science.gov (United States)

    Heo, J.; Kim, S. W.; Kim, J. H.; Ogren, J. A.; Yoon, S. C.

    2015-12-01

    Recently, more attentions have been paid to air quality in East Asia due to the enhanced loading of atmospheric pollutants related to rapid industrialization. Gosan Climate Observatory (GCO), Korea is regarded as an ideal site to study the transport of atmospheric pollutants because it is frequently influenced by various airmasses from China, Korea, Japan and Pacific Ocean. In order to understand aerosol optical and physical properties according to airmass transport routes, three-year (2012-2014) continuous measurements of aerosol scattering/absorption coefficient and number size distribution were analyzed, together with 48-hour backward trajectory calculations. The averaged aerosol absorption (σa) and scattering coefficient (σs) for airmasses transported from North China (NC; 36% of all trajectories) were 6.65 Mm-1 and 94.72 Mm-1 at 550 nm wavelength, respectively, which were similar to those for stagnant airmasses (ST; 22% of all trajectories; σa: 6.26 Mm-1, σs: 93.99 Mm-1). The highest values of σa (7.03 Mm-1) and σs (108.34 Mm-1) were observed when airmasses were traveled from South China (SC; 11% of all trajectories). σa and σs for airmasses from Korean Peninsula (KP; 7% of all trajectories) and Pacific Ocean (PO; 14% of all trajectories; in parenthesis) were 5.63 (2.76) Mm-1 and 73.63 (50.93) Mm-1, respectively. Compared to other airmasses, the higher values of Scattering Angstrom Exponent (SAE) for ST (1.65) is thought to be the build-up of anthropogenic fine particulate pollutants. The Absorption Angstrom Exponent (AAE) was estimated to be 1.32 for NC airmass and 1.02 for SC airmass. Over the study period, 130 days of total 557 days were identified as new particle formation and growth event (NPF) from Scanning Mobility Particle Sizer (SMPS) measurements by Cyclostationary Empirical Orthogonal Function (CSEOF) approach. Especially, 55.4% (72 days) of total 130 NPF days were found when a cold and dry airmass comes from NC after passing the frontal

  4. Chandra observations of an exceptional cluster of galaxies at z=1.7

    Science.gov (United States)

    Hlavacek-Larrondo, Julie

    2017-09-01

    We propose to obtain the first X-ray image of an exceptional cluster of galaxies, which stands out as being an extremely distant (z=1.7) and massive (2-5*10^14M_sun) cluster, harbouring a still-assembling BCG that is forming stars at a prodigious rate of 860M_sun/yr. Combined with our recently awarded VLA and HST data, the goal of this proposal is to: 1) determine the dynamical state of the cluster; 2) provide an independant estimate of the cluster mass; and 3) study the X-ray properties of the extreme central AGN. The observations will significantly help in our understanding of the formation and evolution of massive clusters and BCGs, as well as the role of AGN in astrophysical feedback. In summary, in 170 ks, this proposal will advance several aspects of high-z physics.

  5. Six Years in the Life of a Mother Bear - The Longest Continuous Heart Rate Recordings from a Free-Ranging Mammal

    Science.gov (United States)

    Laske, Timothy G.; Iaizzo, Paul A.; Garshelis, David L.

    2017-01-01

    Physiological monitoring of free-ranging wild animals is providing new insights into their adaptations to a changing environment. American black bears (Ursus americanus) are highly adaptable mammals, spending up to half the year hibernating, and the remainder of the year attempting to gain weight on a landscape with foods that vary seasonally and year to year. We recorded heart rate (HR) and corresponding activity of an adult female black bear over the course of six years, using an implanted monitor. Despite yearly differences in food, and an every-other year reproductive cycle, this bear exhibited remarkable consistency in HR and activity. HR increased for 12 weeks in spring, from minimal hibernation levels (mean 20-25 beats/minute [bpm]; min 10 bpm) to summer active levels (July daytime: mean 95 bpm). Timing was delayed following one cold winter. In August the bear switched from primarily diurnal to nocturnal, coincident with the availability of baits set by legal hunters. Activity in autumn was higher when the bear was with cubs. Birthing of cubs in January was identified by a transient increase in HR and activity. Long-term physiological and behavioral monitoring is valuable for understanding adaptations of free-ranging animals to climate change, food availability, and human-related stressors.

  6. Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief.

    Science.gov (United States)

    Emery, Edward C; Luiz, Ana Paula; Wood, John N

    2016-08-01

    Chronic pain is a massive clinical problem. We discuss the potential of subtype selective sodium channel blockers that may provide analgesia with limited side effects. Sodium channel subtypes have been linked to human pain syndromes through genetic studies. Gain of function mutations in Nav1.7, 1.8 and 1.9 can cause pain, whilst loss of function Nav1.7 mutations lead to loss of pain in otherwise normal people. Intriguingly, both human and mouse Nav1.7 null mutants have increased opioid drive, because naloxone, an opioid antagonist, can reverse the analgesia associated with the loss of Nav1.7 expression. We believe there is a great future for sodium channel antagonists, particularly Nav1.7 antagonists in treating most pain syndromes. This review deals with recent attempts to develop specific sodium channel blockers, the mechanisms that underpin the Nav1.7 null pain-free phenotype and new routes to analgesia using, for example, gene therapy or combination therapy with subtype specific sodium channel blockers and opioids. The use of selective Nav1.7 antagonists together with either enkephalinase inhibitors or low dose opioids has the potential for side effect-free analgesia, as well as an important opioid sparing function that may be clinically very significant.

  7. Cardiac ACE2/angiotensin 1-7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy.

    Science.gov (United States)

    Diniz, Gabriela P; Senger, Nathalia; Carneiro-Ramos, Marcela S; Santos, Robson A S; Barreto-Chaves, Maria Luiza M

    2016-08-01

    Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin-angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1-7 (Ang 1-7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1-7, ACE2 and Mas receptor levels. Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Although plasma Ang 1-7 levels were unchanged by hyperthyroidism, cardiac Ang 1-7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1-7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1-7 levels were accompanied by increased Mas receptor protein levels. The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH. © The Author(s), 2015.

  8. Angiotensin-(1-7) attenuates airway remodelling and hyperresponsiveness in a model of chronic allergic lung inflammation.

    Science.gov (United States)

    Magalhães, G S; Rodrigues-Machado, M G; Motta-Santos, D; Silva, A R; Caliari, M V; Prata, L O; Abreu, S C; Rocco, P R M; Barcelos, L S; Santos, R A S; Campagnole-Santos, M J

    2015-05-01

    A long-term imbalance between pro- and anti-inflammatory mediators leads to airway remodelling, which is strongly correlated to most of the symptoms, severity and progression of chronic lung inflammation. The Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis of the renin-angiotensin system is associated with attenuation of acute and chronic inflammatory processes. In this study, we investigated the effects of Ang-(1-7) treatment in a model of chronic allergic lung inflammation. Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged three times per week (days 21-46). These mice received Ang-(1-7) (1 μg·h(-1) , s.c.) by osmotic mini-pumps, for the last 28 days. Histology and morphometric analysis were performed in left lung and right ventricle. Airway responsiveness to methacholine, analysis of Ang-(1-7) levels (RIA), collagen I and III (qRT-PCR), ERK1/2 and JNK (Western blotting), IgE (elisa), cytokines and chemokines (elisa multiplex), and immunohistochemistry for Mas receptors were performed. Infusion of Ang-(1-7) in OVA-sensitized and challenged mice decreased inflammatory cell infiltration and collagen deposition in the airways and lung parenchyma, and prevented bronchial hyperresponsiveness. These effects were accompanied by decreased IgE and ERK1/2 phosphorylation, and decreased pro-inflammatory cytokines. Mas receptors were detected in the epithelium and bronchial smooth muscle, suggesting a site in the lung for the beneficial actions of Ang-(1-7). Ang-(1-7) exerted beneficial attenuation of three major features of chronic asthma: lung inflammation, airway remodelling and hyperresponsiveness. Our results support an important protective role of Ang-(1-7) in lung inflammation. © 2015 The British Pharmacological Society.

  9. Lidocaine reduces the transition to slow inactivation in Nav1.7 voltage-gated sodium channels

    Science.gov (United States)

    Sheets, Patrick L; Jarecki, Brian W; Cummins, Theodore R

    2011-01-01

    BACKGROUND AND PURPOSE The primary use of local anaesthetics is to prevent or relieve pain by reversibly preventing action potential propagation through the inhibition of voltage-gated sodium channels. The tetrodotoxin-sensitive voltage-gated sodium channel subtype Nav1.7, abundantly expressed in pain-sensing neurons, plays a crucial role in perception and transmission of painful stimuli and in inherited chronic pain syndromes. Understanding the interaction of lidocaine with Nav1.7 channels could provide valuable insight into the drug's action in alleviating pain in distinct patient populations. The aim of this study was to determine how lidocaine interacts with multiple inactivated conformations of Nav1.7 channels. EXPERIMENTAL APPROACH We investigated the interactions of lidocaine with wild-type Nav1.7 channels and a paroxysmal extreme pain disorder mutation (I1461T) that destabilizes fast inactivation. Whole cell patch clamp recordings were used to examine the activity of channels expressed in human embryonic kidney 293 cells. KEY RESULTS Depolarizing pulses that increased slow inactivation of Nav1.7 channels also reduced lidocaine inhibition. Lidocaine enhanced recovery of Nav1.7 channels from prolonged depolarizing pulses by decreasing slow inactivation. A paroxysmal extreme pain disorder mutation that destabilizes fast inactivation of Nav1.7 channels decreased lidocaine inhibition. CONCLUSIONS AND IMPLICATIONS Lidocaine decreased the transition of Nav1.7 channels to the slow inactivated state. The fast inactivation gate (domain III–IV linker) is important for potentiating the interaction of lidocaine with the Nav1.7 channel. PMID:21232038

  10. The Angiotensin-(1-7)/Mas Axis Improves Pancreatic β-Cell Function in Vitro and in Vivo.

    Science.gov (United States)

    Sahr, Anika; Wolke, Carmen; Maczewsky, Jonas; Krippeit-Drews, Peter; Tetzner, Anja; Drews, Gisela; Venz, Simone; Gürtler, Sarah; van den Brandt, Jens; Berg, Sabine; Döring, Paula; Dombrowski, Frank; Walther, Thomas; Lendeckel, Uwe

    2016-12-01

    The angiotensin-converting enzyme 2/angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system often opposes the detrimental effects of the angiotensin-converting enzyme/Ang II/Ang II type 1 receptor axis and has been associated with beneficial effects on glucose homeostasis, whereas underlying mechanisms are mostly unknown. Here we investigate the effects of Ang-(1-7) and its receptor Mas on β-cell function. Isolated islets from Mas-deficient and wild-type mice were stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion determined. Islets' cytoplasmic calcium and cAMP concentrations, mRNA amounts of Ins1, Ins2, Pdx1, and Mafa and effects of inhibitors of cAMP downstream signaling were determined. Ang-(1-7) was also applied to mice by osmotic pumps for 14 days and effects on glucose tolerance and insulin secretion were assessed. Ang-(1-7) increased insulin secretion from wild-type islets, whereas antagonists and genetic Mas deficiency led to reduced insulin secretion. The Mas-dependent effects of Ang-(1-7) on insulin secretion did not result from changes in insulin gene expression or changes in the excitation-secretion coupling but from increased intracellular cAMP involving exchange protein activated directly by cAMP. Administration of Ang-(1-7) in vivo had only marginal effects on glucose tolerance in wild-type mice but still resulted in improved insulin secretion from islets isolated of these mice. Interestingly, although less pronounced than in wild types, Ang-(1-7) still affected insulin secretion in Mas-deficient islets. The data indicate a significant function of Ang-(1-7) in the regulation of insulin secretion from mouse islets in vitro and in vivo, mainly, but not exclusively, by Mas-dependent signaling, modulating the accessory pathway of insulin secretion via increase in cAMP.

  11. Metal–insulator transition tuned by magnetic field in Bi 1.7 V 8 O 16 hollandite

    Energy Technology Data Exchange (ETDEWEB)

    Larson, Amber M.; Wilfong, Brandon; Moetakef, Pouya; Brown, Craig M.; Zavalij, Peter; Rodriguez, Efrain E.

    2017-01-01

    A metal–insulator transition tuned by application of an external magnetic field occurs in the quasi-one dimensional system Bi1.7V8O16, which contains a mix of S = 1 and S = 1/2 vanadium cations. Unlike all other known vanadates, the magnetic susceptibility of Bi1.7V8O16 diverges in its insulating state, although no long-range magnetic ordering is observed from neutron diffraction measurements, possibly due to the frustrated geometry of the triangular ladders. Magnetotransport measurements reveal that the transition temperature is suppressed upon application of an external magnetic field, from 62.5 K at zero field to 40 K at 8 T. This behavior is both hysteretic and anisotropic, suggesting t2g orbital ordering of the V3+ and V4+ cations drives a first-order structural transition. Single crystal X-ray diffraction reveals a charge density wave of Bi3+ cations with a propagation vector of 0.846c*, which runs parallel to the triangular chain direction. Neutron powder diffraction measurements show a first-order structural transition, characterized by the coexistence of two tetragonal phases near the metal–insulator transition. Finally, we discuss the likelihood that ferromagnetic V–V dimers coexist with a majority spin-singlet state below the transition in Bi1.7V8O16.

  12. Key cofactors of photosystem II cores from four organisms identified by 1.7-K absorption, CD and MCD.

    Science.gov (United States)

    Arsköld, Sindra Peterson; Smith, Paul J; Shen, Jian-Ren; Pace, Ron J; Krausz, Elmars

    2005-06-01

    Active Photosystem II (PS II) cores were prepared from spinach, pea, Synechocystis PCC 6803, and Thermosynechococcus vulcanus, the latter of which has been structurally determined [Kamiya and Shen (2003) Proc Natl Acad Sci USA 100: 98-103]. Electrochromic shifts resulting from QA reduction by 1.7-K illumination were recorded, and the Qx and Qy absorption bands of the redox-active pheophytin a thus identified in the different organisms. The Qx transition is approximately 3 nm (100 cm-1) to higher energy in cyanobacteria than in the plants. The predominant Qy shift appears in the range 683-686 nm depending on species, and does not appear to have a systematic shift. Low-temperature absorption, circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of the chlorophyll Qy region are very similar in spinach and pea, but vary in cyanobacteria. We assigned CP43 and CP47 trap-chlorophyll absorption features in all species, as well as a P680 transition. Each absorption identified has an area of one chlorophyll a. The MCD deficit, introduced previously for spinach as an indicator of P680 activity, occurs in the same spectral region and has the same area in all species, pointing to a robustness of this as a signature for P680. MCD and CD characteristics point towards a significant variance in P680 structure between cyanobacteria, thermophilic cyanobacteria, and higher plants.

  13. Measurement of 1.7–74 MeV polarised γ rays with the HARPO TPC

    Energy Technology Data Exchange (ETDEWEB)

    Geerebaert, Y., E-mail: yannick.geerebaert@polytechnique.fr [LLR, École Polytechnique, CNRS/IN2P3, Palaiseau (France); Gros, Ph., E-mail: philippe.gros@llr.in2p3.fr [LLR, École Polytechnique, CNRS/IN2P3, Palaiseau (France); Amano, S. [LASTI, University of Hyôgo (Japan); Attié, D. [CEA, Irfu, CEA-Saclay (France); Bernard, D.; Bruel, P. [LLR, École Polytechnique, CNRS/IN2P3, Palaiseau (France); Calvet, D.; Colas, P. [CEA, Irfu, CEA-Saclay (France); Daté, S. [JASRI/SPring8 (Japan); Delbart, A. [CEA, Irfu, CEA-Saclay (France); Frotin, M.; Giebels, B. [LLR, École Polytechnique, CNRS/IN2P3, Palaiseau (France); Götz, D. [AIM, CEA/DSM-CNRS – Université Paris Diderot (France); IRFU/Service d' Astrophysique, CEA-Saclay (France); Hashimoto, S. [LASTI, University of Hyôgo (Japan); Horan, D. [LLR, École Polytechnique, CNRS/IN2P3, Palaiseau (France); Kotaka, T. [LASTI, University of Hyôgo (Japan); Louzir, M. [LLR, École Polytechnique, CNRS/IN2P3, Palaiseau (France); Minamiyama, Y.; Miyamoto, S. [LASTI, University of Hyôgo (Japan); Ohkuma, H. [JASRI/SPring8 (Japan); and others

    2017-02-11

    Current γ-ray telescopes based on photon conversions to electron-positron pairs, such as Fermi, use tungsten converters. They suffer of limited angular resolution at low energies, and their sensitivity drops below 1 GeV. The low multiple scattering in a gaseous detector gives access to higher angular resolution in the MeV–GeV range, and to the linear polarisation of the photons through the azimuthal angle of the electron-positron pair. HARPO is an R&D programme to characterise the operation of a TPC (Time Projection Chamber) as a high angular-resolution and sensitivity telescope and polarimeter for γ rays from cosmic sources. It represents a first step towards a future space instrument. A 30 cm cubic TPC demonstrator was built, and filled with 2 bar argon-based gas. It was put in a polarised γ-ray beam at the NewSUBARU accelerator in Japan in November 2014. Data were taken at different photon energies from 1.7 MeV to 74 MeV, and with different polarisation configurations. The electronics setup is described, with an emphasis on the trigger system. The event reconstruction algorithm is quickly described, and preliminary measurements of the polarisation of 11 MeV photons are shown.

  14. Molecular and cellular mechanisms of the inhibitory effects of ACE-2/ANG1-7/Mas axis on lung injury.

    Science.gov (United States)

    Gopallawa, Indiwari; Uhal, Bruce D

    2014-01-01

    An established body of recent literature has demonstrated potent inhibitory effects of the angiotensin converting enzyme-2 (ACE-2)/ANG1-7/ Mas axis on acute lung injury and lung fibrogenesis. One of the mechanisms of this inhibition is the enzymatic action of ACE-2 to degrade its main substrate angiotensin (ANG) II, thereby reducing the injurious and profibrotic activities of this octapeptide. Another, potentially more important mechanism is the production by ACE-2 of the heptapeptide ANG1-7, which inhibits the actions of ANGII through its own receptor Mas, the product of the oncogene of the same name. Very recent efforts to define the molecular and cellular mechanisms of ANG1-7/Mas action have revealed a number of similar, but mechanistically distinct, pathways by which ANG1-7 and Mas act on various lung cell types to inhibit lung injury and fibrosis. In this review we summarize the beneficial actions of the ANG1-7/Mas pathway, specifically on lung cells in non-neoplastic lung injury. We also review the currently known downstream signaling mechanisms of the ANG1-7/Mas pathway in various lung cell types known to be key in acute injury and fibrogenesis.

  15. [Statistical methods to optimize immobilization and bacteriocin production by Lactobacillus paracasei HD1.7].

    Science.gov (United States)

    Chen, Jianwei; Li, Xiuliang; Yin, Bo; Liu, Guoming; Wang, Kun; Ping, Wenxiang

    2009-05-01

    To enhance bacteriocin production by Lactobacillus paracasei HD1.7 immobilized with calcium alginate gel by statistical methods. A 2(6-2) two-level fractional factorial design was employed first where 6 variables were studied for their influence on bacteriocin production. The concentration of sodium alginate, inoculation volume and culture time were the most significant variables to improve bacteriocin production. The greatest response area was estimated by the design of steepest ascent approach. A three-level Box-Behnken factorial design was employed for maximizing the bacteriocin production and the number of cell cycle. The repeated batch fermentation using immobilized cells was done. The optimal condition for bacteriocin production and the number of cell cycle was with sodium alginate 2.8%, CaCl2 5%, immobilization time 4 h, the density of entrapped cells 1/20, culture time 63 h and inoculation volume 8.2%. The period of fermentation was 24 h of a batch fermentation after 63 h and bacteriocin production was 70% of free-cell fermentation. After optimizing, the total production of bacteriocin was increased by 19% using the batch fermentation during 327 hours, the beads were intact with little cell leakage and repeatedly used, which laid foundation for the high study of bacteriocin and finally extracted.

  16. Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

    Science.gov (United States)

    Khajah, Maitham A.; Fateel, Maryam M.; Ananthalakshmi, Kethireddy V.; Luqmani, Yunus A.

    2016-01-01

    Background There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. Methods The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Results Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Conclusion Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression. PMID:26963721

  17. ACE2/Ang-(1-7)/Mas axis stimulates vascular repair-relevant functions of CD34+ cells.

    Science.gov (United States)

    Singh, Neha; Joshi, Shrinidh; Guo, Lirong; Baker, Matthew B; Li, Yan; Castellano, Ronald K; Raizada, Mohan K; Jarajapu, Yagna P R

    2015-11-15

    CD34(+) stem/progenitor cells have been identified as a promising cell population for the autologous cell-based therapies in patients with cardiovascular disease. The counter-regulatory axes of renin angiotensin system, angiotensin converting enzyme (ACE)/Ang II/angiotensin type 1 (AT1) receptor and ACE2/Ang-(1-7)/Mas receptor, play an important role in the cardiovascular repair. This study evaluated the expression and vascular repair-relevant functions of these two pathways in human CD34(+) cells. CD34(+) cells were isolated from peripheral blood mononuclear cells (MNCs), obtained from healthy volunteers. Expression of ACE, ACE2, AT1, and angiotensin type 2 and Mas receptors were determined. Effects of Ang II, Ang-(1-7), Norleu(3)-Ang-(1-7), and ACE2 activators, xanthenone (XNT) and diminazene aceturate (DIZE) on proliferation, migration, and adhesion of CD34(+) cells were evaluated. ACE2 and Mas were relatively highly expressed in CD34(+) cells compared with MNCs. Ang-(1-7) or its analog, Norleu(3)-Ang-(1-7), stimulated proliferation of CD34(+) cells that was associated with decrease in phosphatase and tensin homologue deleted on chromosome 10 levels and was inhibited by triciribin, an AKT inhibitor. Migration of CD34(+) cells was enhanced by Ang-(1-7) or Norleu(3)-Ang-(1-7) that was decreased by a Rho-kinase inhibitor, Y-27632. In the presence of Ang II, XNT or DIZE enhanced proliferation and migration that were blocked by DX-600, an ACE2 inhibitor. Treatment of MNCs with Ang II, before the isolation of CD34(+) cells, attenuated the proliferation and migration to stromal derived factor-1α. This attenuation was reversed by apocynin, an NADPH oxidase inhibitor. Adhesion of MNCs or CD34(+) cells to fibronectin was enhanced by Ang II and was unaffected by Ang-(1-7). This study suggests that ACE2/Ang-(1-7)/Mas pathway stimulates functions of CD34(+) cells that are cardiovascular protective, whereas Ang II attenuates these functions by acting on MNCs. These findings imply that activation of ACE2/Ang-(1-7)/Mas axis is a promising approach for enhancing reparative outcomes of cell-based therapies. Copyright © 2015 the American Physiological Society.

  18. Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ

    Science.gov (United States)

    Bi, Rui-Yun; Meng, Zhen; Zhang, Peng; Wang, Xue-Dong

    2017-01-01

    Background Temporomandibular disorders (TMDs) have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7) plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG) is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ). Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored. Methods Estrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund’s adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ), the G protein coupled estrogen receptor (GPR30), and Nav1.7 in TG were examined using immunohistofluorescence. Results Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1.7 expression and head withdrawal threshold in ovariectomized rats. ERα and ERβ, but not GPR30, were mostly co-localized with Nav1.7 in neurons in TG. In the nerve growth factor-induced and ERα-transfected PC12 cells, 17β-estradiol dose-dependently enhanced Nav1.7 promoter activity, whereas mutations of the estrogen response element at -1269/-1282 and -1214/-1227 in the promoter completely abolished its effect on the promoter activity. Conclusion Estradiol could upregulate trigeminal ganglionic Nav1.7 expression to contribute to hyperalgesia of inflamed TMJ. PMID:28582470

  19. AN EXTREME STARBURST IN THE CORE OF A RICH GALAXY CLUSTER AT z = 1.7

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Tracy; Bonaventura, Nina; Delahaye, Anna [Department of Physics, McGill University, 3600 rue University, Montréal, Québec, H3P 1T3 (Canada); Noble, Allison; Yee, H. K. C. [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON, M5S 3H4 (Canada); DeGroot, Andrew; Wilson, Gillian; Foltz, Ryan [Department of Physics and Astronomy, University of California, Riverside, 900 University Avenue, Riverside, CA 92521 (United States); Muzzin, Adam; Chapman, Scott [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge, CB3 0HA (United Kingdom); Cooper, Mike [Centre for Galaxy Evolution, Department of Physics and Astronomy, University of California, Irvine, 4129 Frederick Reines Hall, Irvine, CA 92697 (United States); Lidman, Chris [Australian Astronomical Observatory, P.O. Box 915, North Ryde, NSW 1670 (Australia); Surace, Jason [Spitzer Space Science Centre, California Institute of Technology, Pasadena, CA 91125 (United States); Dunne, Loretta [Department of Physics and Astronomy, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Geach, James [Center for Astrophysics Research, Science and Technology Research Institute, University of Hertfordshire, Hatfield AL10 9AB (United Kingdom); Hayden, Brian [Physics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Hildebrandt, Hendrik [Argelander-Institute fur Astronomie, Auf dem Hugel 71, D-53121 Bonn (Germany); Huang, Jiasheng [National Astronomical Observatories of China, Chinese Academy of Sciences, Beijing 100012 (China); Pope, Alexandra [Department of Astronomy, University of Massachusetts, 710 North Pleasant Street, Amherst, MA 011003 (United States); Smith, Matthew W. L. [School of Physics and Astronomy, Cardiff University, Queens Buildings, The Parade, Cardiff, Wales CF24 3AA (United Kingdom); and others

    2015-08-20

    We have discovered an optically rich galaxy cluster at z = 1.7089 with star formation occurring in close proximity to the central galaxy. The system, SpARCS104922.6+564032.5, was detected within the Spitzer Adaptation of the red-sequence Cluster Survey, and confirmed through Keck-MOSFIRE spectroscopy. The rest-frame optical richness of N{sub gal} (500 kpc) = 30 ± 8 implies a total halo mass, within 500 kpc, of ∼3.8 ± 1.2 × 10{sup 14} M{sub ⊙}, comparable to other clusters at or above this redshift. There is a wealth of ancillary data available, including Canada–France–Hawaii Telescope optical, UKIRT-K, Spitzer-IRAC/MIPS, and Herschel-SPIRE. This work adds submillimeter imaging with the SCUBA2 camera on the James Clerk Maxwell Telescope and near-infrared imaging with the Hubble Space Telescope. The mid/far-infrared (M/FIR) data detect an Ultra-luminous Infrared Galaxy spatially coincident with the central galaxy, with L{sub IR} = 6.2 ± 0.9 × 10{sup 12} L{sub ⊙}. The detection of polycyclic aromatic hydrocarbons at z = 1.7 in a Spitzer-IRS spectrum of the source implies the FIR luminosity is dominated by star formation (an Active Galactic Nucleus contribution of 20%) with a rate of ∼860 ± 130 M{sub ⊙} yr{sup −1}. The optical source corresponding to the IR emission is likely a chain of >10 individual clumps arranged as “beads on a string” over a linear scale of 66 kpc. Its morphology and proximity to the Brightest Cluster Galaxy (BCG) imply a gas-rich interaction at the center of the cluster triggered the star formation. This system indicates that wet mergers may be an important process in forming the stellar mass of BCGs at early times.

  20. Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

    Science.gov (United States)

    Helås, T; Sagafos, D; Kleggetveit, I P; Quiding, H; Jönsson, B; Segerdahl, M; Zhang, Z; Salter, H; Schmelz, M; Jørum, E

    2017-09-01

    Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits NaV 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the NaV 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in NaV 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the NaV 1.7 I848T mutation are normal and only nociceptor sensitivity

  1. Development of Lattice-Matched 1.7 eV GalnAsP Solar Cells Grown on GaAs by MOVPE

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Nikhil; Oshima, Ryuji; France, Ryan; Geisz, John; Norman, Andrew; Dippo, Pat; Levi, Dean; Young, Michelle; Olavarria, Waldo; Steiner, Myles A.

    2016-11-21

    To advance the state-of-the-art in III-V multijunction solar cells towards high concentration efficiencies approaching 50%, development of a high-quality ~1.7 eV second junction solar cell is of key interest for integration in five or more junction devices. Quaternary GalnAsP solar cells grown lattice-matched on GaAs allows bandgap tunability in the range from 1.42 to 1.92 eV and offers an attractive Al-free alternative to conventional AlGaAs solar cells. In this work, we investigate the role of growth temperature towards understanding the optimal growth window for realizing high-quality GalnAsP alloys. We demonstrate bandgap tunability from 1.6 to 1.8 eV in GalnAsP alloys for compositions close to the miscibility gap, while still maintaining lattice-matched condition to GaAs. We perform an in-depth investigation to understand the impact of varying base thickness and doping concentration on the carrier collection and performance of these 1.7 eV GalnAsP solar cells. The photo-response of these cells is found to be very sensitive to p-type zinc dopant incorporation in the base layer. We demonstrate prototype 1.7 eV GalnAsP solar cell designs that leverage enhanced depletion width as an effective method to overcome this issue and boost long-wavelength carrier collection. Short-circuit current density (JSC) measured in field-aided devices were as high as 17.25 m A/cm2. The best GalnAsP solar cell in this study achieved an efficiency of 17.2% with a JSC of 17 m A/cm2 and a fill-factor of 86.4%. The corresponding open-circuit voltage (VOC) 1.7 eV measured on this cell represents the highest Voc reported for a 1.7 eV GalnAsP solar cell. These initial cell results are encouraging and highlight the potential of Al-free GalnAsP solar cells for integration in the next generation of III-V multijunction solar cells.

  2. Angiotensin-(1-7)/Mas Signaling Inhibits Lipopolysaccharide-Induced ADAM17 Shedding Activity and Apoptosis in Alveolar Epithelial Cells.

    Science.gov (United States)

    Ma, Xinhua; Xu, Daomiao; Ai, Yuhang; Zhao, Shuangping; Zhang, Lina; Ming, Guangfeng; Liu, Zhiyong

    2016-01-01

    A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing the shedding activity of ADAM17 and apoptosis in alveolar epithelial cells, counteracting the inhibitory effects of Ang-(1-7). In addition, LPS significantly increased the JNK activity in alveolar epithelial cells; Ang-(1-7) concentration-dependently inhibited LPS-induced JNK activity, which was abolished by A779 and Mas shRNA. In conclusion, this study suggests that Ang-(1-7)/Mas signaling inhibits LPS-induced alveolar epithelial cell apoptosis by inhibiting LPS-induced shedding activity of ADAM17, likely by a JNK-dependent mechanism. © 2015 S. Karger AG, Basel.

  3. Monitoring Salmonella, Campylobacter, Escherichia coli and Staphylococcus aureus in traditional free-range 'Label Rouge' broiler production: a 23-year survey programme.

    Science.gov (United States)

    Salvat, G; Guyot, M; Protino, J

    2017-01-01

    'Label Rouge' broiler free-range carcasses have been monitored since 1991, and broiler flocks since 2010, for contamination by the main foodborne zoonotic bacteria. Initially, the monitoring plan mainly focused on the surveillance of Salmonella, and on indicators of the overall microbiological quality of free-range broiler carcasses such as Staphylococcus aureus and coliforms, but was extended in 2007 to include Campylobacter enumeration on carcasses and in 2010, to Salmonella in the environment of live birds. Salmonella contamination of free-range broiler carcasses rose to a peak of 16% in 1994 but less than 1% of carcasses are now regularly found to be positive. Indicators of the overall microbiological quality of carcasses are also improving. These results correlate with the low prevalence of Salmonella in free-range broiler breeding and production flocks, and with the continuous improvement of hazard analysis and critical control points in slaughterhouses, the implementation of a good manufacturing practice guide since 1997 and the application of EU regulations on Salmonella since 1998 in France. Regarding Campylobacter counts on carcasses, the situation has been improving continuously over the last few years, even if 2·5% of the carcasses are still contaminated by more than 1000 Campylobacter per g of skin. Although the current control system focusing on Salmonella is based on firm epidemiologic data and offers effective means of control (e.g. slaughtering of positive breeder flocks), existing information on Campylobacter makes it more difficult to formulate an effective control plan for free-range broilers, due to their particular exposure to environmental contamination. This long-term surveillance programme provided an extended view of the evolution of the contamination of free-range broilers and a direct measurement of the impact of mandatory and profession-driven interventions on the microbiological quality of carcasses. © 2016 The Society for Applied

  4. ANGIOTENSIN-(1-7) RECRUITS MUSCLE MICROVASCULATURE AND ENHANCES INSULIN’S METABOLIC ACTION VIA MAS RECEPTOR

    Science.gov (United States)

    Fu, Zhuo; Zhao, Lina; Aylor, Kevin W.; Carey, Robert M.; Barrett, Eugene J.; Liu, Zhenqi

    2014-01-01

    Angiotensin (Ang)-(1-7), an endogenous ligand for the G protein-coupled receptor Mas, exerts both vasodilatory and insulin sensitizing effects. In skeletal muscle relaxation of pre-capillary arterioles recruits microvasculature and increases the endothelial surface area available for nutrient and hormone exchanges. To assess whether Ang-(1-7) recruits microvasculature and enhances insulin action in muscle, overnight-fasted adult rats received an intravenous infusion of Ang-(1-7) (0, 10 or 100 ng/kg/min) for 150 min with or without a simultaneous infusion of the Mas inhibitor A-779 and a superimposition of a euglycemic insulin clamp (3 mU/kg/min) from 30 to 150 min. Hindlimb muscle microvascular blood volume (MBV), microvascular flow velocity (MFV) and microvascular blood flow (MBF) were determined. Myographic changes in tension were measured on pre-constricted distal saphenous artery. Ang-(1-7) dose-dependently relaxed the saphenous artery (pmicrovasculature and enhances insulin’s metabolic action. These effects may contribute to the cardiovascular protective responses associated with Mas activation and explain Ang-(1-7)’s insulin sensitizing action. PMID:24711523

  5. Architecture of the Lsm1-7-Pat1 Complex: A Conserved Assembly in Eukaryotic mRNA Turnover

    Directory of Open Access Journals (Sweden)

    Humayun Sharif

    2013-10-01

    Full Text Available The decay of mRNAs is a key step in eukaryotic gene expression. The cytoplasmic Lsm1-7-Pat1 complex is a conserved component of the 5′-to-3′ mRNA decay pathway, linking deadenylation to decapping. Lsm1-7 is similar to the nuclear Sm complexes that bind oligo-uridine tracts in snRNAs. The 2.3 Å resolution structure of S. cerevisiae Lsm1-7 shows the presence of a heptameric ring with Lsm1-2-3-6-5-7-4 topology. A distinct structural feature of the cytoplasmic Lsm ring is the C-terminal extension of Lsm1, which plugs the exit site of the central channel and approaches the RNA binding pockets. The 3.7 Å resolution structure of Lsm1-7 bound to the C-terminal domain of Pat1 reveals that Pat1 recognition is not mediated by the distinguishing cytoplasmic subunit, Lsm1, but by Lsm2 and Lsm3. These results show how the auxiliary domains and the canonical Sm folds of the Lsm1-7 complex are organized in order to mediate and modulate macromolecular interactions.

  6. Beneficial effects of long-term administration of an oral formulation of Angiotensin-(1-7) in infarcted rats.

    Science.gov (United States)

    Marques, Fúlvia D; Melo, Marcos B; Souza, Leandro E; Irigoyen, Maria Claúdia C; Sinisterra, Rúben D; de Sousa, Frederico B; Savergnini, Sílvia Q; Braga, Vinícius B A; Ferreira, Anderson J; Santos, Robson A S

    2012-01-01

    In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang)-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD), in infarcted rats. Myocardial infarction (MI) was induced by left coronary artery occlusion. HPβCD/Ang-(1-7) was administered for 60 days (76 μg/Kg/once a day/gavage) starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1-7) administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1-7) and indicate HPβCD/Ang-(1-7) as a feasible formulation for long-term oral administration of this heptapeptide.

  7. Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Moiseeva, Natalia [National Synchrotron Light Source, Brookhaven National Laboratory, Building 725D, Upton, NY 11973 (United States); Bau, Robert, E-mail: bau@usc.edu [Chemistry Department, University of Southern California, Los Angeles, CA 90089 (United States); Swenson, Stephen D.; Markland, Francis S. Jr [Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Choe, Jun-Yong [Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute/California Institute of Technology, Pasadena, CA 91125 (United States); Liu, Zhi-Jie [Departments of Biochemistry and Molecular Biology and Chemistry, University of Georgia, Athens, GA 30602 (United States); Allaire, Marc, E-mail: bau@usc.edu [National Synchrotron Light Source, Brookhaven National Laboratory, Building 725D, Upton, NY 11973 (United States)

    2008-04-01

    Two acostatin heterodimers interact together to form an αββα tetramer. Disintegrins are a family of small (4–14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an αβ heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R{sub work} and R{sub free} of 18.6% and 21.5%, respectively, using all data in the 20–1.7 Å resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short β-sheets, each of which is formed by a pair of antiparallel β-strands connected by β-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the αβ chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an αββα acostatin tetramer. Further experiments are required to identify whether the αββα acostatin complex plays a functional role in vivo.

  8. The ACE2-angiotensin-(1-7)-Mas axis protects against pancreatic cell damage in cell culture.

    Science.gov (United States)

    Wang, Jing; Liu, Ruixia; Qi, Haiyu; Wang, Yan; Cui, Lijian; Wen, Yan; Li, Huihui; Yin, Chenghong

    2015-03-01

    Angiotensin-converting enzyme 2 (ACE2), its product angiotensin-(1-7), and its receptor Mas have been shown to moderate the adverse effects of the ACE-angiotensin II-AT1 axis in many diseases. The aim of this study was to determine whether the ACE2-Ang-(1-7)-Mas axis could have similar effects in a cell culture model of pancreatic damage. AR42J cells were stimulated with 10 nmol/L cerulein to simulate acute pancreatitis. ACE2, Ang-(1-7), Mas receptor, and PI3K/AKT pathway were measured by quantitative real-time polymerase chain reaction and Western blot analysis. ACE2 and Mas receptor protein levels in AR42J cells were significantly increased (P Mas receptor gene expression was significantly increased (P Mas axis significantly inhibits pancreatitis in response to decreased inflammatory factors by the activation of endothelial nitric oxide synthase and NO signaling pathways.

  9. Discovery of a biarylamide series of potent, state-dependent NaV1.7 inhibitors.

    Science.gov (United States)

    Schenkel, Laurie B; DiMauro, Erin F; Nguyen, Hanh N; Chakka, Nagasree; Du, Bingfan; Foti, Robert S; Guzman-Perez, Angel; Jarosh, Michael; La, Daniel S; Ligutti, Joseph; Milgram, Benjamin C; Moyer, Bryan D; Peterson, Emily A; Roberts, John; Yu, Violeta L; Weiss, Matthew M

    2017-08-15

    The NaV1.7 ion channel has garnered considerable attention as a target for the treatment of pain. Herein we detail the discovery and structure-activity relationships of a novel series of biaryl amides. Optimization led to the identification of several state-dependent, potent and metabolically stable inhibitors which demonstrated promising levels of selectivity over NaV1.5 and good rat pharmacokinetics. Compound 18, which demonstrated preferential inhibition of a slow inactivated state of NaV1.7, was advanced into a rat formalin study where upon reaching unbound drug levels several fold over the rat NaV1.7 IC50 it failed to demonstrate a robust reduction in nociceptive behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Screening and characterization of a novel alkaline lipase from Acinetobacter calcoaceticus 1-7 isolated from Bohai Bay in China for detergent formulation

    Directory of Open Access Journals (Sweden)

    Haikuan Wang

    2012-03-01

    Full Text Available A novel alkaline lipase-producing strain 1-7 identified as Acinetobacter calcoaceticus was isolated from soil samples collected from Bohai Bay, China, using an olive oil alkaline plate, which contained olive oil as the sole carbon source. The lipase from strain 1-7 showed the maximum activity at pH 9.0 under 40ºC. One interesting feature of this enzyme is that it exhibits lipase activity over a broad range of temperatures and good stability. It is also stable at a broad range of pHs from 4.0 to 10.0 for 24 h. Its catalytic activity was highly enhanced in the presence of Ca2+, Mg2+ and K+, but partially inhibited by Cu2+, Al3+, Fe3+ , Ba2+and Zn2+. The fact that it displays marked stability and activity in the presence of TritonX-100, Tween-20, Tween-80, SDS, Hydrogen peroxide, Sodium perborate, Sodium hypochlorite, Sodium citrate, Sodium taurocholate, Glycerine and NaCl suggests that this lipase is suitable as an additive in detergent formulations.

  11. Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn injury.

    Science.gov (United States)

    Shields, Shannon D; Cheng, Xiaoyang; Uçeyler, Nurcan; Sommer, Claudia; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2012-08-08

    Marked hypersensitivity to heat and mechanical (pressure) stimuli develop after a burn injury, but the neural mechanisms underlying these effects are poorly understood. In this study, we establish a new mouse model of focal second-degree burn injury to investigate the molecular and cellular basis for burn injury-induced pain. This model features robust injury-induced behavioral effects and tissue-specific altered cytokine profile, but absence of glial activation in spinal dorsal horn. Three voltage-gated sodium channels, Na(v)1.7, Na(v)1.8, and Na(v)1.9, are preferentially expressed in peripheral somatosensory neurons of the dorsal root ganglia (DRGs) and have been implicated in injury-induced neuronal hyperexcitability. Using knock-out mice, we provide evidence that Na(v)1.7 selectively contributes to burn-induced hypersensitivity to heat, but not mechanical, stimuli. After burn model injury, wild-type mice display increased sensitivity to heat stimuli, and a normally non-noxious warm stimulus induces activity-dependent Fos expression in spinal dorsal horn neurons. Strikingly, both effects are absent in Na(v)1.7 conditional knock-out (cKO) mice. Furthermore, burn injury increases density and shifts activation of tetrodotoxin-sensitive currents in a hyperpolarized direction, both pro-excitatory properties, in DRG neurons from wild-type but not Na(v)1.7 cKO mice. We propose that, in sensory neurons damaged by burn injury to the hindpaw, Na(v)1.7 currents contribute to the hyperexcitability of sensory neurons, their communication with postsynaptic spinal pain pathways, and behavioral thresholds to heat stimuli. Our results offer insights into the molecular and cellular mechanisms of modality-specific pain signaling, and suggest Na(v)1.7-blocking drugs may be effective in burn patients.

  12. Control of Neurotransmission by NaV1.7 in Human, Guinea Pig, and Mouse Airway Parasympathetic Nerves.

    Science.gov (United States)

    Kocmalova, Michaela; Kollarik, Marian; Canning, Brendan J; Ru, Fei; Adam Herbstsomer, R; Meeker, Sonya; Fonquerna, Silvia; Aparici, Monica; Miralpeix, Montserrat; Chi, Xian Xuan; Li, Baolin; Wilenkin, Ben; McDermott, Jeff; Nisenbaum, Eric; Krajewski, Jeffrey L; Undem, Bradley J

    2017-04-01

    Little is known about the neuronal voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic nervous system. We evaluated the expression of the α subunits of each of the nine NaVs in human, guinea pig, and mouse airway parasympathetic ganglia. We combined this information with a pharmacological analysis of selective NaV blockers on parasympathetic contractions of isolated airway smooth muscle. As would be expected from previous studies, tetrodotoxin potently blocked the parasympathetic responses in the airways of each species. Gene expression analysis showed that that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea pig and human airway parasympathetic ganglia, where mouse ganglia expressed NaV1.1, 1.3, and 1.7. Using selective pharmacological blockers supported the gene expression results, showing that blocking NaV1.7 alone can abolish the responses in guinea pig and human bronchi, but not in mouse airways. To block the responses in mouse airways requires that NaV1.7 along with NaV1.1 and/or NaV1.3 is blocked. These results may suggest novel indications for NaV1.7-blocking drugs, in which there is an overactive parasympathetic drive, such as in asthma. The data also raise the potential concern of antiparasympathetic side effects for systemic NaV1.7 blockers. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Nephrotic-range proteinuria in an eight-year-old traveler with severe dengue: Case report and review of the literature.

    Science.gov (United States)

    Hebbal, Pooja; Darwich, Yamil; Fong, Jane; Hagmann, Stefan H F; Purswani, Murli U

    2016-01-01

    We report a case of an eight-year-old male, native of the Dominican Republic, who visited the U.S. and was admitted to a pediatric intensive care unit with severe dengue. He needed aggressive fluid management for dengue shock syndrome and developed proteinuria on the sixth day of his illness, shortly after his nadir thrombocytopenia. His proteinuria peaked on the eight day, and reduced to trace levels by the tenth day of his illness, coinciding with normalization of his platelet count. His highest random urine protein/creatinine ratio was in the nephrotic range, at 3.9 g/g. Dengue fever can cause a wide spectrum of acute kidney injury (AKI), ranging in incidence from 0.9 to 36%. Review of the literature shows that nephrotic-range proteinuria is an uncommon complication of AKI caused by dengue, reported thus far only in Southeast Asia. Immune-mediated mechanisms may explain the observed association between dengue-induced thrombocytopenia and severe proteinuria, in this case, and previously reported cases. Dengue virus infection is the commonest mosquito-borne disease in the world with substantial morbidity and mortality. Well-designed prospective studies are needed to further characterize the extent and mechanisms of AKI in populations living in countries with ongoing transmission, as well as in those with travel-associated disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A search for cyclical sources of γ-ray emission on the period range from days to years in the Fermi-LAT sky

    Science.gov (United States)

    Prokhorov, D. A.; Moraghan, A.

    2017-11-01

    A systematic search for cyclical sources of γ-ray emission on the period range from days to years in the Fermi-LAT sky is performed. Looking for cyclical emission, the sky is binned into equal-area pixels and the generalized Lomb-Scargle periodogram is computed for each of these pixels. The search on the period range between 2.5 and 30 d in the Galactic plane confirms periodicities of three binaries, LSI +61°303, LS 5039 and 1FGL J1018.6-5856. The all-sky search on the period range between 30 d and 2.5 yr confirm quasi-periodicities of three blazars, PG 1553+113, PKS 2155-304 and BL Lacertae. Evidence for quasi-periodic behaviours of four blazars, 4C +01.28, S5 0716+71, PKS 0805-07 and PKS 2052-47, is presented. Three of these blazars, 4C +01.28, PKS 0805-07 and PKS 2052-47, are located at high redshifts. These three sources are potential candidates to binary systems of supermassive black holes, provided that major galaxy mergers are more frequent and that galaxies are more gas-rich at high redshifts.

  15. Association between body mass index and body fat in 9-11-year-old children from countries spanning a range of human development.

    Science.gov (United States)

    Katzmarzyk, P T; Barreira, T V; Broyles, S T; Chaput, J-P; Fogelholm, M; Hu, G; Kuriyan, R; Kurpad, A; Lambert, E V; Maher, C; Maia, J; Matsudo, V; Olds, T; Onywera, V; Sarmiento, O L; Standage, M; Tremblay, M S; Tudor-Locke, C; Zhao, P; Church, T S

    2015-12-01

    The purpose was to assess associations between body mass index (BMI) and body fat in a multinational sample of 9-11-year-old children. The sample included 7265 children from countries ranging in human development. Total body fat (TBF) and percentage body fat (PBF) were measured with a Tanita SC-240 scale and BMI z-scores (BMIz) and percentiles were computed using reference data from the World Health Organization and the U.S. Centers for Disease Control and Prevention, respectively. Mean PBF at BMIz values of -1, 0 and +1 were estimated using multilevel models. Correlations between BMI and TBF were >0.90 in all countries, and correlations between BMI and PBF ranged from 0.76 to 0.96. Boys from India had higher PBF than boys from several other countries at all levels of BMIz. Kenyan girls had lower levels of PBF than girls from several other countries at all levels of BMIz. Boys and girls from Colombia had higher values of PBF at BMIz=-1, whereas Colombian boys at BMIz 0 and +1 also had higher values of PBF than boys in other countries. Our results show a consistently high correlation between BMI and adiposity in children from countries representing a wide range of human development.

  16. The ACE2/Ang-(1-7)/Mas Axis Regulates the Development of Pancreatic Endocrine Cells in Mouse Embryos.

    Science.gov (United States)

    Wang, Lin; Liang, Juan; Leung, Po Sing

    2015-01-01

    Angiotensin-converting enzyme 2 (ACE2), its product Angiotensin-(1-7) [Ang-(1-7)], and Ang-(1-7) receptor Mas, have been shown to regulate organogenesis during embryonic development in various species. However, it is not known whether a local ACE2/Ang-(1-7)/Mas axis is present in the fetal pancreas. It is hypothesized that there is a local ACE2/Ang-(1-7)/Mas axis in the embryonic pancreas in mice that is involved in regulating islet cell development. To address this issue, the endogenous expression profile of axis constituents in embryonic mouse pancreata was examined. Involvement of the ACE2 axis in the regulation of pancreatic development was also examined. The present experiments showed in an in vivo animal model that endogenous expression levels of ACE2 and the Mas receptor were upregulated in mouse pancreata in late embryogenesis, peaking on embryonic day E16.5, when it reached 3 folds compared to that seen at E12.5. Consistently, endogenous expression of Ang-(1-7) also peaked at E16.5. Treatment with the ACE2 inhibitor DX600 did not alter islet development. However, prenatal treatment with A779, a Mas receptor antagonist, reduced the β-cell to α-cell ratio in neonatal islets, impaired islet insulin secretory function, and impaired the pups' glucose tolerance. In ex vivo pancreas explant cultures, A779 again decreased the β-cell to α-cell ratio, apparently through its effects on β-cell proliferation (reduced proliferation shown with Ki67 staining), and also decreased Insulin and Ngn3 mRNA expression. Furthermore, treatment of explant cultures with Ang-(1-7) increased mRNA levels of Insulin and pancreatic progenitor marker Ngn3, as well as Nox4, the ROS generation enzyme; these stimulatory effects were attenuated by co-treatment with A779, suggesting that Ang-(1-7), via Mas receptor signaling, may promote differentiation of pancreatic progenitors into insulin-producing cells via modulation of reactive oxygen species. These data together suggest that a Mas receptor-mediated mechanism may stimulate pancreatic cell development.

  17. Observations on changes in abundance of questing Ixodes ricinus, castor bean tick, over a 35-year period in the eastern part of its range (Russia, Tula region).

    Science.gov (United States)

    Korotkov, Yu; Kozlova, T; Kozlovskaya, L

    2015-06-01

    Ixodes ricinus (Acari: Ixodidae) L. transmit a wide variety of pathogens to vertebrates including viruses, bacteria and protozoa. Understanding of the epidemiology of tick-borne infections requires basic knowledge of the regional and local factors influencing tick population dynamics. The present study describes the results of monitoring of a questing I. ricinus population, conducted over 35 years (1977-2011) in the eastern, poorly studied part of its range (Russia, Tula region). We have found that the multiannual average abundance of ticks is small and varies depending on the biotope and degree of urban transformation. Tick abundance for the first 14 years of observations (1977-1990) was at the lower limit of the sensitivity of our methods throughout the study area (0.1-0.9 specimens per 1-km transect). In the following 21 years (1991-2011), a manifold increase in abundance was observed, which reached 18.1 ± 1.8 individuals per 1-km transect in moist floodplain terraces, and 4.8 ± 0.9 in xerophylic hill woods. Long-term growth of tick abundance occurred in spite of a relatively constant abundance of small mammals and only minor fluctuations in the abundance of large wild animals. Climate and anthropogenic changes appear to be the main contributors to increased abundance of the tick. © 2015 The Royal Entomological Society.

  18. Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1-7 and Escape Variants

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Pham, Long V; Mikkelsen, Lotte S

    2018-01-01

    NS5A inhibitors against HCV genotype 1-7 prototype isolates and resistant escape variants, and investigated the effects of pre-existing resistance-associated substitutions (RAS) on HCV escape from treatment. METHODS: We measured the efficacy of different concentrations of daclatasvir, ledipasvir...

  19. Angiotensin-(1-7)-Induced Plasticity Changes in the Lateral Amygdala Are Mediated by COX-2 and NO

    Science.gov (United States)

    Albrecht, Doris

    2007-01-01

    It is known from studies outside the brain that upon binding to its receptor, angiotensin-(1-7) elicits the release of prostanoids and nitric oxide (NO). Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to prostaglandins. Since there are no data available so far on the role of COX-2 in the amygdala, in a first step we…

  20. Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker

    NARCIS (Netherlands)

    Goldberg, Y.P.; Price, N.; Namdari, R.; Cohen, C.J.; Lamers, M.H.; Winters, C.; Price, J.; Young, C.E.; Verschoof, H.; Sherrington, R.; Pimstone, S.N.; Hayden, M.R.

    2012-01-01

    Mutations in the SCN9A gene leading to deficiency of its protein product, Na(v)1.7, cause congenital indifference to pain (CIP). CIP is characterized by the absence of the ability to sense pain associated with noxious stimuli. In contrast, the opposite phenotype to CIP, inherited erythromelalgia

  1. McStas 1.7 - a new version of the flexible Monte Carlo neutron scattering package

    DEFF Research Database (Denmark)

    Willendrup, P.; Farhi, E.; Lefmann, K.

    2004-01-01

    in collaboration between Riso and ILL. The new version (1.7) has many improvements, among these added support for the popular Microsoft Windows platform. This presentation will demonstrate a selection of the new features through a simulation of the ILL IN6 beamline. (C) 2004 Elsevier B.V. All rights reserved....

  2. A new Nav1.7 sodium channel mutation I234T in a child with severe pain.

    NARCIS (Netherlands)

    Ahn, H.S.; Dib-Hajj, S.D.; Cox, J.J.; Tyrrell, L.; Elmslie, F.V.; Clarke, A.A.; Drenth, J.P.H.; Woods, C.G.; Waxman, S.G.

    2010-01-01

    Dominant gain-of-function mutations that hyperpolarize activation of the Na(v)1.7 sodium channel have been linked to inherited erythromelalgia (IEM), a disorder characterized by severe pain and redness in the feet and hands in response to mild warmth. Pharmacotherapy remains largely ineffective for

  3. Sodium status and angiotensin-converting enzyme inhibition : effects on plasma angiotensin-(1-7) in healthy man

    NARCIS (Netherlands)

    Kocks, MJA; Lely, AT; Boomsma, F; de Jong, PE; Navis, G

    Objective Angiotensin-converting enzyme (ACE) inhibitors provide effective intervention for cardiovascular and renal disease. Changes in angiotensin-(1-7) have been proposed to be involved in the mechanism of action of ACE inhibition (ACEi). In particular, an altered balance between angiotensin II

  4. Interaction between bradykinin B2 and Ang-(1-7) Mas receptors regulates erythrocyte invasion by Plasmodium falciparum.

    Science.gov (United States)

    Silva, Leandro de Souza; Peruchetti, Diogo de Barros; Silva, Claudio Teixeira Ferreira-Da; Ferreira-DaSilva, André Teixeira; Perales, Jonas; Caruso-Neves, Celso; Pinheiro, Ana Acacia Sá

    2016-11-01

    The molecular mechanisms involved in erythrocyte invasion by malaria parasite are well understood, but the contribution of host components is not. We recently reported that Ang-(1-7) impairs the erythrocytic cycle of P. falciparum through Mas receptor-mediated reduction of protein kinase A (PKA) activity. The effects of bradykinin (BK), a peptide of the kallikrein-kinin system (KKS), can be potentiated by Ang-(1-7), or angiotensin-converting enzyme (ACE) inhibitors, such as captopril. We investigated the coordinated action between renin-angiotensin system (RAS) and KKS peptides in the erythrocyte invasion by P. falciparum. We used human erythrocytes infected with P. falciparum to assess the influence of RAS and KKS peptides in the invasion of new erythrocytes. The inhibitory effects of Ang-(1-7) were mimicked by captopril. 10(-8)M BK decreased new ring forms and this effect was sensitive to 10(-8)M HOE-140 and 10(-7)M A779, B2 and Mas receptor antagonists, respectively. However, DALBK, a B1 receptor blocker, had no effect. The inhibitory effect of Ang-(1-7) was reversed by HOE-140 and A779 at the same concentrations. Co-immunoprecipitation assay revealed an association between B2 and Mas receptors. BK also inhibited PKA activity, which was sensitive to both HOE-140 and A779. The results suggest that B2 and Mas receptors are mediators of Ang-(1-7) and BK inhibitory effects, through a cross-signaling pathway, possibly by the formation of a heterodimer. Our results describe new elements in host signaling that could be involved in parasite invasion during the erythrocyte cycle of P. falciparum. Copyright © 2016. Published by Elsevier B.V.

  5. Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis.

    Science.gov (United States)

    Xiao, Hong-Li; Li, Chun-Sheng; Zhao, Lian-Xing; Yang, Jun; Tong, Nan; An, Le; Liu, Qi-Tong

    2016-11-01

    Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.

  6. Tensile properties of the hip joint ligaments are largely variable and age-dependent - An in-vitro analysis in an age range of 14-93 years.

    Science.gov (United States)

    Schleifenbaum, Stefan; Prietzel, Torsten; Hädrich, Carsten; Möbius, Robert; Sichting, Freddy; Hammer, Niels

    2016-10-03

    Hip joint stability is maintained by the surrounding ligaments, muscles, and the atmospheric pressure exerted via these structures. It is unclear whether the ligaments are capable of preventing dislocation solely due to their tensile properties, and to what extent they undergo age-related changes. This study aimed to obtain stress-strain data of the hip ligaments over a large age range. Stress-strain data of the iliofemoral (IL), ischiofemoral (IS) and pubofemoral ligament (PF) were obtained from cadavers ranging between 14 and 93 years using a highly standardized setting. Maximum strains were compared to the distances required for dislocation. Elastic modulus was 24.4 (IL), 22.4 (IS) and 24.9N/mm(2) (PF) respectively. Maximum strain was 84.5%, 86.1%, 72.4% and ultimate stress 10.0, 7.7 and 6.5N/mm(2) for the IL, IS and PF respectively. None of these values varied significantly between ligaments or sides. The IS' elastic modulus was higher and maximum strain lower in males. Lower elastic moduli of the PF and higher maximum strains for the IS and PF were revealed in the ≥55 compared to the ligaments are largely variable. The IS and PF change age-dependently. Though the hip ligaments contribute to hip stability, the IS and cranial IL may not prevent dislocation due to their elasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Infection with Trypanosoma cruzi TcII and TcI in free-ranging population of lion tamarins (Leontopithecus spp: an 11-year follow-up

    Directory of Open Access Journals (Sweden)

    Cristiane Varella Lisboa

    2015-05-01

    Full Text Available Here, we present a review of the dataset resulting from the 11-years follow-up of Trypanosoma cruzi infection in free-ranging populations of Leontopithecus rosalia (golden lion tamarin and Leontopithecus chrysomelas (golden-headed lion tamarin from distinct forest fragments in Atlantic Coastal Rainforest. Additionally, we present new data regarding T. cruzi infection of small mammals (rodents and marsupials that live in the same areas as golden lion tamarins and characterisation at discrete typing unit (DTU level of 77 of these isolates. DTU TcII was found to exclusively infect primates, while TcI infected Didelphis aurita and lion tamarins. The majority of T. cruzi isolates derived from L. rosalia were shown to be TcII (33 out 42 Nine T. cruzi isolates displayed a TcI profile. Golden-headed lion tamarins demonstrated to be excellent reservoirs of TcII, as 24 of 26 T. cruzi isolates exhibited the TcII profile. We concluded the following: (i the transmission cycle of T. cruzi in a same host species and forest fragment is modified over time, (ii the infectivity competence of the golden lion tamarin population fluctuates in waves that peak every other year and (iii both golden and golden-headed lion tamarins are able to maintain long-lasting infections by TcII and TcI.

  8. Production of Short-Rotation Woody Crops Grown with a Range of Nutrient and Water Availability: Establishment Report and First-Year Responses

    Energy Technology Data Exchange (ETDEWEB)

    D.R. Coyle; J. Blake; K. Britton; M.; R.G. Campbell; J. Cox; B. Cregg; D. Daniels; M. Jacobson; K. Johnsen; T. McDonald; K. McLeod; E.; D. Robison; R. Rummer; F. Sanchez; J.; B. Stokes; C. Trettin; J. Tuskan; L. Wright; S. Wullschleger

    2003-12-31

    Coleman, M.D., et. al. 2003. Production of Short-Rotation Woody Crops Grown with a Range of Nutrient and Water Availability: Establishment Report and First-Year Responses. Report. USDA Forest Service, Savannah River, Aiken, SC. 26 pp. Abstract: Many researchers have studied the productivity potential of intensively managed forest plantations. However, we need to learn more about the effects of fundamental growth processes on forest productivity; especially the influence of aboveground and belowground resource acquisition and allocation. This report presents installation, establishment, and first-year results of four tree species (two cottonwood clones, sycamore, sweetgum, and loblolly pine) grown with fertilizer and irrigation treatments. At this early stage of development, irrigation and fertilization were additive only in cottonwood clone ST66 and sweetgum. Leaf area development was directly related to stem growth, but root production was not always consistent with shoot responses, suggesting that allocation of resources varies among treatments. We will evaluate the consequences of these early responses on resource availability in subsequent growing seasons. This information will be used to: (1) optimize fiber and bioenergy production; (2) understand carbon sequestration; and (3) develop innovative applications such as phytoremediation; municipal, industrial, and agricultural wastes management; and protection of soil, air, and water resources.

  9. Lithium diffusion study in Li2MnO3and Li1.17Ni0.17Mn0.67O2: a combined experimental and computational approach.

    Science.gov (United States)

    Sarkar, Tanmay; Prakasha, Kunkanadu R; Bharadwaj, Mridula Dixit; Prakash, Annigere S

    2017-12-06

    A theoretical and experimental diffusivity study of Li 2 MnO 3 and Li 1.17 Ni 0.17 Mn 0.67 O 2 has been carried out to investigate the effect of Mn, Ni and surrounding atoms on Li + diffusion and to understand how the Li + diffusion trajectory changes with different charge spheres. It is observed that due to the presence of Ni in Li 1.17 Ni 0.17 Mn 0.67 O 2 , the activation energy reduces in all the possible diffusion paths, which helps in faster Li + diffusion. This study brings a new physical insight into Li + diffusion based on elliptical and straight diffusion trajectories. In Li 1.17 Ni 0.17 Mn 0.67 O 2 , the Li + diffusion mechanism in different paths based on 2b, 2c and 4h Wyckoff sites of Li has been discussed. Experimentally, the galvanostatic intermittent titration technique is adopted to identify the diffusion coefficient of Li + . The diffusion coefficient of both the compounds varies in different voltage ranges. For L 2 MnO 3 , diffusion varies from 10 -11 to 10 -13 cm 2 s -1 , whereas for Li 1.17 Ni 0.17 Mn 0.67 O 2 , diffusion varies from 10 -9 to 10 -11 cm 2 s -1 in the voltage range of 3.7-4.7 V.

  10. African Journal of Neurological Sciences 2010 - Vol. 29, No 1 17 ...

    African Journals Online (AJOL)

    kim

    Cryptococcal meningitis (CM) is an infection of the brain parenchyma and subarachnoid space by the encapsulated saprophyte yeast organisms such as Cryptococcus neoformans. Over the last twenty years,. HIV has created a large and severely immune compromisized population in whom C. neoformans is a dangerous ...

  11. Ten-year chemical signatures associated with long-range transport observed in the free troposphere over the central North Atlantic

    Directory of Open Access Journals (Sweden)

    B. Zhang

    2017-03-01

    Full Text Available Ten-year observations of trace gases at Pico Mountain Observatory (PMO, a free troposphere site in the central North Atlantic, were classified by transport patterns using the Lagrangian particle dispersion model, FLEXPART. The classification enabled identifying trace gas mixing ratios associated with background air and long- range transport of continental emissions, which were defined as chemical signatures. Comparison between the chemical signatures revealed the impacts of natural and anthropogenic sources, as well as chemical and physical processes during long transport, on air composition in the remote North Atlantic. Transport of North American anthropogenic emissions (NA-Anthro and summertime wildfire plumes (Fire significantly enhanced CO and O3 at PMO. Summertime CO enhancements caused by NA-Anthro were found to have been decreasing by a rate of 0.67 ± 0.60 ppbv/year in the ten-year period, due possibly to reduction of emissions in North America. Downward mixing from the upper troposphere and stratosphere due to the persistent Azores-Bermuda anticyclone causes enhanced O3 and nitrogen oxides. The 'd' [O3]/'d' [CO] value was used to investigate O3 sources and chemistry in different transport patterns. The transport pattern affected by Fire had the lowest 'd' [O3]/'d' [CO], which was likely due to intense CO production and depressed O3 production in wildfire plumes. Slightly enhanced O3 and 'd' [O3]/'d' [CO] were found in the background air, suggesting that weak downward mixing from the upper troposphere is common at PMO. Enhancements of both butane isomers were found during upslope flow periods, indicating contributions from local sources. The consistent ratio of butane isomers associated with the background air and NA-anthro implies no clear difference in the oxidation rates of the butane isomers during long transport. Based on observed relationships between non-methane hydrocarbons, the averaged photochemical age of the air masses at

  12. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-08-01

    The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg-1 d-1), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg-1min-1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. What is driving changes in long-range transport of dust from Africa to the Americas? A 30 year synthesis of the GEOS-Chem model and observations

    Science.gov (United States)

    Ridley, D. A.; Heald, C. L.

    2012-12-01

    The Sahara and Sahelian regions produce approximately half of the world's dust emissions, resulting in significant radiative effects, air quality issues and mineral deposition, not only in Africa, but across the Atlantic and in the Americas. Determining how these impacts may change in the future requires a thorough understanding of the processes controlling emission, transport and deposition of dust. Long-term records of dust concentration measured in the Caribbean have, until the nineties, correlated with Sahelian precipitation and climatic indicators, potentially providing ways to predict changes in dust. However, this relationship is no longer clear and there are significant changes in the seasonality of dust transported to the Americas currently with no obvious explanation. We use the GEOS-Chem global chemical transport model with NASA GMAO meteorological re-analyses (MERRA) to simulate the 30 year period 1979 - 2008. A synthesis of observations from multiple satellite and surface-based platforms is used to evaluate the model, primarily in terms of its ability to simulate the long-range transport of mineral dust from Africa. We then investigate what drives the changes in long-range transport of African dust to the Americas over diurnal to decadal timescales. This enables understanding of the relative importance of the individual processes controlling these changes, and the sensitivity of air quality and dust deposition downwind. This work aims to determine 1) how sensitive air quality and dust deposition in the Americas is to changes in African dust emissions, 2) the role of meteorological variables affecting the inter-annual variability of dust emission and deposition, and 3) the impact that land use changes and desertification in the Sahel may have in terms of the influence on dust transported to the Americas.

  14. Comparing the range of μ and β angles in 6-17-year-old children of Isfahan with normal occlusion

    Directory of Open Access Journals (Sweden)

    Saeed Sadeghian

    2014-01-01

    Full Text Available Background: Linear and angular measurements such as A point, nasion, B point (ANB angle and Wits appraisal index are not accurate enough to evaluate sagittal relationship of the jaws. The aim of this study was to evaluate and compare the range of μ and β angles in 6-17-year-old children of Isfahan, having normal occlusion. Materials and Methods: This was an analytical descriptive study. For this study, 235 cephalometric radiographs of patients who didn′t receive orthodontics treatments and based on 13 indexes had normal occlusion, were selected. After tracing of cephalograms, ANB angle, Wits appraisal index, μ angle (resulted from the intersection of AB line and perpendicular line from point A to mandibular plane and β angle (resulted from the intersection of AB line and perpendicular line from point A on CB line were measured. Data was analyzed by t-test, ANOVA and Pierson-Spearman correlation coefficient (P < 0.05. Results: Mean value of μ and β angles were 17.34 ± 3.47 and 31.7 ± 3.31 and ranged from 8-27 to 21.5-39 respectively. According to t-test, there was a significant difference between two sex groups for μ angle (P = 0.02; however, it was not significant for β angle. According to Spearman correlation coefficient, there was no significant difference between age and μ angle; however, β angle was directly and significantly related to age (r = 0.435. There was significant and reverse relationship between μ and β angles with ANB angle and Wits appraisal index. Conclusion: μ and β angles are reliable and can be used to evaluate the anterior-posterior relationship of the jaws.

  15. Measurement of inclusive radiative B-meson decays with a photon energy threshold of 1.7 GeV.

    Science.gov (United States)

    Limosani, A; Aihara, H; Arinstein, K; Aushev, T; Bakich, A M; Balagura, V; Barberio, E; Bay, A; Belous, K; Bischofberger, M; Bondar, A; Bozek, A; Bracko, M; Browder, T E; Chang, P; Chao, Y; Chen, A; Cheon, B G; Choi, Y; Dalseno, J; Danilov, M; Drutskoy, A; Dungel, W; Eidelman, S; Goldenzweig, P; Golob, B; Ha, H; Hayashii, H; Hoshi, Y; Hou, W-S; Hyun, H J; Inami, K; Itoh, R; Iwasaki, Y; Julius, T; Kah, D H; Kim, H O; Kim, S K; Kim, Y I; Kim, Y J; Kinoshita, K; Ko, B R; Korpar, S; Kreps, M; Krizan, P; Krokovny, P; Kuhr, T; Kumar, R; Kwon, Y-J; Kyeong, S-H; Lesiak, T; Li, J; Liu, C; Liventsev, D; Louvot, R; Matyja, A; Miyabayashi, K; Miyata, H; Miyazaki, Y; Mizuk, R; Mori, T; Nakao, M; Nakazawa, H; Nishida, S; Nishimura, K; Nitoh, O; Nozaki, T; Ogawa, S; Ohshima, T; Okuno, S; Ozaki, H; Pakhlova, G; Park, C W; Park, H; Piilonen, L E; Rozanska, M; Sahoo, H; Sakai, Y; Schneider, O; Schümann, J; Schwanda, C; Schwartz, A J; Senyo, K; Sevior, M E; Shapkin, M; Shebalin, V; Shen, C P; Shiu, J-G; Singh, J B; Stanic, S; Staric, M; Sumisawa, K; Sumiyoshi, T; Suzuki, S; Taylor, G N; Teramoto, Y; Trabelsi, K; Tsuboyama, T; Uehara, S; Unno, Y; Uno, S; Urquijo, P; Ushiroda, Y; Varner, G; Varvell, K E; Vervink, K; Wang, C H; Wang, M-Z; Wang, P; Watanabe, Y; Wedd, R; Wicht, J; Won, E; Yabsley, B D; Yamamoto, H; Yamashita, Y; Zhang, Z P; Zivko, T; Zupanc, A

    2009-12-11

    Using 605 fb(-1) of data collected at the Upsilon(4S) resonance we present a measurement of the inclusive radiative B-meson decay channel, B-->X(s)gamma. For the lower photon energy thresholds of 1.7, 1.8, 1.9, and 2.0 GeV, as defined in the rest frame of the B meson, we measure the partial branching fraction and the mean and variance of the photon energy spectrum. At the 1.7 GeV threshold we obtain the partial branching fraction BF(B-->X(s)}gamma)=(3.45+/-0.15+/-0.40)x10(-4), where the errors are statistical and systematic.

  16. NorLeu(3)-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers.

    Science.gov (United States)

    Rodgers, Kathleen E; Bolton, Laura L; Verco, Shelagh; diZerega, Gere S

    2015-06-01

    Significance: Diabetes is a disorder that is well known to delay wound repair resulting in the formation of colonized chronic wounds. Over their lifetime, diabetic patients have a 25% incidence of foot ulcers (DFUs), which contribute to increased risk of morbidity, including osteomyelitis and amputations, and increased burden to the healthcare system. Recent Advances: The only active product approved for the treatment of diabetic ulcers, Regranex(®), is not widely used due to minimal proven efficacy and recent warnings added to the Instructions for Use. A novel topical agent that accelerates healing and increases the proportion of fully healed DFUs, DSC127 [aclerastide; active ingredient, NorLeu(3)-angiotensin (1-7) (NorLeu(3)-A(1-7))], is recruiting patients in Phase III clinical trials (NCT01830348 and NCT01849965). NorLeu(3)-A(1-7) is an analog of the naturally occurring peptide, angiotensin 1-7. The mechanisms of action include induction of progenitor proliferation, accelerated vascularization, collagen deposition, and re-epithelialization. Critical Issues: Current modalities for the treatment of DFUs include strict offloading, bandaging, debridement and, on a limited basis, application of Regranex. Novel potent therapies are needed to combat this significant burden to the diabetic patient and the healthcare system. Future Direction: Preclinical and clinical research shows that DSC127 is highly effective in the closure of diabetic wounds and is superior to Regranex in animal studies. Clinical development of DSC127 as a topical agent for the healing of DFU is underway. Further investigation into the mechanisms by which this product accelerates healing is warranted.

  17. Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker.

    Science.gov (United States)

    Goldberg, Yigal Paul; Price, Nicola; Namdari, Rostam; Cohen, Charles Jay; Lamers, Mieke H; Winters, Conrad; Price, James; Young, Clint E; Verschoof, Henry; Sherrington, Robin; Pimstone, Simon Neil; Hayden, Michael Reuben

    2012-01-01

    Mutations in the SCN9A gene leading to deficiency of its protein product, Na(v)1.7, cause congenital indifference to pain (CIP). CIP is characterized by the absence of the ability to sense pain associated with noxious stimuli. In contrast, the opposite phenotype to CIP, inherited erythromelalgia (IEM), is a disorder of spontaneous pain caused by missense mutations resulting in gain-of-function in Na(v)1.7 that promote neuronal hyperexcitability. The primary aim of this study was to demonstrate that Na(v)1.7 antagonism could alleviate the pain of IEM, thereby demonstrating the utility of this opposite phenotype model as a tool for rapid proof-of-concept for novel analgesics. An exploratory, randomized, double-blind, 2-period crossover study was conducted in 4 SCN9A mutation-proven IEM patients. In each treatment period (2days), separated by a 2-day washout period, patients were orally administered XEN402 (400mg twice daily) or matching placebo. In 3 patients, pain was induced by heat or exercise during each treatment arm. A fourth patient, in constant severe pain, required no induction. Patient-reported outcomes of pain intensity and/or relief were recorded, and the time taken to induce pain was measured. The ability to induce pain in IEM patients was significantly attenuated by XEN402 compared with placebo. XEN402 increased the time to maximal pain induction and significantly reduced the amount of pain (42% less) after induction (P=.014). This pilot study showed that XEN402 blocks Na(v)1.7-mediated pain associated with IEM, thereby demonstrating target engagement in humans and underscoring the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  18. Inhibition of Nav1.7 channels by methyl eugenol as a mechanism underlying its antinociceptive and anesthetic actions.

    Science.gov (United States)

    Wang, Ze-Jun; Tabakoff, Boris; Levinson, Simon R; Heinbockel, Thomas

    2015-07-01

    Methyl eugenol is a major active component extracted from the Chinese herb Asari Radix et Rhizoma, which has been used to treat toothache and other pain. Previous in vivo studies have shown that methyl eugenol has anesthetic and antinociceptive effects. The aim of this study was to determine the possible mechanism underlying its effect on nervous system disorders. The direct interaction of methyl eugenol with Na(+) channels was explored and characterized using electrophysiological recordings from Nav1.7-transfected CHO cells. In whole-cell patch clamp mode, methyl eugenol tonically inhibited peripheral nerve Nav1.7 currents in a concentration- and voltage-dependent manner, with an IC50 of 295 μmol/L at a -100 mV holding potential. Functionally, methyl eugenol preferentially bound to Nav1.7 channels in the inactivated and/or open state, with weaker binding to channels in the resting state. Thus, in the presence of methyl eugenol, Nav1.7 channels exhibited reduced availability for activation in a steady-state inactivation protocol, strong use-dependent inhibition, enhanced binding kinetics, and slow recovery from inactivation compared to untreated channels. An estimation of the affinity of methyl eugenol for the resting and inactivated states of the channel also demonstrated that methyl eugenol preferentially binds to inactivated channels, with a 6.4 times greater affinity compared to channels in the resting state. The failure of inactivated channels to completely recover to control levels at higher concentrations of methyl eugenol implies that the drug may drive more drug-bound, fast-inactivated channels into drug-bound, slow-inactivated channels. Methyl eugenol is a potential candidate as an effective local anesthetic and analgesic. The antinociceptive and anesthetic effects of methyl eugenol result from the inhibitory action of methyl eugenol on peripheral Na(+) channels.

  19. 1 W tunable near diffraction limited light from a broad area laser diode in an external cavity with a line width of 1.7 MHz

    Science.gov (United States)

    Jechow, Andreas; Raab, Volker; Menzel, Ralf; Cenkier, Michael; Stry, Sandra; Sacher, Joachim

    2007-09-01

    A novel unstable external cavity for a broad area laser diode is presented. The cavity is based on a V-shaped setup that improves the slow axis beam quality by coupling the internal modes of a gain guided laser diode. The novelty here is the compact unstable resonator design without lenses in direction of the slow axis. For frequency stabilisation and to narrow the line width of the laser diode emission a diffraction grating in a Littrow configuration is used. With this setup up to 1 W of near diffraction limited light with a beam quality of M2 ⩽ 1.3 and a line width of 1.7 MHz could be achieved. The external cavity laser was tunable over a range of 35 nm (FWHM) around the center wavelength of 976 nm.

  20. Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.

    Science.gov (United States)

    Mork, Maureen E; Rodriguez, Andrea; Taggart, Melissa W; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; Bannon, Sarah A; You, Y Nancy; Vilar, Eduardo

    2017-07-01

    Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

  1. Evaluation and implementation of FilmArray version 1.7 for improved detection of adenovirus respiratory tract infection.

    Science.gov (United States)

    Doern, Christopher D; Lacey, Damon; Huang, Rong; Haag, Crissie

    2013-12-01

    The BioFire FilmArray respiratory panel is a multiplex PCR technology capable of detecting a number of bacteria and viruses that cause respiratory tract infection. The assay is technically simple to perform and provides rapid results, making it an appealing option for physicians and laboratorians. The initial product released by BioFire (version 1.6) was reported to have poor sensitivity for adenovirus detection and was therefore of concern when testing immunocompromised patients. This study evaluates the redesigned FilmArray assay (version 1.7) for detection of adenovirus. In this evaluation, we performed both retrospective and prospective verification studies, as well as a detailed serotype analysis. We found that version 1.7 demonstrated improved adenovirus sensitivity. In retrospective studies, sensitivity improved from 66.6% to 90.5%, and in prospective studies, it improved from 42.7% to 83.3%. In addition, when 39 clinically relevant serotypes were tested, 8 were not detected by version 1.6 and only 1 was not detected by version 1.7. The limit of detection remained the same when tested against serotype 4 but improved by 2 log units for serotype 7. Lastly, turnaround time analyses showed that the FilmArray assay was completed 3 h and 9 min after collection, which was more than a 37-h improvement over the previous multiplex PCR assay performed in our laboratory.

  2. Substance P(1-7) induces antihyperalgesia in diabetic mice through a mechanism involving the naloxone-sensitive sigma receptors.

    Science.gov (United States)

    Carlsson, Anna; Ohsawa, Masahiro; Hallberg, Mathias; Nyberg, Fred; Kamei, Junzo

    2010-01-25

    We have recently explored the role of the tachykinin substance P neuroactive fragment substance P(1-7) in the mediation of anti-inflammatory effects using a blister model in the rat paw (Wiktelius et al., 2006). We observed that this heptapeptide induced a dose-dependent inhibitory effect on the substance P-induced response, which was reversible by the non-selective opioid receptor antagonist naloxone. In the present study, we examined the ability of substance P(1-7) to induce antihyperalgesic effects in streptozotocin-induced diabetic mice. We found that the substance P fragment strongly and dose-dependently produced antihyperalgesia in diabetic mice. This effect was reversed by naloxone but not by the selective opioid receptor antagonist beta-funaltrexamine, naltrindole or nor-binaltorphimine, selective for the micro-, delta- or kappa-opioid receptor, respectively. In addition, the antihyperalgesic effect induced by substance P(1-7) was partly reversed by a sigma(1) receptor agonist (+)-pentazocine, but not a sigma(1) receptor antagonist BD1047 ([2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(diamino)ethylamine), suggesting that involvement of the naloxone-sensitive sigma-receptor for the action of the SP related heptapeptides. These results suggest that hyperalgesia in diabetic mice may be, in part, due to the enhanced endogenous sigma(1) receptor systems in the spinal cord.

  3. Post-Closure Inspection Report for Corrective Action Unit 426: Cactus Spring Waste Trenches Tonopah Test Range, Nevada Calendar Year 2000

    Energy Technology Data Exchange (ETDEWEB)

    K. B. Campbell

    2001-06-01

    Post-closure monitoring requirements for the Cactus Spring Waste Trenches (Corrective Action Unit [CAW 426]) (Figure 1) are described in Closure Report for corrective Action Unit 426, Cactus Spring Waste Trenches. Tonopah Test Range, Nevada, report number DOE/NV--226. The Closure Report (CR) was submitted to the Nevada Division of Environmental Protection (NDEP) on August 14, 1998. Permeability results of soils adjacent to the engineered cover and a request for closure of CAU 404 were transmitted to the NDEP on April 29, 1999. The CR (containing the Post-Closure Monitoring Plan) was approved by the NDEP on May 13, 1999. Post-closure monitoring at CAU 426 consists of the following: (1) Site inspections done twice a year to evaluate the condition of the unit; (2) Verification that the site is secure; (3) Notice of any subsidence or deficiencies that may compromise the integrity of the unit; (4) Remedy of any deficiencies within 90 days of discovery; and (5) Preparation and submittal of an annual report. Site inspections were conducted on June 19, 2000, and November 21, 2000. All inspections were made after NDEP approval of the CR, and were conducted in accordance with the Post-Closure Monitoring Plan in the NDEP-approved CR. This report includes copies of the inspection checklists, photographs, recommendations, and conclusions. The Post-Closure Inspection Checklists are found in Attachment A, a copy of the field notes is found in Attachment B, and copies of the inspection photographs are found in Attachment C.

  4. Campaign 1.7 Pu Aging. Development of Time of Flight Secondary Ion Mass Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Venhaus, Thomas J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-09-09

    The first application of Time-of-Flight Secondary Ion Mass Spectroscopy (ToF-SIMS) to an aged plutonium surface has resulted in a rich set of surface chemistry data, as well as some unexpected results. FY15 was highlighted by not only the first mapping of hydrogen-containing features within the metal, but also a prove-in series of experiments using the system’s Sieverts Reaction Cell. These experiments involved successfully heating the sample to ~450 oC for nearly 24 hours while the sample was dosed several times with hydrogen, followed by an in situ ToF-SIMS analysis. During this year, the data allowed for better and more consistent identification of the myriad peaks that result from the SIMS sputter process. In collaboration with the AWE (U.K), the system was also fully aligned for sputter depth profiling for future experiments.

  5. Dysprosium-doped ZBLAN fiber laser tunable from 2.8  μm to 3.4  μm, pumped at 1.7  μm.

    Science.gov (United States)

    Majewski, Matthew R; Woodward, Robert I; Jackson, Stuart D

    2018-03-01

    We demonstrate a mid-infrared dysprosium-doped fluoride fiber laser with a continuously tunable output range of 573 nm, pumped by a 1.7 μm Raman fiber laser. To the best of our knowledge, this represents the largest tuning range achieved to date from any rare-earth-doped fiber laser and, critically, spans the 2.8-3.4 μm spectral region, which contains absorption resonances of many important functional groups and is uncovered by other rare-earth ions. Output powers up to 170 mW are achieved, with 21% slope efficiency. We also discuss the relative merits of the 1.7 μm pump scheme, including possible pump excited-state absorption.

  6. Ang-(1-7) promotes the migration and invasion of human renal cell carcinoma cells via Mas-mediated AKT signaling pathway.

    Science.gov (United States)

    Zheng, Shuai; Yang, Ying; Song, Ran; Yang, Xiaomei; Liu, Hua; Ma, Qian; Yang, Longyan; Meng, Ran; Tao, Tao; Wang, Songlin; He, Junqi

    2015-05-01

    Ang-(1-7) is an active peptide component of renin-angiotensin system and endogenous ligand for Mas receptor. In the current study, we showed that Ang-(1-7) enhanced migratory and invasive abilities of renal cell carcinoma cells 786-O and Caki-1 by wound-healing, transwell migration and transwell invasion assays. Mas antagonist A779 pretreatment or shRNA-mediated Mas knockdown abolished the stimulatory effect of Ang-(1-7). Furthermore, Ang-(1-7)-stimulated AKT activation was inhibited by either A779 pretreatment or Mas knockdown. Blockage of AKT signaling by AKT inhibitor VIII inhibited Ang-(1-7)-induced migration and invasion in 786-O cells. Taken together, our results provided the first evidence for the pro-metastatic role of Ang-(1-7) in RCC, which may help to better understand the molecular mechanism underlying the progression of this tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Post-Closure Inspection Report for Corrective Action Unit 404: Roller Coaster Sewage Lagoons and North Disposal Trench Tonopah Test Range, Nevada, Calendar Year 2000

    Energy Technology Data Exchange (ETDEWEB)

    K. B. Campbell

    2001-06-01

    Post-closure monitoring requirements for the Roller Coaster Sewage Lagoons and North Disposal Trench (Corrective Action Unit [CAW 404]) (Figure 1) are described in Closure Report for Corrective Action Unit 404, Roller Coaster Sewage Lagoons and North Disposal Trench, Tonopah Test Range, Nevada, report number DOE/NV--187. The Closure Report (CR) was submitted to the Nevada Division of Environmental Protection (NDEP) on September 11, 1998. Permeability results of soils adjacent to the engineered cover and a request for closure of CAU 404 were transmitted to the NDEP on April 29, 1999. The CR (containing the Post-Closure Monitoring Plan) was approved by the NDEP on May 18, 1999. Post-closure monitoring at CAU 404 consists of the following: (1) Site inspections done twice a year to evaluate the condition of the unit; (2) Verification that the site is secure; (3) Notice of any subsidence or deficiencies that may compromise the integrity of the unit; (4) Remedy of any deficiencies within 90 days of discovery; and (5) Preparation and submittal of an annual report. Site inspections were conducted on June 19, 2000, and November 21, 2000. The site inspections were conducted after completion of the revegetation activities (October 30, 1997) and NDEP approval of the CR (May 18, 1999). All site inspections were conducted in accordance with the Post-Closure Monitoring Plan in the NDEP-approved CR. This report includes copies of inspection checklists, photographs, recommendations, and conclusions. The Post-Closure Inspection Checklists are found in Attachment A, a copy of the field notes is found in Attachment B, and copies of the inspection photographs are found in Attachment C.

  8. Fully Integrated 1.7GHz, 188dBc/Hz FoM, 0.8V, 320uW LC-tank VCO and Frequency Divider

    DEFF Research Database (Denmark)

    Midtgaard, Jesper Stolpe; Jeppesen, Thomas; Christensen, Kåre Tais

    2005-01-01

    This paper presents a 0.13μm CMOS 1.7GHz VCO with frequency divider, suitable for ultra-low-power hearing-aid applications. The circuit has a 16% tuning range, a minimum power consumption of 320μW from a 0.8V power supply, power-supply and temperature compensation, an excellent 188dBc/Hz figure...

  9. Angiotensin-(1-7) attenuated long-term hypoxia-stimulated cardiomyocyte apoptosis by inhibiting HIF-1α nuclear translocation via Mas receptor regulation.

    Science.gov (United States)

    Chang, Ruey-Lin; Lin, Jing-Wei; Kuo, Wei-Wen; Hsieh, Dennis Jine-Yuan; Yeh, Yu-Lan; Shen, Chia-Yao; Day, Cecilia-Hsuan; Ho, Tsung-Jung; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2016-02-01

    Extreme hypoxia often leads to myocardial apoptosis and causes heart failure. Angiotensin-(1-7)Ang-(1-7) is well known for its cardio-protective effects. However, the effects of Ang-(1-7) on long-term hypoxia (LTH)-induced apoptosis remain unknown. In this study, we found that Ang-(1-7) reduced myocardial apoptosis caused by hypoxia through the Mas receptor. Activation of the Ang-(1-7)/Mas axis down-regulated the hypoxia pro-apoptotic signaling cascade by decreasing the protein levels of hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor binding protein-3 (IGFBP3). Moreover, the Ang-(1-7)/Mas axis further inhibited HIF-1α nuclear translocation. On the other hand, Ang-(1-7) activated the IGF1R/PI3K/Akt signaling pathways, which mediate cell survival. However, the above effects were abolished by A779 treatment or silencing of Mas expression. Taken together, our findings indicate that the Ang-(1-7)/Mas axis protects cardiomyocytes from LTH-stimulated apoptosis. The protective effect of Ang-(1-7) is associated with the inhibition of HIF-1α nuclear translocation and the induction of IGF1R and Akt phosphorylation.

  10. Revelation 1:7 − A roadmap of God’s τέλοςfor his creation

    Directory of Open Access Journals (Sweden)

    Kobus de Smidt

    2013-11-01

    Full Text Available Revelation 1:7 points to an anticipated final appearance of Jesus at the consummation. This κηρύσσω developed from the late Jewish apocalyptic eschatology. This apocalyptic end time dawned with Jesus. The present time is thus simultaneously the end time, though the consummation is still in the future. As Jesus appeared on earth with his resurrection, so will he appear at the consummation − his resurrection appearance is a simile of his appearance at the consummation. He will appear in a corporeal form. The writer encourages the second-generation marginalised Christians. The Roman emperor is not the victor − Jesus is the axis mundi of God’s final purpose for his creation. The final appearance of Jesus will bring redemption for the believers and mourning for the unbelievers. The κηρύσσω of Revelation 1:7 is diametrically the opposite of the chiliasts. The country of Israel and her present inhabitants have no eschatological role to fulfil at the consummation. Openbaring 1:7 dui op ’n geantisipeerde finale verskyning van Jesus met die voleinding. Hierdie κηρύσσω het uit die Joodse laat-apokaliptiese eskatologie ontwikkel. Die apokaliptiese eindtyd het met Jesus se opstanding plaasgevind en die Nuwe-Testamentiese hede is dus alreeds die eindtyd. Die voleinding is egter nog in die toekoms. Jesus se verskyning met sy opstanding is ’n metafoor vir sy koms by die voleinding. Hy sal liggaamlik verskyn. Die skrywer bemoedig die gemarginaliseerde tweede generasie Christene. Die Romeinse keiser is nie die oorwinnaar nie − Jesus is die axis mundi van God se finale plan vir sy skepping. Die finale verskyning van Jesus sal vir die gelowiges ewige verlossing bewerk, maar die ongelowiges sal in rou gedompel word. Die κηρύσσω van Openbaring 1:7 is die teenoorgestelde van die standpunt van die chiliasme. Die land en huidige volk van Israel vervul geen eskatologiese rol by die voleinding nie.

  11. Involvement of trigeminal ganglionic Nav 1.7 in hyperalgesia of inflamed temporomandibular joint is dependent on ERK1/2 phosphorylation of glial cells in rats.

    Science.gov (United States)

    Bi, R-Y; Kou, X-X; Meng, Z; Wang, X-D; Ding, Y; Gan, Y-H

    2013-08-01

    Inflammation is a major cause of temporomandibular disorder-related pain. The Nav 1.7 sodium channel has a critical function in pain perceptions. However, whether and how Nav 1.7 in the trigeminal ganglion is involved in temporomandibular joint (TMJ) inflammatory pain remains to be examined. TMJ inflammation was induced by complete Freund's adjuvant in female rats. The expression of trigeminal ganglionic Nav 1.7 and other sodium channels was examined using real-time polymerase chain reaction or Western blotting. Immunohistofluorescence with fluorescent retrograde neuronal tracer DiI was used to confirm Nav 1.7 in the trigeminal neurons innervating TMJ. The functions of trigeminal ganglionic Nav 1.7 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were blocked with the microinjection of the Nav 1.7 antibody or U0126 into the trigeminal ganglion. Head withdrawal threshold and food intake was measured to evaluate TMJ nociceptive responses. TMJ inflammation significantly up-regulated Nav 1.7 mRNA and protein; however, the mRNA of Nav 1.3 was not affected and those of Nav 1.8 and Nav 1.9 were only slightly up-regulated. TMJ inflammation specifically induced Nav 1.7 in the neurons innervating TMJ. In addition, blocking the Nav 1.7 function significantly attenuated the hyperalgesia of the inflamed TMJ. Moreover, TMJ inflammation up-regulated ERK1/2 phosphorylation only in the glials; blocking ERK1/2 phosphorylation in the glials blocked Nav 1.7 up-regulation in the neurons and correspondingly attenuated the hyperalgesia of the inflamed TMJ. Trigeminal ganglionic Nav 1.7 has an important function in the hyperalgesia of the inflamed TMJ, which is dependent on the communication with the satellite glials. © 2012 European Federation of International Association for the Study of Pain Chapters.

  12. Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn

    Directory of Open Access Journals (Sweden)

    Black Joel A

    2012-11-01

    Full Text Available Abstract Background Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn. Results Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF, exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals. Conclusions The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.

  13. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-05-23

    The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.

  14. Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia

    Science.gov (United States)

    Koenig, Jennifer; Werdehausen, Robert; Linley, John E.; Habib, Abdella M.; Vernon, Jeffrey; Lolignier, Stephane; Eijkelkamp, Niels; Zhao, Jing; Okorokov, Andrei L.; Woods, C. Geoffrey; Wood, John N.; Cox, James J.

    2015-01-01

    The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conserved in humans and mice. The NAT has a similar tissue expression pattern to the sense gene and is alternatively spliced within dorsal root ganglia. The human and mouse NATs exist in cis with the sense gene in a tail-to-tail orientation and both share sequences that are complementary to the terminal exon of SCN9A/Scn9a. Overexpression analyses of the human NAT in human embryonic kidney (HEK293A) and human neuroblastoma (SH-SY5Y) cell lines show that it can function to downregulate Nav1.7 mRNA, protein levels and currents. The NAT may play an important role in regulating human pain thresholds and is a potential candidate gene for individuals with chronic pain disorders that map to the SCN9A locus, such as Inherited Primary Erythromelalgia, Paroxysmal Extreme Pain Disorder and Painful Small Fibre Neuropathy, but who do not contain mutations in the sense gene. Our results strongly suggest the SCN9A NAT as a prime candidate for new therapies based upon augmentation of existing antisense RNAs in the treatment of chronic pain conditions in man. PMID:26035178

  15. 1,7-Bis-(N,N-dialkylaminoperylene Bisimides: Facile Synthesis and Characterization as Near-Infrared Fluorescent Dyes

    Directory of Open Access Journals (Sweden)

    Kew-Yu Chen

    2014-11-01

    Full Text Available Three symmetric alkylamino-substituted perylene bisimides with different n-alkyl chain lengths (n = 6, 12, or 18, 1,7-bis-(N,N-dialkylaminoperylene bisimides (1a–1c, were synthesized under mild condition and were characterized by 1H NMR, 13C NMR and high resolution mass spectroscopy. Their optical and electrochemical properties were measured using UV-Vis and emission spectroscopic techniques as well as cyclic voltammetry (CV. These compounds show deep green color in both solution and solid state, and are highly soluble in dichloromethane and even in nonpolar solvents such as hexane. The shapes of the absorption spectra of 1a–1c in the solution and solid state were found to be almost the same, indicating that the long alkyl chains could efficiently prevent intermolecular contact and aggregation. They show a unique charge transfer emission in the near-infrared region, of which the peak wavelengths exhibit strong solvatochromism. The dipole moments of the molecules have been estimated using the Lippert–Mataga equation, and upon excitation, they show larger dipole moment changes than that of 1,7-diaminoperylene bisimide (2. Moreover, all the dyes exhibit two irreversible one-electron oxidations and two quasi-reversible one-electron reductions in dichloromethane at modest potentials. Complementary density functional theory calculations performed on these chromophores are reported in order to rationalize their electronic structure and optical properties.

  16. Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: Synthesis, characterization and anticancer activity.

    Science.gov (United States)

    Coskun, Demet; Erkisa, Merve; Ulukaya, Engin; Coskun, Mehmet Fatih; Ari, Ferda

    2017-08-18

    Cancer treatment still requires new compounds to be discovered. Chalcone and its derivatives exhibit anticancer potential in different cancer cells. A new series of benzofuran substituted chalcone derivatives was synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(7-ethoxy-1-benzofuran-2-yl) ethanone with different aromatic aldehydes to yield 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives 3a-j. The derivatives were characterized by elemental analysis, FT-IR, (1)H NMR and (13)C NMR spectroscopy techniques. The anti-growth effect of chalcone compounds was tested in breast cancer (MCF-7), non-small cell lung cancer (A549) and prostate cancer (PC-3) cell lines by the SRB and ATP cell viability assays. Apoptosis was detected by mitochondrial membrane potential, Annexin V staining and caspase 3/7 activity. Formation of reactive oxygen species was determined by DCFDA. The results revealed that chalcone derivatives have anticancer activity with especially chalcone derivative 3a showing cytotoxic effects on cancer cells. In addition, chalcone derivative 3a induced apoptosis through caspase dependent pathways in prostate, lung and breast cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

    Science.gov (United States)

    Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

    2014-02-07

    Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

  18. Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the population of doublecortin positive cells within the dentate gyrus and the piriform cortex.

    Science.gov (United States)

    Freund, M; Walther, T; von Bohlen Und Halbach, O

    2014-02-01

    Aside from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a G protein-coupled receptor being essential for angiotensin-(1-7) signaling. Mas is not only expressed in the periphery but also within the brain, e.g. in the dentate gyrus (DG) and the piriform cortex (PC). Since the DG is capable of adult neurogenesis, we examined the impact of a deletion of Mas upon adult neurogenesis. Deletion of Mas did not alter cell proliferation in the adult DG (as monitored with phosphohistone H3) and did not alter cell death (as monitored with activated Caspase 3). However, Mas deficiency resulted in an increase in the number of doublecortin (DCX) positive cells, indicating that lack of Mas increases the number of this cell population. Concerning the PC, it is discussed whether adult neurogenesis occurs under physiological conditions in this area. We could demonstrate that Mas deficiency has an impact on cell division and on the population of DCX-positive cells within the PC. Since Mas is not expressed before birth within the brain, our data may suggest that adult hippocampal neurogenesis and neurogenesis occurring during prenatal development share several common mechanisms, but are, at least in part, differentially regulated. Moreover, since deficiency for Mas increases the numbers of DCX-positive young neurons, blockage of Mas might be beneficial in stimulating neurogenesis in adults. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  19. Reduction of thermal conductivity in MnSi{sub 1.7} multi-layered thin films with artificially inserted Si interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Y., E-mail: yosuke.kurosaki.uy@hitachi.com; Yabuuchi, S.; Nishide, A.; Fukatani, N.; Hayakawa, J. [Center for Exploratory Research, Research & Development Group, Hitachi Ltd., 1-280, Higashi-koigakubo, Kokubunji, Tokyo 185-8601 (Japan)

    2016-08-08

    We report a lowered lattice thermal conductivity in nm-scale MnSi{sub 1.7}/Si multilayers which were fabricated by controlling thermal diffusions of Mn and Si atoms. The thickness of the constituent layers is 1.5–5.0 nm, which is comparable to the phonon mean free path of both MnSi{sub 1.7} and Si. By applying the above nanostructures, we reduced the lattice thermal conductivity down to half that of bulk MnSi{sub 1.7}/Si composite materials. The obtained value of 1.0 W/K m is the experimentally observed minimum in MnSi{sub 1.7}-based materials without any heavy element doping and close to the minimum thermal conductivity. We attribute the reduced lattice thermal conductivity to phonon scattering at the MnSi{sub 1.7}/Si interfaces in the multilayers.

  20. Temporal and spatial variations of the absolute reflectivity of Jupiter and Saturn from 0.38 to 1.7 μm with PlanetCam-UPV/EHU

    Science.gov (United States)

    Mendikoa, I.; Sánchez-Lavega, A.; Pérez-Hoyos, S.; Hueso, R.; Rojas, J. F.; López-Santiago, J.

    2017-11-01

    Aims: We provide measurements of the absolute reflectivity of Jupiter and Saturn along their central meridians in filters covering a wide range of visible and near-infrared wavelengths (from 0.38 to 1.7 μm) that are not often presented in the literature. We also give measurements of the geometric albedo of both planets and discuss the limb-darkening behavior and temporal variability of their reflectivity values for a period of four years (2012-2016). Methods: This work is based on observations with the PlanetCam-UPV/EHU instrument at the 1.23 m and 2.2 m telescopes in Calar Alto Observatory (Spain). The instrument simultaneously observes in two channels: visible (VIS; 0.38-1.0 μm) and short-wave infrared (SWIR; 1.0-1.7 μm). We obtained high-resolution observations via the lucky-imaging method. Results: We show that our calibration is consistent with previous independent determinations of reflectivity values of these planets and, for future reference, provide new data extended in the wavelength range and in the time. Our results have an uncertainty in absolute calibration of 10-20%. We show that under the hypothesis of constant geometric albedo, we are able to detect absolute reflectivity changes related to planetary temporal evolution of about 5-10%. Tables A.1-A.4 and B.1-B.8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/607/A72

  1. MAS-mediated antioxidant effects restore the functionality of angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis in diabetic rat carotid.

    Science.gov (United States)

    Pernomian, Larissa; Gomes, Mayara Santos; Restini, Carolina Baraldi Araujo; de Oliveira, Ana Maria

    2014-01-01

    We hypothesized that endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species during type I-diabetes impairs carotid ACE2-angiotensin-(1-7)-Mas axis functionality, which accounts for the impaired carotid flow in diabetic rats. We also hypothesized that angiotensin-(1-7) chronic treatment of diabetic rats restores carotid ACE2-angiotensin-(1-7)-Mas axis functionality and carotid flow. Relaxant curves for angiotensin II or angiotensin-(1-7) were obtained in carotid from streptozotocin-induced diabetic rats. Superoxide or hydrogen peroxide levels were measured by flow cytometry in carotid endothelial cells. Carotid flow was also determined. We found that endothelial AT1-activated NAD(P)H oxidase-driven generation of superoxide and hydrogen peroxide in diabetic rat carotid impairs ACE2-angiotensin-(1-7)-Mas axis functionality, which reduces carotid flow. In this mechanism, hydrogen peroxide derived from superoxide dismutation inhibits ACE2 activity in generating angiotensin-(1-7) seemingly by activating I(Cl,SWELL0, while superoxide inhibits the nitrergic Mas-mediated vasorelaxation evoked by angiotensin-(1-7). Angiotensin-(1-7) treatment of diabetic rats restored carotid ACE2-angiotensin-(1-7)-Mas axis functionality by triggering a positive feedback played by endothelial Mas receptors, that blunts endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species. Mas-mediated antioxidant effects also restored diabetic rat carotid flow, pointing to the contribution of ACE2-angiotensin-(1-7)-Mas axis in maintaining carotid flow.

  2. Femoral morphology and epiphyseal growth plate changes of the hip during maturation: MR assessments in a 1-year follow-up on a cross-sectional asymptomatic cohort in the age range of 9-17 years

    Energy Technology Data Exchange (ETDEWEB)

    Kienle, Karl-Philipp [University of Bern, Department of Orthopedic Surgery, Bern (Switzerland); University of Bern, Inselspital, Bern, Department of Orthopaedic Surgery, Erlangen (Germany); Keck, Johannes; Siebenrock, Klaus-Arno; Mamisch, Tallal Charles [University of Bern, Department of Orthopedic Surgery, Bern (Switzerland); Werlen, Stefan [Department of Radiology, Sonnenhof Clinic, Bern (Switzerland); Kim, Young-Jo [Harvard Medical School, Department of Orthopaedic Surgery, Children' s Hospital, Boston, MA (United States)

    2012-11-15

    The goal of this prospective study was to characterize the morphology and physeal changes of the femoral head during maturation using MRI in a population-based group of asymptomatic volunteers. Sixty-four pupils (127 hips) of 331 pupils from a primary and high school were asked to take part in this study and were willing to participate. 3T MRI of the hip was obtained at baseline and 1-year follow-up. With these images, we analyzed the femoral morphology and epiphyseal changes related to age, status of the physis, and location on the femur. The radius of the femoral head and neck increased with age, as expected, (p < 0.001). The epiphyseal extension increased significantly with age (p < 0.05), but epiphyseal tilt and alpha angle showed no differences (p > 0.05). Building groups by using the epiphyseal status, we found that the epiphyseal extension had the highest changes in the ''open'' group and almost stopped in the ''closed'' group. The tilt angle did not change significantly (p > 0.05). Significant smaller alpha-angles were found in the ''closed'' group, however, these were in a normal range in all of them. Correlated to the position, the highest alpha-angle values were located in anterior-superior and superior-anterior position. Our data can be used as normative values, which can be compared to patients or cohorts with certain risk factors (e.g., professional athletes), this will offer the chance to detect and understand pathological changes. (orig.)

  3. ZP2307, a novel cyclic PTH(1-17) analog, reversed established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Vääräniemi, Jukka; Morko, Jukka; Peng, ZhiQi

    -17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized at 6 months of age. After 6 weeks......Recombinant human parathyroid hormone (PTH) analogs (1-34) and (1-84) are used as bone anabolic agents in clinical practice. Hitherto, PTH analogs shorter than 28 amino acids have not demonstrated any bone anabolic activity in vivo. Recently, Zealand Pharma A/S has developed a novel, cyclic PTH(1......-34). This study demonstrated that the intermittent treatment with ZP2307, the novel cyclic PTH(1-17) analog, is effective in reversing the established osteopenia in adult OVX rats to normal conditions. Due to its broad dose response relationship, ZP2307 may have a wider therapeutic window and a better safety...

  4. Imaging of the human choroid with a 1.7 MHz A-scan rate FDML swept source OCT system

    Science.gov (United States)

    Gorczynska, I.; Migacz, J. V.; Jonnal, R.; Zawadzki, R. J.; Poddar, R.; Werner, J. S.

    2017-02-01

    We demonstrate OCT angiography (OCTA) and Doppler OCT imaging of the choroid in the eyes of two healthy volunteers and in a geographic atrophy case. We show that visualization of specific choroidal layers requires selection of appropriate OCTA methods. We investigate how imaging speed, B-scan averaging and scanning density influence visualization of various choroidal vessels. We introduce spatial power spectrum analysis of OCT en face angiographic projections as a method of quantitative analysis of choroicapillaris morphology. We explore the possibility of Doppler OCT imaging to provide information about directionality of blood flow in choroidal vessels. To achieve these goals, we have developed OCT systems utilizing an FDML laser operating at 1.7 MHz sweep rate, at 1060 nm center wavelength, and with 7.5 μm axial imaging resolution. A correlation mapping OCA method was implemented for visualization of the vessels. Joint Spectral and Time domain OCT (STdOCT) technique was used for Doppler OCT imaging.

  5. A 128 x 128 InGaAs detector array for 1.0 - 1.7 microns

    Science.gov (United States)

    Olsen, G.; Joshi, A.; Lange, M.; Woodruff, K.; Mykietyn, E.; Gay, D.; Ackley, D.; Erickson, G.; Ban, V.; Staller, C.

    1990-01-01

    A two-dimensional 128 x 128 detector array for the 1.0 - 1.7 micron spectral region has been demonstrated with indium gallium arsenide. The 30 micron square pixels had 60 micron spacing in both directions and were designed to be compatible with a 2D Reticon multiplexer. Dark currents below 100 pA, capacitance near 0.1 pF, and quantum efficiencies above 80 percent were measured. Probe maps of dark current and quantum efficiency are presented along with pixel dropout data and wafer yield which was as high as 99.89 percent (7 dropouts) in an area of 6528 pixels and 99.37 percent (103 dropouts) over an entire 128 x 128 pixel region.

  6. The nonpeptide ANG-(1-7) mimic AVE 0991 attenuates cardiac remodeling and improves baroreflex sensitivity in renovascular hypertensive rats.

    Science.gov (United States)

    Cunha, Thelma Maria Bedeti; Lima, Wanderson Geraldo; Silva, Marcelo Eustáquio; Souza Santos, Robson Augusto; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho

    2013-03-12

    The nonpeptide Ang-(1-7) analog, AVE 0991, is recognized as having beneficial cardiovascular effects similar to those induced by Ang-(1-7). In this study, we evaluated the effects of AVE 0991 on cardiovascular functions and on cardiac and renal remodeling in rats with 2K1C renovascular hypertension. Fisher rats underwent surgery to induce 2K1C renovascular hypertension and were then treated with AVE 0991 (1 or 3mg/kg) for 28days. At the end of treatment, the blood pressure (BP), heart rate (HR), and baroreflex sensitivity were evaluated, in conscious animals. The rats were then euthanized and the heart and kidneys removed for subsequent histological analysis. Treatment with AVE 0991 in 2K1C rats restored the baroreflex sensitivity of both bradycardic and tachycardic components to levels comparable to those of normotensive SHAM rats. At a higher dose (3mg/kg), AVE 0991 was also anti-hypertensive in 2K1C rats. Furthermore, AVE 0991 reduced the heart weight, thickness of myocardial fibers, number of inflammatory cells, and area of collagen deposition in the hearts of 2K1C rats compared to SHAM rats. The inflammatory process and tissue area of collagen deposition were decreased in the clipped kidney of AVE 0091-treated 2K1C rats. Our data showed that oral treatment with AVE 0991 reduces blood-pressure cardiac remodeling and improves baroreflex sensitivity in 2K1C renovascular hypertensive rats. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable

    Directory of Open Access Journals (Sweden)

    Tyrrell Lynda

    2008-09-01

    Full Text Available Abstract Background Paroxysmal extreme pain disorder (PEPD is an autosomal dominant painful neuropathy with many, but not all, cases linked to gain-of-function mutations in SCN9A which encodes voltage-gated sodium channel Nav1.7. Severe pain episodes and skin flushing start in infancy and are induced by perianal probing or bowl movement, and pain progresses to ocular and mandibular areas with age. Carbamazepine has been effective in relieving symptoms, while other drugs including other anti-epileptics are less effective. Results Sequencing of SCN9A coding exons from an English patient, diagnosed with PEPD, has identified a methionine 1627 to lysine (M1627K substitution in the linker joining segments S4 and S5 in domain IV. We confirm that M1627K depolarizes the voltage-dependence of fast-inactivation without substantially altering activation or slow-inactivation, and inactivates from the open state with slower kinetics. We show here that M1627K does not alter development of closed-state inactivation, and that M1627K channels recover from fast-inactivation faster than wild type channels, and produce larger currents in response to a slow ramp stimulus. Using current-clamp recordings, we also show that the M1627K mutant channel reduces the threshold for single action potentials in DRG neurons and increases the number of action potentials in response to graded stimuli. Conclusion M1627K mutation was previously identified in a sporadic case of PEPD from France, and we now report it in an English family. We confirm the initial characterization of mutant M1627K effect on fast-inactivation of Nav1.7 and extend the analysis to other gating properties of the channel. We also show that M1627K mutant channels render DRG neurons hyperexcitable. Our new data provide a link between altered channel biophysics and pain in PEPD patients.

  8. Final Environmental Assessment Eglin Gulf Test and Training Range (EGTTR) Precision Strike Weapons (PSW) Test (5-Year Plan) Eglin Air Force Base, Florida

    Science.gov (United States)

    2005-11-01

    Rachycentridae Cobia Sciaenidae Drums Sphymidae Hammerhead sharks Tropical Sphyraenidae Barracudas Fishes of the eastern Gulf can be characterized by...Dusky shark Carcharinus obscurus C One of the larger shark species of continental shelf waters; occurs in Atlantic and Pacific. Feeds on fish...other sharks , rays, squid, octopus, and starfish. Sand tiger shark Odontaspis taurus C In North America, the sand tiger ranges from the Gulf of

  9. Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7.

    Science.gov (United States)

    Kalman, K; Nguyen, A; Tseng-Crank, J; Dukes, I D; Chandy, G; Hustad, C M; Copeland, N G; Jenkins, N A; Mohrenweiser, H; Brandriff, B; Cahalan, M; Gutman, G A; Chandy, K G

    1998-03-06

    We report the isolation of a novel mouse voltage-gated Shaker-related K+ channel gene, Kv1.7 (Kcna7/KCNA7). Unlike other known Kv1 family genes that have intronless coding regions, the protein-coding region of Kv1.7 is interrupted by a 1.9-kilobase pair intron. The Kv1.7 gene and the related Kv3.3 (Kcnc3/KCNC3) gene map to mouse chromosome 7 and human chromosome 19q13.3, a region that has been suggested to contain a diabetic susceptibility locus. The mouse Kv1.7 channel is voltage-dependent and rapidly inactivating, exhibits cumulative inactivation, and has a single channel conductance of 21 pS. It is potently blocked by noxiustoxin and stichodactylatoxin, and is insensitive to tetraethylammonium, kaliotoxin, and charybdotoxin. Northern blot analysis reveals approximately 3-kilobase pair Kv1.7 transcripts in mouse heart and skeletal muscle. In situ hybridization demonstrates the presence of Kv1.7 in mouse pancreatic islet cells. Kv1.7 was also isolated from mouse brain and hamster insulinoma cells by polymerase chain reaction.

  10. Expression and significance of classical ACE-AngII-AT1 axis and new ACE2-Ang (1-7-Mas axis of renin-angiotensin system in local pancreas

    Directory of Open Access Journals (Sweden)

    LIU Xiaoya

    2015-09-01

    Full Text Available The renin-angiotensin system (RAS is a classical circulating enzyme pathway that plays an important role in regulation of pancreatic function. In recent years, with deepening understanding of RAS, researchers found that RAS not only includes the classical ACE-Ang II-AT1 axis, but also includes the new ACE2-Ang (1-7-Mas axis. Extensive studies have confirmed that the ACE2-Ang (1-7-Mas axis can antagonize the effect of the ACE-Ang II-AT1 axis. This paper reviews the composition and function of both axes of the RAS in the local pancreas, and also presents the comparison between the two axes.

  11. Effects of female sex hormones on expression of the Ang-(1-7)/Mas-R/nNOS pathways in rat brain.

    Science.gov (United States)

    Cheng, Yuan; Li, Qiaoying; Zhang, Yidan; Wen, Quan; Zhao, Jianjun

    2015-11-01

    Female sex hormones are considered to reduce the risk of ischemic stroke. As a part of the renin-angiotensin system, angiotensin-(1-7) [Ang-(1-7)] has recently been reported to play a role in protecting neuronal tissues from ischemic stroke. Thus, we examined the effects of female sex hormones on the levels of Ang-(1-7) and its downstream pathways in the brain. Female rats were ovariectomized and 17β-estradiol (17β-EST), progesterone (PGR), or a combination of 17β-EST plus PGR were administered. Our data demonstrated that lack of female sex hormones significantly decreased the levels of Ang-(1-7) in the cerebral cortex and hippocampal CA1 area. Also, we observed a linear relationship between cortex levels of Ang-(1-7) and plasma brain natriuretic peptide levels (as an indicator for risk of ischemic stroke). We further showed that lack of female sex hormones decreased the expression of Ang-(1-7), Mas-receptor (Mas-R), and neuronal nitric oxide synthase (nNOS). Overall, our findings show for the first time that Ang-(1-7) and Mas-R/nNOS in the cortex are influenced by circulating 17β-EST and (or) PGR, whereas Ang-(1-7) and its pathways in the hippocampal CA1 area are primarily altered by 17β-EST. This suggests that female sex hormones play a role in regulating the expression of Ang-(1-7) and its pathways during ischemic brain injuries.

  12. Effects of ranolazine on wild-type and mutant hNav1.7 channels and on DRG neuron excitability

    Directory of Open Access Journals (Sweden)

    Estacion Mark

    2010-06-01

    Full Text Available Abstract Background A direct role of sodium channels in pain has recently been confirmed by establishing a monogenic link between SCN9A, the gene which encodes sodium channel Nav1.7, and pain disorders in humans, with gain-of-function mutations causing severe pain syndromes, and loss-of-function mutations causing congenital indifference to pain. Expression of sodium channel Nav1.8 in DRG neurons has also been shown to be essential for the manifestation of mutant Nav1.7-induced neuronal hyperexcitability. These findings have confirmed key roles of Nav1.7 and Nav1.8 in pain and identify these channels as novel targets for pain therapeutic development. Ranolazine preferentially blocks cardiac late sodium currents at concentrations that do not significantly reduce peak sodium current. Ranolazine also blocks wild-type Nav1.7 and Nav1.8 channels in a use-dependent manner. However, ranolazine's effects on gain-of-function mutations of Nav1.7 and on DRG neuron excitability have not been investigated. We used voltage- and current-clamp recordings to evaluate the hypothesis that ranolazine may be effective in regulating Nav1.7-induced DRG neuron hyperexcitability. Results We show that ranolazine produces comparable block of peak and ramp currents of wild-type Nav1.7 and mutant Nav1.7 channels linked to Inherited Erythromelalgia and Paroxysmal Extreme Pain Disorder. We also show that ranolazine, at a clinically-relevant concentration, blocks high-frequency firing of DRG neurons expressing wild-type but not mutant channels. Conclusions Our data suggest that ranalozine can attenuate hyperexcitability of DRG neurons over-expressing wild-type Nav1.7 channels, as occurs in acquired neuropathic and inflammatory pain, and thus merits further study as an alternative to existing non-selective sodium channel blockers.

  13. Anthropometric Characteristics, Physical Fitness and Motor Coordination of 9 to 11 Year Old Children Participating in a Wide Range of Sports

    NARCIS (Netherlands)

    Opstoel, Katrijn; Pion, Johan; Elferink-Gemser, Marije; Hartman, Esther; Willemse, Bas; Philippaerts, Renaat; Visscher, Chris; Lenoir, Matthieu

    2015-01-01

    Objectives The aim of this study was to investigate to what extent 9 to 11 year old children participating in a specific sport already exhibit a specific anthropometric, physical fitness and motor coordination profile, in line with the requirements of that particular sport. In addition, the profiles

  14. Isoprene levels in the exhaled breath of 200 healthy pupils within the age range 7-18 years studied using SIFT-MS

    Czech Academy of Sciences Publication Activity Database

    Smith, D.; Španěl, Patrik; Enderby, B.; Lenney, W.; Turner, C.; Davies, S. J.

    2010-01-01

    Roč. 4, č. 1 (2010), 017101 ISSN 1752-7155 Institutional research plan: CEZ:AV0Z40400503 Keywords : SIFT-MS * mass spectroscopy * isoprene Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.828, year: 2010

  15. Production of Short-Rotation Woody Crops Grown with a Range of Nutrient and Water Availability: Establishment Report and First-Year Responses

    Science.gov (United States)

    Mark D. Coleman; David R. Coyle; J. Blake; Kerry O. Britton; M. Buford; R.G. Campbell; J. Cox; B. Cregg; D. Daniels; M. Jacobson; Kurt Johnsen; Timothy McDonald; K. McLeod; E. Nelson; D. Robison; R. Rummer; F. Sanchez; John A. Stanturf; B. Stokes; Carl Trettin; J. Tuskan; L. Wright; S. Wullschleger

    2004-01-01

    Many researchers have studied the productivity potential of intensively managed forest plantations. However, we need to learn more about the effects of fundamental growth processes on forest productivity; especially the influence of above- and belowground resource acquisition and allocation. This report presents installation, establishment, and first-year results of...

  16. Pembingkaian Berita Pada Media Lokal (Analisis Framing Pemberitaan Calon Bupati Malang Pada Harian Radar Malang Tanggal 1-7 Oktober 2015

    Directory of Open Access Journals (Sweden)

    Rahadi Rahadi

    2017-01-01

    Full Text Available This research were focused on the news in the newspapers Radar Malang, about construction news regent and deputy regent candidate Malang October 1-7, 2015. There were three candidates for the election of the Regent and Vice Regent 2015-202 period, namely: the candidate regent Malang; (1 Nurcholis Muhammad Mufid of independent elements, (2 Renda Krishna and M Sanusi of coalition Madep Manteb Mantep (PKB, NasDem, Golkar, Gerindra, Democrat, (3 Dewanti Rumpoko and Masrifah Hadi from PDIP. Researchers used the theory of hierarchy levels to understand, how the framing of information on the three pairs of candidates. In this study, researchers used the analytical model and the framing of Zhongdang Pan Geraald Konsicki. The model uses four structural framing is Syntactically, Scripts, Thematic and Rhetoric.Based on study results, the news displayed by Radar Malang less balanced. This is evident from the Renda Krishna as the incumbent is given the space and the number of reports that more than any other potential mates. And their special news column titled Coming 5 Years Madep Manteb. Plus on the first page is kept up Radar Malang given space to direct the reader linked to column 5 Years Ahead Madep Manteb along with the headline raised. Associated with the theory of hierarchy levels, from internal factors, namely the level of the organizational level, and the level of media routines is clear that extremely pro Radar Malang Renda Krishna. This is evidenced by the news that tends to be positive.

  17. Intrarenal Mas and AT1 receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats.

    Science.gov (United States)

    O'Neill, Julie; Healy, Vincent; Johns, Edward J

    2017-09-21

    What is the central question of this study? Dietary sodium manipulation alters the magnitude of angiotensin-(1-7) [Ang-(1-7)]-induced natriuresis. The present study sought to determine whether this was related to relative changes in the activity of intrarenal Mas and/or AT1 receptors. What is the main finding and its importance? Angiotensin-(1-7)-induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT1 receptor blockade also had an inhibitory effect on Ang-(1-7)-induced natriuresis and diuresis. Thus, Ang-(1-7)-induced increases in sodium and water excretion are dependent upon functional Mas and AT1 receptors. We investigated whether angiotensin-(1-7) [Ang-(1-7)]-induced renal haemodynamic and excretory actions were solely dependent upon intrarenal Mas receptor activation or required functional angiotensin II type 1 (AT1 ) receptors. The renin-angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin-(1-7) and AT1 and Mas receptor antagonists were infused into the kidney at the corticomedullary border. Mas receptor expression was measured in the kidney. Mean arterial pressure, urine flow and fractional sodium excretion were 93 ± 4 mmHg, 46.1 ± 15.7 μl min(-1)  kg(-1) and 1.4 ± 0.3%, respectively, in the normal-sodium group and 91 ± 2 mmHg, 19.1 ± 3.3 μl min(-1)  kg(-1) and 0.7 ± 0.2%, respectively, in the low-sodium group. Angiotensin-(1-7) infusion had no effect on mean arterial pressure in rats receiving a normal-sodium diet but decreased it by 4 ± 5% in rats receiving a low-sodium diet (P Mas receptor inhibition after either losartan or A-779, respectively. Thus, AT1 receptor activation, as well as Mas receptor activation, plays an essential role in mediating Ang-(1-7)-induced natriuresis and diuresis. Whether this is because Ang-(1-7) partly antagonizes AT1 receptors or whether Ang-(1-7)-induced natriuresis is mediated through AT1 -Mas receptor dimerization remains unclear. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  18. Microstructure and Mechanical Properties of Mg-1.7Y-1.2Zn Sheet Processed by Hot Rolling and Friction Stir Processing

    Science.gov (United States)

    Jain, V.; Su, J. Q.; Mishra, R. S.; Verma, R.; Javaid, A.; Aljarrah, M.; Essadiqi, E.

    The use of lightweight structural materials is an integral part of mass reduction strategy in transportation applications. Magnesium based sheet products have gained significant interest in the automobile industry. Newer magnesium alloys such as Mg-Y-Zn have potential to develop sheet products with superior mechanical properties owing to improved precipitation hardening response. In the present work, rolled sheet of an Mg-1.7Y-1.2Zn alloy containing small amounts of Al and Ce was investigated. Microstructure and mechanical properties were examined in as-rolled, rolled+aged, friction stir processed (FSP) and FSP+aged conditions. Mechanical properties (YS, UTS and %El) of the sheet showed certain anisotropy in rolling and transverse directions, which was marginally reduced upon ageing. However, FSP led to a significant range of mechanical properties depending on the test direction. Ageing of the FSP sheet showed improvement in mechanical properties and reduced anisotropy in the two directions. The static recrystallization due to ageing caused reduced anisotropy in FSP treated sheet. The overall strength-ductility variation is discussed in terms of relative contributions of grain boundary strengthening, texture and precipitation strengthening.

  19. Home range size and breeding dispersal of a common buzzard (Buteo buteo

    Directory of Open Access Journals (Sweden)

    Väli Ülo

    2017-12-01

    Full Text Available Telemetric studies have provided ample information on threatened raptors, but still little is known about space use and dispersal of common species. Here I describe the home range and breeding dispersal of a GPS-tracked adult male common buzzard, studied in south-eastern Estonia in 2014–16. This buzzard’s home range covered 8.3 km2 (kernel 95% estimate with the core range being 2.1 km2 (kernel 50%. The home range increased in the course of the breeding season but decreased again before migration. Surprisingly, the nests in the two successive breeding years were located in the opposite margins of the home range, 1.7 km from each other.

  20. Angiotensin-(1-7) stimulates high atrial pacing-induced ANP secretion via Mas/PI3-kinase/Akt axis and Na+/H+ exchanger.

    Science.gov (United States)

    Shah, Amin; Gul, Rukhsana; Yuan, Kuichang; Gao, Shan; Oh, Young-Bin; Kim, Uh-Hyun; Kim, Suhn Hee

    2010-05-01

    Angiotensin-(1-7) [ANG-(1-7)], one of the bioactive peptides produced in the renin-angiotensin system, plays a pivotal role in cardiovascular physiology by providing a counterbalance to the function of ANG II. Recently, it has been considered as a potential candidate for therapeutic use in the treatment of various types of cardiovascular diseases. The aim of the present study is to explain the modulatory role of ANG-(1-7) in atrial natriuretic peptide (ANP) secretion and investigate the functional relationship between two peptides to induce cardiovascular effects using isolated perfused beating rat atria and a cardiac hypertrophied rat model. ANG-(1-7) (0.01, 0.1, and 1 muM) increased ANP secretion and ANP concentration in a dose-dependent manner at high atrial pacing (6.0 Hz) with increased cGMP production. However, at low atrial pacing (1.2 Hz), ANG-(1-7) did not cause changes in atrial parameters. Pretreatment with an antagonist of the Mas receptor or with inhibitors of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), or nitric oxide synthase blocked the augmentation of high atrial pacing-induced ANP secretion by ANG-(1-7). A similar result was observed with the inhibition of the Na(+)/H(+) exchanger-1 and Ca(2+)/calmodulin-dependent kinase II (CaMKII). ANG-(1-7) did not show basal intracellular Ca(2+) signaling in quiescent atrial myocytes. In an in vivo study using an isoproterenol-induced cardiac hypertrophy animal model, an acute infusion of ANG-(1-7) increased the plasma concentration of ANP by twofold without changes in blood pressure and heart rate. A chronic administration of ANG-(1-7) increased the plasma ANP level and attenuated isoproterenol-induced cardiac hypertrophy. The antihypertrophic effect was abrogated by a cotreatment with the natriuretic peptide receptor-A antagonist. These results suggest that 1) ANG-(1-7) increased ANP secretion at high atrial pacing via the Mas/PI3K/Akt pathway and the activation of Na(+)/H(+) exchanger-1 and CaMKII and 2) ANG-(1-7) decreased cardiac hypertrophy which might be mediated by ANP.

  1. Angiotensin-(1-7 Prevents Skeletal Muscle Atrophy Induced by Transforming Growth Factor Type Beta (TGF-β via Mas Receptor Activation

    Directory of Open Access Journals (Sweden)

    Johanna Ábrigo

    2016-11-01

    Full Text Available Background: Transforming growth factor type beta 1 (TGF-β1 produces skeletal muscle atrophy. Angiotensin-(1-7 (Ang-(1-7, through the Mas receptor, prevents the skeletal muscle atrophy induced by sepsis, immobilization, or angiotensin II (Ang-II. However, the effect of Ang-(1-7 on muscle wasting induced by TGF-β1 is unknown. Aim: To evaluate whether Ang-(1-7/Mas receptor axis could prevent the skeletal muscle atrophy induced by TGF-β1. Methods: This study assessed the atrophic effect of TGF-β1 in C2C12 myotubes and mice in absence or presence of Ang-(1-7, and the receptor participation using A779, an antagonist of the Mas receptor. The levels of myosin heavy chain (MHC, polyubiquitination, and MuRF-1 were detected by western blot. Myotube diameter was also evaluated. In vivo analysis included the muscle strength, fibre diameter, MHC and MuRF-1 levels by western blot, and ROS levels by DCF probe detection. Results: The results showed that Ang-(1-7 prevented the increase in MuRF-1 and polyubiquitined protein levels, the decrease of MHC levels, the myotubes/fibre diameter diminution, and the increased production of reactive oxygen species (ROS induced by TGF-β1. Utilizing A779 inhibited the anti-atrophic effect of Ang-(1-7. Conclusion: The preventive effect of Ang-(1-7 on skeletal muscle atrophy induced by TGF-β1 is produced through inhibition of ROS production and proteasomal degradation of MHC.

  2. Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain.

  3. Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

    Science.gov (United States)

    Wang, Ying; Mi, Jianxun; Lu, Ka; Lu, Yanxin; Wang, KeWei

    2015-01-01

    Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain. PMID:26068619

  4. Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

    Directory of Open Access Journals (Sweden)

    Aghdas Dehghani

    2015-01-01

    Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

  5. Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry.

    Science.gov (United States)

    Yu, Changhui; Tang, Wei; Wang, Yuhao; Shen, Qiang; Wang, Bin; Cai, Chunqing; Meng, Xiaojing; Zou, Fei

    2016-07-01

    The renin-angiotensin system (RAS) is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, angiogenesis, metabolism, migration and invasion. Meanwhile, the arm of angiotensin-converting enzyme (ACE)2/angiotensin-(1-7) [Ang-(1-7)]/Mas axis in connection with RAS is associated with anti-proliferative, vasodilatory and anti-metastatic properties. Previous studies have shown that Ang-(1-7) reduces the proliferation of orthotopic human breast tumor growth by inhibiting cancer-associated fibroblasts. However, the role of ACE/Ang-(1-7)/Mas axis in the metastasis of breast cancer cells is still unknown. In the present study, we found that ACE2 protein level is negatively correlated with the metastatic ability of breast cancer cells and breast tumor grade. Upregulation of ACE2/Ang-(1-7)/Mas axis inhibits breast cancer cell migration and invasion in vivo and in vitro. Mechanistically, ACE2/Ang-(1-7)/Mas axis activation inhibits store-operated calcium entry (SOCE) and PAK1/NF-κB/Snail1 pathways, and induces E-cadherin expression. In summary, our results demonstrate that downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of SOCE and PAK1/NF-κB/Snail1 pathways. These results provide new mechanisms by which breast cancer develop metastasis and shed light on developing novel anti-metastasis therapeutics for metastatic breast cancer by modulating ACE2/Ang-(1-7)/Mas axis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Efectos hipotalámicos de la angiotensina-[1-7] en ratas con coartación aórtica

    Directory of Open Access Journals (Sweden)

    Clara Peña

    2005-01-01

    Full Text Available Hypothalamic Effects of Angiotensin (1-7 in Rats with Aortic Coarctation Christian Höcht, Javier A. W. Opezzo, Mariela Gironacci, Clara Peña, Carlos A. Taira The objective of the present study was to evaluate the effect of the intrahypothalamic administration of angiotensin-[1-7] (Ang-[1-7] on blood pressure and heart rate and on angiotensin II (Ang-II activity in rats with sham operation (SO and rats with aortic coarctation (ACo in early and chronic stage of hypertension. Wistar rats were used. Seven and 42 days after the corresponding operation one carotid artery was cannulated for the measurement of the mean arterial pressure (MAP in anaesthetized rats and an injection needle was inserted in the anterior hypothalamus by means of a stereotactic frame for the administration of Ang-II (50 ng, Ang-[1-7] (50 ng and Ang-II + Ang-[1-7] (50 + 50 ng. Hypothalamic administration of Ang-II produced an increased MAP in the ACo rats when compared to the control group in the early and chronic stages of hypertension, whereas Ang-[1-7] did not induce significant changes in any experimental group. The co-administration of Ang -[1-7] reduced the pressure activity of the Ang-II in both early and chronic stages of hypertension in the ACo rats, whereas it had no effect on the pressure activity of Ang-II in the normotensive rats. In conclusion, the pressure activity of Ang-II is increased in rats with early and chronic stages of arterial hypertension. The antagonistic effect of Ang-[1-7] may indicate that this peptide could modulate the pressure activity of an already increased Ang-II, since it has been only observed in the hypertensive rats.

  7. Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients: Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age Range.

    Science.gov (United States)

    Hanley, Michael J; Mould, Diane R; Taylor, Timothy J; Gupta, Neeraj; Suryanarayan, Kaveri; Neuwirth, Rachel; Esseltine, Dixie-Lee; Horton, Terzah M; Aplenc, Richard; Alonzo, Todd A; Lu, Xiaomin; Milton, Ashley; Venkatakrishnan, Karthik

    2017-09-01

    This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1.3 mg/m(2) twice-weekly, on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11 of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood samples were obtained and the plasma was harvested on day 8 over 0-72 hours postdose to measure bortezomib concentrations by liquid chromatography-tandem mass spectrometry. Concentration-time data were analyzed by nonlinear mixed-effects modeling. Covariates were examined using forward addition (P < .01)/backward elimination (P < .001). Data were included from 104 patients (49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2-11 years/12-16 years). Bortezomib pharmacokinetics were described by a 3-compartment model with linear elimination. Body surface area adequately accounted for variability in clearance (exponent 0.97), supporting body surface area-based dosing. Stratified visual predictive check simulations verified that neither age group nor patient population represented sources of meaningful pharmacokinetic heterogeneity not accounted for by the final population pharmacokinetic model. Following administration of 1.3 mg/m(2) intravenous bortezomib doses, body surface area-normalized clearance in pediatric patients was similar to that observed in adult patients, thereby indicating that this dose achieves similar systemic exposures in pediatric patients. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley

  8. Selective propagation of mouse-passaged scrapie prions with long incubation period from a mixed prion population using GT1-7 cells.

    Science.gov (United States)

    Miyazawa, Kohtaro; Masujin, Kentaro; Okada, Hiroyuki; Ushiki-Kaku, Yuko; Matsuura, Yuichi; Yokoyama, Takashi

    2017-01-01

    In our previous study, we demonstrated the propagation of mouse-passaged scrapie isolates with long incubation periods (L-type) derived from natural Japanese sheep scrapie cases in murine hypothalamic GT1-7 cells, along with disease-associated prion protein (PrPSc) accumulation. We here analyzed the susceptibility of GT1-7 cells to scrapie prions by exposure to infected mouse brains at different passages, following interspecies transmission. Wild-type mice challenged with a natural sheep scrapie case (Kanagawa) exhibited heterogeneity of transmitted scrapie prions in early passages, and this mixed population converged upon one with a short incubation period (S-type) following subsequent passages. However, when GT1-7 cells were challenged with these heterologous samples, L-type prions became dominant. This study demonstrated that the susceptibility of GT1-7 cells to L-type prions was at least 105 times higher than that to S-type prions and that L-type prion-specific biological characteristics remained unchanged after serial passages in GT1-7 cells. This suggests that a GT1-7 cell culture model would be more useful for the economical and stable amplification of L-type prions at the laboratory level. Furthermore, this cell culture model might be used to selectively propagate L-type scrapie prions from a mixed prion population.

  9. Reduced anxiety-like behavior in transgenic rats with chronically overproduction of angiotensin-(1-7): Role of the Mas receptor.

    Science.gov (United States)

    Kangussu, Lucas M; Almeida-Santos, Ana Flávia; Moreira, Fabrício A; Fontes, Marco A P; Santos, Robson A S; Aguiar, Daniele C; Campagnole-Santos, Maria José

    2017-07-28

    Angiotensin-(1-7) [Ang-(1-7)], a counterregulatory peptide of the renin-angiotensin system (RAS), exerts its cardiovascular and renal functions through the G-protein-coupled receptor Mas. More recently, Ang-(1-7) has also been implicated in the control of emotional states related to fear and anxiety. Here, we tested the hypothesis that transgenic rats overexpressesing Ang-(1-7) (TGR) show reduced anxiety-like behavior in two distinct animals models, the Elevated Plus Maze (EPM) and Vogel Conflict Test (VCT). Sprague-Dawley rats (SDs) were used as controls. In addition, we also verified whether this phenotype depend on activation of the Mas receptor. In line with our hypothesis, TGR rats showed an increase in the percentage of time and entries in the open arms of the EPM. There was also an increase in the number of punished licks in VCT. These phenotypes were reversed by ICV injection of the Mas receptor antagonist, A779, but not by the AT2 and MrgD receptor antagonist, PD123319. These results suggest that chronic elevation of Ang-(1-7) levels results in a phenotype characterized by reduced anxiety-like behavior, possibly due to higher activation of the Mas receptor. Therefore, facilitation of the Ang-(1-7)/Mas receptor signaling may be further investigated as an additional strategy for the treatment of anxiety-related disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Enhanced in utero allogeneic engraftment in mice after mobilizing fetal HSCs by α4β1/7 inhibition.

    Science.gov (United States)

    Kim, Aimee G; Vrecenak, Jesse D; Boelig, Matthew M; Eissenberg, Linda; Rettig, Michael P; Riley, John S; Holt, Matthew S; Conner, Michael A; Loukogeorgakis, Stavros P; Li, Haiying; DiPersio, John F; Flake, Alan W; Peranteau, William H

    2016-11-17

    In utero hematopoietic cell transplantation (IUHCT) is a novel nonmyeloablative approach that results in donor-specific tolerance and mixed allogeneic chimerism. Clinical application is limited by low levels of donor cell engraftment. Competition from endogenous hematopoietic stem cells (HSCs) for limited "space" in fetal hematopoietic organs remains a significant barrier to successful IUHCT. AMD3100, a CXCR4 inhibitor, and firategrast, an α4β1 and α4β7 integrin inhibitor (α4β1/7), have been shown to disrupt HSC retention in the postnatal hematopoietic niche. We hypothesized that maternal administration of AMD3100 and/or firategrast prior to IUHCT would mobilize endogenous HSCs from the fetal liver (FL) and result in preferential FL homing of donor HSCs and enhanced long-term engraftment following IUHCT in an allogeneic mouse model. We demonstrate that (1) both agents cross the placenta with rapidly detectable fetal serum concentrations following maternal administration; (2) firategrast treatment alone or with AMD3100 mobilizes endogenous HSCs from the FL and results in increased FL homing of donor HSCs following IUHCT; and (3) enhanced donor HSC homing following firategrast treatment translates into increased long-term multilineage donor cell engraftment. This approach highlights the potential of mobilization strategies to overcome barriers to successful engraftment and increase the clinical promise of IUHCT. © 2016 by The American Society of Hematology.

  11. The influence of elastic strain on the early stages of decomposition in Cu–1.7at% Fe

    KAUST Repository

    Rademacher, Thomas

    2009-04-01

    The initial stage of decomposition of homogenized Cu-1.7 at% Fe at 722 K was investigated by means of field ion microscopy (FIM), atom probe tomography (APT) and computer-assisted field ion image tomography (cFIIT). The agglomeration of atoms depending on time could be investigated and the growth of precipitates with a diameter of few nanometers was observed during ongoing nucleation. For the cFIIT measurements, an improved reconstruction algorithm was developed. Employing cFIIT in combination with FIM images, alignments of precipitates mainly in < 100 > directions were found. Besides, a general experimental concept to evaluate strain-related effects on the position of the proximate precipitate will be introduced. These analyses of the APT and cFIIT data show tendencies of a preferred < 100 > directed configuration as well. This effect can be associated with the elastic anisotropy of the Cu matrix (f.c.c.) to accommodate the volume misfit of precipitates. In accordance with previous model calculations, a preferred nucleation in < 100 > directions with respect to existing clusters can be concluded. For such cluster arrangements strain energy reduction is largest for precipitates adapting their sizes. Thus, additional stabilization against coarsening can be inferred for < 100 > alignments which result in the observed effects. (C) 2008 Published by Elsevier B.V.

  12. Probing The Electronic Properties of Dichromium Oxide Clusters Cr2On-(n=1-7) Using Photoelectron Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Hua-jin; Wang, Lai S.

    2006-10-28

    In an effort to elucidate the variation of the electronic structure as a function of oxidation and composition, we investigated an extensive series of dichromium oxide clusters, Cr2On- (n = 1-7) using photoelectron spectroscopy (PES). Well-resolved PES spectra were obtained at several photon energies. While low photon energy spectra yielded much better spectral resolution, high photon energy data allowed both Cr 3d- and O 2p-dreived detachment features to be observed. The overall spectral evolution of Cr2On– exhibits a behavior of sequential oxidation with increasing oxygen content, where low binding energy Cr 3d-based spectral features diminish in numbers and the spectra shift towards higher binding energies as a result of charge transfer from Cr to O. Evidence was obtained for the population of low-lying isomers for Cr2O2-, Cr2O3-, and Cr2O6-. The current data are compared with previous studies and with related studies on W2On- and Mo2On-.

  13. High-speed intravascular photoacoustic imaging at 1.7 μm with a KTP-based OPO.

    Science.gov (United States)

    Hui, Jie; Yu, Qianhuan; Ma, Teng; Wang, Pu; Cao, Yingchun; Bruning, Rebecca S; Qu, Yueqiao; Chen, Zhongping; Zhou, Qifa; Sturek, Michael; Cheng, Ji-Xin; Chen, Weibiao

    2015-11-01

    Lipid deposition inside the arterial wall is a hallmark of plaque vulnerability. Based on overtone absorption of C-H bonds, intravascular photoacoustic (IVPA) catheter is a promising technology for quantifying the amount of lipid and its spatial distribution inside the arterial wall. Thus far, the clinical translation of IVPA technology is limited by its slow imaging speed due to lack of a high-pulse-energy high-repetition-rate laser source for lipid-specific first overtone excitation at 1.7 μm. Here, we demonstrate a potassium titanyl phosphate (KTP)-based optical parametric oscillator with output pulse energy up to 2 mJ at a wavelength of 1724 nm and with a repetition rate of 500 Hz. Using this laser and a ring-shape transducer, IVPA imaging at speed of 1 frame per sec was demonstrated. Performance of the IVPA imaging system's resolution, sensitivity, and specificity were characterized by carbon fiber and a lipid-mimicking phantom. The clinical utility of this technology was further evaluated ex vivo in an excised atherosclerotic human femoral artery with comparison to histology.

  14. Computational Investigation of Cationic, Anionic and Neutral Ag2AuN (N = 1-7) Nanoalloy Clusters

    Science.gov (United States)

    Ranjan, Prabhat; Chakraborty, Tanmoy; Kumar, Ajay

    2017-08-01

    The study of bimetallic nanoalloy clusters is of immense importance due to their diverse applications in the field of science and engineering. A deep theoretical insight is required to explain the physico-chemical properties of such compounds. Among such nanoalloy clusters, the compound formed between Ag and Au has received a lot of attention because of their marked electronic, catalytic, optical and magnetic properties. Density Functional Theory (DFT) is one of the most successful approaches of quantum mechanics to study the electronic properties of materials. Conceptual DFT-based descriptors have turned to be indispensable tools for analysing and correlating the experimental properties of compounds. In this report, we have investigated the ground state configurations and physico-chemical properties of Ag2AuNλ (N = 1-7, λ=±1, 0) nanoalloy clusters invoking DFT methodology. Our computed data exhibits interesting odd-even oscillation behaviour. A close agreement between experimental and our computed bond length supports our theoretical analysis.

  15. Attenuation of electromagnetic waves at the frequency ~1.7 kHz in the upper ionosphere observed by the DEMETER satellite in the vicinity of earthquakes

    Directory of Open Access Journals (Sweden)

    Michel Parrot

    2012-04-01

    Full Text Available

    The DEMETER satellite was the first satellite specifically dedicated to the recording of electromagnetic phenomena connected with seismic activity. Almost 6.5 years of measurements provide good opportunities to analyze a unique dataset with global Earth coverage. We present the results of a statistical study of the intensity of very low frequency electromagnetic waves recorded in the upper ionosphere. Robust two-step data processing has been used. The expected unperturbed distribution of the power spectral densities of electromagnetic emissions was calculated first. Then, the power spectral densities measured in the vicinities of earthquakes are compared with the unperturbed distribution and are examined for the presence of uncommon effects related to seismic activity. The statistical significance of the observed effects is evaluated. We confirm the previously reported results of a very small, but statistically significant, decrease in wave intensities a few hours before times of main shocks using this much larger dataset. The wave intensity decrease at a frequency of about 1.7 kHz is observed only during the night and only for shallow earthquakes. This can potentially be explained by increases in the cut-off frequency of the Earth ionosphere waveguide caused by imminent earthquakes.

     

  16. Triple-ionised carbon associated with the low-density neutral hydrogen gas at 1.7 < z < 3.3: the integrated N(HI)-N(CIV) relation

    OpenAIRE

    Kim, Tae-Sun; Carswell, R F; Mongardi, C.; Partl, A. M.; Muecket, J. P.; Barai, P; Criatiani, S.

    2016-01-01

    From the Voigt profile fitting analysis of 183 intervening CIV systems at 1.7 < z < 3.3 in 23 high-quality UVES/VLT and HIRES/Keck QSO spectra, we find that a majority of CIV systems (~75%) display a well-characterised scaling relation between integrated column densities of HI and CIV with a negligible redshift evolution, when column densities of all the HI and CIV components are integrated within a given (-150, +150) km/sec range centred at the CIV flux minimum. The integrated CIV column den...

  17. Anthropometric characteristics, physical fitness and motor coordination of 9 to 11 year old children participating in a wide range of sports.

    Science.gov (United States)

    Opstoel, Katrijn; Pion, Johan; Elferink-Gemser, Marije; Hartman, Esther; Willemse, Bas; Philippaerts, Renaat; Visscher, Chris; Lenoir, Matthieu

    2015-01-01

    The aim of this study was to investigate to what extent 9 to 11 year old children participating in a specific sport already exhibit a specific anthropometric, physical fitness and motor coordination profile, in line with the requirements of that particular sport. In addition, the profiles in children with a different training volume were compared and possible differences in training hours per week between children from a low, moderate, and high level of physical fitness and motor coordination were investigated. Data of 620 children, 347 boys and 273 girls, who participated in the Flemish Sports Compass were used. Only the primary sport of each child was considered and six groups of sports (Ball sports, Dance, Gymnastics, Martial arts, Racquet sports and Swimming) were formed based on common characteristics. Measurements consisted of 17 tests. Independent T-tests and Mann-Whitney U-tests revealed few differences between the groups of sports and the discriminant analyses with the moderate and low active group did not show any significant results (p > .05). However, when discriminating among the high active children, a 85.2 % correct classification between six groups of sports was found (Wilks' Λ = .137 and p sport per week (2.50 ± 1.84 hours) compared to the children performing best (3.25 ± 2.60 hours) (p = .016) and the children performing above average (2.90 ± 1.96 hours) (p = .029) on physical fitness and motor coordination. The study showed that in general, children at a young age do not exhibit sport-specific characteristics, except in children with a high training volume. It is possible that on the one hand, children have not spent enough time yet in their sport to develop sport-specific qualities. On the other hand, it could be possible that they do not take individual qualities into account when choosing a sport.

  18. Anthropometric Characteristics, Physical Fitness and Motor Coordination of 9 to 11 Year Old Children Participating in a Wide Range of Sports

    Science.gov (United States)

    Elferink-Gemser, Marije; Hartman, Esther; Willemse, Bas; Philippaerts, Renaat; Visscher, Chris; Lenoir, Matthieu

    2015-01-01

    Objectives The aim of this study was to investigate to what extent 9 to 11 year old children participating in a specific sport already exhibit a specific anthropometric, physical fitness and motor coordination profile, in line with the requirements of that particular sport. In addition, the profiles in children with a different training volume were compared and possible differences in training hours per week between children from a low, moderate, and high level of physical fitness and motor coordination were investigated. Methods and Results Data of 620 children, 347 boys and 273 girls, who participated in the Flemish Sports Compass were used. Only the primary sport of each child was considered and six groups of sports (Ball sports, Dance, Gymnastics, Martial arts, Racquet sports and Swimming) were formed based on common characteristics. Measurements consisted of 17 tests. Independent T-tests and Mann-Whitney U-tests revealed few differences between the groups of sports and the discriminant analyses with the moderate and low active group did not show any significant results (p > .05). However, when discriminating among the high active children, a 85.2 % correct classification between six groups of sports was found (Wilks’ Λ = .137 and p sport per week (2.50 ± 1.84 hours) compared to the children performing best (3.25 ± 2.60 hours) (p = .016) and the children performing above average (2.90 ± 1.96 hours) (p = .029) on physical fitness and motor coordination. Discussion The study showed that in general, children at a young age do not exhibit sport-specific characteristics, except in children with a high training volume. It is possible that on the one hand, children have not spent enough time yet in their sport to develop sport-specific qualities. On the other hand, it could be possible that they do not take individual qualities into account when choosing a sport. PMID:25978313

  19. Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo

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    J.H. Williams

    2005-06-01

    Full Text Available A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.

  20. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

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    Freddyson J Martínez-Rivera

    Full Text Available The abuse of anabolic androgenic steroids (AAS has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH. In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM. These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

  1. ALMA Resolves the Molecular Gas in a Young Low-metallicity Starburst Galaxy at z = 1.7

    Science.gov (United States)

    González-López, Jorge; Barrientos, L. Felipe; Gladders, M. D.; Wuyts, Eva; Rigby, Jane; Sharon, Keren; Aravena, Manuel; Bayliss, Matthew B.; Ibar, Eduardo

    2017-09-01

    We present Atacama Large Millimeter/submillimeter Array observations of CO lines and dust continuum emission of the source RCSGA 032727-132609, a young z = 1.7 low-metallicity starburst galaxy. The CO(3-2) and CO(6-5) lines and continuum at rest-frame 450 μm are detected and show a resolved structure in the image plane. We use the corresponding lensing model to obtain a source plane reconstruction of the detected emissions revealing an intrinsic flux density of {S}450μ {{m}}={23.5}-8.1+26.8 μJy and intrinsic CO luminosities {L}{CO(3-2)}{\\prime }={2.90}-0.23+0.21 × {10}8 {{K}} {km} {{{s}}}-1 {{pc}}2 and {L}{CO(6-5)}{\\prime }={8.0}-1.3+1.4× {10}7 {{K}} {km} {{{s}}}-1 {{pc}}2. We used the resolved properties in the source plane to obtain molecular gas and star formation rate surface densities of {{{Σ }}}{{H}2}={16.2}-3.5+5.8 {M}⊙ {{pc}}-2 and {{{Σ }}}{SFR}={0.54}-0.27+0.89 {M}⊙ {{yr}}-1 {{kpc}}-2, respectively. The intrinsic properties of RCSGA 032727-132609 show an enhanced star formation activity compared to local spiral galaxies with similar molecular gas densities, supporting the ongoing merger-starburst phase scenario. RCSGA 032727-132609 also appears to be a low-density starburst galaxy similar to local blue compact dwarf galaxies, which have been suggested as local analogs to high-redshift low-metallicity starburst systems. Finally, the CO excitation level in the galaxy is consistent with having the peak at J˜ 5, with a higher excitation concentrated in the star-forming clumps.

  2. Glutamate increases toxicity of inorganic lead in GT1-7 neurons: partial protection induced by flunarizine

    Energy Technology Data Exchange (ETDEWEB)

    Loikkanen, Jarkko; Vaehaekangas, Kirsi H. [Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211, Kuopio (Finland); Naarala, Jonne [Department of Environmental Sciences, University of Kuopio, PO Box 1627, 70211, Kuopio (Finland); Savolainen, Kai M. [Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, 00250, Helsinki (Finland)

    2003-12-01

    Recent studies point to an interaction between the glutamatergic neurotransmitter system and inorganic lead (Pb) neurotoxicity. Pb (1-100 {mu}M) evoked cytotoxicity over the period of 72 h in mouse hypothalamic GT1-7 neurons. Glutamate (0.1 or 1 mM) on its own did not have any effect on cell viability. However, 1 mM glutamate clearly increased Pb-induced cell death at 48 and 72 h. Although flunarizine (0.1-10 {mu}M), an antagonist of L- and T-type voltage-sensitive calcium channels (VSCCs), partially protected from the cytotoxicity induced by co-exposure to Pb (10 or 100 {mu}M) and glutamate (1 mM), it had no protective effect on cytotoxicity induced by Pb alone. The flunarizine-induced protection was dependent on time and observed only at 48 h. Neither verapamil, an antagonist of L-type VSCCs, nor DIDS, an inhibitor of anion exchange, at non-toxic concentrations (0.1-10 {mu}M) had any effect on cytotoxicity induced by Pb alone or together with glutamate at any studied time point. Co-exposure to Pb and glutamate also resulted in more prominent production of reactive oxygen species (ROS) than either of the compounds alone. Interestingly, we observed an increase in intracellular glutathione (GSH) levels in cells exposed to micromolar concentrations of Pb. Glutamate decreased the levels of intracellular GSH and also partially reduced the Pb-induced increase in GSH levels. These results suggest that the interaction of glutamate and Pb results in increased neuronal cell death via mechanisms that involve an increase in ROS production, a decrease in intracellular GSH defense against oxidative stress and probably T-type VSCCs. (orig.)

  3. A case study of an extremely luminous, highly spatially extended starburst only 1.7Gyr after the Big Bang

    Science.gov (United States)

    Farrah, Duncan

    2017-08-01

    Luminous starbursts, systems with SFRs exceeding 1000Msun yr-1, are predicted to be extremely rare at z>3. However, recent observations find such systems at rates of tens to hundreds above predictions. This discrepancy is extremely difficult to explain. Case studies of such luminous starbursts are thus of profound importance to understand how star formation is triggered and quenched at z > 3, and help reconcile models with observations. Our group has been intensively studying the quasar SDSS J160705.16, at z = 3.65 (or 1.7Gyr after the Big Bang). This quasar is an excellent case study of luminous star formation at z > 3, and how AGN activity may affect such star formation. SDSS J160705.16 harbors both a broad-line, luminous quasar and an extremely high star formation rate, with an AGN luminosity of 10^47 ergs s-1 and an SFR of 2000 Msol yr-1. Sub-mm interferometry has further revealed that the star formation is highly spatially extended on scales up to 40kpc. Furthermore, VLA observations show an emerging 4kpc radio jet.We here propose WFC3 imaging with the following goals: (1) to set precise constraints on any lensing magnification, (2) to determine the morphology and color structure of the extended star formation, (3) to compare the optical morphology of the star formation to that seen in the sub-mm data, and (4) to search for evidence that SDSS J160705.16 resides in a protocluster.

  4. Mir-21 Mediates the Inhibitory Effect of Ang (1-7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts.

    Science.gov (United States)

    Sun, Na-Na; Yu, Chang-Hui; Pan, Miao-Xia; Zhang, Yue; Zheng, Bo-Jun; Yang, Qian-Jie; Zheng, Ze-Mao; Meng, Ying

    2017-10-30

    MicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis. However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown. Angiotensin-converting enzyme 2/angiotensin(1-7) [ACE2/Ang(1-7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1-7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression. This study's aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1-7) on lung fibroblast apoptosis and collagen synthesis. In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome. In contrast, ACE2/Ang(1-7) attenuated BLM-induced lung fibrosis, and decreased mir-21 and the NLRP3 inflammasome. In vitro, AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1-7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21. Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1-7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.

  5. Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats.

    Science.gov (United States)

    Kangussu, Lucas M; Guimaraes, Priscila S; Nadu, Ana Paula; Melo, Marcos B; Santos, Robson A S; Campagnole-Santos, Maria Jose

    2015-10-01

    Activation of the peripheral angiotensin-(1-7)/Mas axis of the renin-angiotensin system produces important cardioprotective actions, counterbalancing the deleterious actions of an overactivity of Ang II/AT1 axis. In the present study we evaluated whether the chronic increase in Ang-(1-7) levels in the brain could ameliorate cardiac disorders observed in transgenic (mRen2)27 hypertensive rats through actions on Mas receptor. Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats, instrumented with telemetry probe for arterial pressure (AP) measurement were subjected to 14 days of ICV infusion of Ang-(1-7) (200 ng/h) or Ang-(1-7) associated with Mas receptor antagonist (A779, 1 μg/h) or 0.9% sterile saline (0.5 μl/h) through osmotic mini-pumps. Ang-(1-7) infusion in (mRen2)27 rats reduced blood pressure, normalized the baroreflex control of HR, restored cardiac autonomic balance, reduced cardiac hypertrophy and pre-fibrotic alterations and decreased the altered imbalance of Ang II/Ang-(1-7) in the heart. In addition, there was an attenuation of the increased levels of atrial natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF-β in the heart of (mRen2)27 rats. Furthermore, most of these effects were mediated in the brain by Mas receptor, since were blocked by its selective antagonist, A779. These data indicate that increasing Ang-(1-7) levels in the brain can attenuate cardiovascular disorders observed in (mRen2)27 hypertensive rats, probably by improving the autonomic balance to the heart due to centrally-mediated actions on Mas receptor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Oxidation differentially modulates the recombinant voltage-gated Na(+) channel α-subunits Nav1.7 and Nav1.8.

    Science.gov (United States)

    Schlüter, Friederike; Leffler, Andreas

    2016-10-01

    Voltage-gated Na(+) channels regulate neuronal excitability by generating the upstroke of action potentials. The α-subunits Nav1.7 and Nav1.8 are required for normal function of sensory neurons and thus for peripheral pain processing, but also for an increased excitability leading to an increased pain sensitivity under several conditions associated with oxidative stress. While little is known about the direct effects of oxidants on Nav1.7 and Nav1.8, a recent study on mouse dorsal root ganglion neurons suggested that oxidant-induced alterations of nociceptor excitability are primarily driven by Nav1.8. Here we performed whole-cell patch clamp recordings to explore how oxidation modulates functional properties of recombinant Nav1.7 and Nav1.8 channels. The strong oxidant chloramine-T (ChT) at 100 and 500µM induced a shift of the voltage-dependency of activation towards more hyperpolarized potentials. While fast inactivation was stabilized by 100µM ChT, it was partially removed by 500µM ChT on both α-subunits (Nav1.7

  7. The importance of community education for individual mortality: a fixed-effects analysis of longitudinal multilevel data on 1.7 million Norwegian women and men.

    Science.gov (United States)

    Kravdal, Oystein

    2010-12-01

    Earlier investigations have shown mortality effects of community socio-economic resources. However, the sex differences have not been clear, and the estimates may well have been biased because of inadequate control for community factors affecting both the socio-economic resources and mortality. The objective of this study was to see whether any effects appeared when time-invariant community characteristics were controlled by including community dummies (fixed effects) and whether there were any differences between women and men. Discrete-time hazard models for all-cause mortality were estimated for 1981-2002 for all Norwegians aged 60-89, using register data. There were 730 000 deaths among 1.7 million people observed during 19 million person-years. Average education was measured for 433 municipalities for each of the 22 years. According to the simplest models, a high average education in the municipality is associated with increased mortality. Control for population size (time-averaged) reversed the effects. Inclusion of municipality dummies instead of population size, to control also for additional unobserved time-invariant municipality characteristics, gave very different results: the effects were even stronger for men, while those for women were no longer significant. The results were quite robust to alternative specifications, including the use of a lagged average-education variable. The study supports the idea that community socio-economic resources may affect mortality and suggests that sex differentials may deserve more attention. It also illustrates the importance of controlling for time-invariant community factors. Unless these can be easily measured, in future investigations one may consider establishing longitudinal data and using a fixed-effects approach such as that used here.

  8. The Anti-Inflammatory Potential of ACE2/Angiotensin-(1-7)/Mas Receptor Axis: Evidence from Basic and Clinical Research.

    Science.gov (United States)

    Rodrigues Prestes, Thiago Ruiz; Rocha, Natalia Pessoa; Miranda, Aline Silva; Teixeira, Antônio Lúcio; Simoes-E-Silva, Ana Cristina

    2017-01-01

    The renin angiotensin system (RAS) plays an important role in inflammation and fibrosis. The classical axis of the RAS, formed by angiotensin converting en-zyme (ACE), angiotensin II (Ang II) and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signaling pathways related to tissue injury, inflammation and fibrosis. In sharp contrast, the RAS axis composed by angiotensin converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas receptor exerts opposite effects in relation to inflammatory response and tissue fibrosis. In this review, we have the aim to summarize recent findings on the anti-inflammatory and anti-fibrogenic role of ACE2/Ang-(1-7)/Mas axis in the context of basic research, experimental human dis-eases and clinical studies. Several studies showed that ACE2/Angiotensin-(1-7)/Mas axis reduces cytokine release and inhibits signaling pathways of tissue fibrosis in experimental models of human diseases including atherosclerosis, cerebral ischemia, obesity, chronic kidney disease, liver diseases and asthma. On the other hand, very few data was provided by clinical studies. Experimental studies clearly support the anti-inflammatory and anti-fibrotic effects of ACE2/ Ang-(1-7)/Mas axis. Clinical studies, especially phase III and IV trials, will be necessary to establish the therapeutic role of ACE2/Ang-(1-7)/Mas axis in controlling inflammation in different human diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency, Pharmacokinetics, and Metabolic Properties to Obtain Atropisomeric Quinolinone (AM-0466) that Affords Robust in Vivo Activity.

    Science.gov (United States)

    Graceffa, Russell F; Boezio, Alessandro A; Able, Jessica; Altmann, Steven; Berry, Loren M; Boezio, Christiane; Butler, John R; Chu-Moyer, Margaret; Cooke, Melanie; DiMauro, Erin F; Dineen, Thomas A; Feric Bojic, Elma; Foti, Robert S; Fremeau, Robert T; Guzman-Perez, Angel; Gao, Hua; Gunaydin, Hakan; Huang, Hongbing; Huang, Liyue; Ilch, Christopher; Jarosh, Michael; Kornecook, Thomas; Kreiman, Charles R; La, Daniel S; Ligutti, Joseph; Milgram, Benjamin C; Lin, Min-Hwa Jasmine; Marx, Isaac E; Nguyen, Hanh N; Peterson, Emily A; Rescourio, Gwen; Roberts, John; Schenkel, Laurie; Shimanovich, Roman; Sparling, Brian A; Stellwagen, John; Taborn, Kristin; Vaida, Karina R; Wang, Jean; Yeoman, John; Yu, Violeta; Zhu, Dawn; Moyer, Bryan D; Weiss, Matthew M

    2017-07-27

    Because of its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. Herein, we report the discovery and optimization of a series of atropisomeric quinolinone sulfonamide inhibitors [ Bicyclic sulfonamide compounds as sodium channel inhibitors and their preparation . WO 2014201206, 2014 ] of NaV1.7, which demonstrate nanomolar inhibition of NaV1.7 and exhibit high levels of selectivity over other sodium channel isoforms. After optimization of metabolic and pharmacokinetic properties, including PXR activation, CYP2C9 inhibition, and CYP3A4 TDI, several compounds were advanced into in vivo target engagement and efficacy models. When tested in mice, compound 39 (AM-0466) demonstrated robust pharmacodynamic activity in a NaV1.7-dependent model of histamine-induced pruritus (itch) and additionally in a capsaicin-induced nociception model of pain without any confounding effect in open-field activity.

  10. IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus.

    Science.gov (United States)

    Ke, Xingrao; McKnight, Robert A; Gracey Maniar, Lia E; Sun, Ying; Callaway, Christopher W; Majnik, Amber; Lane, Robert H; Cohen, Susan S

    2015-07-15

    Intrauterine growth restriction (IUGR) increases the risk for neurodevelopment delay and neuroendocrine reprogramming in both humans and rats. Neuroendocrine reprogramming involves the glucocorticoid receptor (GR) gene that is epigenetically regulated in the hippocampus. Using a well-characterized rodent model, we have previously shown that IUGR increases GR exon 1.7 mRNA variant and total GR expressions in male rat pup hippocampus. Epigenetic regulation of GR transcription may involve chromatin remodeling of the GR gene. A key chromatin remodeler is Brahma-related gene-1(Brg1), a member of the ATP-dependent SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Brg1 regulates gene expression by affecting nucleosome repositioning and recruiting transcriptional components to target promoters. We hypothesized that IUGR would increase hippocampal Brg1 expression and binding to GR exon 1.7 promoter, as well as alter nucleosome positioning over GR promoters in newborn male pups. Further, we hypothesized that IUGR would lead to accumulation of specificity protein 1 (Sp1) and RNA pol II at GR exon 1.7 promoter. Indeed, we found that IUGR increased Brg1 expression and binding to GR exon 1.7 promoter. We also found that increased Brg1 binding to GR exon 1.7 promoter was associated with accumulation of Sp1 and RNA pol II carboxy terminal domain pSer-5 (a marker of active transcription). Furthermore, the transcription start site of GR exon 1.7 was located within a nucleosome-depleted region. We speculate that changes in hippocampal Brg1 expression mediate GR expression and subsequently trigger neuroendocrine reprogramming in male IUGR rats. Copyright © 2015 the American Physiological Society.

  11. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin

    Directory of Open Access Journals (Sweden)

    Fang Zhao

    2016-02-01

    Full Text Available Voltage-gated sodium channels (VGSCs are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1–Nav1.9, Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR membrane potential (FMP blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  12. The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-07-15

    The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT1) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The expression of angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis are upregulated after acute cerebral ischemic stroke in rats.

    Science.gov (United States)

    Lu, Jie; Jiang, Teng; Wu, Liang; Gao, Li; Wang, Yao; Zhou, Feng; Zhang, Shugang; Zhang, Yingdong

    2013-10-01

    There is now unequivocal evidence that the angiotensin-converting enzyme 2(ACE2)-Ang-(1-7)-Mas axis is a key component of the renin-angiotensin system (RAS) cascade, which is closely correlated with ischemic insult occurrence. Our previous studies demonstrated that the Ang-(1-7), was an active member of the brain RAS. However, the ACE2-Ang-(1-7)-Mas axis expression after cerebral ischemic injury are currently unclear. In the present study, we investigated the time course of ACE2-Ang-(1-7) and Mas receptor expression in the acute stage of cerebral ischemic stroke. The content of Ang-(1-7) in ischemic tissues and blood serum was measured by specific EIA kits. Real-time PCR and western blot were used to determine messenger RNA (mRNA) and protein levels of the ACE2 and Mas. The cerebral ischemic lesion resulted in a significant increase of regional cerebral and circulating Ang-(1-7) at 6-48 h compared with sham operation group following focal ischemic stroke (12h: 7.276±0.320 ng/ml vs. 2.466±0.410 ng/ml, serum; 1.024±0.056 ng/mg vs. 0.499±0.032, brain) (PMas expression were markedly enhanced compared to the control in the ischemic tissues (PMas immunopositive neurons were also seen stronger expression in the ischemic cortex (19.167±2.858 vs. 7.833±2.483) (PMas axis are upregulated after acute ischemic stroke and would play a pivotal role in the regulation of acute neuron injury in ischemic cerebrovascular diseases. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  14. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin.

    Science.gov (United States)

    Zhao, Fang; Li, Xichun; Jin, Liang; Zhang, Fan; Inoue, Masayuki; Yu, Boyang; Cao, Zhengyu

    2016-02-16

    Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  15. Transmission over 5.6 km large effective area and low-loss (1.7 dB/km) photonic crystal fibre

    DEFF Research Database (Denmark)

    Zsigri, Beata; Peucheret, Christophe; Nielsen, Martin Dybendal

    2003-01-01

    A 10 Gbit/s non-return-to-zero signal at 1550 ran over 5.6 km photonic crystal fibre (PCF) with 1.7 dB/km loss has been successfully transmitted, demonstrating the potential of PCF as transmission fibre.......A 10 Gbit/s non-return-to-zero signal at 1550 ran over 5.6 km photonic crystal fibre (PCF) with 1.7 dB/km loss has been successfully transmitted, demonstrating the potential of PCF as transmission fibre....

  16. ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors.

    Science.gov (United States)

    Schmalhofer, William A; Calhoun, Jeffrey; Burrows, Rachel; Bailey, Timothy; Kohler, Martin G; Weinglass, Adam B; Kaczorowski, Gregory J; Garcia, Maria L; Koltzenburg, Martin; Priest, Birgit T

    2008-11-01

    Voltage-gated sodium (Na(V)1) channels play a critical role in modulating the excitability of sensory neurons, and human genetic evidence points to Na(V)1.7 as an essential contributor to pain signaling. Human loss-of-function mutations in SCN9A, the gene encoding Na(V)1.7, cause channelopathy-associated indifference to pain (CIP), whereas gain-of-function mutations are associated with two inherited painful neuropathies. Although the human genetic data make Na(V)1.7 an attractive target for the development of analgesics, pharmacological proof-of-concept in experimental pain models requires Na(V)1.7-selective channel blockers. Here, we show that the tarantula venom peptide ProTx-II selectively interacts with Na(V)1.7 channels, inhibiting Na(V)1.7 with an IC(50) value of 0.3 nM, compared with IC(50) values of 30 to 150 nM for other heterologously expressed Na(V)1 subtypes. This subtype selectivity was abolished by a point mutation in DIIS3. It is interesting that application of ProTx-II to desheathed cutaneous nerves completely blocked the C-fiber compound action potential at concentrations that had little effect on Abeta-fiber conduction. ProTx-II application had little effect on action potential propagation of the intact nerve, which may explain why ProTx-II was not efficacious in rodent models of acute and inflammatory pain. Mono-iodo-ProTx-II ((125)I-ProTx-II) binds with high affinity (K(d) = 0.3 nM) to recombinant hNa(V)1.7 channels. Binding of (125)I-ProTx-II is insensitive to the presence of other well characterized Na(V)1 channel modulators, suggesting that ProTx-II binds to a novel site, which may be more conducive to conferring subtype selectivity than the site occupied by traditional local anesthetics and anticonvulsants. Thus, the (125)I-ProTx-II binding assay, described here, offers a new tool in the search for novel Na(V)1.7-selective blockers.

  17. Impairment of cardiac function and remodeling induced by myocardial infarction in rats are attenuated by the nonpeptide angiotensin-(1-7) analog AVE 0991.

    Science.gov (United States)

    Zeng, Wu-tao; Chen, Wei-yan; Leng, Xiu-yu; Tang, Li-long; Sun, Xiu-ting; Li, Cui-ling; Dai, Gang

    2012-06-01

    We evaluated effects of the nonpeptide angiotensin (ANG)-(1-7) analog AVE 0991 (AVE) on cardiac function and remodeling as well as transforming growth factor-beta1 (TGF-β1)/tumor necrosis factor-alpha (TNF-α) expression in myocardial infarction rat models. Sprague-Dawley rats underwent either sham surgery or coronary ligation. They were divided into four groups: sham, control, AVE, and AVE+A-779 [[D-Ala(7) ]-ANG-(1-7), a selective antagonist for the ANG-(1-7)] group. After 4 weeks of treatment, the AVE group displayed a significant elevation in left ventricular fractional shorting (LVFS) (25.5 ± 7.3% vs. 18.4 ± 3.3%, P AVE group when compared to the control group. There were no differences in LVFS, LVEF, myocyte diameter, and infarct size between the control and AVE+A-779 groups. AVE also markedly attenuated the increased mRNA expression of collagen I (P AVE could improve cardiac function and attenuate ventricular remodeling in MI rat models. It may involve the inhibition of inflammatory factors TGF-β1/TNF-α overexpression and the action on the specific receptor Mas of ANG-(1-7). © 2010 Blackwell Publishing Ltd.

  18. The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin I metabolism in aorta of apoE-knockout mice.

    Science.gov (United States)

    Olszanecki, R; Suski, M; Gebska, A; Toton-Zuranska, J; Kus, K; Madej, J; Bujak-Gizycka, B; Jawien, J; Korbut, R

    2013-06-01

    The detrimental role of over activation of renin-angiotensin system (RAS) in atherogenesis is widely recognized. Recently, we have demonstrated that Ang-(1-7) peptidomimetic - AVE0991, as well as known beta-adrenolytic agent nebivolol, exert anti-atherogenic actions in mouse model of atherosclerosis - apoE-knockout mice. Here, using LC-ESI-MS ex vivo system, we tested whether prolonged treatment of apoE-knockout mice by these drugs can influence RAS in aorta of apoE-knockout mice in regard to generation of most active metabolites of Ang I-Ang II and Ang-(1-7). As compared to wild type animals there was increased generation of Ang II in aorta of apoE-knockout mice, while the formation of Ang-(1-7) did not differ between both groups. Either treatment with AVE0991 or nebivolol resulted in significant attenuation of Ang II production in aorta of apoE-knockout mice. In conclusion, for the first time we directly demonstrated that there is increase in ability of aortic tissue to generate Ang II in mouse model of atherosclerosis of apoE knockout mice, and that such effect could be efficiently attenuated either by treatment of nebivolol or Ang-(1-7) peptidomimetic - AVE0991. The exact mechanism(s) responsible for interference of both drugs with RAS require further investigation.

  19. Papel de la angiotensina-(1-7 sobre la recaptación neuronal de noradrenalina en la hipertensión

    Directory of Open Access Journals (Sweden)

    Mariela M. Gironacci

    2010-01-01

    Full Text Available RESUMENPreviamente demostramos que la angiotensina (Ang-(1-7, en contraste con la Ang II, disminuyela liberación y la síntesis de noradrenalina (NA en ratas espontáneamentehipertensas (SHR. En el presente trabajo investigamos en ratas SHR el efecto de la Ang-(1-7 sobre la recaptación neuronal y la expresión del transportador de NA (NET, principalresponsable de la eliminación de NA del espacio sináptico. Si bien la Ang-(1-7 no presentaun efecto agudo sobre la recaptación neuronal de noradrenalina, tiene un papel estimuladorsobre el contenido proteico del NET a largo plazo. Esta acción la ejerce a través de laestimulación de la síntesis proteica de novo del transportador por la activación del receptorMas. Esto sugeriría que, a través de la regulación de los niveles de NA en el espacio sináptico,la Ang-(1-7 contribuiría a la regulación de la presión arterial.REV ARGENT CARDIOL 2010;78:151-155.

  20. Protective role of ACE2-Ang-(1-7)-Mas in myocardial fibrosis by downregulating KCa3.1 channel via ERK1/2 pathway.

    Science.gov (United States)

    Wang, Li-Ping; Fan, Su-Jing; Li, Shu-Min; Wang, Xiao-Jun; Gao, Jun-Ling; Yang, Xiu-Hong

    2016-11-01

    The intermediate-conductance Ca(2+)-activated K(+) (KCa3.1) channel plays a vital role in myocardial fibrosis induced by angiotensin (Ang) II. However, as the antagonists of Ang II, the effect of angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis on KCa3.1 channel during myocardial fibrosis remains unknown. This study was designed to explore the function of KCa3.1 channel in the cardioprotective role of ACE2-Ang-(1-7)-Mas. Wild-type (WT) mice, hACE2 transgenic mice (Tg), and ACE2 deficiency mice (ACE2(-/-)) were administrated with Ang II by osmotic mini-pumps. As the activator of ACE2, diminazene aceturate (DIZE) inhibited increase of blood pressure, collagen deposition, and KCa3.1 protein expression in myocardium of WT mice induced by Ang II. In Tg and ACE2(-/-) mice, besides the elevation of blood pressure, Ang II induced transformation of cardiac fibroblast into myofibroblast and resulted in augmentation of hydroxyproline concentration and collagen deposition, as well as KCa3.1 protein expression, but the changes in ACE2(-/-) mice were more obvious than those in Tg mice. Mas antagonist A779 reduced blood pressure, myocardium fibrosis, and myocardium KCa3.1 protein expression by Ang II in Tg mice, but activation of KCa3.1 with SKA-31 in Tg mice promoted the pro-fibrogenic effects of Ang II. Respectively, in ACE2(-/-) mice, TRAM-34, the KCa3.1 blocker, and Ang-(1-7) inhibited increase of blood pressure, collagen deposition, and KCa3.1 protein expression by Ang II. Moreover, DIZE and Ang-(1-7) depressed p-ERK1/2/t-ERK increases by Ang II in WT mice, and after blockage of ERK1/2 pathway with PD98059, the KCa3.1 protein expression was reduced in WT mice. In conclusion, the present study demonstrates that ACE2-Ang-(1-7)-Mas protects the myocardium from hypertension-induced injury, which is related to its inhibiting effect on KCa3.1 channels through ERK1/2 pathway. Our results reveal that KCa3.1 channel is likely to be a critical target on the ACE2-Ang-(1-7)-Mas axis for its protective role in myocardial fibrosis and changes of KCa3.1 induced by homeostasis of ACE-Ang II-AT1 axis and ACE2-Ang-(1-7)-Mas axis may be a new therapeutic target in myocardial fibrosis.

  1. MAS receptors mediate vasoprotective and atheroprotective effects of candesartan upon the recovery of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality.

    Science.gov (United States)

    Pernomian, Larissa; do Prado, Alejandro F; Gomes, Mayara S; Pernomian, Laena; da Silva, Carlos H T P; Gerlach, Raquel F; de Oliveira, Ana M

    2015-10-05

    AT1 antagonists effectively prevent atherosclerosis since AT1 upregulation and angiotensin II-induced proinflammatory actions are critical to atherogenesis. Despite the classic mechanisms underlying the vasoprotective and atheroprotective actions of AT1 antagonists, the cross-talk between angiotensin-converting enzyme-angiotensin II-AT1 and angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axes suggests other mechanisms beyond AT1 blockage in such effects. For instance, angiotensin-converting enzyme 2 activity is inhibited by reactive oxygen species derived from AT1-mediated proinflammatory signaling. Since angiotensin-(1-7) promotes antiatherogenic effects, we hypothesized that the vasoprotective and atheroprotective effects of AT1 antagonists could result from their inhibitory effects on the AT1-mediated negative modulation of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality. Interestingly, our results showed that early atherosclerosis triggered in thoracic aorta from high cholesterol fed-Apolipoprotein E-deficient mice impairs angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality by a proinflammatory-redox AT1-mediated pathway. In such mechanism, AT1 activation leads to the aortic release of tumor necrosis factor-α, which stimulates NAD(P)H oxidase/Nox1-driven generation of superoxide and hydrogen peroxide. While hydrogen peroxide inhibits angiotensin-converting enzyme 2 activity, superoxide impairs MAS functionality. Candesartan treatment restored the functionality of angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis by inhibiting the proinflammatory-redox AT1-mediated mechanism. Candesartan also promoted vasoprotective and atheroprotective effects that were mediated by MAS since A779 (MAS antagonist) co-treatment inhibited them. The role of MAS receptors as the final mediators of the vasoprotective and atheroprotective effects of candesartan was supported by the vascular actions of angiotensin-(1-7) upon the recovery of the functionality of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. http://dx.doi.org/10.4314/jae.v18i1.7 Climate Change Information ...

    African Journals Online (AJOL)

    PROF. MADUKWE

    billion-year history, but most of the changes occur in astronomical and geological time scale and are too low to be observed on a human scale (Killiman, 2008). The author further stated that natural climate variation on these scales is sometimes referred to as climate variability as distinct from human induced climate change.

  3. Room-temperature InGaAs detector arrays for 1.0 - 1.7 microns spectroscopy

    Science.gov (United States)

    Olsen, G. H.; Joshi, A. M.; Mykietyn, E.; Colosi, J.; Woodruff, K. M.

    1989-01-01

    Linear arrays of 256 element InGaAs detectors with 100 x 30 micron pixels were mounted in multiplexer packages and tested in an optical multichannel analyzer (OMA). Typical performance characteristics include dark current (-5V) of 400 picoamps and responsivities of 0.75 A/W (1.3 microns) and 0.14 A/W (0.85 microns). The 256 element exhibited a mean room-temperature dark current of under 400 picoamps when mounted in the OMA and a dynamic range over 11 bits (2000:1). Future applications, including room-temperature detector arrays for 2.5 microns and avalanche photodiode arrays for 1.0-1.7 microns, are discussed.

  4. The influence of angiotensin-(1-7) Mas receptor agonist (AVE 0991) on mitochondrial proteome in kidneys of apoE knockout mice.

    Science.gov (United States)

    Suski, Maciej; Olszanecki, Rafał; Stachowicz, Aneta; Madej, Józef; Bujak-Giżycka, Beata; Okoń, Krzysztof; Korbut, Ryszard

    2013-12-01

    Excessive action of angiotensin II on mitochondria has been shown to play an important role in mitochondrial dysfunction, a common feature of atherogenesis and kidney injury. Angiotensin-(1-7)/Mas receptor axis constitutes a countermeasure to the detrimental effects of angiotensin II on AT1 receptors. The aim of the study was to assess the effects of angiotensin-(1-7) peptidomimetic AVE0991 on the kidney mitochondrial proteome in widely used animal model of atherosclerosis (apoE(-/-) mice). Proteins changed in apoE(-/-) mice belonged to the groups of antioxidant enzymes, apoptosis regulators, inflammatory factors and metabolic enzymes. Importantly, AVE0991 partially reversed atherosclerosis-related changes in apoE(-/-) mice. © 2013.

  5. Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis.

    Science.gov (United States)

    Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Palaniyandi, Suresh S; Giridharan, Vijayasree V; Arozal, Wawaimuli; Sari, Flori R; Soetikno, Vivian; Harima, Meilei; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi

    2012-01-27

    Candesartan cilexetil, an angiotensin (Ang) II receptor 1 blocker was reported to suppress the myocardial damage in various cardiovascular complications but the mode by which it is effective in preventing the progression of dilated cardiomyopathy (DCM) is unknown. Emerging evidences suggest that, at least, part of the benefits observed with the use of AT1 receptor blockers could be attributed to the increased Ang (1-7) levels observed during administration of these agents. Identification of the novel components of the RAS, ACE2 and Ang (1-7) receptor mas, provided essential elements for considering the existence of a vasodilator arm of the RAS, represented by the ACE2-Ang (1-7)-mas axis. In this study, rat model of DCM was prepared by injection with porcine cardiac myosin. Twenty-eight days after immunization, candesartan cilexetil was administered intraperitoneally at 1 or 10mg/kg/day to rats for four weeks. Myocardial expression of Ang receptors and markers of calcium homeostasis, endoplasmic reticulum (ER) stress and apoptosis were measured by Western blotting and histopathological staining techniques. Candesartan improved the functional markers in a dose-dependent manner and also upregulated Ang (1-7), ACE2 and mas1 in the myocardium of DCM rats. Various ER stress and apoptosis markers were attenuated and the number apoptotic cells were significantly lower in the candesartan treated rats compared with those of the vehicle group. These findings suggest that candesartan treatment prevented the progression of DCM by activation of the counter regulatory arm of the RAS and possibly through modulation of ER stress and subsequently, cardiac apoptosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats.

    Science.gov (United States)

    Hao, Yuewen; Liu, Yan

    2016-01-01

    Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

  7. Increased nerve fiber expression of sensory sodium channels Nav1.7, Nav1.8, And Nav1.9 in rhinitis.

    Science.gov (United States)

    Keh, Siew M; Facer, Paul; Simpson, Karen D; Sandhu, Guri; Saleh, Hesham A; Anand, Praveen

    2008-04-01

    Voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 are involved in nerve action potentials and have been proposed to underlie neuronal hypersensitivity. We have therefore studied their levels in allergic and nonallergic rhinitis. Inferior turbinate biopsies from 50 patients (n = 18 controls, n = 20 allergic, and n = 12 nonallergic rhinitis) were studied by immunohistology using antibodies to Nav1.7, Nav1.8, and Nav1.9, the structural nerve marker (protein gene product [PGP]9.5), nerve growth factor (NGF), mast cells (c-kit), macrophages (CD68), and T cells (CD3). Sodium channel-positive nerve fibers were counted per millimeter length of subepithelium, and immunoreactivity for inflammatory cell markers PGP9.5 and NGF were image analyzed. All three sodium channel-immunoreactive nerve fiber numbers were significantly increased in allergic (Nav1.7, P = .0004; Nav1.8, P = .028; Nav1.9, P = .02) and nonallergic (Nav1.7, P = .006; Nav1.8, P = .019; Nav1.9, P = .0037) rhinitis. There was a significant increase of subepithelial innervation (PGP9.5, P = .01) and epithelial NGF immunoreactivity (P = .03) in nonallergic rhinitis, comparable with our previous report in allergic rhinitis. Inflammatory cell markers were significantly increased in allergic (mast cells, P = .06; macrophages, P = .044; T cells, P = .007) but not nonallergic rhinitis. The increased levels of sensory sodium channels in allergic and nonallergic rhinitis may contribute to the hypersensitive state, irrespective of the degree of active inflammation. Selective blockers of these sodium channels, administered topically, may have therapeutic potential in rhinitis.

  8. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    2007-04-01

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  9. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  10. Structure-activity relationship studies of 1,7-diheteroarylhepta-1,4,6-trien-3-ones with two different terminal rings in prostate epithelial cell models.

    Science.gov (United States)

    Wang, Rubing; Zhang, Xiaojie; Chen, Chengsheng; Chen, Guanglin; Sarabia, Cristian; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong

    2017-06-16

    To systematically investigate the structure-activity relationships of 1,7-diheteroarylhepta-1,4,6-trien-3-ones in three human prostate cancer cell models and one human prostate non-neoplastic epithelial cell model, thirty five 1,7-diarylhepta-1,4,6-trien-3-ones with different terminal heteroaromatic rings have been designed for evaluation of their anti-proliferative potency in vitro. These target compounds have been successfully synthesized through two sequential Horner-Wadsworth-Emmons reactions starting from the appropriate aldehydes and tetraethyl (2-oxopropane-1,3-diyl)bis(phosphonate). Their anti-proliferative potency against PC-3, DU-145 and LNCaP human prostate cancer cell lines can be significantly enhanced by the manipulation of the terminal heteroaromatic rings, further demonstrating the utility of 1,7-diarylhepta-1,4,6-trien-3-one as a potential scaffold for the development of anti-prostate cancer agents. The optimal analog 40 is 82-, 67-, and 39-fold more potent than curcumin toward the three prostate cancer cell lines, respectively. The experimental data also reveal that the trienones with two different terminal aromatic rings possess greater potency toward three prostate cancer cell lines, but also have greater capability of suppressing the proliferation of PWR-1E benign human prostate epithelial cells, as compared to the corresponding counterparts with two identical terminal rings and curcumin. The terminal aromatic rings also affect the cell apoptosis perturbation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Propiedades metalúrgicas y electroquímicas de la aleación Au-1,7% Ti para aplicaciones odontológicas

    Directory of Open Access Journals (Sweden)

    Hector Darío Sánchez

    2006-01-01

    Full Text Available En el presente trabajo se evalúa la microestructura y la micro-dureza de una aleación Au-1,7% Ti en las condiciones centrifugada, solubilizada y con posterior envejecimiento a 400°C por 4 horas. En estas condiciones, se comparan las curvas de polarización obtenidas en solución de fisiológica artificial (Ringer de la aleación Au-1,7% Ti, con tratamiento superficial de pasivación y sin, con respecto a las de la aleación Au-Pd-Ga-In y oro puro. Se concluye que la aleación Au-1,7% Ti, tiene buena respuesta al tratamiento térmico de envejecimiento y presenta satisfactorio, aunque menor, comportamiento electroquímico en la condición pasivada, con respecto a la aleación comercial de Au-Pd-Ga-In.

  12. Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution.

    Science.gov (United States)

    Moiseeva, Natalia; Bau, Robert; Swenson, Stephen D; Markland, Francis S; Choe, Jun Yong; Liu, Zhi Jie; Allaire, Marc

    2008-04-01

    Disintegrins are a family of small (4-14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an alphabeta heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R(work) and R(free) of 18.6% and 21.5%, respectively, using all data in the 20-1.7 A resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short beta-sheets, each of which is formed by a pair of antiparallel beta-strands connected by beta-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the alphabeta chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an alphabetabetaalpha acostatin tetramer. Further experiments are required to identify whether the alphabetabetaalpha acostatin complex plays a functional role in vivo.

  13. Structure of Acostatin, a Dimeric Disintegrin From Southern Copperhead (Agkistrodon Contortrix Contortrix), at 1.7 Angstrom Resolution

    Energy Technology Data Exchange (ETDEWEB)

    Moiseeva, N.; Bau, R.; Swenson, S.D.; Marklund, F.S.; Jr.; Choe, J.-Y.; Liu, Z.-J.; Allaire, M.

    2009-05-26

    Disintegrins are a family of small (4-14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an {alpha}{beta} heterodimeric disintegrin, has been isolated from the venom of Southern copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure of acostatin has been determined by macromolecular crystallography using the molecular-replacement method. The asymmetric unit of the acostatin crystals consists of two heterodimers. The structure has been refined to an R{sub work} and R{sub free} of 18.6% and 21.5%, respectively, using all data in the 20-1.7 {angstrom} resolution range. The structure of all subunits is similar and is well ordered into N-terminal and C-terminal clusters with four intramolecular disulfide bonds. The overall fold consists of short {beta}-sheets, each of which is formed by a pair of antiparallel {beta}-strands connected by {beta}-turns and flexible loops of different lengths. Conformational flexibility is found in the RGD loops and in the C-terminal segment. The interaction of two N-terminal clusters via two intermolecular disulfide bridges anchors the {alpha}{beta}chains of the acostatin dimers. The C-terminal clusters of the heterodimer project in opposite directions and form a larger angle between them in comparison with other dimeric disintegrins. Extensive interactions are observed between two heterodimers, revealing an {alpha}{beta}{beta}{alpha} acostatin tetramer. Further experiments are required to identify whether the {alpha}{beta}{beta}{alpha} acostatin complex plays a functional role in vivo.

  14. Effects of angiotensin (1-7 on nephrosis of the mice with metabolic syndrome induced by high-salt and high-fat diet

    Directory of Open Access Journals (Sweden)

    Nan ZHU

    2013-11-01

    Full Text Available Objective  To establish a metabolic syndrome model of C57BL/6 mice by high-salt and high-fat diet, and investigate the effects of angiotensin converting enzyme 2 (ACE 2 and angiotensin (1-7 on renal damage in mice. Methods Fifty-six male C57BL/6 mice were randomly divided into 7 groups (8 each, and fed with normal diet (0.3% NaCl, 10% fat, high-salt diet (8% NaCl, 10% fat, high-fat diet (0.3% NaCl, 60% fat, high-salt and high-fat diet (8% NaCl, 60% fat, high-salt and high-fat diet with enalapril 20mg/(kg•d, with valsartan 50mg/(kg•d, and with valsartan 50mg/(kg•d plus Mas receptor antagonist (A-779 150ng/(kg•d, respectively for 16 weeks. Basal metabolic index including blood pressure, body weight, blood glucose and urinary albumin excretion rate (UAER were tested. After intraperitoneal anesthesia with chloral hydrate, the blood was collected from the carotid artery. Serum angiotensin Ⅱ and angiotensin (1-7 levels were detected by ELISA; Western blotting was performed to evaluate the expression of ACE 2 protein and collagen Ⅲ in renal tissue; renal pathological changes were observed by HE and Masson staining. Results The blood pressure, ratio of visceral fat weight/body weight, blood lipid, blood glucose and UAER increased significantly in the C57BL/6 mice fed with high-salt and high-fat diet for 16 weeks, and the renal fibrosis change was obvious, serum angiotensin Ⅱ level increased, expressions of ACE 2 and angiotensin (1-7 decreased significantly in the renal tissue. In different intervention groups, valsartan obviously alleviated the abnormal metabolism, ameliorated renal injury, promoted the expression of ACE2 and angiotensin (1-7 in the kidney and serum. However, no significant change was observed in the groups with intervention of enalapril or valsartan+A-779 compared with non-intervention group. Conclusions High-salt and high-fat diet can be used to successfully establish the model of metabolic syndrome in C57BL/6 mice. Valsartan, an angiotensin Ⅱ receptor blocker, can alleviate the metabolic abnormality caused by the high-salt and high-fat diet, and the protection mechanism may be related to up-regulation of angiotensin (1-7. DOI: 10.11855/j.issn.0577-7402.2013.10.001

  15. Bromodomain-containing Protein 4 Activates Voltage-gated Sodium Channel 1.7 Transcription in Dorsal Root Ganglia Neurons to Mediate Thermal Hyperalgesia in Rats.

    Science.gov (United States)

    Hsieh, Ming-Chun; Ho, Yu-Cheng; Lai, Cheng-Yuan; Wang, Hsueh-Hsiao; Lee, An-Sheng; Cheng, Jen-Kun; Chau, Yat-Pang; Peng, Hsien-Yu

    2017-11-01

    Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1.7, which is a key pain-related ion channel. The intraplantar complete Freund's adjuvant injections resulted in thermal hyperalgesia (4.0 ± 1.5 s; n = 7). The immunohistochemistry and immunoblotting results demonstrated an increase in the bromodomain-containing protein 4-expressing dorsal root ganglia neurons (3.78 ± 0.38 fold; n = 7) and bromodomain-containing protein 4 protein levels (2.62 ± 0.39 fold; n = 6). After the complete Freund's adjuvant injection, histone H3 protein acetylation was enhanced in the voltage-gated sodium channel 1.7 promoter, and cyclin-dependent kinase 9 and phosphorylation of RNA polymerase II were recruited to this area. Furthermore, the voltage-gated sodium channel 1.7-mediated currents were enhanced in neurons of the complete Freund's adjuvant rats (55 ± 11 vs. 19 ± 9 pA/pF; n = 4 to 6 neurons). Using bromodomain-containing protein 4-targeted antisense small interfering RNA to the complete Freund's adjuvant-treated rats, the authors demonstrated a reduction in the expression of bromodomain-containing protein 4 (0.68 ± 0.16 fold; n = 7), a reduction in thermal hyperalgesia (7.5 ± 1.5 s; n = 7), and a reduction in the increased voltage-gated sodium channel 1.7 currents (21 ± 4 pA/pF; n = 4 to 6 neurons). Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is likely mediated by the enhanced expression of voltage-gated sodium channel 1.7.

  16. P1-7: Modern Display Technology in Vision Science: Assessment of OLED and LCD Monitors for Visual Experiments

    Directory of Open Access Journals (Sweden)

    Tobias Elze

    2012-10-01

    Full Text Available For many decades, cathode ray tube (CRT monitors have been the dominant display technology in vision science. However, in recent years, most manufacturers stopped their CRT production lines, which enforces the application of alternative display technology in the field of vision science. Here, we analyze liquid crystal displays (LCDs and organic light-emitting diode (OLED monitors for their applicability in vision science experiments. Based on extensive measurements of their photometric output, we compare these technologies and contrast them with classical CRT monitors. Vision scientists aim to accurately present both static and dynamic stimuli on their display devices. As for the presentation of static stimuli, we demonstrate an increased accuracy for LCD and OLED devices compared to CRT monitors, because the former exhibit a higher degree of independence of neighboring pixels. As for dynamic presentations, both CRTs and OLEDs outperform LCD devices in terms of accuracy, because dynamic presentations on LCDs require a reorientation of the liquid crystal molecules, so that successive frames in time depend on each other. Together with widely unknown and uncontrolled technical artifacts, these properties of LCDs may impair visual experiments that require high temporal precision. Therefore, OLED monitors are more suitable for vision science experiments with respect to both their static and their temporal characteristics. However, for certain applications in visual neuroscience, the low duty cycle of some OLED devices may introduce frequencies to the photometric output which fall within the window of visibility of neurons in the visual cortex and therefore interfere with single unit recordings.

  17. Quality of management of oral anticoagulation as assessed by time in therapeutic INR range in elderly and younger patients with low mean years of formal education: a prospective cohort study.

    Science.gov (United States)

    Costa, Gustavo Lamego de Barros; Ferreira, Diana Carvalho; Valacio, Reginaldo Aparecido; Vieira Moreira, Maria da Consolação

    2011-05-01

    despite the overwhelming evidence of its effectiveness, oral anticoagulation continues to be underused in the elderly, presumably due to physicians' misconceptions when estimating bleeding risk and ability to comply with treatment. to investigate the quality of anticoagulation control among deprived elderly and younger patients. prospective observational study. a public anticoagulation clinic in a developing country. all adult patients on intended long-term (>90 days) oral anticoagulation. We studied 171 patients (79 elderly and 92 non-elderly) with a mean follow-up of 273 ± 84.9 days. the main outcome measure was the quality of anticoagulation management as measured by the time in therapeutic (TTR) international normalised ratio (INR) range. Elderly patients (≥60 years) were compared with younger patients with respect to the educational level and co-morbidities. the mean number of years of formal education was 4.37 ± 3.2 years. The mean TTR was 62.50 ± 17.9% in non-elderly and 62.10 ± 16.6% in elderly (P = 0.862) subjects, despite the higher prevalence of co-morbidities in the latter group: heart failure (46.3 versus 28.6%, P = 0.042), diabetes mellitus (22.8 versus 8.7%, P = 0.011), renal failure (estimated glomerular filtration rate educational levels (3.42 ± 2.5 versus 5.55 ± 3.4 years of formal education, P quality management of oral anticoagulation is achievable in deprived populations attending an anticoagulation clinic. Elderly patients may experience similar quality of anticoagulation despite having higher levels of co-morbidities and polypharmacy. These results add evidence to the safety of such therapeutic interventions in the elderly.

  18. Hydrothermal heat discharge in the Cascade Range, northwestern United States

    Science.gov (United States)

    Ingebritsen, S.E.; Mariner, R.H.

    2010-01-01

    Hydrothermal heat discharge in the Cascade Range includes the heat discharged by thermal springs, by "slightly thermal" springs that are only a few degrees warmer than ambient temperature, and by fumaroles. Thermal-spring heat discharge is calculated on the basis of chloride-flux measurements and geothermometer temperatures and totals ~ 240 MW in the U.S. part of the Cascade Range, excluding the transient post-1980 discharge at Mount St. Helens (~80 MW as of 2004-5). Heat discharge from "slightly thermal" springs is based on the degree of geothermal warming (after correction for gravitational potential energy effects) and totals ~. 660. MW. Fumarolic heat discharge is calculated by a variety of indirect and direct methods and totals ~160 MW, excluding the transient mid-1970s discharge at Mount Baker (~80 MW) and transient post-1980 discharge at Mount St. Helens (>. 230. MW as of 2005). Other than the pronounced transients at Mount St. Helens and Mount Baker, hydrothermal heat discharge in the Cascade Range appears to be fairly steady over a ~25-year period of measurement. Of the total of ~. 1050. MW of "steady" hydrothermal heat discharge identified in the U.S. part of the Cascade Range, less than 50. MW occurs north of latitude 45??15' N (~0.1 MW per km arc length from 45??15' to 49??N). Much greater rates of hydrothermal heat discharge south of 45??15'N (~1.7 MW per km arc length from 40?? to 45??15'N) may reflect the influence of Basin and Range-style extensional tectonics (faulting) that impinges on the Cascades as far north as Mount Jefferson but is not evident farther north. ?? 2010.

  19. Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells

    Science.gov (United States)

    Terasaka, Tomohiro; Otsuka, Fumio; Tsukamoto, Naoko; Nakamura, Eri; Inagaki, Kenichi; Toma, Kishio; Ogura-Ochi, Kanako; Glidewell-Kenney, Christine; Lawson, Mark A.; Makino, Hirofumi

    2014-01-01

    Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentrationdependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ERα and ERβ, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells. PMID:23880664

  20. Identification of the para-nitrophenol catabolic pathway, and characterization of three enzymes involved in the hydroquinone pathway, in pseudomonas sp. 1-7

    Directory of Open Access Journals (Sweden)

    Zhang Shuangyu

    2012-03-01

    Full Text Available Abstract Background para-Nitrophenol (PNP, a priority environmental pollutant, is hazardous to humans and animals. However, the information relating to the PNP degradation pathways and their enzymes remain limited. Results Pseudomonas sp.1-7 was isolated from methyl parathion (MP-polluted activated sludge and was shown to degrade PNP. Two different intermediates, hydroquinone (HQ and 4-nitrocatechol (4-NC were detected in the catabolism of PNP. This indicated that Pseudomonas sp.1-7 degraded PNP by two different pathways, namely the HQ pathway, and the hydroxyquinol (BT pathway (also referred to as the 4-NC pathway. A gene cluster (pdcEDGFCBA was identified in a 10.6 kb DNA fragment of a fosmid library, which cluster encoded the following enzymes involved in PNP degradation: PNP 4-monooxygenase (PdcA, p-benzoquinone (BQ reductase (PdcB, hydroxyquinol (BT 1,2-dioxygenase (PdcC, maleylacetate (MA reductase (PdcF, 4-hydroxymuconic semialdehyde (4-HS dehydrogenase (PdcG, and hydroquinone (HQ 1,2-dioxygenase (PdcDE. Four genes (pdcDEFG were expressed in E. coli and the purified pdcDE, pdcG and pdcF gene products were shown to convert HQ to 4-HS, 4-HS to MA and MA to β-ketoadipate respectively by in vitro activity assays. Conclusions The cloning, sequencing, and characterization of these genes along with the functional PNP degradation studies identified 4-NC, HQ, 4-HS, and MA as intermediates in the degradation pathway of PNP by Pseudomonas sp.1-7. This is the first conclusive report for both 4-NC and HQ- mediated degradation of PNP by one microorganism.

  1. Throttling Characteristics of the RL10 Derivative Common Extensible Cryogenic Engine -- Demo 1.6 and 1.7 Test Results

    Science.gov (United States)

    Devine, Matthew K.; Hulka, James; Adamski, Walt; Brown, Corey

    2010-01-01

    The Common Extensible Cryogenic Engine (CECE) is a deep throttling cryogenic Lunar Module Descent Engine (LMDE) technology development demonstrator based on the Pratt & Whitney Rocketdyne (PWR) RL10 engine. Previous testing on this engine occurred during 2006 as Demo 1.0, then Demo 1.5 in 2007, Demo 1.6 in 2008 and finally Demo 1.7 in 2010. A review of Demo 1.0, 1.5, and preliminary results of 1.6 were reported in previous JANNAF papers. Demo 1.6 was tested at the PWR E-6 test facility in November 2008. The primary goal of this series was to mitigate low frequency combustion instability observed at low power levels. To mitigate the chug, the Demo 1.6 injector was modified from the previous configurations to include an approximately 0.050 inch thick teflon-type spray-on insulation to reduce heat transfer to the LOX manifold, which was believed to be a significant contributor to the low power instability. In addition, gaseous helium injection into the LOX manifold was used as a means to stabilize the system. Also explored in this test series was mitigation for a low power 1 Hz fuel system oscillation caused by sub-critical hydrogen boiling in the chamber cooling jacket. Reduced area gas venturis were utilized to avoid the 1 Hz fuel-size oscillation by keeping the cooling jacket supercritical down to lower engine power levels. Demo 1.7 began testing in March 2010. Its primary objectives were to demonstrate closed loop control capability on mixture ratio and chamber pressure, start to lower power levels and increased throttling ramp rates. Secondary test objectives that are discussed include multiple engine starts, higher mixture ratio excursions and additional time at low power level. While the complete test series and data reduction is not yet complete for Demo 1.7, an overview and up-to-date status is provided.

  2. Effects of a new potent analog of tocainide on hNav1.7 sodium channels and in vivo neuropathic pain models.

    Science.gov (United States)

    Ghelardini, C; Desaphy, J-F; Muraglia, M; Corbo, F; Matucci, R; Dipalma, A; Bertucci, C; Pistolozzi, M; Nesi, M; Norcini, M; Franchini, C; Camerino, D Conte

    2010-08-25

    The role of voltage-gated sodium channels in the transmission of neuropathic pain is well recognized. For instance, genetic evidence recently indicate that the human Nav1.7 sodium channel subtype plays a crucial role in the ability to perceive pain sensation and may represent an important target for analgesic/anti-hyperalgesic drugs. In this study a newly synthesized tocainide congener, named NeP1, was tested in vitro on recombinant hNav1.4 and hNav1.7 channels using patch-clamp technique and, in vivo, in two rat models of persistent neuropathic pain obtained either by chronic constriction injury of the sciatic nerve or by oxaliplatin treatment. NeP1 efficiently blocked hNav1.4 and hNav1.7 channels in a dose- and use-dependent manner, being by far more potent than tocainide. Importantly, the new compound displayed a remarkable use-dependent effect, which likely resulted from a very high affinity for inactivated compared to closed channels. In both models of neuropathic pain, NeP1 was greatly more potent than tocainide in reverting the reduction of pain threshold in vivo. In oxaliplatin-treated rats, NeP1 even produced greater and more durable anti-hyperalgesia than the reference drug tramadol. In addition, in vivo and in vitro studies suggest a better toxicological and pharmacokinetic profile for NeP1 compared to tocainide. Overall, these results indicate NeP1 as a new promising lead compound for further development in the treatment of chronic pain of neuropathic origin. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Beneficial effects of the activation of the angiotensin-(1-7) MAS receptor in a murine model of adriamycin-induced nephropathy.

    Science.gov (United States)

    Silveira, Kátia Daniela; Barroso, Lívia Corrêa; Vieira, Angélica Thomáz; Cisalpino, Daniel; Lima, Cristiano Xavier; Bader, Michael; Arantes, Rosa Maria Esteves; Dos Santos, Robson Augusto Souza; Simões-E-Silva, Ana Cristina; Teixeira, Mauro Martins

    2013-01-01

    Angiotensin-(1-7) [Ang-(1-7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-β. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas(+/+) ) and Mas knockout (Mas (-/-)) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas(+/+) , but not in Mas (-/-) mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1-7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies.

  4. Expression and function of the ACE2/angiotensin(1-7)/Mas axis in osteosarcoma cell lines U-2 OS and MNNG-HOS.

    Science.gov (United States)

    Ender, Stephan Albrecht; Dallmer, Andrea; Lässig, Florian; Lendeckel, Uwe; Wolke, Carmen

    2014-08-01

    The renin-angiotensin-system (RAS), via its classical angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type 1 receptor (AT1R)-axis, is associated with proliferation and metastasis of numerous types of solid tumor. AT1R blockers reduce tumor volume and decrease liver and lung metastasis in murine models of osteosarcoma. Expression and function of the alternative ACE2/Ang(1-7)/Mas axis in osteosarcoma is yet to be studied. In the present study, the basic and interleukin (IL)-1β-stimulated expression of components of this alternative RAS axis were analyzed and the impact of Mas on proliferation and/or migration of U-2 OS and MNNG-HOS osteosarcoma cells was studied. Quantitative polymerase chain reaction revealed that the two cell lines expressed the Ang(1‑7)-generating peptidases ACE2, neutral endopeptidase 24.11 and prolyl-endopeptidase together with the putative receptor for Ang(1-7), Mas. IL-1β provoked an induction of Mas mRNA and protein expression which was associated with a reduction of proliferation and migration. By contrast, small interfering RNA-mediated knockdown of Mas expression led to increased cell proliferation. In conclusion, osteosarcoma cells express a functional active alternative ACE2/Ang(1-7)/Mas axis. The induction and reinforcement of this axis may be beneficial for the treatment of osteosarcoma by reducing growth and preventing cancer metastasis. These effects may be achieved directly by the administration of Mas agonists or, indirectly, via blocking the classical AngII RAS axis via ACE inhibitors or AT1R antagonists.

  5. Melanocortin-induced PKA activation inhibits AMPK activity via ERK-1/2 and LKB-1 in hypothalamic GT1-7 cells.

    Science.gov (United States)

    Damm, Ellen; Buech, Thomas R H; Gudermann, Thomas; Breit, Andreas

    2012-04-01

    α-Melanocyte-stimulating hormone (α-MSH)-induced activation of the melanocortin-4 receptor in hypothalamic neurons increases energy expenditure and inhibits food intake. Active hypothalamic AMP-activated protein kinase (AMPK) has recently been reported to enhance food intake, and in vivo experiments suggested that intrahypothalamic injection of melanocortins decreased food intake due to the inhibition of AMPK activity. However, it is not clear whether α-MSH affects AMPK via direct intracellular signaling cascades or if the release of paracrine factors is involved. Here, we used a murine, hypothalamic cell line (GT1-7 cells) and monitored AMPK phosphorylation at Thr(172), which has been suggested to increase AMPK activity. We found that α-MSH dephosphorylated AMPK at Thr(172) and consequently decreased phosphorylation of the established AMPK substrate acetyl-coenzyme A-carboxylase at Ser(79). Inhibitory effects of α-MSH on AMPK were blocked by specific inhibitors of protein kinase A (PKA) or ERK-1/2, pointing to an important role of both kinases in this process. Because α-MSH-induced activation of ERK-1/2 was blunted by PKA inhibitors, we propose that ERK-1/2 serves as a link between PKA and AMPK in GT1-7 cells. Furthermore, down-regulation of liver kinase B-1, but not inhibition of calcium-calmodulin-dependent kinase kinase-β or TGFβ-activated kinase-1 decreased basal phosphorylation of AMPK and its dephosphorylation induced by α-MSH. Thus, we propose that α-MSH inhibits AMPK activity via a linear pathway, including PKA, ERK-1/2, and liver kinase B-1 in GT1-7 cells. Given the importance of the melanocortin system in the formation of adipositas, detailed knowledge about this pathway might help to develop drugs targeting obesity.

  6. Dissipation mechanism in a high-T{sub c} Bi{sub 1.7}Pb{sub 0.3}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} granular superconductor

    Energy Technology Data Exchange (ETDEWEB)

    Bhalla, G.L.; Pratima; Malik, Amita; Singh, K.K

    2003-08-01

    Magneto-resistance studies in a high-T{sub c} granular superconductor Bi{sub 1.7}Pb{sub 0.3}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} in an applied magnetic field ranging from 0 to 0.6 T in the low current limits (1 mA) have been carried out to understand the dissipation mechanism in high-T{sub c} superconducting materials. The Kosterlitz-Thouless (KT) as well as the Ambegaoker-Halperin (AH) widely employed models are invoked to interpret the results. The KT theory is found to account for dissipation in the temperature range T{sub KT}range of temperature can be accounted for on the basis of a modified Ambegaokar-Halperin theory incorporating two mechanisms, viz. vortex-dynamics and the fluctuations of the order parameter and the two mechanisms crossover at a transition temperature (T{sub BP})

  7. Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

    OpenAIRE

    Ying Wang; Jianxun Mi; Ka Lu; Yanxin Lu; KeWei Wang

    2015-01-01

    Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While...

  8. Microwave-assisted reactive sintering and lithium ion conductivity of Li 1.3 Al 0.3 Ti 1.7 (PO 4 ) 3 solid electrolyte

    OpenAIRE

    Hallopeau, Leopold; Bregiroux, Damien; Rousse, Gwenaëlle; Portehault, David; Stevens, Philippe; Toussaint, Gwenaëlle; Laberty-Robert, Christel

    2018-01-01

    International audience; Li1.3Al0.3Ti1.7(PO4)3 (LATP) materials are made of a three−dimensional framework of TiO6 octahedra and PO4 tetrahedra, which provides several positions for Li+ ions. The resulting high ionic conductivity is promising to yield electrolytes for all-solid-state Li-ion batteries. In order to elaborate dense ceramics, conventional sintering methods often use high temperature (≥1000 °C) with long dwelling times (several hours) to achieve high relative density (∼90%). In this...

  9. Angiotensin II and angiotensin-(1-7 decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

    Directory of Open Access Journals (Sweden)

    Moorefield Cheryl

    2010-11-01

    Full Text Available Abstract Background During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF, placental growth factor (PLGF, soluble VEGF receptor 1 (sFlt1, and soluble endoglin (sEng are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy. Methods We evaluated the effects of angiotensin II (Ang II and angiotensin-(1-7 [Ang-(1-7] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV. CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM or Ang-(1-7 (1 nM and 1 microM. The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH, and human placenta lactogen (HPL was measured by ELISA. Results The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM and Ang-(1-7 (1 nM and 1 microM. There was a time-dependent increase in HPL indicating that the CV were functioning normally. Conclusions Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.

  10. Signature of surface periodicity in the electronic structure of Si(1 1 1)-(7 × 7)

    Science.gov (United States)

    Sheverdyaeva, P. M.; Mahatha, S. K.; Ronci, F.; Colonna, S.; Moras, P.; Satta, M.; Flammini, R.

    2017-06-01

    The surface electronic structure of Si(1 1 1)-7× 7 has been studied by angle-resolved photo electron spectroscopy. Replicas of the S 1 surface state are found in correspondence with several 7× 7 unit cells in the reciprocal space. This observation resolves in a direct way the long-standing dichotomy between the structural and electronic properties of the system previously discussed on the basis of the 2× 2 or \\sqrt{3}× \\sqrt{3} R30° surface models.

  11. Evidence of Gate Voltage Oscillations during Short Circuit of Commercial 1.7 kV/ 1 kA IGBT Power Modules

    DEFF Research Database (Denmark)

    Reigosa, Paula Diaz; Wu, Rui; Iannuzzo, Francesco

    2015-01-01

    This paper analyzes the evidence of critical gate voltage oscillations in 1.7 kV/1 kA Insulated-Gate Bipolar Transistor (IGBT) power modules under short circuit conditions. A 6 kA/1.1 kV Non-Destructive Test (NDT) set up for repeatable short circuit tests has been built with a 40 nH stray...... inductance. A large amount of measurements have been acquired on commercial IGBT modules evidencing gate voltage oscillations under short circuit conditions. To tackle this problem, similar tests have been performed on a modified version of the same modules with two parallel sections and one single section...

  12. Challenges and advantages in wide-field optical coherence tomography angiography imaging of the human retinal and choroidal vasculature at 1.7-MHz A-scan rate

    Science.gov (United States)

    Poddar, Raju; Migacz, Justin V.; Schwartz, Daniel M.; Werner, John S.; Gorczynska, Iwona

    2017-10-01

    We present noninvasive, three-dimensional, depth-resolved imaging of human retinal and choroidal blood circulation with a swept-source optical coherence tomography (OCT) system at 1065-nm center wavelength. Motion contrast OCT imaging was performed with the phase-variance OCT angiography method. A Fourier-domain mode-locked light source was used to enable an imaging rate of 1.7 MHz. We experimentally demonstrate the challenges and advantages of wide-field OCT angiography (OCTA). In the discussion, we consider acquisition time, scanning area, scanning density, and their influence on visualization of selected features of the retinal and choroidal vascular networks. The OCTA imaging was performed with a field of view of 16 deg (5 mm×5 mm) and 30 deg (9 mm×9 mm). Data were presented in en face projections generated from single volumes and in en face projection mosaics generated from up to 4 datasets. OCTA imaging at 1.7 MHz A-scan rate was compared with results obtained from a commercial OCTA instrument and with conventional ophthalmic diagnostic methods: fundus photography, fluorescein, and indocyanine green angiography. Comparison of images obtained from all methods is demonstrated using the same eye of a healthy volunteer. For example, imaging of retinal pathology is presented in three cases of advanced age-related macular degeneration.

  13. Dual Polarized Dual Fed Vivaldi Antenna for Cellular Base Station Operating at 1.7–2.7 GHz

    Directory of Open Access Journals (Sweden)

    Marko Sonkki

    2017-01-01

    Full Text Available The paper presents a novel dual polarized dual fed Vivaldi antenna structure for 1.7–2.7 GHz cellular bands. The radiating element is designed for a base station antenna array with high antenna performance criteria. One radiating element contains two parallel dual fed Vivaldi antennas for one polarization with 65 mm separation. Both Vivaldi antennas for one polarization are excited symmetrically. This means that the amplitudes for both antennas are equal, and the phase difference is zero. The orthogonal polarization is implemented in the same way. The dual polarized dual fed Vivaldi is positioned 15 mm ahead from the reflector to improve directivity. The antenna is designed for -14 dB impedance bandwidth (1.7–2.7 GHz with better than 25 dB isolation between the antenna ports. The measured total efficiency is better than -0.625 dB (87% and the antenna presents a flat, approximately 8.5 dB, gain in the direction of boresight over the operating bandwidth whose characteristics promote it among the best antennas in the field. Additionally, the measured cross polarization discrimination (XPD is between 15 and 30 dB and the 3 dB beamwidth varies between 68° and 75° depending on the studied frequency.

  14. Structure of a putative trans-editing enzyme for prolyl-tRNA synthetase from Aeropyrum pernix K1 at 1.7 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Murayama, Kazutaka; Kato-Murayama, Miyuki; Katsura, Kazushige; Uchikubo-Kamo, Tomomi; Yamaguchi-Hirafuji, Machiko; Kawazoe, Masahito; Akasaka, Ryogo; Hanawa-Suetsugu, Kyoko; Hori-Takemoto, Chie [RIKEN Genomic Sciences Center, Yokohama (Japan); Terada, Takaho [RIKEN Genomic Sciences Center, Yokohama (Japan); RIKEN Harima Institute at SPring-8, Hyogo (Japan); Shirouzu, Mikako [RIKEN Harima Institute at SPring-8, Hyogo (Japan); Yokoyama, Shigeyuki, E-mail: yokoyama@biochem.s.u-tokyo.ac.jp [RIKEN Genomic Sciences Center, Yokohama (Japan); RIKEN Harima Institute at SPring-8, Hyogo (Japan); Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo (Japan)

    2005-01-01

    The three-dimensional structure of the APE2540 protein from A. pernix K1 has been determined by the multiple anomalous dispersion method at 1.7 Å resolution. The structure includes two monomers in the asymmetric unit and shares structural similarity with the YbaK protein or cysteinyl-tRNA{sup Pro} deacylase from H. influenzae. The crystal structure of APE2540, the putative trans-editing enzyme ProX from Aeropyrum pernix K1, was determined in a high-throughput manner. The crystal belongs to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 47.4, b = 58.9, c = 53.6 Å, β = 106.8°. The structure was solved by the multiwavelength anomalous dispersion method at 1.7 Å and refined to an R factor of 16.8% (R{sub free} = 20.5%). The crystal structure includes two protein molecules in the asymmetric unit. Each monomer consists of eight β-strands and seven α-helices. A structure-homology search revealed similarity between the trans-editing enzyme YbaK (or cysteinyl-tRNA{sup Pro} deacylase) from Haemophilus influenzae (HI1434; 22% sequence identity) and putative ProX proteins from Caulobacter crescentus (16%) and Agrobacterium tumefaciens (21%)

  15. Nrf2 Deficiency Upregulates Intrarenal Angiotensin-converting Enzyme-2 and Angiotensin 1-7 Receptor Expression and Attenuates Hypertension and Nephropathy in Diabetic Mice.

    Science.gov (United States)

    Zhao, Shuiling; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Scholey, James W; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao-Ling; Chan, John S D

    2017-12-01

    We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout (KO) mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined immortalized rat RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2) or angiotensin 1-7 receptor (MasR) gene promoters. Genetic deletion of Nrf2 or pharmacological inhibition of Nrf2 attenuated hypertension, renal injury, and tubulointerstitial fibrosis, and lowered the urinary albumin/creatinine ratio as well as upregulated RPTC Ace2 and MasR expression, increased urinary angiotensin 1-7 levels parallel with down-regulation of Agt, ACE and pro-fibrotic gene expression compared to non-treated Akita mice. In cultured IRPTCs, Nrf2 small interfering RNA transfection or trigonelline treatment prevented high glucose-stimulation of Nrf2 nuclear translocation, Agt and ACE transcription with augmentation of Ace2 and MasR transcription, which was reversed by oltipraz. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal RAS gene expression, by which chronic hyperglycemia induces hypertension and renal injury in diabetes. Copyright © 2017 Endocrine Society.

  16. Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis.

    Science.gov (United States)

    Li, Yonghong; Cai, Shanglang; Wang, Qixin; Zhou, Jingwei; Hou, Bo; Yu, Haichu; Ge, Zhiming; Guan, Renyan; Liu, Xu

    2016-05-15

    The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Behavioural and physiological indicators of shelter dogs' welfare: reflections on the no-kill policy on free-ranging dogs in Italy revisited on the basis of 15 years of implementation.

    Science.gov (United States)

    Cafazzo, S; Maragliano, L; Bonanni, R; Scholl, F; Guarducci, M; Scarcella, R; Di Paolo, M; Pontier, D; Lai, O; Carlevaro, F; Bucci, E; Cerini, N; Carlevaro, L; Alfieri, L; Fantini, C; Natoli, E

    2014-06-22

    The Italian National Law 281 of 1991 forbids the euthanatization of free-ranging dogs, unless they have an incurable illness or are proved to be dangerous. Without neglecting the undeniable benefits of the "no-kill" policy, nevertheless it has brought about a chronic overpopulation in shelters and, as a result, higher costs of management and welfare problems since some dogs remain in the shelter for life. In 2004-2008, the Istituto Zooprofilattico Sperimentale of the Lazio and Tuscany regions carried out a survey in the Lazio Region to verify the effects of the Italian National Law 281/91 on free-ranging dog management following 15 years from its implementation. One of the aims of the study was an assessment of the welfare of dogs in a shelter sample (8 shelters out of 47 censused in the Lazio Region). 97 mixed-breed dogs were selected, their behaviour was studied and a blood sample was taken for each dog in order to determine the individual blood concentration of cortisol and the amount of oxidative damage (level of dRoms), as well as the amount of antioxidants to cope with it. Moreover, the total leukocyte count (leukogram) was accomplished. We ran general backward stepwise regression models using "level of antioxidant", "level of dRoms" and "level of serum cortisol" as dependent variables respectively. The results showed that the most important variable that improved the level of welfare of dogs consisted in having the opportunity to regularly go out of the cage for a walk, whereas other variables like gender, size of the cage (small, medium, large), being alone in the cage, and being neutered/entire, had no significant effect on the physiological indicators of welfare. Dogs that enjoyed the regular walk had a higher total antioxidant capacity, and performed a lower frequency of displacing activities and stereotyped behaviour. Moreover, oxidative stress parameters seem to be indicators well matched with behavioural indicators of stress. Thus, for the first time

  18. Social transformation served at the table: cultural interpretation and sócio-religious of the of the footwashy in Jo 13, 1-17

    OpenAIRE

    Lara, Valter Luiz

    2014-01-01

    O lava-pés em Jo 13,1-17 é objeto dessa tese que tem por objetivo apresentar sua significação cultural e sociorreligiosa. Em meio à complexidade do caráter polissêmico do relato joanino o foco da análise volta-se para o contexto das características do costume cultural implicados no lava-pés em ambiente de refeição no mundo mediterrâneo do primeiro século da EC. Com base na análise da história da redação o relato joanino é apresentado como fruto de um processo de recuperação da memória tradici...

  19. Measurement of deflection on germanium and gold prisms using 1.7 MeV laser Compton scattering γ-rays

    Science.gov (United States)

    Kawasaki, T.; Naito, S.; Sano, Y.; Hayakawa, T.; Shizuma, T.; Hajima, R.; Miyamoto, S.

    2017-09-01

    We measured the refractive index of germanium and gold prisms at 1.7 MeV to explore if there are refractive index enhancements to 6th power of atomic number due to high order nonlinear process of Delbrück scattering in quantum electrodynamics. We measured the deflection by prisms using imaging plates and laser Compton scattering γ-rays with linear and random polarization. We used crystal and polycrystalline prisms for Au. The measured upper limit of the refractive index, δ, for crystal Ge, crystal Au, or polycrystal Au prisms is 4.0 ×10-8, 2.9 ×10-7, or 2.4 ×10-7. We could not find any signature for high order nonlinear process. This result does not support the hypothesis suggested by Habs et al. (2012) [3].

  20. A Novel Cyclic PTH(1-17) analog with bone anabolic activity and efficacy sufficient to treat established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Morko, Jukka; Peng, ZhiQi; Vääräniemi, Jukka

    of a novel, cyclic PTH(1-17) analog, ZP2307, on the treatment of established osteopenia in adult ovariectomized (OVX) rats. ZP2307 has been developed at Zealand Pharma A/S. Female Sprague-Dawley rats were ovariectomized at the age of 6 months. After 6 weeks without treatment, the development of metaphyseal...... exacerbated in OVX rats treated with vehicle. Treatment with ZP2307 reversed the development of osteopenia in tibial metaphysis and lumbar vertebra at all doses in a dose-dependent manner, and enhanced bone formation on their trabecular bone surface at the dose of 200.0 µg/kg/d. Treatment with ZP2307 also......, is the shortest PTH analog reported hitherto to exhibit bone anabolic activity and efficacy sufficient to treat established osteopenia in adult OVX rats. Due to its mild efficacy, ZP2307 may be very tolerable and have a broad therapeutic window and a better safety/efficacy profile than the PTH analogs currently...

  1. Highly efficient Tm:CaYAlO4 laser in-band pumped by a Raman fiber laser at 1.7  μm.

    Science.gov (United States)

    Yao, Weichao; Wu, Fan; Zhao, Yongguang; Chen, Hao; Xu, Xiaodong; Shen, Deyuan

    2016-05-10

    This paper discusses the high power, efficient operation of a Tm:CaYAlO4 (Tm:CYA) laser in-band pumped by a Raman fiber laser at 1.7 μm. We have investigated and compared laser characteristics of 4.0 at. % and 6.0 at. % doped Tm:CYA samples with both a-cut and c-cut configurations. Up to 6.8 W of output power has been generated at 1968.3 nm using a 6.0 at. % doped and a-cut Tm:CYA crystal, corresponding to a slope efficiency with respect to incident pump power of 52.3%. Laser output from both a- and c-cut samples are nearly linearly polarized with the polarization extinction ratio (PER) reaching 24 dB for the a-cut sample.

  2. Orientation-dependent physical properties of layered perovskite La1.3Sr1.7Mn2O7 epitaxial thin films

    Science.gov (United States)

    Niu, Li-Wei; Guo, Bing; Chen, Chang-Le; Luo, Bing-Cheng; Dong, Xiang-Lei; Jin, Ke-Xin

    2017-04-01

    In this paper, the resistivity and magnetization of orientation-engineered layered perovskite La1.3Sr1.7Mn2O7 epitaxial thin films have been investigated. Epitaxial thin films were deposited on single-crystalline LaAlO3 (LAO) (001), (110) and (111) substrates by pulse laser deposition (PLD) technique. It is found that only the (100)-oriented thin film performs insulator behavior, whereas the (110) and (111)-oriented thin films exhibit obvious metal-insulator transition at 70 K and between 85 and 120 K, respectively. Moreover, the same spin freezing temperature and different spin-glass-like transition temperatures have been observed in various oriented films. The observed experimental results were discussed according to the electron-transport mechanism and spin dynamics.

  3. Structure of a putative trans-editing enzyme for prolyl-tRNA synthetase from Aeropyrum pernix K1 at 1.7 A resolution.

    Science.gov (United States)

    Murayama, Kazutaka; Kato-Murayama, Miyuki; Katsura, Kazushige; Uchikubo-Kamo, Tomomi; Yamaguchi-Hirafuji, Machiko; Kawazoe, Masahito; Akasaka, Ryogo; Hanawa-Suetsugu, Kyoko; Hori-Takemoto, Chie; Terada, Takaho; Shirouzu, Mikako; Yokoyama, Shigeyuki

    2005-01-01

    The crystal structure of APE2540, the putative trans-editing enzyme ProX from Aeropyrum pernix K1, was determined in a high-throughput manner. The crystal belongs to the monoclinic space group P2(1), with unit-cell parameters a = 47.4, b = 58.9, c = 53.6 A, beta = 106.8 degrees. The structure was solved by the multiwavelength anomalous dispersion method at 1.7 A and refined to an R factor of 16.8% (Rfree = 20.5%). The crystal structure includes two protein molecules in the asymmetric unit. Each monomer consists of eight beta-strands and seven alpha-helices. A structure-homology search revealed similarity between the trans-editing enzyme YbaK (or cysteinyl-tRNAPro deacylase) from Haemophilus influenzae (HI1434; 22% sequence identity) and putative ProX proteins from Caulobacter crescentus (16%) and Agrobacterium tumefaciens (21%).

  4. Comparison of Heat Treatments on the Toughness of 1.7Ni-1.5Cu-0.5Mo Pre-alloyed P/M Steels

    Science.gov (United States)

    Güral, Ahmet; Türkan, Mustafa

    2015-05-01

    Effects of quenching plus tempering and intercritical annealing plus quenching heat treatments on the impact toughness properties of 1.7Ni-1.5Cu-0.5Mo pre-alloyed powder metallurgy steels with 0.2 (in mass%) graphite were investigated. Specimens were prepared by pressing at 670 MPa and sintering at 1250 °C. Different heat treatments, namely quenching and tempering, directly intercritically annealing and fully austenization plus intercritically annealing were carried out on the sintered specimens. The results showed that the impact toughness decreased with increasing intercritical annealing temperature in ferrite plus martensite dual phase powder metallurgy steels and with increasing tempering temperature in the quenched plus tempered specimens. Besides, impact toughness of fully austenizated plus intercritically annealed specimens was higher than those of quenched plus tempered and directly intercritically annealed specimens at the same hardness levels.

  5. Targeting voltage gated sodium channels NaV1.7, Na V1.8, and Na V1.9 for treatment of pathological cough.

    Science.gov (United States)

    Muroi, Yukiko; Undem, Bradley J

    2014-02-01

    Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1-NaV1.9), the afferent nerves involved in initiating cough, in common with nociceptive neurons in the somatosensory system, express mainly NaV1.7, NaV1.8, and NaV1.9. Although knowledge about the effect of selectively blocking these channels on the cough reflex is limited, their biophysical properties indicate that each may contribute to the hypertussive and allotussive state that typifies subacute and chronic nonproductive cough.

  6. Oestrogen Induces Rhythmic Expression of the Kisspeptin-1 Receptor 1 GPR54 in Hypothalamic Gonadotrophin-Releasing Hormone (GnRH)-Secreting GT1-7 Cells

    Science.gov (United States)

    Tonsfeldt, Karen J.; Goodall, Cheri P.; Latham, Kristin L.; Chappell, Patrick E.

    2011-01-01

    Oestrogen-stimulated preovulatory gonadotrophin surges are temporally regulated in a way which remains not fully understood. Mammalian ovulation requires surges of gonadotrophin-releasing hormone (GnRH), released from specialized neurones in the hypothalamus. Surge regulation is mediated by ovarian oestrogen (E2) feedback- acting as a negative signal until the early afternoon of the pro-oestrus phase, at which point it stimulates robust increases in GnRH release. Multiple lines of evidence suggest a role for the circadian clock in surge generation, but the presence of endogenous oscillators in several neuronal populations throughout the mediobasal hypothalamus complicates elucidating the underlying mechanisms of circadian regulation. In this study, we propose that endogenous oscillators within GnRH neurones are modulated by oestrogen to elicit GnRH surge secretion. One mechanism by which this may occur is through the upregulation of receptors of known stimulators of GnRH, such as kisspeptin’s cognate receptor, GPR54. Through analysis of mRNA and protein abundance patterns, we found that high levels of E2 elicit circadian expression profiles of GPR54 in vitro, and that disruption of endogenous GnRH oscillators of the clock dampens this effect. Additionally, while kisspeptin administration to GT1-7 cells does not result in surge-level secretion, we observed increased GnRH secretion from GT1-7 cells treated with positive feedback levels of E2. These results in this in vitro neuronal model system suggest a possible mechanism whereby receptor expression levels, and thus GnRH sensitivity to kisspeptin, may change dramatically over the pro-oestrus day. In this way, elevated ovarian E2 may increase kisspeptidergic tone while simultaneously increasing GnRH neuronal sensitivity to this neuropeptide for maximal surge release. PMID:21756268

  7. Oestrogen induces rhythmic expression of the Kisspeptin-1 receptor GPR54 in hypothalamic gonadotrophin-releasing hormone-secreting GT1-7 cells.

    Science.gov (United States)

    Tonsfeldt, K J; Goodall, C P; Latham, K L; Chappell, P E

    2011-09-01

    Oestrogen-stimulated preovulatory gonadotrophin surges are temporally regulated in a way that remains not fully understood. Mammalian ovulation requires surges of gonadotrophin-releasing hormone (GnRH), released from specialised neurones in the hypothalamus. Surge regulation is mediated by ovarian oestrogen (17 β-oestradiol; E(2) ) feedback-acting as a negative signal until the early afternoon of the pro-oestrous phase, at which point it stimulates robust increases in GnRH release. Multiple lines of evidence suggest a role for the circadian clock in surge generation, although the presence of endogenous oscillators in several neuronal populations throughout the mediobasal hypothalamus complicates an elucidation of the underlying mechanisms of circadian regulation. In the present study, we propose that endogenous oscillators within GnRH neurones are modulated by oestrogen to elicit GnRH surge secretion. One mechanism by which this may occur is through the up-regulation of receptors of known stimulators of GnRH, such as kisspeptin's cognate receptor, GPR54. Through analysis of mRNA and protein abundance patterns, we found that high levels of E(2) elicit circadian expression profiles of GPR54 in vitro, and that disruption of endogenous GnRH oscillators of the clock dampens this effect. Additionally, although kisspeptin administration to GT1-7 cells does not result in surge-level secretion, we observed increased GnRH secretion from GT1-7 cells treated with positive feedback levels of E(2) . These results in this in vitro neuronal model system suggest a possible mechanism whereby receptor expression levels, and thus GnRH sensitivity to kisspeptin, may change dramatically over the pro-oestrous day. In this way, elevated ovarian E(2) may increase kisspeptidergic tone at the same time as increasing GnRH neuronal sensitivity to this neuropeptide for maximal surge release. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  8. AVE 0991, a non-peptide mimic of angiotensin-(1-7) effects, attenuates pulmonary remodelling in a model of chronic asthma.

    Science.gov (United States)

    Rodrigues-Machado, M G; Magalhães, G S; Cardoso, J A; Kangussu, L M; Murari, A; Caliari, M V; Oliveira, M L; Cara, D C; Noviello, M L M; Marques, F D; Pereira, J M; Lautner, R Q; Santos, R A S; Campagnole-Santos, M J

    2013-10-01

    AVE 0991 (AVE) is a non-peptide compound, mimic of the angiotensin (Ang)-(1-7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)-induced chronic allergic lung inflammation. We used BALB/c mice (6-8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 μg·mouse(-1) , i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg(-1) ·per day, s.c.) or saline (100 μL·kg(-1) ·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates. Treatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL-5 and increased IL-10 levels in the BAL, accompanied by decreased Ang II levels in lungs. AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang-(1-7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma. © 2013 The British Pharmacological Society.

  9. Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade.

    Science.gov (United States)

    Sukumaran, Vijayakumar; Tsuchimochi, Hirotsugu; Tatsumi, Eisuke; Shirai, Mikiyasu; Pearson, James T

    2017-11-15

    Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3mg/kg/d oral gavage) from the age of 8 to 16weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obesity, hyperglycemia, hyperinsulinemia and diastolic dysfunction along with cardiac hypertrophy and fibrosis. AZL treatment lowered blood pressure, fasting blood glucose and reduced peak plasma glucose during an oral glucose tolerance test. AZL-3 treatment resulted in a significant decrease in the expression of cytokines, oxidative DNA damage and cardiac dysfunction. Moreover, AZL-3 treatment significantly abrogated the downregulation of ACE-2 and Mas R protein levels in db/db mice. Furthermore, AZL treatment significantly reduced cardiac fibrosis, hypertrophy and their marker molecules (osteopontin, CTGF, TGF-β1 and ANP). Short-term treatment with AZL-3 reversed abnormal cardiac structural remodeling and partially improved glucose metabolism in db/db mice by modulating the ACE-2/ANG 1-7/Mas R pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effect of substructure on mechanical properties and fracture behavior of lath martensite in 0.1C–1.1Si–1.7Mn steel

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shengci [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Zhu, Guoming, E-mail: zhuguoming@ustb.edu.cn [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Kang, Yonglin, E-mail: kangylin@ustb.edu.cn [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China)

    2016-08-05

    The purpose of this study was to analyze the microstructure of lath martensite in 0.1C–1.1Si–1.7Mn (wt.%) steel and its effect on mechanical properties and fracture behavior. The microstructure was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and electron back scattering diffraction (EBSD). Charpy V-notch impact samples and compact tension (CT) samples were used to investigate the Charpy impact properties and fatigue crack growth behavior of the steel, respectively. The propagation of cleavage crack and fatigue crack were analyzed to figure out the effective grain size. The results showed that the typical hierarchical lath martensite structure contained prior austenite grains, packets, blocks and laths; packet size and block width were positively correlated to prior austenite grain size, while lath width was maintained at about 0.29 μm. Yield strength was related to prior austenite grain size, packet size and block width, and obeyed Hall–Petch relationship. Grain refinement was effective in improving the resistance to cleavage fracture by introducing barriers to crack propagation; packet boundaries and block boundaries hold similar ability to impede the propagation of crack. Paris model can well describe the FCG behavior of the investigated steel. Block width governs the effective grain size for strength, toughness and fatigue crack propagation. - Graphical abstract: Mechanical properties and fracture behavior of 0.1C–1.1Si–1.7Mn steel. - Highlights: • Hall–Petch relationship is obeyed between yield strength and martensite microstructure size. • Packet boundaries and block boundaries hold similar ability to impede the propagation of crack. • Block width is the effective grain size for strength, toughness and fatigue crack propagation.

  11. Long-range forecast of all India summer monsoon rainfall using adaptive neuro-fuzzy inference system: skill comparison with CFSv2 model simulation and real-time forecast for the year 2015

    Science.gov (United States)

    Chaudhuri, S.; Das, D.; Goswami, S.; Das, S. K.

    2016-11-01

    All India summer monsoon rainfall (AISMR) characteristics play a vital role for the policy planning and national economy of the country. In view of the significant impact of monsoon system on regional as well as global climate systems, accurate prediction of summer monsoon rainfall has become a challenge. The objective of this study is to develop an adaptive neuro-fuzzy inference system (ANFIS) for long range forecast of AISMR. The NCEP/NCAR reanalysis data of temperature, zonal and meridional wind at different pressure levels have been taken to construct the input matrix of ANFIS. The membership of the input parameters for AISMR as high, medium or low is estimated with trapezoidal membership function. The fuzzified standardized input parameters and the de-fuzzified target output are trained with artificial neural network models. The forecast of AISMR with ANFIS is compared with non-hybrid multi-layer perceptron model (MLP), radial basis functions network (RBFN) and multiple linear regression (MLR) models. The forecast error analyses of the models reveal that ANFIS provides the best forecast of AISMR with minimum prediction error of 0.076, whereas the errors with MLP, RBFN and MLR models are 0.22, 0.18 and 0.73 respectively. During validation with observations, ANFIS shows its potency over the said comparative models. Performance of the ANFIS model is verified through different statistical skill scores, which also confirms the aptitude of ANFIS in forecasting AISMR. The forecast skill of ANFIS is also observed to be better than Climate Forecast System version 2. The real-time forecast with ANFIS shows possibility of deficit (65-75 cm) AISMR in the year 2015.

  12. Range-Space Predictive Control for Optimal Robot Motion

    Czech Academy of Sciences Publication Activity Database

    Belda, Květoslav; Böhm, Josef

    2008-01-01

    Roč. 1, č. 1 (2008), s. 1-7 ISSN 1998-0140 R&D Projects: GA ČR GP102/06/P275 Institutional research plan: CEZ:AV0Z10750506 Keywords : Accurate manipulation * Industrial robot ics * Predictive control * Range-space control Subject RIV: BC - Control Systems Theory http://library.utia.cas.cz/separaty/historie/belda-0305644.pdf

  13. Range management visual impacts

    Science.gov (United States)

    Bruce R. Brown; David Kissel

    1979-01-01

    Historical overgrazing of western public rangelands has resulted in the passage of the Public Rangeland Improvement Act of 1978. The main purpose of this Act is to improve unsatisfactory range conditions. A contributing factor to unfavorable range conditions is adverse visual impacts. These visual impacts can be identified in three categories of range management: range...

  14. Mandibular movement range in children.

    Science.gov (United States)

    Machado, Barbara Cristina Zanandréa; Medeiros, Ana Paula Magalhães; Felício, Cláudia Maria de

    2009-01-01

    identification of the mandibular movement range is an important procedure in the evaluation of the stomatognathic system. However, there are few studies in children that focus on normal parameters or abnormalities. to determine the average range of mandibular movements in Brazilian children aged 6 to 12 years; to verify the difference between genders, in each age group, and between the different age groups: 6-8 years; 8.1-10 years; and 10.1-12 years. participants of the study were 240 healthy children selected among regular students from local schools of São Paulo State. The maximum mandibular opening, lateral excursion and protrusive movements, and deviation of the medium line, if present, were measured using a digital caliper. Student T test, Analysis of variance and Tukey test were considered significant for p mandibular opening; 7.71mm for lateral excursion to the right; 7.92mm for lateral excursion to the left; 7.45mm for protrusive movements. No statistical difference was observed between genders. There was a gradual increase in the range of mandibular movements, with significant differences mainly between the ages of 6-8 years and 10.1-12 years. during childhood the range of mandibular movements increases. Age should be considered in this analysis for a greater precision in the diagnosis.

  15. A combined experimental and theoretical approach for structural, spectroscopic, NLO, NBO, thermal and photophysical studies of new fluorescent 5-amino-1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazole-4-carbonitrile using density functional theory

    Science.gov (United States)

    Singh, Harjinder; Singh, Ashima; Khurana, J. M.

    2017-11-01

    We have synthesized a new fluorescent 5-amino-1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazole-4-carbonitrile containing 1,2,3-triazole moiety. The properties such as optimized structural parameters, spectroscopic (FT-IR and NMR), electronic and photophysical properties were investigated experimentally as well as theoretically using density functional theory calculations. The NMR spectrum was recorded in DMSO and the chemical shifts of hydrogen and carbon atoms were studied experimentally as well as theoretically. Electronic properties of molecule such as electrostatic surface potential analysis, charge analysis, the frontier molecular orbital analysis, total density of states, absorption-emission characteristics of molecule were studied. Nonlinear optical properties, reduced density gradient and natural bond orbital analysis were also studied. The first order hyperpolarizability (β0) was calculated and found to be six times higher than urea which makes it a potential NLO material. This new compound showed absorption spectra at 326-386 nm while emission band in range of 375-403 nm in different solvents. The ground state and excited state dipole moments were determined using solvatochromic methods and compared with theoretically calculated values. The interaction of synthesized compound with different solvents was also investigated using Kamlet-Taft and Catalan methods. The chemical reactivity indices and thermodynamic properties were also evaluated.

  16. Lithium1.3Aluminum0.3Titanium1.7Phosphate as a solid state Li-ion conductor: Issues with microcracking and stability in aqueous solutions

    Science.gov (United States)

    Jackman, Spencer D.

    Lithium aluminum titanium phosphate (LATP) with formula Li1.3Al0.3Ti1.7(PO4)3 was analyzed and tested to better understand its applicability as a solid state ion conducting ceramic material for electrochemical applications. Sintered samples were obtained from Ceramatec, Inc. in Salt Lake City and characterized in terms of density, phase-purity, fracture toughness, Young's modulus, thermal expansion behavior, mechanical strength, a.c. and d.c. ionic conductivity, and susceptibility to static and electrochemical corrosion in aqueous Li salt solutions. It was shown that LATP is prone to microcrack generation because of high thermal expansion anisotropy. A.c. impedance spectra of high-purity LATP of varying grain sizes showed that microcracking had a negative impact on the ionic conduction of Li along grain boundaries, with fine-grained (1.7±0.7 µm) LATP having twice the ionic conductivity of the same purity of coarse-grained (4.8±1.9 µm) LATP at 50°C. LATP with detectible secondary phases had lower ionic conductivity for similar grain sizes, as would be expected. The Young's modulus of fine-grained LATP was measured to be 115 GPa, and the highest biaxial strength was 191±11 MPa when tested in mineral oil, 144±13 MPa as measured in air, and 26±7 MPa after exposure to deionized water, suggesting that LATP undergoes stress-corrosion cracking. After exposure to LiOH, the strength was 76±19 MPa. This decrease in strength was observed despite there being no measureable change in a.c. impedance spectra, X-ray diffraction, or sample mass, suggesting phosphate glasses at grain boundaries. The chemical and electrochemical stability of high-purity LATP in aqueous electrochemical cells was evaluated using LiOH, LiCl, LiNO3, and LiCOOCH3 salts as the Li source. LATP was found to be most stable between pH 8-9, with the longest cell operating continuously at 25 mA cm-2 for 625 hours at 40°C in LiCOOCH3. At pH values outside of the 7-10 range, eventual membrane degradation

  17. Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes NaV1.9, NaV1.7 and NaV1.1

    Directory of Open Access Journals (Sweden)

    Filip Touska

    2017-08-01

    Full Text Available Ciguatoxins (CTXs are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1 into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP ion channels. In contrast, lidocaine and tetrodotoxin (TTX reduce CGRP release by 53–75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC. Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics.

  18. Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes NaV1.9, NaV1.7 and NaV1.1.

    Science.gov (United States)

    Touska, Filip; Sattler, Simon; Malsch, Philipp; Lewis, Richard J; Reeh, Peter W; Zimmermann, Katharina

    2017-08-30

    Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA) to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP) ion channels. In contrast, lidocaine and tetrodotoxin (TTX) reduce CGRP release by 53-75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC). Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC) NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics.

  19. Minnesota Pheasant Range

    Data.gov (United States)

    Minnesota Department of Natural Resources — This dataset delineates the spatial range of wild pheasant populations in Minnesota as of 2002 by dividing the MN state boundary into 2 units: pheasant range and...

  20. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li

    2014-01-01

    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. We give efficient reductions for each of the above problems...... to a new problem, which we call substring range reporting. Hence, we unify the previous work by showing that we may restrict our attention to a single problem rather than studying each of the above problems individually. We show how to solve substring range reporting with optimal query time and little...... for substring range reporting generalize to substring range counting and substring range emptiness variants. We also obtain non-trivial time-space trade-offs for these problems. Our bounds for substring range reporting are based on a novel combination of suffix trees and range reporting data structures...

  1. Processing effects on the thermoelectric properties of Bi{sub 2}Ca{sub 2}Co{sub 1}.7O{sub x} ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Rasekhi, S. H.; Constantinescu, G.; Madre, M. A.; Torres, M. A.; Diez, J. C.; Sotelo, A.

    2014-07-01

    Bi{sub 2}Ca{sub 2}Co{sub 1}.7O{sub x} bulk polycrystalline ceramics were prepared by the solid state method and by directional growth. Moreover, the effect of annealing on the textured materials has been studied. Microstructure has shown randomly oriented grains in the classical sintered materials while in the textured samples those were well oriented with their c-axis nearly perpendicular to the growth direction. Furthermore, the textured-annealed samples showed much lower amount of secondary phases than the as-grown ones. These microstructural changes are reflected on the thermoelectric properties which increase with the grain orientation and with the decrease on the secondary phase content mainly due to the electrical resistivity reduction. As a consequence, a raise on the power factor of about 6 and 9 times, compared with the classically sintered samples, was obtained for the as-grown and textured-annealed ones, respectively. The maximum power factor obtained at 650 degree centigrade in the textured-annealed samples (∼0.31 mW/K{sup 2}m) is about 50 % higher, at the same temperature, than the obtained in one of the most used methods for texturing this kind of materials, the sinter-forging process. (Author)

  2. Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991.

    Science.gov (United States)

    Ferreira, Anderson J; Oliveira, Thauana L; Castro, Maria Carolina M; Almeida, Alvair P; Castro, Carlos H; Caliari, Marcelo V; Gava, Elisandra; Kitten, Gregory T; Santos, Robson A S

    2007-08-23

    The aim of this study was to evaluate the effects of AVE 0991 (AVE), a nonpeptide compound that mimics Ang-(1-7) actions, on cardiac remodeling. Heart hypertrophy and heart dysfunction were induced by isoproterenol (ISO) (2 mg/kg i.p./day for 7 days) in male Wistar rats. At the end of the 7-day period, the hearts were perfused according to the Langendorff method to evaluate cardiac function. The hearts, atria, and right and left ventricles wet weights were recorded, normalized for body weight and then expressed as muscle mass index (mg/g). In addition, serial sections from left ventricle were stained with hematoxylin-eosin for cell morphometry and with collagen-specific Masson's trichrome for detection of fibrosis. Immunofluorescence-labeling and confocal microscopy were used to investigate the distribution and deposition of collagen types I, III, VI, and fibronectin. AVE reduced the ISO-induced hypertrophy as quantified by myocyte diameter measurements (Control: 10.60+/-0.08 microm; ISO: 14.60+/-0.11 mum; ISO+AVE: 11.22+/-0.08 microm, n = 5). In addition, AVE markedly attenuated the increase of extracellular matrix proteins induced by ISO. AVE treatment also attenuated the decrease in systolic tension and +/-dT/dt and exacerbated the vasodilatation induced by ISO. These results show that AVE has a cardioprotective effect on ISO-induced cardiac remodeling.

  3. Effect of AVE 0991 angiotensin-(1-7) receptor agonist treatment on elemental and biomolecular content and distribution in atherosclerotic plaques of apoE-knockout mice

    Science.gov (United States)

    Kowalska, J.; Gajda, M.; Jawień, J.; Kwiatek, W. M.; Appel, K.; Dumas, P.

    2013-12-01

    Gene-targeted apolipoprotein E-knockout (apoE-KO) mice display early and highly progressive vascular lesions containing lipid deposits and they became a reliable animal model to study atherosclerosis. The aim of the present study was to investigate the effect of AVE 0991 angiotensin-(1-7) receptor agonist on the distribution of selected pro- and anti- inflammatory elements as well as biomolecules in atherosclerotic plaques of apoE-knockout mice. Synchrotron radiation-based X-ray fluorescence (micro-XRF) and Fourier Transform Infrared (micro-FTIR) microspectroscopies were applied. Two-month-old apoE-KO mice were fed for following four months diet supplemented with AVE 0991 (0.58 μmol/kg b.w. per day). Histological sections of ascending aortas were analyzed spectroscopically. The distribution of P, Ca, Fe and Zn were found to correspond with histological structure of the lesion. Significantly lower contents of P, Ca, Zn and significantly higher content of Fe were observed in animals treated with AVE 0991. Biomolecular analysis showed lower lipids saturation level and lower lipid to protein ratio in AVE 0991 treated group. Protein secondary structure was studied according to the composition of amide I band (1660 cm-1) and it demonstrated higher proportion of β-sheet structure as compared to α-helix in both studied groups.

  4. Buffer-gas cooling of antiprotonic helium to 1.5 to 1.7 K, and antiproton-to–electron mass ratio

    CERN Document Server

    Hori, Masaki; Sótér, Anna; Barna, Daniel; Dax, Andreas; Hayano, Ryugo; Kobayashi, Takumi; Murakami, Yohei; Todoroki, Koichi; Yamada, Hiroyuki; Horváth, Dezső; Venturelli, Luca

    2016-01-01

    Charge, parity, and time reversal (CPT) symmetry implies that a particle and its antiparticle have the same mass. The antiproton-to-electron mass ratio Embedded Image can be precisely determined from the single-photon transition frequencies of antiprotonic helium. We measured 13 such frequencies with laser spectroscopy to a fractional precision of 2.5 × 10−9 to 16 × 10−9. About 2 × 109 antiprotonic helium atoms were cooled to temperatures between 1.5 and 1.7 kelvin by using buffer-gas cooling in cryogenic low-pressure helium gas; the narrow thermal distribution led to the observation of sharp spectral lines of small thermal Doppler width. The deviation between the experimental frequencies and the results of three-body quantum electrodynamics calculations was reduced by a factor of 1.4 to 10 compared with previous single-photon experiments. From this, Embedded Image was determined as 1836.1526734(15), which agrees with a recent proton-to-electron experimental value within 8 × 10−10.

  5. Cytotoxic activity of butane type of 1,7-seco-2,7'-cyclolignanes and apoptosis induction by Caspase 9 and 3.

    Science.gov (United States)

    Wukirsari, Tuti; Nishiwaki, Hisashi; Nishi, Kosuke; Sugahara, Takuya; Akiyama, Koichi; Kishida, Taro; Yamauchi, Satoshi

    2014-09-01

    All stereoisomers of methoxybutane and fluorobutane type of 1,7-seco-2,7'-cyclolignane were synthesized and cytotoxic activities of these compounds were compared with those of all stereoisomers of butane and butanol type compounds. Both enantiomers of butane type secocyclolignane showed higher cytotoxic activity (IC50=16-20 μM) than methoxy type compounds, whereas none was observed for all the stereoisomers of butanol type secocyclolignane, however, (-)-Kadangustin J showed stereospecific cytotoxic activity (IC50=47-67 μM). Since (R)-9'-fluoro derivative 23 was most potent (IC50=19 μM) among the corresponding fluoro stereoisomers, (R)-9'-alkyl derivatives were synthesized, hydrophobic 9'-heptyl derivative 27 showing highest activity (IC50=3.7 μM against HL-60, IC50=3.1 μM against HeLa) in this experiment. Apoptosis induction caused by Caspase 3 and 9 for (R)-9'-heptyl derivative 27 was observed in the research on the mechanism. A degradation of DNA into small fragments was also shown by DNA ladder assay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. A Scanning Tunnelling Microscopy Study on an Alloyed Topological Insulator, Bi1.5Sb0.5Te1.7Se1.3

    Science.gov (United States)

    Ko, Wonhee; Jeon, Insu; Kim, Hyo Won; Kwon, Hyeokshin; Oh, Youngtek; Kahng, Se-Jong; Park, Joonbum; Kim, Jun Sung; Hwang, Sung Woo; Suh, Hwansoo

    2015-03-01

    Efficient doping of topological insulators while protecting its topological nature is key ingredient to realize topological devices. Engineering the chemical potential in the alloyed compound Bi2-xSbxTe3-ySey has been achieved by tuning its chemical composition. However, the effect of alloying in microscopic scale has not yet been fully investigated with local probes. Here we report on the atomic and electronic structures of Bi1.5Sb0.5Te1.7Se1.3 studied using scanning tunnelling microscopy/spectroscopy (STM/STS). Although there is significant surface disorder due to the alloying of constituent atoms, cleaved surfaces of the crystals present a well-ordered hexagonal lattice in STM topographs with 1 nm high quintuple layer steps. STS results reflect the band structure and indicate that the surface state and Fermi energy are both located inside the energy gap. The surface states do not show any electron back-scattering; due to their topological nature they are extremely robust. Landau levels generated by perpendicular magnetic field follow the massless Dirac fermions. This finding demonstrates that alloying is a promising route for efficient doping of topological insulators whilst keeping the topological surface state intact.

  7. A 1.7-Mb YAC contig around the human BDNF gene (11p13): integration of the physical, genetic, and cytogenetic maps in relation to WAGR syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rosier, M.F.; Martin, A.; Houlgatte, R. [Genetique Moleculaire et Biologie du Development, Villejuif (France)] [and others

    1994-11-01

    WAGR (Wilms tumor, aniridia, genito-urinary abnormalities, mental retardation) syndrome in humans is associated with deletions of the 11p13 region. The brain-derived neurotrophic factor (BDNF) gene maps to this region, and its deletion seems to contribute to the severity of the patient`s mental retardation. Yeast artificial chromosomes (YACs) carrying the BDNF gene have been isolated and characterized. Localization of two known exons of this gene leads to a minimal estimation of its size of about 40 kb. Chimerism of the BDNF YACs has been investigated by fluorescence in situ hybridization and chromosome assignment on somatic cell hybrids. Using the BDNF gene, YAC end sequence tagged sites (STS), and Genethon microsatellite markers, the authors constructed a 1.7-Mb contig and refined the cytogenetic map at 11p13. The resulting integrated physical, genetic, and cytogenetic map constitutes a resource for the characterization of genes that may be involved in the WAGR syndrome. 42 refs., 2 figs., 3 tabs.

  8. Dual RNA Processing Roles of Pat1b via Cytoplasmic Lsm1-7 and Nuclear Lsm2-8 Complexes

    Directory of Open Access Journals (Sweden)

    Caroline Vindry

    2017-08-01

    Full Text Available Pat1 RNA-binding proteins, enriched in processing bodies (P bodies, are key players in cytoplasmic 5′ to 3′ mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA. Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6.U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP components in Cajal bodies, the site of snRNP biogenesis. RNA sequencing following Pat1b depletion revealed the preferential upregulation of mRNAs normally found in P bodies and enriched in 3′ UTR AU-rich elements. Changes in >180 alternative splicing events were also observed, characterized by skipping of regulated exons with weak donor sites. Our data demonstrate the dual role of a decapping enhancer in pre-mRNA processing as well as in mRNA decay via distinct nuclear and cytoplasmic Lsm complexes.

  9. Characterizing K2 Candidate Planetary Systems Orbiting Low-Mass Stars. I. Classifying Low-Mass Host Stars Observed During Campaigns 1-7

    Science.gov (United States)

    Dressing, Courtney D.; Newton, Elisabeth R.; Schlieder, Joshua E.; Charbomeau, David; Krutson, Heather A.; Vanderburg, Andrew; Sinukoff, Evan

    2017-01-01

    We present near-infrared spectra for 144 candidate planetary systems identified during Campaigns 1-7 of the NASA K2 Mission. The goal of the survey was to characterize planets orbiting low-mass stars, but our Infrared Telescope Facility/SpeX and Palomar/TripleSpec spectroscopic observations revealed that 49% of our targets were actually giant stars or hotter dwarfs reddened by interstellar extinction. For the 72 stars with spectra consistent with classification as cool dwarfs (spectral types K3-M4), we refined their stellar properties by applying empirical relations based on stars with interferometric radius measurements. Although our revised temperatures are generally consistent with those reported in the Ecliptic Plane Input Catalog (EPIC), our revised stellar radii are typically 0.13 solar radius (39%) larger than the EPIC values, which were based on model isochrones that have been shown to underestimate the radii of cool dwarfs. Our improved stellar characterizations will enable more efficient prioritization of K2 targets for follow-up studies.

  10. Characterizing K2 Candidate Planetary Systems Orbiting Low-mass Stars. I. Classifying Low-mass Host Stars Observed during Campaigns 1-7

    Science.gov (United States)

    Dressing, Courtney D.; Newton, Elisabeth R.; Schlieder, Joshua E.; Charbonneau, David; Knutson, Heather A.; Vanderburg, Andrew; Sinukoff, Evan

    2017-02-01

    We present near-infrared spectra for 144 candidate planetary systems identified during Campaigns 1-7 of the NASA K2 Mission. The goal of the survey was to characterize planets orbiting low-mass stars, but our Infrared Telescope Facility/SpeX and Palomar/TripleSpec spectroscopic observations revealed that 49% of our targets were actually giant stars or hotter dwarfs reddened by interstellar extinction. For the 72 stars with spectra consistent with classification as cool dwarfs (spectral types K3-M4), we refined their stellar properties by applying empirical relations based on stars with interferometric radius measurements. Although our revised temperatures are generally consistent with those reported in the Ecliptic Plane Input Catalog (EPIC), our revised stellar radii are typically 0.13 {R}⊙ (39%) larger than the EPIC values, which were based on model isochrones that have been shown to underestimate the radii of cool dwarfs. Our improved stellar characterizations will enable more efficient prioritization of K2 targets for follow-up studies.

  11. Antioxidant, antiapoptotic and amino acid balance regulating activities of 1,7-dihydroxy-3,4,8-trimethoxyxanthone against dimethylnitrosamine-induced liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Xi-Yuan Zheng

    Full Text Available Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injury which could be caused by viral, autoimmune, drugs, and so on. Unfortunately, there was no effective therapy available for liver fibrosis in clinic. In this study, we identified the anti-fibrotic effects of 1,7-dihydroxy-3,4,8-trimethoxyxanthone (ZYC-1 on the dimethylnitrosamine (DMN-induced rat model. ZYC-1 was isolated from Swertia punicea Hemsl and was administrated to DMN-induced rat model. ZYC decreased the hyaluronic acid (HA, type IV collagen (CIV and hydroxyproline (Hyp levels and inhibited the expression of α smooth muscle actin (α-SMA and transforming growth factor beta 1 (TGF-1β. The anti-fibrotic effect of ZYC-1 was also confirmed by Sirius Red staining. Finally, we identified 42 differentially expressed proteins by using proteomics analysis after ZYC-1 treatment, of which 17 were up-regulated and 25 were down-regulated. These Most of the 42 proteins are involved in the oxidative stress pathway, the mitochondrial-mediated apoptotic pathway and the amino acid metabolism pathway. Our study presented the first elucidated mechanisms of xanthone on liver fibrosis in vivo. This study pointed out that ZYC-1 may be used as a lead compound for hepatofibrosis treatment.

  12. In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Xiaodong Gao

    2016-05-01

    Full Text Available Checkpoint kinase 1 (Chk1 is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure–activity relationship (3D-QSAR modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q2 values (0.531, 0.726, fitted correlation r2 coefficients (higher than 0.90, and standard error of prediction (less than 0.250. These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

  13. Structure of a putative trans-editing enzyme for prolyl-tRNA synthetase from Aeropyrum pernix K1 at 1.7 Å resolution

    Science.gov (United States)

    Murayama, Kazutaka; Kato-Murayama, Miyuki; Katsura, Kazushige; Uchikubo-Kamo, Tomomi; Yamaguchi-Hirafuji, Machiko; Kawazoe, Masahito; Akasaka, Ryogo; Hanawa-Suetsugu, Kyoko; Hori-Takemoto, Chie; Terada, Takaho; Shirouzu, Mikako; Yokoyama, Shigeyuki

    2005-01-01

    The crystal structure of APE2540, the putative trans-editing enzyme ProX from Aeropyrum pernix K1, was determined in a high-throughput manner. The crystal belongs to the monoclinic space group P21, with unit-cell parameters a = 47.4, b = 58.9, c = 53.6 Å, β = 106.8°. The structure was solved by the multiwavelength anomalous dispersion method at 1.7 Å and refined to an R factor of 16.8% (R free = 20.5%). The crystal structure includes two protein molecules in the asymmetric unit. Each monomer consists of eight β-strands and seven α-helices. A structure-homology search revealed similarity between the trans-editing enzyme YbaK (or cysteinyl-tRNAPro deacylase) from Haemophilus influenzae (HI1434; 22% sequence identity) and putative ProX proteins from Caulobacter crescentus (16%) and Agrobacterium tumefaciens (21%). PMID:16508081

  14. Microwave-assisted reactive sintering and lithium ion conductivity of Li1.3Al0.3Ti1.7(PO4)3 solid electrolyte

    Science.gov (United States)

    Hallopeau, Leopold; Bregiroux, Damien; Rousse, Gwenaëlle; Portehault, David; Stevens, Philippe; Toussaint, Gwenaëlle; Laberty-Robert, Christel

    2018-02-01

    Li1.3Al0.3Ti1.7(PO4)3 (LATP) materials are made of a three-dimensional framework of TiO6 octahedra and PO4 tetrahedra, which provides several positions for Li+ ions. The resulting high ionic conductivity is promising to yield electrolytes for all-solid-state Li-ion batteries. In order to elaborate dense ceramics, conventional sintering methods often use high temperature (≥1000 °C) with long dwelling times (several hours) to achieve high relative density (∼90%). In this work, an innovative synthesis and processing approach is proposed. A fast and easy processing technique called microwave-assisted reactive sintering is used to both synthesize and sinter LATP ceramics with suitable properties in one single step. Pure and crystalline LATP ceramics can be achieved in only 10 min at 890 °C starting from amorphous, compacted LATP's precursors powders. Despite a relative density of 88%, the ionic conductivity measured at ambient temperature (3.15 × 10-4 S cm-1) is among the best reported so far. The study of the activation energy for Li+ conduction confirms the high quality of the ceramic (purity and crystallinity) achieved by using this new approach, thus emphasizing its interest for making ion-conducting ceramics in a simple and fast way.

  15. Long-lasting mnemotropic effect of substance P and its N-terminal fragment (SP1-7 on avoidance learning

    Directory of Open Access Journals (Sweden)

    C. Tomaz

    1997-02-01

    Full Text Available We investigated the long-lasting effect of peripheral injection of the neuropeptide substance P (SP and of some N- or C-terminal SP fragments (SPN and SPC, respectively on retention test performance of avoidance learning. Male Wistar rats (220 to 280 g were trained in an inhibitory step-down avoidance task and tested 24 h or 21 days later. Immediately after the training trial rats received an intraperitoneal injection of SP (50 µg/kg, SPN 1-7 (167 µg/kg or SPC 7-11 (134 µg/kg. Control groups were injected with vehicle or SP 5 h after the training trial. The immediate post-training administration of SP and SPN, but not SPC, facilitated avoidance behavior in rats tested 24 h or 21 days later, i.e., the retention test latencies of the SP and SPN groups were significantly longer (P<0.05, Mann-Whitney U-test during both training-test intervals. These observations suggest that the memory-enhancing effect of SP is long-lasting and that the amino acid sequence responsible for this effect is encoded by its N-terminal part

  16. High-dynamic-range cationic two-photon photopolymerization

    Science.gov (United States)

    Boiko, Yuri B.; Costa, Joannes M.; Wang, Mark M.; Esener, Sadik C.

    2001-06-01

    Cationic-induced two-photon photopolymerization is demonstrated at 710 nm, using an isopropylthioxanthone/diarylidonium salt initiating system for the cationic polymerization of an epoxide. The polymerization threshold J2th is found to be approximately 1 GW/cm2, with a dynamic range of > 100, i.e. the material can be fully polymerized at intensities > 100 times the threshold level without damage. The polymerization rate R is found to be proportional to the m equals 1.7 power of the intensity, or R equals [C (J-J2th)]m equals [C (J-J2th)]1.7, which implies a significantly stronger localization of the photochemical response than that of free radical photoinitiators. R and J2th significantly improve when the concentration z of the initiator (onium salt) increases.

  17. Intravenous Bisphosphonate Therapy of Young Children With Osteogenesis Imperfecta: Skeletal Findings During Follow Up Throughout the Growing Years.

    Science.gov (United States)

    Palomo, Telma; Fassier, François; Ouellet, Jean; Sato, Atsuko; Montpetit, Kathleen; Glorieux, Francis H; Rauch, Frank

    2015-12-01

    Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis imperfecta (OI), but little is known about long-term treatment outcomes. We therefore reviewed 37 children with OI (OI type I, n = 1; OI type III, n = 14; and OI type IV, n = 22) who started intravenous bisphosphonate therapy before 5 years of age (median 2.2 years; range, 0.1 to 4.8 years), and who had a subsequent follow-up period of at least 10 years (median 14.8 years; range, 10.7 to 18.2 years), during which they had received intravenous bisphosphonate treatment (pamidronate or zoledronic acid) for at least 6 years. During the observation period, the mean lumbar spine areal bone mineral density Z-score increased from -6.6 (SD 3.1) to -3.0 (SD 1.8), and weight Z-score increased from -2.3 (SD 1.5) to -1.7 (SD 1.7) (p intravenous bisphosphonate therapy was associated with higher Z-scores for lumbar spine areal bone mineral density and vertebral reshaping, but long-bone fracture rates were still high and the majority of patients developed scoliosis. © 2015 American Society for Bone and Mineral Research.

  18. Beginnings of range management: Albert F. Potter, first Chief of Grazing, U.S. Forest Service, and a photographic comparison of his 1902 Forest Reserve Survey in Utah with conditions 100 years later

    Science.gov (United States)

    David A. Prevedel; Curtis M. Johnson

    2005-01-01

    The period from 1880 to 1900 is regarded as the period of "spoilation" of western rangelands. In Albert Potters own words, "Quick profits and fortunes lead to speculation and incredible numbers of stock were placed upon the range. Cowman was arrayed against sheep man, big owners against small, and might ruled more often than right." The Government...

  19. Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All.

    Science.gov (United States)

    Song, Eunkyung; Wang, Huanyu; Salamon, Doug; Jaggi, Preeti; Leber, Amy

    2016-06-01

    The FilmArray Respiratory Panel (RP) v1.7 assay has improved sensitivity for detection of human adenovirus (HAdV), compared to an earlier version (RP v1.6). RP v1.7 was designed for detection of species B, C, and E but may show variable detection of species A, D, and F. We sought to evaluate the clinical and analytical performance of RP v1.7 for detection of HAdV in a large pediatric cohort. Respiratory specimens obtained from a tertiary care children's hospital between February 2014 and February 2015 were tested for HAdV by RP v1.7. If the RP v1.7 results were negative for HAdV, then the specimens were reflexed to a HAdV-specific laboratory-developed PCR (LD-PCR) assay for confirmation. A subset of specimens underwent secondary confirmatory testing using another commercially available HAdV PCR assay and a molecular typing assay for species identification. Among 4,750 specimens, a total of 146 specimens (3.1%) were HAdV positive by RP v1.7. HAdV was detected by LD-PCR in an additional 220 specimens that were negative by RP v1.7. Overall, a nearly 5% increase in HAdV detection was observed when RP v1.7-negative specimens were reflexed to LD-PCR testing. RP v1.7 did not detect HAdV with either low viral burden (threshold cycle values of >30) or nonrespiratory species (species A, D, and F), as shown in both clinical and analytic data. While the level of sensitivity of RP v1.7 may be adequate for testing among otherwise healthy children, the decreased sensitivity may be problematic for immunocompromised patients, in whom low levels of HAdV in the respiratory tract may precede systemic infection and require early intervention. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Camouflaged carborarods derived from B-permethyl-1,12-diethynyl-para- and B-octamethyl-1,7-diethylnyl-meta-carborane modules.

    Science.gov (United States)

    Herzog, Axel; Jalisatgi, Satish S; Knobler, Carolyn B; Wedge, Timothy J; Hawthorne, M Frederick

    2005-12-09

    Rigid camouflaged carborarods constructed from the corresponding C,C'-diethynyl derivatives of B-decamethyl-1,12-dicarbadodecaborane(12) (6) and B-octamethyl-1,7-dicarbadodecaborane(12) (48) have been synthesized by largely conventional organic transformations. These carborarods are the longest discrete rod species available by this method in which B-methylated p-carborane and m-carborane cages are linked through their carbon vertices by using butadiynylene moieties. They exhibit enhanced solubility in common organic solvents relative to all other presently known carborane-based rigid-rod molecules. The oxidative coupling of bis(ethynyl) derivatives of 6 generates oligomers containing, on average, 16 carborane modules. The structural characterization of the corresponding dimeric species revealed that the carborarods possess a sinusoidal chain distortion in the solid state. The stereoelectronic properties of these and related model carborarods were evaluated by using molecular dimensions as a monitor for the comparison of computational and experimental methods. In addition, the effect of exhaustive B-methylation of 12- and 10-vertex para-carborane cages in a series of model C,C'-diethynyl derivatives was similarly investigated by computational and structural studies. As expected, a correlation of intercage C--C bond lengths with cage size was observed and was attributed to hybridization effects. B-Permethylation had no significant structural effect with either 10- or 12-vertex cage derivatives. Relative to unsubstituted compounds, thermal and chemical stabilities of B-permethylated derivatives were increased through the operation of a steric "bumper-car" process, and solubilities in organic solvents were enhanced. The formation of linear, sterically encumbered platina-carborarods using ethynyl derivatives of 6 as precursors is described.

  1. Structural Determinants of Substrate Recognition in the HAD Superfamily Member D-glycero-D-manno-Heptose-1,7-bisphosphate Phosphatase (GmhB)

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, H.; Wang, L; Huang, H; Peisach, E; Dunaway-Mariano, D; Allen, K

    2010-01-01

    The haloalkanoic acid dehalogenase (HAD) enzyme superfamily is the largest family of phosphohydrolases. In HAD members, the structural elements that provide the binding interactions that support substrate specificity are separated from those that orchestrate catalysis. For most HAD phosphatases, a cap domain functions in substrate recognition. However, for the HAD phosphatases that lack a cap domain, an alternate strategy for substrate selection must be operative. One such HAD phosphatase, GmhB of the HisB subfamily, was selected for structure-function analysis. Herein, the X-ray crystallographic structures of Escherichia coli GmhB in the apo form (1.6 {angstrom} resolution), in a complex with Mg{sup 2+} and orthophosphate (1.8 {angstrom} resolution), and in a complex with Mg{sup 2+} and D-glycero-D-manno-heptose 1{beta},7-bisphosphate (2.2 {angstrom} resolution) were determined, in addition to the structure of Bordetella bronchiseptica GmhB bound to Mg{sup 2+} and orthophosphate (1.7 {angstrom} resolution). The structures show that in place of a cap domain, the GmhB catalytic site is elaborated by three peptide inserts or loops that pack to form a concave, semicircular surface around the substrate leaving group. Structure-guided kinetic analysis of site-directed mutants was conducted in parallel with a bioinformatics study of sequence diversification within the HisB subfamily to identify loop residues that serve as substrate recognition elements and that distinguish GmhB from its subfamily counterpart, the histidinol-phosphate phosphatase domain of HisB. We show that GmhB and the histidinol-phosphate phosphatase domain use the same design of three substrate recognition loops inserted into the cap domain yet, through selective residue usage on the loops, have achieved unique substrate specificity and thus novel biochemical function.

  2. Phase behavior and properties of the liquid-crystal dimer 1'',7''-bis(4-cyanobiphenyl-4'-yl) heptane: a twist-bend nematic liquid crystal.

    Science.gov (United States)

    Cestari, M; Diez-Berart, S; Dunmur, D A; Ferrarini, A; de la Fuente, M R; Jackson, D J B; Lopez, D O; Luckhurst, G R; Perez-Jubindo, M A; Richardson, R M; Salud, J; Timimi, B A; Zimmermann, H

    2011-09-01

    The liquid-crystal dimer 1'',7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) exhibits two liquid-crystalline mesophases on cooling from the isotropic phase. The high-temperature phase is nematic; the identification and characterization of the other liquid-crystal phase is reported in this paper. It is concluded that the low-temperature mesophase of CB7CB is a new type of uniaxial nematic phase having a nonuniform director distribution composed of twist-bend deformations. The techniques of small-angle x-ray scattering, modulated differential scanning calorimetry, and dielectric spectroscopy have been applied to establish the nature of the nematic-nematic phase transition and the structural features of the twist-bend nematic phase. In addition, magnetic resonance studies (electron-spin resonance and (2)H nuclear magnetic resonance) have been used to investigate the orientational order and director distribution in the liquid-crystalline phases of CB7CB. The synthesis of a specifically deuterated sample of CB7CB is reported, and measurements showed a bifurcation of the quadrupolar splitting on entering the low-temperature mesophase from the high-temperature nematic phase. This splitting could be interpreted in terms of the chirality of the twist-bend structure of the director. Calculations using an atomistic model and the surface interaction potential with Monte Carlo sampling have been carried out to determine the conformational distribution and predict dielectric and elastic properties in the nematic phase. The former are in agreement with experimental measurements, while the latter are consistent with the formation of a twist-bend nematic phase.

  3. Rescuing the Cahoon Mine drill cores: Opportunities for modern mapping of the ca. 1.7 Ga Freedom Formation in southern Wisconsin

    Science.gov (United States)

    Stanley, V.; Stewart, E.

    2016-12-01

    Rock cores collected during historic mineral exploration can provide invaluable data for modern analyses, but only if the samples are properly curated. The Cahoon Mine operated in Baraboo, WI during the 1910's and produced iron ore from the ca. 1.7 Ga Freedom Formation. The Freedom Formation is part of the well-known Baraboo-interval stratigraphy and is only present in the subsurface of Wisconsin (Weidman, 1904). Seventeen exploratory drill cores were rescued by Wisconsin Geological and Natural History Survey (WGNHS) from the original drying house at the mine site. The condition of the containers endangered the stratigraphic context of the collection; identifiers and depth markings were often obscured or lost. The individual core pieces were coated in residue and dust. Most of what is known about the Freedom Formation is from core logs and master's theses from the early 1900's (Leith, 1935; Schmidt, 1951). Ongoing subsurface mapping of the Baraboo-interval sediments and underlying basement of southern Wisconsin integrates new and existing subsurface and regional geophysical datasets. Mapping involves calibrating unique signals in regional aeromagnetic data to known lithology from drill core and cuttings. The Freedom Formation is especially important in this process as its iron-rich composition and regional continuity causes it to have a somewhat unique signal in regional aeromagnetic data. The Cahoon Mine cores in the WGNHS repository are the most extensive collection of physical samples from the Freedom Formation still in existence. We are in the process of curating the cores to facilitate their use in ongoing bedrock mapping. Today the cost and logistics of extensive sampling of this unit makes the existing core collection irreplaceable. We transferred the material to new containers, digitally recorded metadata, and created archival labels. As a result of this effort, the Cahoon Mine cores are now stored in a format that is physically and digitally accessible.

  4. Over-expressing the C3 photosynthesis cycle enzyme Sedoheptulose-1-7 Bisphosphatase improves photosynthetic carbon gain and yield under fully open air CO2 fumigation (FACE

    Directory of Open Access Journals (Sweden)

    Ort Donald R

    2011-08-01

    Full Text Available Abstract Background Biochemical models predict that photosynthesis in C3 plants is most frequently limited by the slower of two processes, the maximum capacity of the enzyme Rubisco to carboxylate RuBP (Vc,max, or the regeneration of RuBP via electron transport (J. At current atmospheric [CO2] levels Rubisco is not saturated; consequently, elevating [CO2] increases the velocity of carboxylation and inhibits the competing oxygenation reaction which is also catalyzed by Rubisco. In the future, leaf photosynthesis (A should be increasingly limited by RuBP regeneration, as [CO2] is predicted to exceed 550 ppm by 2050. The C3 cycle enzyme sedoheptulose-1,7 bisphosphatase (SBPase, EC 3.1.3.17 has been shown to exert strong metabolic control over RuBP regeneration at light saturation. Results We tested the hypothesis that tobacco transformed to overexpressing SBPase will exhibit greater stimulation of A than wild type (WT tobacco when grown under field conditions at elevated [CO2] (585 ppm under fully open air fumigation. Growth under elevated [CO2] stimulated instantaneous A and the diurnal photosynthetic integral (A' more in transformants than WT. There was evidence of photosynthetic acclimation to elevated [CO2] via downregulation of Vc,max in both WT and transformants. Nevertheless, greater carbon assimilation and electron transport rates (J and Jmax for transformants led to greater yield increases than WT at elevated [CO2] compared to ambient grown plants. Conclusion These results provide proof of concept that increasing content and activity of a single photosynthesis enzyme can enhance carbon assimilation and yield of C3 crops grown at [CO2] expected by the middle of the 21st century.

  5. Over-expressing the C3 photosynthesis cycle enzyme Sedoheptulose-1-7 Bisphosphatase improves photosynthetic carbon gain and yield under fully open air CO2 fumigation (FACE)

    Science.gov (United States)

    2011-01-01

    Background Biochemical models predict that photosynthesis in C3 plants is most frequently limited by the slower of two processes, the maximum capacity of the enzyme Rubisco to carboxylate RuBP (Vc,max), or the regeneration of RuBP via electron transport (J). At current atmospheric [CO2] levels Rubisco is not saturated; consequently, elevating [CO2] increases the velocity of carboxylation and inhibits the competing oxygenation reaction which is also catalyzed by Rubisco. In the future, leaf photosynthesis (A) should be increasingly limited by RuBP regeneration, as [CO2] is predicted to exceed 550 ppm by 2050. The C3 cycle enzyme sedoheptulose-1,7 bisphosphatase (SBPase, EC 3.1.3.17) has been shown to exert strong metabolic control over RuBP regeneration at light saturation. Results We tested the hypothesis that tobacco transformed to overexpressing SBPase will exhibit greater stimulation of A than wild type (WT) tobacco when grown under field conditions at elevated [CO2] (585 ppm) under fully open air fumigation. Growth under elevated [CO2] stimulated instantaneous A and the diurnal photosynthetic integral (A') more in transformants than WT. There was evidence of photosynthetic acclimation to elevated [CO2] via downregulation of Vc,max in both WT and transformants. Nevertheless, greater carbon assimilation and electron transport rates (J and Jmax) for transformants led to greater yield increases than WT at elevated [CO2] compared to ambient grown plants. Conclusion These results provide proof of concept that increasing content and activity of a single photosynthesis enzyme can enhance carbon assimilation and yield of C3 crops grown at [CO2] expected by the middle of the 21st century. PMID:21884586

  6. Structure of Aeropyrum pernix fibrillarin in complex with natively bound S-adenosyl-L-methionine at 1.7 Å resolution.

    Science.gov (United States)

    de Silva, Udesh; Zhou, Zhaoli; Brown, Bernard A

    2012-08-01

    Fibrillarin is the key methyltransferase associated with the C/D class of small nuclear ribonucleoproteins (snRNPs) and participates in the preliminary step of pre-ribosomal rRNA processing. This molecule is found in the fibrillar regions of the eukaryotic nucleolus and is involved in methylation of the 2'-O atom of ribose in rRNA. Human fibrillarin contains an N-terminal GAR domain, a central RNA-binding domain comprising an RNP-2-like superfamily consensus sequence and a catalytic C-terminal helical domain. Here, Aeropyrum pernix fibrillarin is described, which is homologous to the C-terminal domain of human fibrillarin. The protein was crystallized with an S-adenosyl-L-methionine (SAM) ligand bound in the active site. The molecular structure of this complex was solved using X-ray crystallography at a resolution of 1.7 Å using molecular replacement with fibrillarin structural homologs. The structure shows the atomic details of SAM and its active-site interactions; there are a number of conserved residues that interact directly with the cofactor. Notably, the adenine ring of SAM is stabilized by π-π interactions with the conserved residue Phe110 and by electrostatic interactions with the Asp134, Ala135 and Gln157 residues. The π-π interaction appears to play a critical role in stabilizing the association of SAM with fibrillarin. Furthermore, comparison of A. pernix fibrillarin with homologous structures revealed different orientations of Phe110 and changes in α-helix 6 of fibrillarin and suggests key differences in its interactions with the adenine ring of SAM in the active site and with the C/D RNA. These differences may play a key role in orienting the SAM ligand for catalysis as well as in the assembly of other ribonucleoproteins and in the interactions with C/D RNA.

  7. Definition of a SNOMED CT pathology subset and microglossary, based on 1.17 million biological samples from the Catalan Pathology Registry.

    Science.gov (United States)

    Sanz, Xavier; Pareja, Laura; Rius, Ariadna; Rodenas, Pepi; Abdón, Núria; Gálvez, Jordi; Esteban, Laura; Escribà, Josep Maria; Borràs, Josep Maria; Ribes, Josepa

    2017-11-20

    SNOMED CT terminology is not backed by standard norms of encoding among pathologists. The vast number of concepts ordered in hierarchies and axes, together with the lack of rules of use, complicates the functionality of SNOMED CT for coding, extracting, and analyzing the data. Defining subgroups of SNOMED CT by discipline could increase its functionality. The challenge lies in how to choose the concepts to be included in a subset from a total of over 300,000. Besides, SNOMED CT does not cover daily need, as the clinical reality is dynamic and changing. To adapt SNOMED CT to needs in a flexible way, the possibility exists to create extensions. In Catalonia, most pathology departments have been migrating from SNOMED II to SNOMED CT in a bid to advance the development of the Catalan Pathology Registry, which was created in 2014 as a repository for all the pathological diagnoses. This article explains the methodology used to: (a) identify the clinico-pathological entities and the molecular diagnostic procedures not included in SNOMED CT; (b) define the theoretical subset and microglossary of pathology; (c) describe the SNOMED CT concepts used by pathologists of 1.17 million samples of the Catalan Pathology Registry; and (d) adapt the theoretical subset and the microglossary according to the actual use of SNOMED CT. Of the 328,365 concepts available for coding the diagnoses (326,732 in SNOMED CT and 1576 in Catalan extension), only 2% have been used. Combining two axes of SNOMED CT, body structure and clinical findings, has enabled coding most of the morphologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Spectral analysis of the effects of 1.7 MeV electron irradiation on the current transfer characteristic of cadmium telluride solar cells.

    Science.gov (United States)

    Tian, Jin-Xiu; Zeng, Guang-Gen; He, Xu-Lin; Zhang, Jing-Quan; Wu, Li-Li; Li, Wei; Li, Bing; Wang, Wen-Wu; Feng, Liang-Huan

    2014-04-01

    The effects of device performance of 1.7 MeV electron irradiation on cadmium telluride polycrystalline thin film solar cells with the structure of anti-radiation glass/ITO/ZnO/CdS/CdTe/ZnTe/ZnTe : Cu/Ni have been studied. Light and dark I-V characteristics, dark C-V characteristics, quantum efficiency (QE), admittance spectrum (AS) and other testing methods were used to analyze cells performance such as the open-circuit voltage (Voc), short-circuit current (Isc), fill factor (FF) and conversion efficiency (eta). It was explored to find out the effects of irradiation on the current transfer characteristic of solar cells combined with the dark current density (Jo), diode ideal factor (A), quantum efficiency, carrier concentration and the depletion layer width. The decline in short-circuit current was very large and the efficiency of solar cells decreased obviously after irradiation. Reverse saturation current density increased, which indicates that p-n junction characteristics of solar cells were damaged, and diode ideal factor was almost the same, so current transport mechanism of solar cells has not changed. Quantum efficiency curves proved that the damage of solar cells' p-n junction influenced the collection of photo-generated carriers. Irradiation made carrier concentration reduce to 40.6%. The analyses have shown that. A new defect was induced by electron irradiation, whose position is close to 0.58 eV above the valence band in the forbidden band, and capture cross section is 1.78 x 10(-16) cm2. These results indicate that irradiation influences the generation of photo-generated carriers, increases the risk of the carrier recombination and the reverse dark current, and eventually makes the short-circuit current of solar cells decay.

  9. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li

    2011-01-01

    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. – We give efficient reductions for each of the above problems...... to a new problem, which we call substring range reporting. Hence, we unify the previous work by showing that we may restrict our attention to a single problem rather than studying each of the above problems individually. – We show how to solve substring range reporting with optimal query time and little...... range reporting are based on a novel combination of suffix trees and range reporting data structures. The reductions are simple and general and may apply to other combinations of string indexing with range reporting....

  10. Compact Antenna Range

    Data.gov (United States)

    Federal Laboratory Consortium — Facility consists of a folded compact antenna range including a computer controlled three axis position table, parabolic reflector and RF sources for the measurement...

  11. Dryden Aeronautical Test Range

    Data.gov (United States)

    Federal Laboratory Consortium — Recently redesignated to honor Dr. Hugh L. Dryden, NASA's Dryden Aeronautical Test Range (DATR) supports aerospace flight research and technology integration, space...

  12. A biodegradable porous composite scaffold of PCL/BCP containing Ang-(1-7 for bone tissue engineering Um suporte compósito poroso biodegradável de PCL/BCP contendo Ang-(1-7 para engenharia de tecido ósseo

    Directory of Open Access Journals (Sweden)

    F. A. Macedo

    2012-12-01

    Full Text Available Highly porous three-dimensional biodegradable scaffolds was obtained from beta-tricalcium phosphate-hydroxyapatite bioceramic (BCP, PCL, and Angiotensin-(1-7. We used the solvent casting and particulate leaching methods (SC/PL. The processed scaffolds were characterized by X-ray microtomography (µ-CT. Biocompatibility tests in vitro were performed during three and seven days using MTT and Alkaline Phosphatase Activity (APA assays. Both the MTT activity and APA were evaluated using a one-way ANOVA test. The µ-CT results showed that the increase of the PCL:BCP weight ratio leads to structures with lower pore sizes. The pore interconnectivity of the processed scaffolds was evaluated in terms of the fragmentation index (FI. We observed that the obtained composites present poorly connected structures, with close values of FI. However, as the polymer phase is almost transparent to the X-rays, it was not taken into consideration in the µ-CT tests. The MTT activity assay revealed that scaffolds obtained with and without Angiotensin-(1-7 present mild and moderate cytotoxic effects, respectively. The APA assay showed that the rat osteoblasts, when in contact for three days with the PCL composites, presented an APA similar to that observed for the control cells. Nevertheless, for an incubation time of seven days we observed a remarkable decrease in the alkaline phosphatase activity. In conclusion, using the solvent casting and salt leaching method we obtained 3D porous that are composites of PCL, BC and Ang-(1-7, which have suitable shapes for the bone defects, a high porosity and interconnect pores. Furthermore, the viability in vitro showed that the scaffolds have potential for drug delivery system and could be used in future in vivo tests.A estrutura de um biomaterial para regeneração óssea é fator chave para seu sucesso clínico. Não existe um único biomaterial usado para reparo e regeneração óssea capaz de preencher todos os requisitos para um enxerto ósseo ideal. Assim, optou-se por utilizar neste estudo dois biomateriais largamente utilizados na engenharia de tecido ósseo, a policaprolactona (PCL e cerâmica bifásica (BCP. Neste estudo, compósitos porosos tridimensionais de PCL:BCP (3:1 e 1:1 p:p foram fabricados utilizando a combinação das técnicas de evaporação do solvente e lavagem de partículas de sal com ou sem a adição de Angiotensina (Ang-(1-7. Os compósitos de PCL:BCP com alta porosidade e interconectividade obtidos foram analisados usando microtomografia computadorizada (µ-CT. A viabilidade dos compósitos com e sem a adição da Ang-(1-7 foram analisados utilizando osteoblastos de cultura primária nos períodos de 3 e 7 dias utilizando o teste de MTT e secreção de Fosfatase Alcalina. Diferenças significativas de todas as variáveis foram testadas através de análises multivariáveis (p<0,05. Demonstrou-se uma estrutura mais uniformemente distribuída quando a razão PCL/BCP foi aumentada. A conectividade dos poros foi mensurada através do índice de fragmentação (FI demonstrando estruturas desconexas nas amostras analisadas possuindo valores de FI próximos. Quanto maior a razão PCL/BCP, maior a dimensão fractal (FD. Análises in vitro utilizando o teste do MTT demonstraram que as amostras contendo ou não Ang-(1-7 possuíram efeitos citotóxico médio e moderado, respectivamente. A análise da atividade de fosfatase alcalina não monstrou diferença entre as amostras no período de 3 dias decrescendo sua atividade nas amostras contendo Ang-(1-7 no período de 7 dias. Dessa forma, utilizando a combinação das técnicas de evaporação do solvente e lavagem do sal, obtiveram-se estruturas porosas tridimensionais, desejável para defeitos ósseos tendo capacidade para sistema de transporte de drogas podendo ser avaliada em futuros testes in vivo.

  13. On Range of Skill

    DEFF Research Database (Denmark)

    Hansen, Thomas Dueholm; Miltersen, Peter Bro; Sørensen, Troels Bjerre

    2008-01-01

    size (and doubly exponential in its depth). We also provide techniques that yield concrete bounds for unbalanced game trees and apply these to estimate the Range of Skill of Tic-Tac-Toe and Heads-Up Limit Texas Hold'em Poker. In particular, we show that the Range of Skill of Tic-Tac-Toe is more than...

  14. Range Scheduling Aid (RSA)

    Science.gov (United States)

    Logan, J. R.; Pulvermacher, M. K.

    1991-01-01

    Range Scheduling Aid (RSA) is presented in the form of the viewgraphs. The following subject areas are covered: satellite control network; current and new approaches to range scheduling; MITRE tasking; RSA features; RSA display; constraint based analytic capability; RSA architecture; and RSA benefits.

  15. Home range and travels

    Science.gov (United States)

    Stickel, L.F.; King, John A.

    1968-01-01

    The concept of home range was expressed by Seton (1909) in the term 'home region,' which Burr (1940, 1943) clarified with a definition of home range and exemplified in a definitive study of Peromyscus in the field. Burt pointed out the ever-changing characteristics of home-range area and the consequent absence of boundaries in the usual sense--a finding verified by investigators thereafter. In the studies summarized in this paper, sizes of home ranges of Peromyscus varied within two magnitudes, approximately from 0.1 acre to ten acres, in 34 studies conducted in a variety of habitats from the seaside dunes of Florida to the Alaskan forests. Variation in sizes of home ranges was correlated with both environmental and physiological factors; with habitat it was conspicuous, both in the same and different regions. Food supply also was related to size of home range, both seasonally and in relation to habitat. Home ranges generally were smallest in winter and largest in spring, at the onset of the breeding season. Activity and size also were affected by changes in weather. Activity was least when temperatures were low and nights were bright. Effects of rainfall were variable. Sizes varied according to sex and age; young mice remained in the parents' range until they approached maturity, when they began to travel more widely. Adult males commonly had larger home ranges than females, although there were a number of exceptions. An inverse relationship between population density and size of home range was shown in several studies and probably is the usual relationship. A basic need for activity and exploration also appeared to influence size of home range. Behavior within the home range was discussed in terms of travel patterns, travels in relation to home sites and refuges, territory, and stability of size of home range. Travels within the home range consisted of repeated use of well-worn trails to sites of food, shelter, and refuge, plus more random exploratory travels

  16. Testing the strong equivalence principle with spacecraft ranging towards the nearby Lagrangian points

    Science.gov (United States)

    Congedo, Giuseppe; De Marchi, Fabrizio

    2016-05-01

    General relativity is supported by great experimental evidence. Yet there is a lot of interest in precisely setting its limits with on going and future experiments. A question to answer is about the validity of the strong equivalence principle. Ground experiments and lunar laser ranging have provided the best upper limit on the Nordtvedt parameter σ [η ]=4.4 ×10-4 . With the future planetary mission BepiColombo, this parameter will be further improved by at least an order of magnitude. In this paper we envisage yet another possible testing environment with spacecraft ranging towards the nearby Sun-Earth collinear Lagrangian points. Neglecting errors in planetary masses and ephemerides, we forecast σ [η ]=6.4 (2.0 )×10-4 (5 yr integration time) via ranging towards L1 in a realistic (optimistic) scenario depending on current (future) range capabilities and knowledge of the Earth's ephemerides. A combined measurement, L1+L2, gives instead 4.8 (1.7 )×10-4. In the optimistic scenario a single measurement of one year would be enough to reach ≈3 ×10-4. All figures are comparable with lunar laser ranging, but worse than BepiColombo. Performances could be much improved if data were integrated over time and over the number of satellites flying around either of the two Lagrangian points. We point out that some systematics (gravitational perturbations of other planets or figure effects) are much more in control compared to other experiments. We do not advocate a specific mission to constrain the strong equivalence principle, but we do suggest analyzing ranging data of present and future spacecrafts flying around L1/L2 (one key mission is, for instance, LISA Pathfinder). This spacecraft ranging would be a new and complementary probe to constrain the strong equivalence principle in space.

  17. Structural basis for species specific inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1: computational study and biological validation.

    Directory of Open Access Journals (Sweden)

    Tobias Klein

    Full Text Available 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1 catalyzes the reduction of estrone to estradiol, which is the most potent estrogen in humans. Inhibition of 17β-HSD1 and thereby reducing the intracellular estradiol concentration is thus a promising approach for the treatment of estrogen dependent diseases. In the past, several steroidal and non-steroidal inhibitors of 17β-HSD1 have been described but so far there is no cocrystal structure of the latter in complex with 17β-HSD1. However, a distinct knowledge of active site topologies and protein-ligand interactions is a prerequisite for structure-based drug design and optimization. An elegant strategy to enhance this knowledge is to compare inhibition values obtained for one compound toward ortholog proteins from various species, which are highly conserved in sequence and differ only in few residues. In this study the inhibitory potencies of selected members of different non-steroidal inhibitor classes toward marmoset 17β-HSD1 were determined and the data were compared with the values obtained for the human enzyme. A species specific inhibition profile was observed in the class of the (hydroxyphenylnaphthols. Using a combination of computational methods, including homology modelling, molecular docking, MD simulation, and binding energy calculation, a reasonable model of the three-dimensional structure of marmoset 17β-HSD1 was developed and inhibition data were rationalized on the structural basis. In marmoset 17β-HSD1, residues 190 to 196 form a small α-helix, which induces conformational changes compared to the human enzyme. The docking poses suggest these conformational changes as determinants for species specificity and energy decomposition analysis highlighted the outstanding role of Asn152 as interaction partner for inhibitor binding. In summary, this strategy of comparing the biological activities of inhibitors toward highly conserved ortholog proteins might be an alternative to

  18. Stability of Coordinates of The Slr Stations On A Basis of Lageos-1 and Lageos-2 Laser Ranging In 2000

    Science.gov (United States)

    Schillak, S.; Wnuk, E.

    Determination of the stations coordinates and the control of their stability is one of the most important task in the satellite geodesy and geodynamics. This work is continu- ation of the similar paper about coordinates stability of the all SLR stations in 1999. The paper present results of positions determination for all SLR stations in 2000 cal- culated in the ITRF2000 system on the basis of data provided by the LAGEOS-1 and LAGEOS-2 laser ranging. The calculations were performed with the usage of the GEODYN II program. Coordinates of the stations were determined from monthly arcs for 2000. Typical RMS of (O-C) values for the monthly orbital arcs was on a level of 1.7 cm. The final stability of the geocentric coordinates of SLR stations per one year for all components varies from 5 millimetres to several centimetres.

  19. Long range image enhancement

    CSIR Research Space (South Africa)

    Duvenhage, B

    2015-11-01

    Full Text Available and Vision Computing, Auckland, New Zealand, 23-24 November 2015 Long Range Image Enhancement Bernardt Duvenhage Council for Scientific and Industrial Research South Africa Email: bduvenhage@csir.co.za Abstract Turbulent pockets of air...

  20. SNOWY RANGE WILDERNESS, WYOMING.

    Science.gov (United States)

    Houston, Robert S.; Bigsby, Philip R.

    1984-01-01

    A mineral survey of the Snowy Range Wilderness in Wyoming was undertaken and was followed up with more detailed geologic and geochemical surveys, culminating in diamond drilling of one hole in the Snowy Range Wilderness. No mineral deposits were identified in the Snowy Range Wilderness, but inasmuch as low-grade uranium and associated gold resources were identified in rocks similar to those of the northern Snowy Range Wilderness in an area about 5 mi northeast of the wilderness boundary, the authors conclude that the northern half of the wilderness has a probable-resource potential for uranium and gold. Closely spaced drilling would be required to completely evaluate this mineral potential. The geologic terrane precludes the occurrence of fossil fuels.

  1. Atlantic Test Range (ATR)

    Data.gov (United States)

    Federal Laboratory Consortium — ATR controls fully-instrumented and integrated test ranges that provide full-service support for cradle-to-grave testing. Airspace and surface target areas are used...

  2. Light Detection And Ranging

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — LiDAR (Light Detection and Ranging) discrete-return point cloud data are available in the American Society for Photogrammetry and Remote Sensing (ASPRS) LAS format....

  3. On Range of Skill

    DEFF Research Database (Denmark)

    Hansen, Thomas Dueholm; Miltersen, Peter Bro; Sørensen, Troels Bjerre

    2008-01-01

    is a small number, but only gave heuristic arguments for this. In this paper, we provide the first methods for rigorously estimating the Range of Skill of a given game. We provide some general, asymptotic bounds that imply that the Range of Skill of a perfectly balanced game tree is almost exponential in its......At AAAI'07, Zinkevich, Bowling and Burch introduced the Range of Skill measure of a two-player game and used it as a parameter in the analysis of the running time of an algorithm for finding approximate solutions to such games. They suggested that the Range of Skill of a typical natural game...... size (and doubly exponential in its depth). We also provide techniques that yield concrete bounds for unbalanced game trees and apply these to estimate the Range of Skill of Tic-Tac-Toe and Heads-Up Limit Texas Hold'em Poker. In particular, we show that the Range of Skill of Tic-Tac-Toe is more than...

  4. Differential effect of D623N variant and wild-type Na(v)1.7 sodium channels on resting potential and interspike membrane potential of dorsal root ganglion neurons.

    Science.gov (United States)

    Ahn, Hye-Sook; Vasylyev, Dmytro V; Estacion, Mark; Macala, Lawrence J; Shah, Palak; Faber, Catharina G; Merkies, Ingemar S J; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2013-09-05

    Sodium channel NaV1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function NaV1.7 mutations/variants have been identified in the painful disorders inherited erythromelalgia and small-fiber neuropathy (SFN). DRG neurons transfected with these channel variants display depolarized resting potential, reduced current-threshold, increased firing-frequency and spontaneous firing. Whether the depolarizing shift in resting potential and enhanced spontaneous firing are due to persistent activity of variant channels, or to compensatory changes in other conductance(s) in response to expression of the variant channel, as shown in model systems, has not been studied. We examined the effect of wild-type NaV1.7 and a NaV1.7 mutant channel, D623N, associated with SFN, on resting potential and membrane potential during interspike intervals in DRG neurons. Resting potential in DRG neurons expressing D623N was depolarized compared to neurons expressing WT-NaV1.7. Exposure to TTX hyperpolarized resting potential by 7mV, increased current-threshold, decreased firing-frequency, and reduced NMDG-induced-hyperpolarization in DRG neurons expressing D623N. To assess the contribution of depolarized resting potential to DRG neuron excitability, we mimicked the mutant channel's depolarizing effect by current injection to produce equivalent depolarization; the depolarization decreased current threshold and increased firing-frequency. Voltage-clamp using ramp or repetitive action potentials as commands showed that D623N channels enhance the TTX-sensitive inward current, persistent at subthreshold membrane voltages, as predicted by a Hodgkin-Huxley model. Our results demonstrate that a variant of NaV1.7 associated with painful neuropathy depolarizes resting membrane potential and produces an enhanced inward current during interspike intervals, thereby contributing to DRG neuron hyperexcitability. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Preliminary design of four aircraft to service the California Corridor in the year 2010: The California Condor, California Sky-Hopper, high capacity short range transport tilt rotor aircraft needed to simplify intercity transportation

    Science.gov (United States)

    1989-01-01

    The major objective of this project was to design an aircraft for use in the California Corridor in the year 2010. The design process, completed by students in a senior design class at California Polytechnic State University, San Luis Obispo, used a Class 1 airplane design analysis from Jan Roskam's Airplane Design. The California Condor (CC-38), a 38 passenger, 400 mph aircraft, was designed to meet the needs of tomorrow's passengers while conforming to the California Corridor's restrictions. Assumptions were made using today's technology with forecasts into 21st Century technology. Doubling today's commuter aircraft passenger capacity, travelling at Mach .57 with improved cruise efficiencies of over 10 percent, with the ability to land within field lengths of 4000 feet, are the CC-38's strongest points. The California Condor has a very promising future in helping to relieve the air traffic and airport congestion in the 21st Century.

  6. Range Selection and Median

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Larsen, Kasper Green

    2011-01-01

    that supports queries in constant time, needs n1+ (1) space. For data structures that uses n logO(1) n space this matches the best known upper bound. Additionally, we present a linear space data structure that supports range selection queries in O(log k= log log n + log log n) time. Finally, we prove that any...

  7. Electric vehicles: Driving range

    Science.gov (United States)

    Kempton, Willett

    2016-09-01

    For uptake of electric vehicles to increase, consumers' driving-range needs must be fulfilled. Analysis of the driving patterns of personal vehicles in the US now shows that today's electric vehicles can meet all travel needs on almost 90% of days from a single overnight charge.

  8. Range of motion and cervical myofascial pain.

    Science.gov (United States)

    Wilke, J; Niederer, D; Fleckenstein, J; Vogt, L; Banzer, W

    2016-01-01

    Several studies investigating myofascial pain syndrome include assessments of range of motion (ROM) as a diagnostic criterion. However, the value of ROM in this context has not yet been evaluated in controlled clinical studies. We aimed to examine whether patients with myofascial pain syndrome display alterations of ROM when compared to healthy subjects. Twenty-two individuals (13 females, 9 males; aged 33.4 ± 13.9 yrs) afflicted with active myofascial trigger points in the upper trapezius muscle as well as 22 age and sex matched healthy controls were included. All subjects underwent an examination of maximal active cervical ROM in flexion/extension assessed by means of a 3D ultrasonic movement analysis system (30 Hz; Zebris CMS 70). In the patients group, pressure pain threshold (PPT) of the trigger points was determined using a pressure algometer. Maximum range of motion in the sagittal plane did not differ between individuals with MTrP (125.9 ± 23.2°, 95% CI: 116.2-135.6°) and asymptomatic subjects (128.2 ± 20.4°, 95% CI: 119.7-136.7°; p > .05). In patients, PPT (1.7 ± .6, 95% CI: 1.5-1.9) was not correlated with cervical mobility (r = -.13; p > .05). Based on these pilot data, range of motion in flexion/extension is not a valid criterion for the detection of myofascial trigger points. Additional research incorporating movement amplitudes in other anatomical planes and additional afflicted muscles should be conducted in order to further delineate the relative impact of MTrP on range of motion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Intrapulmonary activation of the angiotensin-converting enzyme type 2/angiotensin 1-7/G-protein-coupled Mas receptor axis attenuates pulmonary hypertension in Ren-2 transgenic rats exposed to chronic hypoxia.

    Science.gov (United States)

    Hampl, V; Herget, J; Bíbová, J; Baňasová, A; Husková, Z; Vaňourková, Z; Jíchová, Š; Kujal, P; Vernerová, Z; Sadowski, J; Červenka, L

    2015-01-01

    The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT₁) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT₁receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT₁receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

  10. The renin-angiotensin system and its vasoactive metabolite angiotensin-(1-7) in the mechanism of the healing of preexisting gastric ulcers. The involvement of Mas receptors, nitric oxide, prostaglandins and proinflammatory cytokines.

    Science.gov (United States)

    Pawlik, M W; Kwiecien, S; Ptak-Belowska, A; Pajdo, R; Olszanecki, R; Suski, M; Madej, J; Targosz, A; Konturek, S J; Korbut, R; Brzozowski, T

    2016-02-01

    The inhibition of angiotensin-converting enzyme (ACE) or the blockade of angiotensin (Ang) AT-1 receptors affords protection against acute gastric mucosal injury, but whether the major metabolite of renin-angiotensin system (RAS), Ang-(1-7), accelerates the healing process of preexisting gastric ulcers remains unknown. Previous studies documented that Ang-(1-7) acting via its own Mas receptor exerts vascular responses opposing those of Ang II. We studied the effects of the Ang-(1-7)/Mas receptor axis on the healing rate of acetic-acid-induced gastric ulcers with or without the blockade of Mas receptors by A 779 and compared it with the effects of activation and blockade of the AT-1 receptor by the treatment with Ang II and losartan, respectively, the inhibition of ACE by lisinopril, the NO/cNOS inhibition by L-NAME and inhibition of prostaglandin/COX system by indomethacin in the presence of Ang-(1-7). Additionally, ex vivo metabolism of Ang I in gastric tissue was assessed by LC/MS method. At day 9 after ulcer induction, the area of these ulcers and the accompanying changes in total gastric blood flow (GBF) were determined as were gastric mucosal blood flow (GMBF) at ulcer margin and gastric oxygen uptake (GVO2). The gastric mucosal expression of mRNAs for constitutive nitric oxide synthase (cNOS), superoxide dismutase (SOD), and pro-inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) and plasma level of both cytokines were determined by RT-PCR and ELISA. The 9 days treatment with Ang II dose-dependently increased the area of gastric ulcers and this effect was accompanied by a significant fall in the GBF, GVO2 and GMBF at ulcer margin. In contrast, treatment with Ang-(1-7) which produced a significant rise in the luminal content of NO significantly reduced the area of gastric ulcer and significantly increased the GBF, GVO2 and the GMBF at ulcer margin. Similar GMBF changes and significant reduction the area of gastric ulcer was observed in rats with gastric ulcers treated with the agonist of Mas receptor, AVE 0991. These effects of Ang-(1-7) and AVE 0991 were eliminated by blockade of the Mas receptor with A779. Similarly to Ang-(1-7), treatment with losartan or lisinopril significantly reduced the area of gastric ulcers and the accompanying increase in the GMBF at ulcer margin and these effects were significantly attenuated by a concomitant administration of L-NAME and indomethacin. The rate of healing of ulcers was associated with a decrease in ex vivo Ang-(1-7) formation and this effect was attenuated by lisinopril. The treatment with Ang-(1- 7) or AVE 0991 increased the expression of mRNA for cNOS and SOD and downregulated that of IL-1β and TNF-α followed by the decrease in the plasma IL-1β and TNF-α levels. We conclude that the Ang-(1-7)/Mas receptor system accelerates the healing of preexisting gastric ulcers via an increase in the gastric macro- and microcirculations, and an increase in gastric tissue oxygenation. These effects are mediated by PG and NO derived from overexpression of cNOS, an increase in the expression of antioxidizing enzyme SOD 2 and an anti-inflammatory action involving the inhibition of expression and release of pro-inflammatory cytokines IL-1β and TNF-α. Our results seem to underlie the importance of the Ang-(1-7), AT-1 and Mas receptors in the regulation of local vascular and metabolic effects associated with mechanism of gastric ulcer healing.

  11. Toyotarity. Term, model, range

    Directory of Open Access Journals (Sweden)

    Stanisław Borkowski

    2013-04-01

    Full Text Available The Toyotarity and BOST term was presented in the chapter. The BOST method allows to define relations between material resources and human resources and between human resources and human resources (TOYOTARITY. This term was also invented by the Author (and is legally protected. The idea of methodology is an outcome of 12 years of work.

  12. Long-range antigravity

    Energy Technology Data Exchange (ETDEWEB)

    Macrae, K.I.; Riegert, R.J. (Maryland Univ., College Park (USA). Center for Theoretical Physics)

    1984-10-01

    We consider a theory in which fermionic matter interacts via long-range scalar, vector and tensor fields. In order not to be in conflict with experiment, the scalar and vector couplings for a given fermion must be equal, as is natural in a dimensionally reduced model. Assuming that the Sun is not approximately neutral with respect to these new scalar-vector charges, and if the couplings saturate the experimental bounds, then their strength can be comparable to that of gravity. Scalar-vector fields of this strength can compensate for a solar quadrupole moment contribution to Mercury's anomalous perihelion precession.

  13. Online Sorted Range Reporting

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf; Greve, Mark

    2009-01-01

    We study the following one-dimensional range reporting problem: On an arrayA of n elements, support queries that given two indices i ≤ j and an integerk report the k smallest elements in the subarray A[i..j] in sorted order. We present a data structure in the RAM model supporting such queries...... in optimal O(k) time. The structure uses O(n) words of space and can be constructed in O(n logn) time. The data structure can be extended to solve the online version of the problem, where the elements in A[i..j] are reported one-by-one in sorted order, in O(1) worst-case time per element. The problem...... is motivated by (and is a generalization of) a problem with applications in search engines: On a tree where leaves have associated rank values, report the highest ranked leaves in a given subtree. Finally, the problem studied generalizes the classic range minimum query (RMQ) problem on arrays....

  14. Sentinel node biopsy in breast cancer: five years experience from Denmark

    DEFF Research Database (Denmark)

    Christiansen, Peter; Balslev, E.; Jensen, D.

    2008-01-01

    INTRODUCTION: Danish experience from the first five years with sentinel lymph node biopsy (SLNB) as a routine staging procedure in early breast cancer is reported. METHODS: During the period January 1, 2002 to December 31, 2006, 14 923 patients were diagnosed at Danish breast surgical centers...... certified for the sentinel node method. SLNB was performed in 8 338 patients (55.9%). The fraction increased steadily from 43% in 2002 to 67% in 2006. The median follow-up was 1.7 year (range 0-5.2 years). RESULTS: Patients staged with SLNB were younger, had more often BCS, had smaller tumor size, were more...... classification by SN was known. In the group of 1 563 patients with macrometastases in SN, 45% had non-sentinel node metastases, and in the group of 942 patients with micrometastases only, 23% had more positive nodes. Regional lymph node metastases were found in 15% with ITC in sentinel nodes. Lymph node...

  15. Measurement of individual loudness functions by trisection of loudness ranges.

    Science.gov (United States)

    Villchur, Edgar; Killion, Mead C

    2008-10-01

    Loudness-balance measurements with monaurally impaired subjects have shown that the shape of the loudness versus sound-pressure curve among hearing-impaired persons varies significantly. But the effectiveness of adjusting the compression characteristics of wide-dynamic-range compression hearing aids-the compression ratios, the variation of compression ratio with level, and the threshold of compression-to restore normal loudness growth for the individual patient has never been properly tested; individual loudness measurements have been too uncertain to permit meaningful individual adjustments. Recent investigators have reported standard deviations of such measurements in normal-hearing subjects of 6.4 dB and 7.8 dB. This investigation describes a method of measuring loudness function with a standard deviation in normal-hearing subjects of the order of 1 dB, both significantly lower than that of previous methods and sufficiently accurate for individual-subject adjustments. Each of nine normal-hearing subjects-seven of them inexperienced and one a 9-year-old was asked to make three successive loudness trisections within an amplitude range of 40 to 80 dB SPL, providing six points from which to plot a loudness-function curve between these limits. The individual and average curves were validated as accurate loudness functions by comparing them to the curve defined by the equation of loudness versus amplitude in current Standards. In a second validation experiment, the loudness functions of masked ears measured by trisection were compared to the loudness function of those ears measured by loudness balance between masked and unmasked ears. The difference between a loudness function based on the average of subject trisections and the loudness function defined by the ANSI Standard loudness equation was -1.92 dB at the lowest trisection level and +0.05 dB at the highest level. The standard deviations of subject responses were 1.63 dB for the lowest trisection level and 0.68 d

  16. 2008 NASA Range Safety Annual Report

    Science.gov (United States)

    Lamoreaux, Richard W.

    2008-01-01

    Welcome to the 2008 edition of the NASA Range Safety Annual Report. Funded by NASA Headquarters, this report provides a NASA Range Safety overview for current and potential range users. This year, along with full length articles concerning various subject areas, we have provided updates to standard subjects with links back to the 2007 original article. Additionally, we present summaries from the various NASA Range Safety Program activities that took place throughout the year, as well as information on several special projects that may have a profound impact on the way we will do business in the future. The sections include a program overview and 2008 highlights of Range Safety Training; Range Safety Policy; Independent Assessments and Common Risk Analysis Tools Development; Support to Program Operations at all ranges conducting NASA launch operations; a continuing overview of emerging Range Safety-related technologies; Special Interests Items that include recent changes in the ELV Payload Safety Program and the VAS explosive siting study; and status reports from all of the NASA Centers that have Range Safety responsibilities. As is the case each year, contributors to this report are too numerous to mention, but we thank individuals from the NASA Centers, the Department of Defense, and civilian organizations for their contributions. We have made a great effort to include the most current information available. We recommend that this report be used only for guidance and that the validity and accuracy of all articles be verified for updates. This is the third year we have utilized this web-based format for the annual report. We continually receive positive feedback on the web-based edition, and we hope you enjoy this year's product as well. It has been a very busy and productive year on many fronts as you will note as you review this report. Thank you to everyone who contributed to make this year a successful one, and I look forward to working with all of you in the

  17. Lightning detection and ranging

    Science.gov (United States)

    Lennon, C. L.; Poehler, H. A.

    1982-01-01

    A lightning detector and ranging (LDAR) system developed at the Kennedy Space Center and recently transferred to Wallops Island is described. The system detects pulsed VHF signals due to electrical discharges occurring in a thunderstorm by means of 56-75 MHz receivers located at the hub and at the tips of 8 km radial lines. Incoming signals are transmitted by wideband links to a central computing facility which processes the times of arrival, using two independent calculations to determine position in order to guard against false data. The results are plotted on a CRT display, and an example of a thunderstorm lightning strike detection near Kennedy Space Center is outlined. The LDAR correctly identified potential ground strike zones and additionally provided a high correlation between updrafts and ground strikes.

  18. Kenai National Moose Range : Narrative report : 1968

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Kenai National Moose Range outlines Refuge accomplishments during the 1968 calendar year. The report begins by summarizing the...

  19. Effects of long-range transported pollutants on vegetation in boreal coniferous forests: Results from an five year investigation in the Solholmfjell area, Gjerstad, Aust-Agder; Effekter av langtransporterte luftforurensninger i boreal barskog: resultater av fem aars undersoekelser i Solhomfjell-omraadet, Gjerstad, Aust-Agder

    Energy Technology Data Exchange (ETDEWEB)

    Oekland, R.H.

    1996-01-01

    The conference paper relates to a project on investigating the effects of long-range transported pollutants in Norway. The paper gives a brief description of the more important results obtained in the project. The aim of the project was to investigate the pollution load in vegetation, soils and trees in Norwegian forest areas of the coniferous type. The project included the collection of samples from 200 test areas in a period of five years. 11 refs.

  20. ANÁLISE CELULAR E MOLECULAR DO PROCESSO APOPTÓTICO EM CÉLULAS ESTRELADAS HEPÁTICAS TRATADAS COM O PEPTÍDEO ANGIOTENSINA-(1-7.

    Directory of Open Access Journals (Sweden)

    Letícia Ferreira Ramos

    2017-03-01

    Full Text Available O fígado possui funções importantes e danos excessivos neste órgão acarretam em alterações metabólicas que podem induzir o aparecimento da fibrose do órgão. Dependendo da intensidade e persistência do estímulo indutor da fibrose, estes podem levar à cirrose e até mesmo ao hepatocarcinoma. Sabe-se que a necrose e a apoptose podem ocorrer em resposta a danos crônicos, mas também podem reverter o quadro fibrosante. Além disso, durante estímulos negativos, o estresse oxidativo também contribui para o estabelecimento da fibrose.  Uma das células relacionadas com a fibrogênese do órgão são as células estreladas hepáticas. Estas se apresentam quiescentes em fígados saudáveis e ativadas em fígados doentes. Atualmente terapias inovadoras são objetivadas e a Angiotensina-(1-7 [Ang-(1-7], desponta-se como um possível elemento modulador da fibrose. Neste estudo observou-se a atuação da Ang-(1-7 no controle de mecanismos negativos no equilíbrio dessas células.

  1. Changes in the expression of voltage-gated sodium channels Nav1.3, Nav1.7, Nav1.8, and Nav1.9 in rat trigeminal ganglia following chronic constriction injury.

    Science.gov (United States)

    Xu, Wenhua; Zhang, Jun; Wang, Yuanyin; Wang, Liecheng; Wang, Xuxia

    2016-08-17

    Voltage-gated sodium channels (VGSCs), especially the tetrodotoxin-sensitive Nav1.3 and Nav1.7, and the tetrodotoxin-resistant Nav1.8 and Nav1.9, have been implicated in acute and chronic neuropathic pain. The aim of this study was to investigate the expression of VGSC Nav1.3, Nav1.7, Nav1.8, and Nav1.9 after nerve injury and their roles in the development of trigeminal neuralgia (TN). We used the infraorbital nerve-chronic constriction injury model of TN in the rat. The time course of changes in the mechanical pain threshold was examined. In addition, real-time PCR and double immunofluorescence staining of VGSC α subunits were used to evaluate messenger RNA and protein expression, respectively, in the trigeminal ganglion. Behavioral tests showed that the mechanical pain threshold decreased significantly 4-42 days after surgery and reached the lowest observed value by day 12. Compared with sham-operated controls, we found that trigeminal ganglion in rats subjected to an infraorbital nerve-chronic constriction injury showed upregulation of Nav1.3 and downregulation of Nav1.7, Nav1.8, and Nav1.9 messenger RNA and protein levels. Our findings suggest that VGSC may participate in the regulation of TN.

  2. Range management research, Fort Valley Experimental Forest

    Science.gov (United States)

    Henry A. Pearson; Warren P. Clary; Margaret M. Moore; Carolyn Hull Sieg

    2008-01-01

    Range management research at the Fort Valley Experimental Forest during the past 100 years has provided scientific knowledge for managing ponderosa pine forests and forest-range grazing lands in the Southwest. Three research time periods are identified: 1908 to 1950, 1950 to 1978, and 1978 to 2008. Early research (1908-1950) addressed ecological effects of livestock...

  3. Tvindkraft: Implementing a 500 kW 21-IGBT-Based Frequency Converter for a 1.7 MW Wind Power Conversion System

    DEFF Research Database (Denmark)

    Gonzalez, Pablo Casado; Pang, Ying; Reigosa, Paula Diaz

    2013-01-01

    The 54-meter-high Tvindkraft windmill was built by a group of volunteers during 1975-1978, as an argument for renewable energy sources as well as an argument against nuclear power. At that time it was the world’s biggest windmill. So far, Tvindkraft has been running for 35 years, proving...... that a wellconstructed wind turbine is a sustainable approach to renewable energy utilization. This paper deals with the analysis, simulation, implementation and experimental testing of a new 500 kW 21- IGBT-based frequency converter that will run in parallel with the former 12-Thyristor-based frequency converter...... to fully utilize the capacity of the windmill. Simulations and experimental results are presented side-by-side to verify the proper functionalities of the frequency converter described in this paper....

  4. Safety and Biodistribution Evaluation in Cynomolgus Macaques of rAAV2tYF-PR1.7-hCNGB3, a Recombinant AAV Vector for Treatment of Achromatopsia.

    Science.gov (United States)

    Ye, Guo-jie; Budzynski, Ewa; Sonnentag, Peter; Nork, T Michael; Miller, Paul E; Sharma, Alok K; Ver Hoeve, James N; Smith, Leia M; Arndt, Tara; Calcedo, Roberto; Gaskin, Chantelle; Robinson, Paulette M; Knop, David R; Hauswirth, William W; Chulay, Jeffrey D

    2016-03-01

    Applied Genetic Technologies Corporation (AGTC) is developing rAAV2tYF-PR1.7-hCNGB3, a recombinant adeno-associated viral (rAAV) vector expressing the human CNGB3 gene, for treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. We report here results of a study evaluating the safety and biodistribution of rAAV2tYF-PR1.7-hCNGB3 in cynomolgus macaques. Three groups of animals (n = 2 males and 2 females per group) received a subretinal injection in one eye of 300 μl containing either vehicle or rAAV2tYF-PR1.7-hCNGB3 at one of two concentrations (4 × 10(11) or 4 × 10(12) vector genomes/ml) and were evaluated over a 3-month period before being euthanized. Administration of rAAV2tYF-PR1.7-hCNGB3 was associated with a dose-related anterior and posterior segment inflammatory response that was greater than that observed in eyes injected with the vehicle control. Most manifestations of inflammation improved over time except that vitreous cells persisted in vector-treated eyes until the end of the study. One animal in the lower vector dose group was euthanized on study day 5, based on a clinical diagnosis of endophthalmitis. There were no test article-related effects on intraocular pressure, visual evoked potential responses, hematology or clinical chemistry parameters, or gross necropsy observations. Histopathological examination demonstrated minimal mononuclear infiltrates in all vector-injected eyes. Serum anti-AAV antibodies developed in all vector-injected animals. No animals developed antibodies to CNGB3. Biodistribution studies demonstrated high levels of vector DNA in the injected eye but minimal or no vector DNA in any other tissue. These results support the use of rAAV2tYF-PR1.7-hCNGB3 in clinical studies in patients with achromatopsia caused by CNGB3 mutations.

  5. Structural analysis and cations distribution of nanocrystalline Ni{sub 1−x}Zn{sub x}Fe{sub 1.7}Ga{sub 0.3}O{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Heiba, Zein K. [Ain Shams University, Faculty of Science, Physics Dept., Cairo (Egypt); Taif University, Faculty of Science, Physics Dept., Al-Haweiah, Taif (Saudi Arabia); Mohamed, Mohamed Bakr [Ain Shams University, Faculty of Science, Physics Dept., Cairo (Egypt); Hamdeh, H.H. [Wichita State Univ., Faculty of Science, Physics Dept., Wichita, KS 67260 (United States); Ahmed, M.A., E-mail: mamdouh_2000_2000@yahoo.com [Al-Azhar University, Faculty of Science, Physics Dept., Nasr City, Cairo (Egypt)

    2015-01-05

    Highlights: • Mossbauer characterization of Ni{sub 1−x}Zn{sub x}Fe{sub 1.7}Ga{sub 0.3}O{sub 4} prepared by citrate method. • X-ray powder diffraction analysis of Ni{sub 1−x}Zn{sub x}Fe{sub 1.7}Ga{sub 0.3}O{sub 4} prepared by citrate. • Bertaut method to calculate the cation distribution in nanocrystaline Ni{sub 1−x}Zn{sub x}Fe{sub 1.7}Ga{sub 0.3}O{sub 4}. • Estimation of cation distribution of Ni{sub 1−x}Zn{sub x}Fe{sub 1.7}Ga{sub 0.3}O{sub 4} ferrite synthesized by citrate method. - Abstract: Nanostructured Ni{sub 1−x}Zn{sub x}Fe{sub 1.7}Ga{sub 0.3}O{sub 4}, with x = 0.0, 0.1, 0.2, 0.3, 0.4 and 0.5 were prepared by citrate method and were investigated using X-ray diffraction and Mossbauer spectroscopy. The structure characterized using X-ray powder diffraction and Rietveld method showed that upon increasing Zn{sup 2+} content, the lattice parameter gradually increases from a = 8.3493 to 8.390 Ǻ and also the crystallite size increases from 4 to 8 nm for x = 0.0 and x = 0.5 respectively. Furthermore, the Mössbauer spectra, measured at 20 K showing spinel magnetic ordering in all the samples, whereas at room temperature, are superposition of collapsing broadened sextet and doublet because of the dependency of particle size. The cation distribution was estimated from the analysis of the Mossbauer spectra as well as Bertaut method, and then confirmed by Rietveld analysis. The results showed that both Zn and Ga ions exclusively occupy the A-site while Ni and Fe ions are distributed over the A- and B-sites.

  6. The Problematic Practical Application of Section 1(6 and 1(7 Of the Intestate Succession Act under a New Dispensation

    Directory of Open Access Journals (Sweden)

    Juanita Jamneck

    2014-08-01

    Full Text Available In recent years many developments have taken place in the field of the law of succession. Du Toit aptly states that "despite the static image that the law of succession often projects, it is a vibrant area of the law that has undergone dramatic changes in recent times and will continue to do so in future". This is indeed the case, as has been illustrated numerous times by the decisions in our courts as to the meaning of the word "spouse" and the recognition of the family as an important social institution. Although the family as an institution is not per se protected in the Constitution, our courts have recognised it as a vital social institution that comes in many different shapes and sizes and it has stressed that one form of family cannot be entrenched at the expense of other forms. As a result of various decisions on the meaning of the word "spouse" under a new dispensation, a Discussion Paper, in the form of Discussion Paper 129 (Project 25 Statutory law revision: Legislation administered by the Department of Justice and Constitutional Development (2011, has seen the light in order to suggest amendments to certain legislative provisions. Unfortunately certain issues covered in this Discussion Paper have not been clearly set out and need further investigation.

  7. Medium Range Forecasts Representation (and Long Range Forecasts?)

    Science.gov (United States)

    Vincendon, J.-C.

    2009-09-01

    The progress of the numerical forecasts urges us to interest us in more and more distant ranges. We thus supply more and more forecasts with term of some days. Nevertheless, precautions of use are necessary to give the most reliable and the most relevant possible information. Available in a TV bulletin or on quite other support (Internet, mobile phone), the interpretation and the representation of a medium range forecast (5 - 15 days) must be different from those of a short range forecast. Indeed, the "foresee-ability” of a meteorological phenomenon decreases gradually in the course of the ranges, it decreases all the more quickly that the phenomenon is of small scale. So, at the end of some days, the probability character of a forecast becomes very widely dominating. That is why in Meteo-France the forecasts of D+4 to D+7 are accompanied with a confidence index since around ten years. It is a figure between 1 and 5: the more we approach 5, the more the confidence in the supplied forecast is good. In the practice, an indication is supplied for period D+4 / D+5, the other one for period D+6 / D+7, every day being able to benefit from a different forecast, that is be represented in a independent way. We thus supply a global tendency over 24 hours with less and less precise symbols as the range goes away. Concrete examples will be presented. From now on two years, we also publish forecasts to D+8 / J+9, accompanied with a sign of confidence (" good reliability " or " to confirm "). These two days are grouped together on a single map because for us, the described tendency to this term is relevant on a duration about 48 hours with a spatial scale slightly superior to the synoptic scale. So, we avoid producing more than two zones of types of weather over France and we content with giving an evolution for the temperatures (still, in increase or in decline). Newspapers began to publish this information, it should soon be the case of televisions. It is particularly

  8. Cationic two-photon induced polymerization with high dynamic range

    Science.gov (United States)

    Boiko, Yuri B.; Costa, Joannes; Wang, Mark M.; Esener, Sadik C.

    2001-05-01

    Cationic-induced two-photon photo-polymerization is demonstrated at 710 nm, using an isopropylthioxanthone / diarylidonium salt initiating system for the cationic polymerization of an epoxide. In-situ monitoring of the polymer conversion using interferometry allows for determination of the polymerization threshold J2th, polymerization rate R and its dependence of initiator's concentration z. Best J2th achieved is 1 GW/cm 2 , with a dynamic range of > 100, i.e. the material can be fully polymerized at intensities > 100 times the threshold level without damage. The R is found to be proportional to the m=1.7 power of the intensity, or R =[C(J-J2th)]m =[C(J-J2th)]1.7 , which implies a significantly stronger localization of the photochemical response than that of free radical photoinitiators. Both R and J2th significantly improve when the concentration z of the initiator (onium salt) increases, reduction of J2th exhibiting z -m trend.

  9. THE RELIABILITY OF A NOVEL HEEL-RISE TEST VERSUS GONIOMETRY TO ASSESS PLANTARFLEXION RANGE OF MOTION.

    Science.gov (United States)

    Ness, Brandon M; Sudhagoni, Ramu G; Tao, Hanz; Full, Olivia R; Seehafer, Lucas O; Walder, Chelsie M; Zimney, Kory

    2018-02-01

    Ankle plantarflexion (PF) active range of motion (ROM) is traditionally assessed in a non-weight-bearing (NWB) position with a universal goniometer. However, a convenient, reliable, low-cost means of assessing functional PF active ROM in a weight-bearing (WB) position has yet to be established. To compare the intra- and interrater reliability of PF active ROM measurements obtained from a goniometric NWB assessment, and a functional heel-rise test (FHRT) performed in WB. Reliability study. Two physical therapy student examiners, blinded to each other's measurements, assessed PF active ROM through a NWB goniometric technique and a FHRT on all subjects within the same test session. Intra- and interrater reliability values were calculated using an intraclass correlation coefficient (ICC 2,1 , ICC 2,k ) and 95% confidence intervals. Standard error of measurement (SEM) and minimal detectable change (MDC) were recorded for each method. 43 healthy participants (mean ± SD, age: 22.7 ± 1.7 years, height: 1.7 ± 0.1 m, mass: 77.8 ± 17.2 kg) completed testing procedures. The within-session intrarater reliability (ICC 2,1 ) estimates were observed for goniometry (right: 0.96, left: 0.95 - 0.97) and FHRT (right: 0.99, left: 0.99), as well as the interrater reliability (ICC 2,k ) of goniometry (right: 0.79, left: 0.79) and FHRT (right: 0.79, left: 0.87). Goniometry SEM (3.3 - 3.6 °) and MDC (9.2 - 9.8 °) were observed, in addition to FHRT SEM (0.6 cm) and MDC (1.6 - 1.7 cm). A weak correlation was found between FHRT and goniometric measurements (r = -0.03 - 0.13). The FHRT was found to have good to excellent intra- and interrater reliability, similar to goniometric measurement. The lack of agreement between these measurements requires further exploration of a WB assessment of ankle PF active ROM. 2b.

  10. Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype.

    Science.gov (United States)

    Price, Nicola; Namdari, Rostam; Neville, Judith; Proctor, Katie J W; Kaber, Samer; Vest, Jeffery; Fetell, Michael; Malamut, Richard; Sherrington, Robin P; Pimstone, Simon N; Goldberg, Yigal P

    2017-04-01

    The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism. This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with postherpetic neuralgia with moderate or greater pain received TV-45070 and placebo ointments, each applied twice daily for 3 weeks. The primary efficacy measure was the difference in change in mean daily pain score from baseline compared with the last week of placebo and active treatment. Secondary endpoints included responder rate analyses and a further exploratory analysis of response in carriers of the Nav1.7 R1150W polymorphism was conducted. Seventy patients were enrolled and 54 completed the study. TV-45070 was safe and well tolerated. No statistical difference was observed between treatments for the primary endpoint. However, the proportion of patients with ≥50% reduction in mean pain scores at week 3 was greater on TV-45070 than on placebo (26.8% vs. 10.7%, P=0.0039). Similarly, a greater proportion of patients on TV-45070 had a ≥30% reduction in mean pain scores at week 3 (39.3% on TV-45070 vs. 23.2% on placebo, P=0.0784). Of note, 63% of patients with the R1150W polymorphism versus 35% of wild-type carriers had a ≥30% reduction in mean pain score on TV-45070 at week 3 (no inferential analysis performed). The 50% responder analysis suggests a subpopulation may exist with a more marked analgesic response to TV-45070.The trend toward a larger proportion of responders within Nav1.7 R1150W carriers warrants further investigation.

  11. Cellular localization and kinetic properties of Na(V)1.9-, Na(V)1.8-, and Na(V)1.7-like channel subtypes in Helix pomatia.

    Science.gov (United States)

    Kiss, T; László, Z; Pirger, Z

    2012-02-17

    This article concerns the kinetics, selectivity, and distribution of the Na(V)1.9, Na(V)1.8, and Na(V)1.7 channel subtypes in the CNS of the snail, Helix pomatia. Within the snail brain, Na(V)1.9- and Na(V)1.8-like channel subtypes are widely expressed, with particularly high levels in the pedal, cerebral, and buccal ganglia. The suboesophageal ganglion contains equal amounts of neurons labeled with Na(V)1.9, 1.8, and 1.7 antibodies. Our data show that different types of ion channels are localized to discrete neurons and regions of the neuronal membrane affecting by this way the physiology of synaptic transmission or nerve conduction. Based on the voltage dependence and kinetics, the non- or slowly inactivating currents were observed in identified and nonidentified neurons of the snail CNS attributed to separate Na-channel subtypes. These observations provide the first evidence for the presence of the composite Na-current in snail neurons. The significance of Na(V)1.9 channels in gastropod neurons is assigned to regulating the subthreshold membrane depolarization. First time, we have demonstrated that in addition to the Na(V)1.2-like channels most of the neurons contain Na(V)1.8- or 1.7-like channels carrying the composite inward sodium current. In this way, neurons containing different sets of channels differently are regulated, which allows further dynamic modulation of neuronal activity. The neuronal soma membrane revealed low ion selectivity of the Na-channels with slow kinetics, which is a general property of gastropod molluscs. In addition, the relative similarity of the biophysical properties of voltage-gated currents between vertebrates and invertebrates may reflect a structural similarity existing between Na-channel subtypes pointing to a common evolutionary origin. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Effect of doping of trivalent cations Ga{sup 3+}, Sc{sup 3+}, Y{sup 3+} in Li{sub 1.3}Al{sub 0.3}Ti{sub 1.7} (PO{sub 4}){sub 3} (LATP) system on Li{sup +} ion conductivity

    Energy Technology Data Exchange (ETDEWEB)

    Kothari, Dharmesh H.; Kanchan, D.K., E-mail: dkkanchan.ssi@gmail.com

    2016-11-15

    We report the effect of trivalent cations dopants in the Li{sub 1.3}Al{sub 0.3−x}R{sub x}Ti{sub 1.7}(PO{sub 4}){sub 3} (R=Ga{sup 3+}, Sc{sup 3+}, Y{sup 3+}) NASICON ceramic system in the concentration range x=0.01,0.03,0.05,0.07, on the Li{sup +} ion conducting properties using impedance spectroscopy. The samples were prepared by solid state reaction method and characterized by X-Ray Diffraction and density measurements. The electrical properties were studied using impedance spectroscopy in frequency range 10 Hz to 20 MHz and temperature range 303 K to 423 K. Although the porosity of the material decreased with doping, the overall Li{sup +} ion conductivity of the system did not improve with doping. Ionic radii of the dopant cations was found to be an important factor in formation of impurity phases and low Li{sup +} ion conductivity. Gallium doped samples exhibited a higher Li{sup +} ion conductivity compared to its scandium and yttrium doped counterparts.

  13. Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice.

    Science.gov (United States)

    Tyrankiewicz, Urszula; Olkowicz, Mariola; Skórka, Tomasz; Jablonska, Magdalena; Orzylowska, Anna; Bar, Anna; Gonet, Michal; Berkowicz, Piotr; Jasinski, Krzysztof; Zoladz, Jerzy A; Smolenski, Ryszard T; Chlopicki, Stefan

    2018-01-01

    Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1-7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1-10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1-7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1-7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.

  14. Targeting Voltage Gated Sodium Channels NaV1.7, NaV1.8, and NaV1.9 for Treatment of Pathological Cough

    OpenAIRE

    Muroi, Yukiko; Undem, Bradley J.

    2013-01-01

    Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1–NaV1.9), the afferent nerves involved in initiating cough, in common with nociceptive neurons in the somatosensory system, express mainly NaV1.7, NaV1.8, and NaV1.9. Although knowledge about the effect of selectively bloc...

  15. Safety and Biodistribution Evaluation in CNGB3-Deficient Mice of rAAV2tYF-PR1.7-hCNGB3, a Recombinant AAV Vector for Treatment of Achromatopsia.

    Science.gov (United States)

    Ye, Guo-jie; Budzynski, Ewa; Sonnentag, Peter; Nork, T Michael; Miller, Paul E; McPherson, Leslie; Ver Hoeve, James N; Smith, Leia M; Arndt, Tara; Mandapati, Savitri; Robinson, Paulette M; Calcedo, Roberto; Knop, David R; Hauswirth, William W; Chulay, Jeffrey D

    2016-03-01

    Applied Genetic Technologies Corporation (AGTC) is developing rAAV2tYF-PR1.7-hCNGB3, a recombinant adeno-associated virus (rAAV) vector expressing the human CNGB3 gene, for treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. We report here results of a study evaluating safety and biodistribution of rAAV2tYF-PR1.7-hCNGB3 in CNGB3-deficient mice. Three groups of animals (n = 35 males and 35 females per group) received a subretinal injection in one eye of 1 μl containing either vehicle or rAAV2tYF-PR1.7-hCNGB3 at one of two dose concentrations (1 × 10(12) or 4.2 × 10(12) vg/ml) and were euthanized 4 or 13 weeks later. There were no test-article-related changes in clinical observations, body weights, food consumption, ocular examinations, clinical pathology parameters, organ weights, or macroscopic observations at necropsy. Cone-mediated electroretinography (ERG) responses were detected after vector administration in the treated eyes in 90% of animals in the higher dose group and 31% of animals in the lower dose group. Rod-mediated ERG responses were reduced in the treated eye for all groups, with the greatest reduction in males given the higher dose of vector, but returned to normal by the end of the study. Microscopic pathology results demonstrated minimal mononuclear cell infiltrates in the retina and vitreous of some animals at the interim euthanasia and in the vitreous of some animals at the terminal euthanasia. Serum anti-AAV antibodies developed in most vector-injected animals. No animals developed antibodies to hCNGB3. Biodistribution studies demonstrated high levels of vector DNA in vector-injected eyes but little or no vector DNA in nonocular tissue. These results support the use of rAAV2tYF-PR1.7-hCNGB3 in clinical studies in patients with achromatopsia caused by CNGB3 mutations.

  16. Magento 1.7 development cookbook

    CERN Document Server

    Delvaux, Bart

    2014-01-01

    A collection of straightforward and practical recipes filled with examples to build a faster and more impressive Magento store. The recipes will provide you step-by-step instructions for installing, customizing, and managing your Magento store.If you are a developer with minor PHP knowledge and you want to start with Magento development, this book is for you. With its specially tailored recipes, we will guide you from simple development in Magento to the more advanced stuff. Even if you are an experienced Magento developer, some recipes in this book will interest you. The other recipes will se

  17. Kapitel 1-7, 13, 15

    DEFF Research Database (Denmark)

    Heiberg, Morten Rievers

    2009-01-01

    Den 30. september 1968 udsendte VKR-regeringen en erklæring, hvis hovedsynspunkt var "...at registrering af danske statsborgere ikke længere må finde sted alene på grundlag af lovlig politisk virksomhed." Det fremgik ydermere af erklæringen, at såfremt tjenesten lå inde med sådanne registreringer...

  18. Nigerian Veterinary Journal (1) 1-7

    African Journals Online (AJOL)

    Ingredients diet(%) Matter Matter Protein. Maize 26.1. Cottonseed cake 43.1. Wheat bran 27.8. Bone meal 2. Salt 1. Supplement 95.59 90.16 20.63. Hay 93.6 85.86 7.74. Maize. Stover feeds. The works of various scientists demonstrate that browses and shrubs are able to sustain and improve goat productivity in the.

  19. Theoretical Prediction of the Heats of Formation, Densities, and Relative Sensitivities for 1,7-dinitro-3,4,5,8-tetra N-oxide-bis([1,2,3]triazolo)[4,5-b:5’,4’ e]pyrazine, 1,7-dinitro-3,5,8-tri N-oxide bis([1,2,3]triazolo)[4,5-b:5’,4’ e]pyrazine, 1,7-dinitro 3,5-bis N-oxide bis([1,2,3]triazolo)[4,5-b:5’,4’ e]pyrazine, 1,7-dinitro 1,7-dihydrobis([1,2,3]triazolo)[4,5-b:4’,5’-e]pyrazine

    Science.gov (United States)

    2016-09-01

    the 0.001 isosurfaces were generated with the scalar range of the electrostatic surface potential ( ESP ) ranging from –0.05 to 0.075. Recall that for...this visualization methodology , regions of large positive charge (i.e., electron deficient regions, labeled as red) over the backbone of the...215.463 1.997 3 204.528 1.970 4 207.026 1.885 Additionally, we plot the ESP maps for 1 (Fig. 2a–b), 2 (Fig. 3a–b), 3 (Fig. 4a–b), and 4 (Fig. 5a–b

  20. Ulnar Head Replacement: 21 Cases; Mean Follow-Up, 7.5 Years.

    Science.gov (United States)

    Axelsson, Peter; Sollerman, Christer; Kärrholm, Johan

    2015-09-01

    To report clinical and radiographic outcomes for the Herbert ulnar head prosthesis after a mean of 7.5 years (range, 2.0-12.5 years). We performed 22 Herbert ulnar head prosthesis arthroplasties between 2000 and 2011. Five were primary procedures, and the remaining 17 were done after an average of 2 (range, 1-5) previous operations. The mean age at surgery was 55 years (range, 31-74 years). Follow-up including clinical examination, standardized questionnaires, and radiographic examination was done after mean 7.5 years (range, 2.0-12.5 years) in 21 cases. We used the Disabilities of the Arm, Shoulder, and Hand questionnaire, the Patient-Rated Wrist Evaluation questionnaire, and the Mayo wrist score questionnaire. Pain and satisfaction were evaluated with a 10-cm visual analog scale (VAS). Measurements of range of motion and strength for grip were recorded. Wrist range of motion was not affected by the arthroplasty except for supination, which significantly improved from 55° to 70°. At follow-up, grip strength averaged 25 kg (range, 10-48 kg) in the operated wrists and 31 kg (range, 8-74 kg) on the contralateral side. Visual analog scale-pain averaged 2.9 (range, 0-8.7) during activity and 1.7 (range, 0-7) at rest. Satisfaction VAS was 8.9 (range, 4.3-10). Five patients had VAS-pain above 5 during activity, and 1 patient was dissatisfied and regretted having undergone arthroplasty. Mean outcomes were 27 (range, 5-50) for Disabilities of the Arm, Shoulder, and Hand measure, 31 (range, 0-90) for the Patient-Rated Wrist Evaluation score, and 71 (range, 30-90) for the Mayo wrist score. One patient was reoperated with capsuloplasty 9 months after the arthroplasty owing to recurrence of painful instability. Full stability was not achieved but the pain resolved. None of the implants showed any radiographic signs of loosening. The Herbert ulnar head prosthesis was a safe method of treatment and provided satisfactory midterm results for selected cases of distal radioulnar

  1. Delayed Diagnosis, Range of Severity, and Multiple Sleep Comorbidities: A Clinical and Polysomnographic Analysis of 100 Patients of the Innsbruck Narcolepsy Cohort

    Science.gov (United States)

    Frauscher, Birgit; Ehrmann, Laura; Mitterling, Thomas; Gabelia, David; Gschliesser, Viola; Brandauer, Elisabeth; Poewe, Werner; Högl, Birgit

    2013-01-01

    Study Objectives: Narcolepsy is reported to affect 26-56/100,000 in the general population. We aimed to describe clinical and polysomnographic features of a large narcolepsy cohort in order to comprehensively characterize the narcoleptic spectrum. Methods: We performed a chart- and polysomnographybased review of all narcolepsy patients of the Innsbruck narcolepsy cohort. Results: A total of 100 consecutive narcolepsy patients (87 with cataplexy [NC], 13 without cataplexy [N]) were included in the analysis. All subjects had either excessive daytime sleepiness or cataplexy as their initial presenting clinical feature. Age at symptom onset was 20 (6-69) years. Diagnostic delay was 6.5 (0-39) years. The complete narcolepsy tetrad was present in 36/100 patients; 28/100 patients had three cardinal symptoms; 29/100 had two; and 7/100 had only excessive daytime sleepiness. Severity varied broadly with respect to excessive daytime sleepiness (median Epworth Sleepiness Scale score: 18, range 10-24), cataplexy (8-point Likert scale: median 4.5, range 1-8), hypnagogic hallucinations (median 4.5, range 1-7), and sleep paralysis (median 3, range 1-7). Sleep comorbidity was highly prevalent and ranged from sleeprelated movement disorders (n = 55/100), parasomnias (n = 34/100), and sleeprelated breathing disorders (n = 24/100), to insomnia (n = 28/100). REM sleep without atonia or a periodic limb movement in sleep index > 5/h were present in most patients (90/100 and 75/100). A high percentage of narcoleptic patients in the present study had high frequency leg movements (35%) and excessive fragmentary myoclonus (22%). Of the narcolepsy patients with clinical features of REM sleep behavior disorder (RBD), 76.5% had EMG evidence for RBD on the multiple sleep latency test (MSLT), based on a standard cutoff of a minimum of 18% of 3-sec miniepochs. Conclusion: This study is one of the largest monocentric polysomnographic studies to date of patients with narcolepsy and confirms the

  2. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

    Directory of Open Access Journals (Sweden)

    Chun-Ping Huang

    2013-01-01

    Full Text Available Several voltage-gated sodium channels (Navs from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG. We injected carrageenan and complete Freund's adjuvant (CFA into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36 acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36 acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

  3. Kinetic study of the 7-endo selective radical cyclization of N-tert-butyl-o-bromobenzylmethacryl amides: kinetic investigation of the cyclization and 1,7-hydrogen transfer of aromatic radicals.

    Science.gov (United States)

    Kamimura, Akio; Kotake, Tomoko; Ishihara, Yuriko; So, Masahiro; Hayashi, Takahiro

    2013-04-19

    A kinetic investigation of the radical cyclization of N-tert-butyl-o-bromobenzylmethacryl amides to give 2-benzazepines via 7-endo selective cyclization was undertaken. The aryl radical generated from the amide precursor by treatment with Bu3SnH gave the three compounds, which are a 7-endo cyclized adduct, a 6-exocyclized adduct, and a reduced product. The cyclization reactions under various Bu3SnH concentrations were traced by GC analysis. The 7-endo/6-exo selectivity was constant irrespective of variation in Bu3SnH concentration. These results revealed that regioselectivity is controlled in a kinetic manner and that there is no possibility of a neophyl rearrangement. The use of Bu3SnD revealed that 1,7-hydrogen transfer, in which an aryl radical abstracts a hydrogen atom from the methallylic methyl group, occurs during the reaction. Hydrogen abstraction from toluene, the reaction solvent, was also observed. The 1,7-transfer rate depended on the Bu3SnX (X = H or D), and the reaction kinetics was examined. The k(H)/k(D) value for the hydrogen abstraction of aryl radical from Bu3SnX (X = H or D) was estimated using 4-bromoanisol. The utilization of these values revealed the overall reaction kinetics and relative rates for the cyclization and reduction by Bu3SnX (X = H or D). Kinetic parameters for hydrogen abstraction from toluene by aryl radicals were also estimated.

  4. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

    Science.gov (United States)

    Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

    2013-01-01

    Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

  5. Tests of Gravity Using Lunar Laser Ranging

    Directory of Open Access Journals (Sweden)

    Stephen M. Merkowitz

    2010-11-01

    Full Text Available Lunar laser ranging (LLR has been a workhorse for testing general relativity over the past four decades. The three retroreflector arrays put on the Moon by the Apollo astronauts and the French built arrays on the Soviet Lunokhod rovers continue to be useful targets, and have provided the most stringent tests of the Strong Equivalence Principle and the time variation of Newton’s gravitational constant. The relatively new ranging system at the Apache Point 3.5 meter telescope now routinely makes millimeter level range measurements. Incredibly, it has taken 40 years for ground station technology to advance to the point where characteristics of the lunar retroreflectors are limiting the precision of the range measurements. In this article, we review the gravitational science and technology of lunar laser ranging and discuss prospects for the future.

  6. Correlation between microstructure and electrical properties of Cu{sub 1.3}Mn{sub 1.7}O{sub 4}/La{sub 2}O{sub 3} composite-coated ferritic stainless steel interconnects

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, N., E-mail: nazaneen_hosseini@ma.iut.ac.ir [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Karimzadeh, F.; Abbasi, M.H. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Choi, G.M. [Fuel Cell Research Center and Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of)

    2016-07-15

    The goal of this study was to investigate the effect of screen-printed Cu{sub 1.3}Mn{sub 1.7}O{sub 4}/La{sub 2}O{sub 3} composite coating on chromia scale growth and electrical behavior of AISI430 stainless steel interconnects. The coated samples were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy equipped with energy dispersive spectroscopy (FESEM-EDS) and 4-probe area specific resistance (ASR) tests. The results showed that LaCrO{sub 3} conductive perovskite is formed due to the interdiffusion between Cr{sub 2}O{sub 3} and/or CrO{sub 3} and La{sub 2}O{sub 3}. The presence of LaCrO{sub 3} through the composite coating and Cr{sub 2}O{sub 3} sub-scale accompanied by the effective role of spinel phase, acted as a barrier to mitigate the sub-scale growth preventing chromium diffusion through the coating and the cathode. Besides, LaCrO{sub 3} particles within the sub-scale provided suitable conductive paths decreasing ASR from 19.3 mΩ cm{sup 2} for spinel coated sample to 15 mΩ cm{sup 2} for composite coated sample at the end of 500 h oxidation at 750° C. - Highlights: • Cu{sub 1.3}Mn{sub 1.7}O{sub 4}/La{sub 2}O{sub 3} coating was deposited on AISI 430 by screen-printing method. • LaCrO{sub 3} perovskite was formed due to the interdiffusion between Cr species and La{sub 2}O{sub 3}. • LaCrO{sub 3} particles within the chromia provided conductive paths causing ASR reduction. • The co-existence of LaCrO{sub 3} and Cu{sub 1.3}Mn{sub 1.7}O{sub 4} noticeably retarded the chromia growth.

  7. Photon Pressure Force on Space Debris TOPEX/Poseidon Measured by Satellite Laser Ranging

    Science.gov (United States)

    Kucharski, D.; Kirchner, G.; Bennett, J. C.; Lachut, M.; Sośnica, K.; Koshkin, N.; Shakun, L.; Koidl, F.; Steindorfer, M.; Wang, P.; Fan, C.; Han, X.; Grunwaldt, L.; Wilkinson, M.; Rodríguez, J.; Bianco, G.; Vespe, F.; Catalán, M.; Salmins, K.; del Pino, J. R.; Lim, H.-C.; Park, E.; Moore, C.; Lejba, P.; Suchodolski, T.

    2017-10-01

    The (TOPography EXperiment) TOPEX/Poseidon (T/P) altimetry mission operated for 13 years before the satellite was decommissioned in January 2006, becoming a large space debris object at an altitude of 1,340 km. Since the end of the mission, the interaction of T/P with the space environment has driven the satellite's spin dynamics. Satellite laser ranging (SLR) measurements collected from June 2014 to October 2016 allow for the satellite spin axis orientation to be determined with an accuracy of 1.7°. The spin axis coincides with the platform yaw axis (formerly pointing in the nadir direction) about which the body rotates in a counterclockwise direction. The combined photometric and SLR data collected over the 11 year time span indicates that T/P has continuously gained rotational energy at an average rate of 2.87 J/d and spins with a period of 10.73 s as of 19 October 2016. The satellite attitude model shows a variation of the cross-sectional area in the Sun direction between 8.2 m2 and 34 m2. The direct solar radiation pressure is the main factor responsible for the spin-up of the body, and the exerted photon force varies from 65 μN to 228 μN around the mean value of 138.6 μN. Including realistic surface force modeling in orbit propagation algorithms will improve the prediction accuracy, giving better conjunction warnings for scenarios like the recent close approach reported by the ILRS Space Debris Study Group—an approximate 400 m flyby between T/P and Jason-2 on 20 June 2017.

  8. Great Basin Experimental Range: Annotated bibliography

    Science.gov (United States)

    E. Durant McArthur; Bryce A. Richardson; Stanley G. Kitchen

    2013-01-01

    This annotated bibliography documents the research that has been conducted on the Great Basin Experimental Range (GBER, also known as the Utah Experiment Station, Great Basin Station, the Great Basin Branch Experiment Station, Great Basin Experimental Center, and other similar name variants) over the 102 years of its existence. Entries were drawn from the original...

  9. Orientation-dependent physical properties of layered perovskite La{sub 1.3}Sr{sub 1.7}Mn{sub 2}O{sub 7} epitaxial thin films

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Li-Wei; Guo, Bing; Chen, Chang-Le, E-mail: chenchl@nwpu.edu.cn; Luo, Bing-Cheng; Dong, Xiang-Lei; Jin, Ke-Xin

    2017-04-01

    In this paper, the resistivity and magnetization of orientation-engineered layered perovskite La{sub 1.3}Sr{sub 1.7}Mn{sub 2}O{sub 7} epitaxial thin films have been investigated. Epitaxial thin films were deposited on single-crystalline LaAlO{sub 3} (LAO) (001), (110) and (111) substrates by pulse laser deposition (PLD) technique. It is found that only the (100)-oriented thin film performs insulator behavior, whereas the (110) and (111)-oriented thin films exhibit obvious metal-insulator transition at 70 K and between 85 and 120 K, respectively. Moreover, the same spin freezing temperature and different spin-glass-like transition temperatures have been observed in various oriented films. The observed experimental results were discussed according to the electron-transport mechanism and spin dynamics.

  10. Targeting Voltage Gated Sodium Channels NaV1.7, NaV1.8, and NaV1.9 for Treatment of Pathological Cough

    Science.gov (United States)

    Muroi, Yukiko

    2015-01-01

    Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1–NaV1.9), the afferent nerves involved in initiating cough, in common with nociceptive neurons in the somatosensory system, express mainly NaV1.7, NaV1.8, and NaV1.9. Although knowledge about the effect of selectively blocking these channels on the cough reflex is limited, their biophysical properties indicate that each may contribute to the hypertussive and allotussive state that typifies subacute and chronic nonproductive cough. PMID:24272479

  11. Ranging Behaviour of Commercial Free-Range Laying Hens

    Directory of Open Access Journals (Sweden)

    Leonard Ikenna Chielo

    2016-04-01

    Full Text Available In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources. These were: apron (0–10 m from shed normally without cover or other enrichments; enriched belt (10–50 m from shed where resources such as manmade cover, saplings and dust baths were provided; and outer range (beyond 50 m from shed with no cover and mainly grass pasture. Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range

  12. Ranging Behaviour of Commercial Free-Range Laying Hens.

    Science.gov (United States)

    Chielo, Leonard Ikenna; Pike, Tom; Cooper, Jonathan

    2016-04-26

    In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources). These were: apron (0-10 m from shed normally without cover or other enrichments); enriched belt (10-50 m from shed where resources such as manmade cover, saplings and dust baths were provided); and outer range (beyond 50 m from shed with no cover and mainly grass pasture). Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND) of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range areas tend to be

  13. [Effect of Chinese herbs for stasis removing and collaterals dredging upon angiotensin-converting enzyme 2-angiotensin-(1-7)-mas axis in the renal cortex of diabetic nephropathy rats].

    Science.gov (United States)

    Xu, Jing; Ma, Er-wei; Bai, Lu; Ma, Yun; Guo, Qian; Jia, Rui; Zhang, Jiang-hua; Chen, Zhi-qiang

    2014-06-01

    To observe the effect of Chinese herbs for stasis removing and collaterals dredging (CHSRCD) upon angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis in the renal cortex of diabetic nephropathy rats. Totally 89 male Sprague-Dawley rats were randomly divided into the blank control group (C group, n=22), the high-glucose high-fat control group (H group, n=10), and the streptozotocin (STZ)-injecting group (n=57). The diabetes rat model (n=50) was induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ, which were further divided into the model group (M group, n=24), the irbesartan group (I group, n=13), and the CHSRCD (Z group, n=13). Rats in I and Z groups were intragastrically fed with suspension of irbesartan and CHSRCD, once daily for 16 weeks. Equal volume of drinking water was administrated to rats in the rest groups. Blood glucose and 24 h urine protein quantitation were tested at four time points. And the mRNA expression of ACE2 and Mas at various time points was detected by Real-time PCR, immunohistochemical assay, and Western blot. Quantitative analyses of ACE2 and Mas protein expression were performed at the end of week 16. Compared with the C group, blood glucose increased in the H and M groups (P Mas mRNA at the end of week 16 between the C group and the M group (P > 0.05). It was lower in the M group than in the H group (P Mas protein in the M group decreased as time went by. The expression quantitation of ACE2 and Mas protein at the end of week 16 was lower in the M group than in the C group (P Mas of the I and Z groups increased more significantly (P Mas, promoting the ACE2-Ang-(1-7)-Mas axis, and lowering urinary protein.

  14. Osprey Range - CWHR [ds601

    Data.gov (United States)

    California Department of Resources — Vector datasets of CWHR range maps are one component of California Wildlife Habitat Relationships (CWHR), a comprehensive information system and predictive model for...

  15. Short-range fundamental forces

    CERN Document Server

    Antoniadis, I; Buchner, M; Fedorov, V V; Hoedl, S; Lambrecht, A; Nesvizhevsky, V V; Pignol, G; Protasov, K V; Reynaud, S; Sobolev, Yu

    2011-01-01

    We consider theoretical motivations to search for extra short-range fundamental forces as well as experiments constraining their parameters. The forces could be of two types: 1) spin-independent forces, 2) spin-dependent axion-like forces. Differe nt experimental techniques are sensitive in respective ranges of characteristic distances. The techniques include measurements of gravity at short distances, searches for extra interactions on top of the Casimir force, precision atomic and neutron experim ents. We focus on neutron constraints, thus the range of characteristic distances considered here corresponds to the range accessible for neutron experiments.

  16. Cascade Mountain Range in Oregon

    Science.gov (United States)

    Sherrod, David R.

    2016-01-01

    The Cascade mountain system extends from northern California to central British Columbia. In Oregon, it comprises the Cascade Range, which is 260 miles long and, at greatest breadth, 90 miles wide (fig. 1). Oregon’s Cascade Range covers roughly 17,000 square miles, or about 17 percent of the state, an area larger than each of the smallest nine of the fifty United States. The range is bounded on the east by U.S. Highways 97 and 197. On the west it reaches nearly to Interstate 5, forming the eastern margin of the Willamette Valley and, farther south, abutting the Coast Ranges

  17. Ranging Behaviour of Commercial Free-Range Laying Hens

    Science.gov (United States)

    Chielo, Leonard Ikenna; Pike, Tom; Cooper, Jonathan

    2016-01-01

    Simple Summary Commercial free-range production has become a significant sector of the fresh egg market due to legislation banning conventional cages and consumer preference for products perceived as welfare friendly, as access to outdoor range can lead to welfare benefits such as greater freedom of movement and enhanced behavioural opportunities. This study investigated dispersal patterns, feather condition and activity of laying hens in three distinct zones of the range area; the apron area near shed; enriched zone 10–50 m from shed; and outer range beyond 50 m, in six flocks of laying hens under commercial free-range conditions varying in size between 4000 and 24,000 hens. Each flock was visited for four days to record number of hens in each zone, their behaviour, feather condition and nearest neighbour distances (NND), as well as record temperature and relative humidity during the visit. Temperature and relative humidity varied across the study period in line with seasonal variations and influenced the use of range with fewer hens out of shed as temperature fell or relative humidity rose. On average, 12.5% of the hens were observed on the range and most of these hens were recorded in the apron zone as hen density decreased rapidly with increasing distance from the shed. Larger flocks appeared to have a lower proportion of hens on range. The hens used the range more in the early morning followed by a progressive decrease through to early afternoon. The NND was greatest in the outer range and decreased towards the shed. Feather condition was generally good and hens observed in the outer range had the best overall feather condition. Standing, pecking, walking and foraging were the most commonly recorded behaviours and of these, standing occurred most in the apron whereas walking and foraging behaviours were recorded most in the outer range. This study supported the findings of previous studies that reported few hens in the range and greater use of areas closer

  18. Desert Experimental Range: Annotated bibliography

    Science.gov (United States)

    E. Durant McArthur; Stanley G. Kitchen

    2013-01-01

    Entries qualify for inclusion if they were conducted in whole or part at the Desert Experimental Range (DER, also known as the Desert Range Experiment Station) or were based on DER research in whole or part. They do not qualify merely by the author having worked at the DER when the research was performed or prepared. Entries were drawn from the original abstracts or...

  19. Foraging optimally for home ranges

    Science.gov (United States)

    Mitchell, Michael S.; Powell, Roger A.

    2012-01-01

    Economic models predict behavior of animals based on the presumption that natural selection has shaped behaviors important to an animal's fitness to maximize benefits over costs. Economic analyses have shown that territories of animals are structured by trade-offs between benefits gained from resources and costs of defending them. Intuitively, home ranges should be similarly structured, but trade-offs are difficult to assess because there are no costs of defense, thus economic models of home-range behavior are rare. We present economic models that predict how home ranges can be efficient with respect to spatially distributed resources, discounted for travel costs, under 2 strategies of optimization, resource maximization and area minimization. We show how constraints such as competitors can influence structure of homes ranges through resource depression, ultimately structuring density of animals within a population and their distribution on a landscape. We present simulations based on these models to show how they can be generally predictive of home-range behavior and the mechanisms that structure the spatial distribution of animals. We also show how contiguous home ranges estimated statistically from location data can be misleading for animals that optimize home ranges on landscapes with patchily distributed resources. We conclude with a summary of how we applied our models to nonterritorial black bears (Ursus americanus) living in the mountains of North Carolina, where we found their home ranges were best predicted by an area-minimization strategy constrained by intraspecific competition within a social hierarchy. Economic models can provide strong inference about home-range behavior and the resources that structure home ranges by offering falsifiable, a priori hypotheses that can be tested with field observations.

  20. Reference Ranges & What They Mean

    Science.gov (United States)

    ... Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle ... If you're trying to follow a healthy lifestyle, take test results that are within range as ...

  1. Kenai National Moose Range Alaska

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This book presents a summary of the history, wildlife, recreational opportunities, economic uses, and future plans for Kenai National Moose Range.

  2. Hip strength and range of motion

    DEFF Research Database (Denmark)

    Mosler, Andrea B.; Crossley, Kay M.; Thorborg, Kristian

    2017-01-01

    Objectives To determine the normal profiles for hip strength and range of motion (ROM) in a professional football league in Qatar, and examine the effect of leg dominance, age, past history of injury, and ethnicity on these profiles. Design Cross-sectional cohort study. Methods Participants...... values are documented for hip strength and range of motion that can be used as reference profiles in the clinical assessment, screening, and management of professional football players. Leg dominance, recent past injury history and ethnicity do not need to be accounted for when using these profiles...... included 394 asymptomatic, male professional football players, aged 18–40 years. Strength was measured using a hand held dynamometer with an eccentric test in side-lying for hip adduction and abduction, and the squeeze test in supine with 45° hip flexion. Range of motion measures included: hip internal...

  3. Thulium-doped fiber laser utilizing a photonic crystal fiber-based optical low-pass filter with application in 1.7 μm and 1.8 μm band.

    Science.gov (United States)

    Emami, Siamak Dawazdah; Khodaei, Amin; Gandan, Shumithira; Penny, Richard; Lim, Kok Sing; Abdul-Rashid, Hairul Azhar; Ahmad, Harith

    2015-07-27

    This paper describes a low pass filter based on photonics crystal fiber (PCF) partial ASE suppression, and its application within a 1.7 µm to 1.8 µm band thulium-doped fiber amplifier (TDFA) and a thulium-doped fiber laser (TDFL). The enlargement of air holes around the doped core region of the PCF resulted in a low-pass filter device that was able to attenuate wavelengths above the conventional long cut-off wavelength. These ensuing long cut-off wavelengths were 1.85 μm and 1.75 μm, and enabled a transmission mechanism that possessed a number of desirable characteristics. The proposed optical low-pass filter was applied within a TDFA and TDFL system. Peak spectrum was observed at around 1.9 μm for conventional TDF lasers, while the proposed TDF laser with PCF setup had fiber laser peak wavelengths measured at downshifted values of 1.74 μm and 1.81 μm.

  4. Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

    DEFF Research Database (Denmark)

    Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

    2013-01-01

    Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (cLDs) or on the ......Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...... recombinants produced infectivity titres of 10(2.5)-10(4.5) f.f.u. ml(-1). Co-localization analysis demonstrated that the core and NS5A proteins from all genotypes co-localized extensively, and there was no significant difference in protein co-localization among genotypes. In addition, we found that the core...

  5. The origin of persistent spin dynamics and residual entropy in the stuffed spin ice Ho{sub 2.3}Ti{sub 1.7}O{sub 7-{delta}}

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, H D [National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306-4005 (United States); Wiebe, C R [National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306-4005 (United States); Jo, Y J [National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306-4005 (United States); Balicas, L [National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306-4005 (United States); Qiu, Y [NIST Center for Neutron Research, Gaithersburg, MD 20899-5682 (United States); Copley, J R D [NIST Center for Neutron Research, Gaithersburg, MD 20899-5682 (United States); Ehlers, G [SNS Project, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6475 (United States); Fouquet, P [Institut Laue-Langevin, BoIte Postale 156X, F-38042, Grenoble Cedex 9 (France); Gardner, J S [NIST Center for Neutron Research, Gaithersburg, MD 20899-5682 (United States)

    2007-08-29

    The so-called 'spin ices' form when exchange interactions, crystal fields, and dipolar interactions are in a delicate balance. This gives rise to a ground state which has a considerable amount of residual spin entropy, much like the proton entropy in water ice through the freezing transition. Recently, 'stuffed' spin ices have provided a means to probe how delicate a balance is needed to stabilize the disordered ground state. Surprisingly, it is found that an increase of the density of spins results in very little change in the residual entropy, which leads to the interesting idea that residual entropy states might be more common than once believed for magnetism. In this communication, we detail the crystal growth of stuffed spin ice Ho{sub 2.3}Ti{sub 1.7}O{sub 7-{delta}}, and we complete neutron scattering experiments to observe how the spins order at low temperatures. It is found that even with this large perturbation, the system still has some key signatures of the spin ice state, but the spin dynamics is significantly altered. With this new data, an explanation emerges for the zero-point entropy in the stuffed spin ices. (fast track communication)

  6. DNA incision evaluation, binding investigation and biocidal screening of novel metallonucleases of 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione based Knoevenagel condensate having methionine: Synthesis and structural validation

    Science.gov (United States)

    Chandrasekar, Thiravidamani; Pravin, Narayanaperumal; Raman, Natarajan

    2015-02-01

    Four new metallonucleases of the composition [MLCl] (where M = Cu(II), Ni(II), Zn(II) and Co(II); L = Knoevenagel condensate Schiff base, obtained by the condensation reaction of 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione with p-nitrobenzaldehyde and methionine amino acid) have been synthesised and characterized thoroughly by microanalytical data, magnetic susceptibility, molar conductivity, UV-Vis., IR, 1H NMR, 13C NMR and EPR spectral techniques. Their geometry is investigated and established to have square planar geometry. Electronic absorption spectroscopy, cyclic voltammetry and viscosity measurements reveal that the complexes strongly bind to calf thymus DNA via an intercalation mechanism. DNA cleavage efficiency of these complexes is explored by gel electrophoresis, and they are found to endorse the cleavage of pBR322 DNA in presence of oxidant H2O2. These results reveal that all the complexes show better nuclease activity. Moreover, the biological screening against few pathogens reveals that that the complexes have potent biocidal activity than the free ligand.

  7. SGA Children in Pediatric Primary Care: What Is the Best Choice, Large or Small? A 10-Year Prospective Longitudinal Study.

    Science.gov (United States)

    Gallo, Patrizia; Cioffi, Luigi; Limauro, Raffaele; Farris, Evelina; Bianco, Vincenzo; Sassi, Roberto; De Giovanni, Maria; Gallo, Valeria; D'Onofrio, Antonietta; Di Maio, Salvatore

    2016-01-01

    Epidemiologic evidences suggest a strong association between low birth weight and some diseases in adult life ( hypertension, diabetes, cardiovascular diseases).Aim of this study was to evaluate the obesity/overweight prevalence in a population of children born small for gestation age, SGA children 400, 208 males and 192 females compared to a population of children born appropriate for gestational age 6818 AGA children, 3502 males and 3316 females, during childhood. Our intention was also to build the natural history of weight gain during prepubertal age in children born SGA and AGA. Observational prospective longitudinal study. We followed our patients from January2001 up to December 2010; weight, height and body mass index (BMI) were evaluated in all the SGA and AGA children. BMI z-score range for defining overweight and obesity was, respectively, 1.13 to 1.7 and >1.7 according to CDC growth charts. In transversal evaluation, we prove that 10-year-old SGA females are twice obese and more overweight compared to equal age AGA females. In longitudinal evaluation, we highlight different observations: SGA children obese at 2 years are still obese at 10 years; the number of obese SGA children increases gradually until the age of 10; AGA children, appear to be less obese than SGA children at 10 years. SGA males and females are more obese at 5 and 10 years compared to the AGA population. Primary care pediatricians, through early detection of the children at risk, can carry out an effective obesity prevention project in SGA children.

  8. Cultural resources of the Santa Rita Experimental Range

    Science.gov (United States)

    John H. Madsen

    2003-01-01

    The Santa Rita Experimental Range is a vast open space with few signs of houses or human habitation, but at one time it was quite the opposite scene. Archaeological surface inspections reveal heavy use of the Range dating back hundreds of years. This paper will review the history of cultural resource management on the Range and provide a timeline of local cultural...

  9. Climate-driven range extension of Amphistegina (protista, foraminiferida: models of current and predicted future ranges.

    Directory of Open Access Journals (Sweden)

    Martin R Langer

    Full Text Available Species-range expansions are a predicted and realized consequence of global climate change. Climate warming and the poleward widening of the tropical belt have induced range shifts in a variety of marine and terrestrial species. Range expansions may have broad implications on native biota and ecosystem functioning as shifting species may perturb recipient communities. Larger symbiont-bearing foraminifera constitute ubiquitous and prominent components of shallow water ecosystems, and range shifts of these important protists are likely to trigger changes in ecosystem functioning. We have used historical and newly acquired occurrence records to compute current range shifts of Amphistegina spp., a larger symbiont-bearing foraminifera, along the eastern coastline of Africa and compare them to analogous range shifts currently observed in the Mediterranean Sea. The study provides new evidence that amphisteginid foraminifera are rapidly progressing southwestward, closely approaching Port Edward (South Africa at 31°S. To project future species distributions, we applied a species distribution model (SDM based on ecological niche constraints of current distribution ranges. Our model indicates that further warming is likely to cause a continued range extension, and predicts dispersal along nearly the entire southeastern coast of Africa. The average rates of amphisteginid range shift were computed between 8 and 2.7 km year(-1, and are projected to lead to a total southward range expansion of 267 km, or 2.4° latitude, in the year 2100. Our results corroborate findings from the fossil record that some larger symbiont-bearing foraminifera cope well with rising water temperatures and are beneficiaries of global climate change.

  10. Climate-driven range extension of Amphistegina (protista, foraminiferida): models of current and predicted future ranges.

    Science.gov (United States)

    Langer, Martin R; Weinmann, Anna E; Lötters, Stefan; Bernhard, Joan M; Rödder, Dennis

    2013-01-01

    Species-range expansions are a predicted and realized consequence of global climate change. Climate warming and the poleward widening of the tropical belt have induced range shifts in a variety of marine and terrestrial species. Range expansions may have broad implications on native biota and ecosystem functioning as shifting species may perturb recipient communities. Larger symbiont-bearing foraminifera constitute ubiquitous and prominent components of shallow water ecosystems, and range shifts of these important protists are likely to trigger changes in ecosystem functioning. We have used historical and newly acquired occurrence records to compute current range shifts of Amphistegina spp., a larger symbiont-bearing foraminifera, along the eastern coastline of Africa and compare them to analogous range shifts currently observed in the Mediterranean Sea. The study provides new evidence that amphisteginid foraminifera are rapidly progressing southwestward, closely approaching Port Edward (South Africa) at 31°S. To project future species distributions, we applied a species distribution model (SDM) based on ecological niche constraints of current distribution ranges. Our model indicates that further warming is likely to cause a continued range extension, and predicts dispersal along nearly the entire southeastern coast of Africa. The average rates of amphisteginid range shift were computed between 8 and 2.7 km year(-1), and are projected to lead to a total southward range expansion of 267 km, or 2.4° latitude, in the year 2100. Our results corroborate findings from the fossil record that some larger symbiont-bearing foraminifera cope well with rising water temperatures and are beneficiaries of global climate change.

  11. Wide Operational Range Thermal Sensor

    Science.gov (United States)

    Goebel, John H. (Inventor); McMurray, Robert E., Jr. (Inventor)

    2005-01-01

    Bolometer system and method for detecting, at BLIP levels, presence of radiation over a broad range of wavelengths in an infrared spectrum and in a temperature range from 20 K to as high as room temperature. The radiation is received by a Si crystal having a region that is doped with one or more of In, Ga, S, Se, Te, B, Al, P, As and Sb in a concentration ratio in a range such as 5 x 10(exp -11) to 5 x 10(exp -6). Change in electrical resistance delta R due to receipt of the radiation is measured through a change in voltage difference or current within the crystal, and the quantity delta R is converted to an estimate of the amount of radiation received. Optionally, incident radiation having an energy high enough to promote photoconductivity is removed before detection.

  12. GEA CRDA Range Data Analysis

    Science.gov (United States)

    1999-07-28

    E1, July-August 1998 18 3.3. Example 3: SatMex, Solidaridad 2, May-June 1998 27 3.4. Example 4: PanAmSat, Galaxy IV, May-June 1998 33 3.5...17 Millstone measurements residuals for Telstar 401 on Days 181-263. 26 3-18 Millstone measurement residuals for Solidaridad 1 on Days 141-153...with 29 SatMex range data. 3-19 Hermosillo B-- Solidaridad 1 range residuals through Days 135-144 with bias 30 removed. 3-20 Iztapalapa D

  13. Radio pill antenna range test

    Science.gov (United States)

    Cummins, W. F.; Kane, R. J.

    1992-05-01

    In order to investigate the potential of a proposed 'radio pill' beacon transmitter, a range test experiment was devised and carried out in the VHF frequency range. Calculations and previous work indicated that optimum sensitivity and, thus, distance would be obtained in this frequency range provided body radio-frequency (RF) absorption was not too great. A ferrite-core loop antenna is compatible with a pill geometry and has better radiation efficiency than an air core loop. The ferrite core may be a hollow cylinder with the electronics and batteries placed inside. However, this range test was only concerned with experimentally developing test range data on the ferrite core antenna itself. A one turn strap loop was placed around a 9.5 mm diameter by 18.3 mm long stack of ferrite cores. This was coupled to a 50 Omega transmission line by 76 mm of twisted pair line and a capacitive matching section. This assembly was excited by a signal generator at output levels of -10 to +10 dBm. Signals were received on a VHF receiver and tape recorder coupled to a 14 element, circularly polarized Yagi antenna at a height of 2.5 m. Field strength measurements taken at ranges of 440, 1100, and 1714 m. Maximum field strengths referenced to 0 dBm transmitter level were -107 to -110 dB at 440 m, -124 to -127 dBm at 1100 m, and -116 to -119 dBm at 1714 m when the antenna cylinder was horizontal. Field strengths with a vertical antenna were about 6 dB below these values. The latter transmit site was elevated and had a clear line-of-site path to the receiving site. The performance of this test antenna was better than that expected from method-of-moment field calculations. When this performance data is scaled to a narrow bandwidth receiving system, ground level receiving ranges of a few to 10 km can be expected. Clear line-of-sight ranges where either or both the transmitter and receiver are elevated could vary from several km to 100 km.

  14. Optics At White Sands Missile Range

    Science.gov (United States)

    Fronczek, Ron C.; Hayslett, Charles R.

    1985-11-01

    We present an overview of the optics and optical data gathering programs conducted at White Sands Missile Range. Activities at White Sands Missile Range have always been diverse - the first test conducted there was the world's first nuclear explosion. In the forty years since that event the range has hosted a large assortment of vehicles including V2, Nike, Aerobee, Space Shuttle, Cruise, and the Copperhead. The last three of these devices illustrate the difficulty of the White Sands optical data gathering task. One is acquired in orbit, one as it crosses through a mountain pass, and one as it issues from the muzzle of a cannon. A combination of optical, radar, video, computer, and communications technology has produced a versatile system that can satisfy the data gathering requirements of most range users. Another example of the diverse optics programs at the range is the development of the High Energy Laser Systems Test Facility (HELSTF). Because of the nature of the systems being tested, the HELSTF is full of optics and optical systems including the TRW MIRACL laser and the Hughes SEA LITE Beam Director.

  15. Improved Range Searching Lower Bounds

    DEFF Research Database (Denmark)

    Larsen, Kasper Green; Nguyen, Huy L.

    2012-01-01

    by constructing a hard input set and query set, and then invoking Chazelle and Rosenberg's [CGTA'96] general theorem on the complexity of navigation in the pointer machine. For the group model, we show that input sets and query sets that are hard for range reporting in the pointer machine (i.e. by Chazelle...

  16. Anatomy of a Mountain Range.

    Science.gov (United States)

    Chew, Berkeley

    1993-01-01

    Provides written tour of Colorado Rockies along San Juan Skyway in which the geological features and formation of the mountain range is explored. Discusses evidence of geologic forces and products such as plate tectonic movement and the Ancestral Rockies; subduction and the Laramide Orogeny; volcanism and calderas; erosion, faulting, land…

  17. Mobile Lunar Laser Ranging Station

    Science.gov (United States)

    Intellect, 1977

    1977-01-01

    Harlan Smith, chairman of the University of Texas's Astronomy Department, discusses a mobile lunar laser ranging station which could help determine the exact rates of movement between continents and help geophysicists understand earthquakes. He also discusses its application for studying fundamental concepts of cosmology and physics. (Editor/RK)

  18. Range Compressed Holographic Aperture Ladar

    Science.gov (United States)

    2017-06-01

    step 1. This image can be obtained through any digital holography processing technique and contains no range information. Since the penny has a... digital holography, laser, active imaging , remote sensing, laser imaging 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT: SAR 8...30 15. Digital Hologram Image

  19. Tectonic setting and metallogenesis of volcanogenic massive sulfide deposits in the Bonnifield Mining District, Northern Alaska Range: Chapter B in Recent U.S. Geological Survey studies in the Tintina Gold Province, Alaska, United States, and Yukon, Canada--results of a 5-year project

    Science.gov (United States)

    Dusel-Bacon, Cynthia; Aleinikoff, John N.; Premo, Wayne R.; Paradis, Suzanne; Lohr-Schmidt, Ilana; Gough, Larry P.; Day, Warren C.

    2007-01-01

    This paper summarizes the results of field and laboratory investigations, including whole-rock geochemistry and radiogenic isotopes, of outcrop and drill core samples from volcanogenic massive sulfide (VMS) deposits and associated metaigneous rocks in the Wood River area of the Bonnifield mining district, northern Alaska Range (see fig. 1 of Editors’ Preface and Overview). U-Pb zircon igneous crystallization ages from felsic rocks indicate a prolonged period of Late Devonian to Early Mississippian (373±3 to 357±4 million years before present, or Ma) magmatism. This magmatism occurred in a basinal setting along the ancient Pacific margin of North America. The siliceous and carbonaceous compositions of metasedimentary rocks, Precambrian model ages based on U-Pb dating of zircon and neodymium ages, and for some units, radiogenic neodymium isotopic compositions and whole-rock trace-element ratios similar to those of continental crust are evidence for this setting. Red Mountain (also known as Dry Creek) and WTF, two of the largest VMS deposits, are hosted in peralkaline metarhyolite of the Mystic Creek Member of the Totatlanika Schist. The Mystic Creek Member is distinctive in having high concentrations of high-field-strength elements (HFSE) and rare-earth elements (REE), indicative of formation in a within-plate (extensional) setting. Mystic Creek metarhyolite is associated with alkalic, within-plate basalt of the Chute Creek Member; neodymium isotopic data indicate an enriched mantle component for both members of this bimodal (rhyolite-basalt) suite. Anderson Mountain, the other significant VMS deposit, is hosted by the Wood River assemblage. Metaigneous rocks in the Wood River assemblage span a wide compositional range, including andesitic rocks, which are characteristic of arc volcanism. Our data suggest that the Mystic Creek Member likely formed in an extensional, back-arc basin that was associated with an outboard continental-margin volcanic arc that included

  20. The Infant Aphakia Treatment Study Contact Lens Experience to Age 5 Years.

    Science.gov (United States)

    Russell, Buddy; DuBois, Lindreth; Lynn, Michael; Ward, Michael A; Lambert, Scott R

    2017-11-01

    To describe our experience treating a cohort of unilateral aphakic infants with contact lenses in the Infant Aphakia Treatment Study (IATS). Fifty-seven of the 114 infants in the IATS were randomized to contact lens wear; all were followed until age 5 years, although a few had lapses in care. An examination under anesthesia, including keratometry, was performed at the time of enrollment and at approximately 1 year of age; keratometry was performed again at 5 years of age. A traveling examiner assessed visual acuity at approximately 1 year of age and again at 4.5 years of age. Twenty-four treated eyes (46%) wore silicone elastomer (SE) contact lenses, 11 eyes (19%) rigid gas permeable (GP) contact lenses and 17 eyes (29%) wore both lens types at various points of time. Median logMAR visual acuity was +0.70 (interquartile range (IQR), +0.30 to 1.20) in the SE group and 2.03 (IQR, +0.20 to 2.28) in the GP group at age 4.5 years. The mean (±SD) keratometric power of the treated eyes was 46.3±2.8 diopter (D) at baseline, 44.6±2.3 D at 1 year of age, and 44.3±1.7 D at 5 years of age. Keratometric astigmatism of treated eyes was 1.98±1.37 D at baseline, 1.62±0.98 D at 1 year of age, and 2.00±1.00 D at 5 years of age. Thirteen contact lens-related adverse events occurred among 7 patients after age 1 year. A cohort of infants with unilateral aphakia successfully wore contact lenses with relatively few adverse events.

  1. NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial.

    Science.gov (United States)

    Balingit, Peter P; Armstrong, David G; Reyzelman, Alexander M; Bolton, Laura; Verco, Shelagh J; Rodgers, Kathleen E; Nigh, Katherine A; diZerega, Gere S

    2012-01-01

    This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu(3)-A(1-7) (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks' once-daily topical treatment with 0.03% DSC127 (n = 26), 0.01% DSC127 (n = 27), or Placebo (n = 24), followed by 20 weeks' standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent-to-treat groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log-linear pattern for both intent-to-treat and per-protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo-treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03%DSC127 (p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers. © 2012 by the Wound Healing Society.

  2. The protection effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione, a curcumin analogue, against operative liver injury in rats.

    Science.gov (United States)

    Chi, Xiaowei; Yu, Dan; Li, Peijing; Lu, Qianfeng; Jiang, Wenjiao; Hao, Kun

    2017-03-30

    The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2-4.8mmol/kg) was administrated 10min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8mmol/kg) administrated 10min before ischemia and N-acetylcysteine (NAC) (4.8mmol/kg) administrated 10min before reperfusion were included for comparative studies. The plasma liver enzyme activities, histopathological indices and markers of lipid peroxide were determined to evaluate the hepatic protection effects. Effects of DDD on succinate dehydrogenase (SDH) activity were also investigated. DDD showed dose-dependent hepatocyte protections when administrated 10min before reperfusion stages in hepatic IRI rats. DDD showed almost equivalent hepatoprotective effects when administrated 10min before ischemia phase demonstrating that DDD acted on the reperfusion stages selectively against the hepatic IRI, instead of ischemia phase. NAC was not effective against hepatic IRI when treated 10min before reperfusion because of the higher pKa of NAC. In additional, DDD had no effect on the SDH both in hepatic IRI rats and in mitochondria. In conclusion, DDD had dose-dependent hepatocyte protections in the reperfusion stages in hepatic IRI rats, while the observed hepatocyte protections of DDD did not involve SDH activities. β-Diketone structures of DDD were crucial for the hepatocyte protections. The abilities of DDD to clear up the unsaturated aldehydes related with the enolate nucleophilicity and the pKa. DDD might be a promising candidate to treat hepatic IRI. Copyright © 2016. Published by Elsevier B.V.

  3. Enhancement of photosynthetic capacity in Euglena gracilis by expression of cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase leads to increases in biomass and wax ester production.

    Science.gov (United States)

    Ogawa, Takahisa; Tamoi, Masahiro; Kimura, Ayako; Mine, Ayaka; Sakuyama, Harumi; Yoshida, Eriko; Maruta, Takanori; Suzuki, Kengo; Ishikawa, Takahiro; Shigeoka, Shigeru

    2015-01-01

    Microalgae have recently been attracting attention as a potential platform for the production of biofuels. Euglena gracilis, a unicellular phytoflagellate, has been proposed as an attractive feedstock to produce biodiesel because it can produce large amounts of wax esters, consisting of medium-chain fatty acids and alcohols with 14:0 carbon chains. E. gracilis cells highly accumulate a storage polysaccharide, a β-1,3-glucan known as paramylon, under aerobic conditions. When grown aerobically and then transferred into anaerobic conditions, E. gracilis cells degrade paramylon to actively synthesize and accumulate wax esters. Thus, the enhanced accumulation of paramylon through the genetic engineering of photosynthesis should increase the capacity for wax ester production. We herein generated transgenic Euglena (EpFS) cells expressing the cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), which is involved in the Calvin cycle, to enhance its photosynthetic activity. FBP/SBPase was successfully expressed within Euglena chloroplasts. The cell volume of the EpFS4 cell line was significantly larger than that of wild-type cells under normal growth conditions. The photosynthetic activity of EpFS4 cells was significantly higher than that of wild type under high light and high CO2, resulting in enhanced biomass production, and the accumulation of paramylon was increased in transgenic cell lines than in wild-type cells. Furthermore, when EpFS cell lines grown under high light and high CO2 were placed on anaerobiosis, the productivity of wax esters was approximately 13- to 100-fold higher in EpFS cell lines than in wild-type cells. Our results obtained here indicate that the efficiency of biomass production in E. gracilis can be improved by genetically modulating photosynthetic capacity, resulting in the enhanced production of wax esters. This is the first step toward the utilization of E. gracilis as a sustainable source for biofuel production under photoautotrophic cultivation.

  4. Angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axis prevents pancreatic acinar cell inflammatory response via inhibition of the p38 mitogen-activated protein kinase/nuclear factor-κB pathway.

    Science.gov (United States)

    Yu, Xiaozheng; Cui, Lijian; Hou, Fei; Liu, Xiaoya; Wang, Yan; Wen, Yan; Chi, Cheng; Li, Chunyun; Liu, Ruixia; Yin, Chenghong

    2017-11-13

    The aim of the present study was to investigate the role of the angiotensin-converting enzyme (ACE)2-angiotensin‑(Ang)-(1-7)-Mas axis in the pathogenesis of pancreatitis and the association between this axis and the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor (NF-κB) signaling pathway in pancreatic acinar cells. Mouse pancreatic acinar cancer (MPC-83) cells were stimulated with 10 nM caerulein (CAE) to create an in vitro model of acute pancreatitis, and collected for analysis at 2, 6, 12, 24 and 48 h post stimulation. In addition, cells were pretreated with different concentrations of Ang‑(1‑7), Ang‑(1‑7) antagonist A779, p38 MAPK inhibitor SB203580 or ACE2 inhibitor DX600 for 30 min, and then stimulated with CAE for 24 h. The ACE2, Mas receptor, p38 MAPK, phosphorylated (p)-p38 MAPK and NF-κB expression levels were evaluated using western blotting and immunofluorescence. p38 MAPK, NF-κB, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8 and IL-10 mRNA expression levels were assessed using reverse transcription-quantitative polymerase chain reaction. The results of the immunofluorescence assay demonstrated that ACE2 and p38 MAPK were present mainly in the cytoplasm, while the Mas receptor was located mainly in the cell membrane. ACE2, p38 MAPK and p-p38 MAPK protein levels were significantly increased (PMas receptor protein levels were significantly upregulated (PMas axis significantly inhibits pancreatitis by inhibition of the p38 MAPK/NF-κB signaling pathway.

  5. Short-range communication system

    Science.gov (United States)

    Alhorn, Dean C. (Inventor); Howard, David E. (Inventor); Smith, Dennis A. (Inventor)

    2012-01-01

    A short-range communication system includes an antenna, a transmitter, and a receiver. The antenna is an electrical conductor formed as a planar coil with rings thereof being uniformly spaced. The transmitter is spaced apart from the plane of the coil by a gap. An amplitude-modulated and asynchronous signal indicative of a data stream of known peak amplitude is transmitted into the gap. The receiver detects the coil's resonance and decodes same to recover the data stream.

  6. Countering short range ballistic missiles

    OpenAIRE

    Conner, George W.; Ehiers, Mark A.; Marshall, Kneale T.

    1993-01-01

    Approved for public release; distribution is unlimited. Concepts commonly found in ASW search are used to model the flow and detection of mobile launchers for short range ballistic missiles. Emphasis is on detection and destruction of the launcher before launch. The benefit of pre-hostility intelligence and pre-missile-launch prosecution, the backbone of successful ASW, is revealed through the analysis of a circulation model which reflects the standard operations of a third world mobile mi...

  7. Chronic Treatment with Ang-(1-7 Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Mariam H. M. Yousif

    2014-01-01

    Full Text Available Angiotensin-(1-7 [Ang-(1-7] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED but its molecular actions in the diabetic corpus cavernosum (CC are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7 on vascular reactivity in the rat corpus cavernosum (CC and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS such as angiotensin-converting enzyme (ACE, ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2, and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7 with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7 reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7 treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7 in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism.

  8. Marked hyperandrogenicity in a 60-year-old woman

    Directory of Open Access Journals (Sweden)

    Khaled Aljenaee

    2017-09-01

    Full Text Available Markedly elevated androgen levels can lead to clinical virilization in females. Clinical features of virilization in a female patient, in association with biochemical hyperandrogenism, should prompt a search for an androgen-producing tumor, especially of ovarian or adrenal origin. We herein report the case of a 60-year-old woman of Pakistani origin who presented with the incidental finding of male pattern baldness and hirsutism. Her serum testosterone level was markedly elevated at 21 nmol/L (normal range: 0.4–1.7 nmol/L, while her DHEAS level was normal, indicating a likely ovarian source of her elevated testosterone. Subsequently, a CT abdomen-pelvis was performed, which revealed a bulky right ovary, confirmed on MRI of the pelvis as an enlarged right ovary, measuring 2.9 × 2.2 cm transaxially. A laparoscopic bilateral salpingo-oophorectomy was performed, and histopathological examination and immunohistochemistry confirmed the diagnosis of a Leydig cell tumor, a rare tumor accounting for 0.1% of ovarian tumors. Surgical resection led to normalization of testosterone levels.

  9. Normal values for cervical range of motion.

    Science.gov (United States)

    Swinkels, Raymond A H M; Swinkels-Meewisse, Ilse E J C M

    2014-03-01

    Cohort study. To generate normal values for active range of motion (ACROM) of the cervical spine in asymptomatic persons. There is a lack of normal values for ACROM based on large groups and stratified for different age categories. Four hundred asymptomatic persons were included, 100 for each decade of age from 20 years to 60 years and in each subgroup 50 males and 50 females. ACROM was measured with the cervical range of motion (CROM) device. Analysis of variance and the Scheffé post hoc test was used to investigate the differences of ACROM between the decades of age. Linear regression analysis was performed to examine the influence of age and sex on ACROM. The results of this study show that the ACROM decreases significantly in persons older than 50 years for all directions except extension and side flexion compared with that in the subgroup aged 40 to 50. Age had an overall significant effect on the ACROM for all directions. Sex proved to have no significant effect on the ACROM. Normal values were established for ACROM in a group of 400 persons without neck complaints. It was demonstrated that age has a significant influence on the ACROM, but sex has no influence. N/A.

  10. Visual Control of Robots Using Range Images

    Directory of Open Access Journals (Sweden)

    Fernando Torres

    2010-08-01

    Full Text Available In the last years, 3D-vision systems based on the time-of-flight (ToF principle have gained more importance in order to obtain 3D information from the workspace. In this paper, an analysis of the use of 3D ToF cameras to guide a robot arm is performed. To do so, an adaptive method to simultaneous visual servo control and camera calibration is presented. Using this method a robot arm is guided by using range information obtained from a ToF camera. Furthermore, the self-calibration method obtains the adequate integration time to be used by the range camera in order to precisely determine the depth information.

  11. Long-range correlation and market segmentation in bond market

    Science.gov (United States)

    Wang, Zhongxing; Yan, Yan; Chen, Xiaosong

    2017-09-01

    This paper investigates the long-range auto-correlations and cross-correlations in bond market. Based on Detrended Moving Average (DMA) method, empirical results present a clear evidence of long-range persistence that exists in one year scale. The degree of long-range correlation related to maturities has an upward tendency with a peak in short term. These findings confirm the expectations of fractal market hypothesis (FMH). Furthermore, we have developed a method based on a complex network to study the long-range cross-correlation structure and applied it to our data, and found a clear pattern of market segmentation in the long run. We also detected the nature of long-range correlation in the sub-period 2007-2012 and 2011-2016. The result from our research shows that long-range auto-correlations are decreasing in the recent years while long-range cross-correlations are strengthening.

  12. Truthful approximations to range voting

    DEFF Research Database (Denmark)

    Filos-Ratsika, Aris; Miltersen, Peter Bro

    We consider the fundamental mechanism design problem of approximate social welfare maximization under general cardinal preferences on a finite number of alternatives and without money. The well-known range voting scheme can be thought of as a non-truthful mechanism for exact social welfare......-unilateral has an approximation ratio between 0.610 and 0.611, the best ordinal mechanism has an approximation ratio between 0.616 and 0.641, while the best mixed-unilateral mechanism has an approximation ratio bigger than 0.660. In particular, the best mixed-unilateral non-ordinal (i.e., cardinal) mechanism...

  13. Nonlinear dynamic range compression deconvolution

    Science.gov (United States)

    Haji-Saeed, Bahareh; Sengupta, Sandip K.; Goodhue, William; Khoury, Jed; Woods, Charles L.; Kierstead, John

    2006-07-01

    We introduce a dynamic range image compression technique for nonlinear deconvolution; the impulse response of the distortion function and the noisy distorted image are jointly transformed to pump a clean reference beam in a two-beam coupling arrangement. The Fourier transform of the pumped reference beam contains the deconvolved image and its conjugate. In contrast to standard deconvolution approaches, for which noise can be a limiting factor in the performance, this approach allows the retrieval of distorted signals embedded in a very high-noise environment.

  14. Current Trends in Satellite Laser Ranging

    Science.gov (United States)

    Pearlman, M. R.; Appleby, G. M.; Kirchner, G.; McGarry, J.; Murphy, T.; Noll, C. E.; Pavlis, E. C.; Pierron, F.

    2010-01-01

    Satellite Laser Ranging (SLR) techniques are used to accurately measure the distance from ground stations to retroreflectors on satellites and the moon. SLR is one of the fundamental techniques that define the international Terrestrial Reference Frame (iTRF), which is the basis upon which we measure many aspects of global change over space, time, and evolving technology. It is one of the fundamental techniques that define at a level of precision of a few mm the origin and scale of the ITRF. Laser Ranging provides precision orbit determination and instrument calibration/validation for satellite-borne altimeters for the better understanding of sea level change, ocean dynamics, ice budget, and terrestrial topography. Laser ranging is also a tool to study the dynamics of the Moon and fundamental constants. Many of the GNSS satellites now carry retro-reflectors for improved orbit determination, harmonization of reference frames, and in-orbit co-location and system performance validation. The GNSS Constellations will be the means of making the reference frame available to worldwide users. Data and products from these measurements support key aspects of the GEOSS 10-Year implementation Plan adopted on February 16, 2005, The ITRF has been identified as a key contribution of the JAG to GEOSS and the ILRS makes a major contribution for its development since its foundation. The ILRS delivers weekly additional realizations that are accumulated sequentially to extend the ITRF and the Earth Orientation Parameter (EOP) series with a daily resolution. Additional products are currently under development such as precise orbits of satellites, EOP with daily availability, low-degree gravitational harmonics for studies of Earth dynamics and kinematics, etc. SLR technology continues to evolve toward the next generation laser ranging systems as programmatic requirements become more stringent. Ranging accuracy is improving as higher repetition rate, narrower pulse lasers and faster

  15. Spectral optical properties of long-range transport Asian dust and pollution aerosols over Northeast Asia in 2007 and 2008

    Directory of Open Access Journals (Sweden)

    J. Jung

    2010-06-01

    Full Text Available As a part of the IGAC (International Global Atmospheric Chemistry Mega-cities program, aerosol physical and optical properties were continuously measured from March 2007 to March 2008 at an urban site (37.57° N, 126.94° E in Seoul, Korea. Spectral optical properties of long-range transported Asian dust and pollution aerosols have been investigated based on the year long measurement data. Optically measured black carbon/thermally measured elemental carbon (BC/EC ratio showed clear monthly variation with high values in summer and low values in winter mainly due to the enhancement of light attenuation by the internal mixing of EC. Novel approach has been suggested to retrieve the spectral light absorption coefficient (babs from Aethalometer raw data by using BC/EC ratio. Mass absorption efficiency, σabs (=babs/EC at 550 nm was determined to be 9.0±1.3, 8.9±1.5, 9.5±2.0, and 10.3±1.7 m2 g−1 in spring, summer, fall, and winter, respectively with an annual mean of 9.4±1.8 m2 g−1. Threshold values to classify severe haze events were suggested in this study. Increasing trend of aerosol single scattering albedo (SSA with wavelength was observed during Asian dust events while little spectral dependence of SSA was observed during long-range transport pollution (LTP events. Satellite aerosol optical thickness (AOT and Hysplit air mass backward trajectory analyses as well as chemical analysis were performed to characterize the dependence of spectral optical properties on aerosol type. Results from this study can provide useful information for studies on regional air quality and aerosol's effects on climate change.

  16. [Molecular criteria in insects systematics: bar-coding gene COI range of variability as a taxonomic criterion for genus, tribe, and subfamily, with Chironominae and Orthocladiinae midges (Chironomidae, Diptera) as a case study].

    Science.gov (United States)

    Polukonova, N V; Demin, A G; Miuge, N S

    2013-01-01

    Contemporary systematics of insects is based mainly on morphological traits. However, their usage is limited both by high variability and complications in comparisons of remote taxa due to low number of common traits. In whole, this leads to a somewhat subjective view when elaborating the system. Unlike morphological ones, molecular traits of taxa, revealed by use of marker genes such as gene cytochrome-c-oxidase I (COI), are less variable and more uniform, which allows them to be used as a criterion of genus, tribe, and subfamily for a wide range of organisms. Application of molecular criteria appears to be all the more important when constructing the system for groups of organisms with high morphological and specific diversity, such as midges (Chironomidae, Diptera). Last years, the DNA-sequence of gene COI is becoming widely used for species identification as a bar-coding one. Its use as a criterion for taxa of super-species level is hampered by its high nucleotide variability. We established the bounds of COI nucleotide and aminoacid divergence between midge species of Chironominae subfamily belonging to the same genus, same tribe, different tribes, as well as between species of Chironominae and Orthocladiinae subfamilies. It is shown that the level of aminoacid divergence reflects molecular boundaries of genus and tribe better than nucleotide one. It can be stated that if the level of aminoacid divergence falls within the limits from 0 to 1.7% then a pair of species compared belongs to the same genus; if it falls within the limits from 1.7 to 4.0% then they belong to the same tribe; within the limits from 4.6 to 6.3%--to different tribes; if it exceeds 7.9%--to different subfamilies. The accuracy of identification when using these ranges turns out to be not less than 75%. In this regard, bounds of COI sequence aminoacid divergence may be used as taxonomic criteria for midge genus, tribe or subfamily.

  17. Metal-insulator transition in Bi{sub 1.7}Pb{sub 0.3}Sr{sub 2}Ca{sub 1-x}Gd{sub x}Cu{sub 2}O{sub 8+{delta}} solid solutions

    Energy Technology Data Exchange (ETDEWEB)

    Sangeetha, M.; Hari Babu, V. [Osmania Univ., Hyderabad (India). Dept. of Physics; Nagabhushanam, M. [Department of Physics, University College of Technology, Osmania University, Hyderabad-500 007 (India); Beniere, F. [Groupe Matiere Condensee et Materiaux, Batiment 24, Universite de Rennes I, F-35042, Rennes Cedex (France); Pena, O. [C.I.S.M.-URA 1495, Universite de Rennes I, F-35042, Rennes Cedex (France)

    1999-03-29

    Substitution of rare earth ions for Ca in Bi{sub 2}Sr{sub 2}Ca{sub 1}Cu{sub 2}O{sub 8+{delta}} compounds causes a depression in T{sub c} and a metal-insulator transition. In order to understand the mechanism governing the process, we made systematic studies on Bi{sub 1.7}Pb{sub 0.3}Sr{sub 2}Ca{sub 1-x}Gd{sub x}Cu{sub 2}O{sub 8+{delta}} compounds in which Ca{sup 2+} is replaced with different concentrations of Gd{sup 3+} ion. The structural parameters, oxygen content and hole carrier concentration were observed to change with Gd concentration. From the X-ray diffractograms of the samples, the single phase nature of the compounds was confirmed. Lattice parameters were calculated and the results show that the c parameter decreases and the a parameter increases with increasing Gd content. At room temperature, the oxygen content of the samples was estimated using iodometric titration while the hole concentration was calculated from TEP measurements. The T{sub c} (onset)`s obtained from AC susceptibility were found to be close to those obtained from resistance versus temperature plots. The materials exhibited superconductivity in the 0.0{<=}x{<=}0.4 concentration range and for higher concentration of Gd they became insulating. The initial susceptibility dM/dH relating to the superconducting volume, decreased gradually up to x=0.1, and sharply for higher concentrations of Gd. Both transport and magnetic properties have confirmed metal-insulator transition in the x>0.4 region. (orig.) 17 refs.

  18. Live Fire Range Environmental Assessment

    Energy Technology Data Exchange (ETDEWEB)

    None

    1993-08-01

    The Central Training Academy (CTA) is a DOE Headquarters Organization located in Albuquerque, New Mexico, with the mission to effectively and efficiently educate and train personnel involved in the protection of vital national security interests of DOE. The CTA Live Fire Range (LFR), where most of the firearms and tactical training occurs, is a complex separate from the main campus. The purpose of the proposed action is to expand the LFR to allow more options of implementing required training. The Department of Energy has prepared this Environmental Assessment (EA) for the proposed construction and operation of an expanded Live Fire Range Facility at the Central Training Academy in Albuquerque, New Mexico. Based on the analysis in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, the preparation of an environmental impact statement is not required and DOE is issuing this Finding of No Significant Impact (FONSI).

  19. Safety and Efficacy Evaluation of rAAV2tYF-PR1.7-hCNGA3 Vector Delivered by Subretinal Injection in CNGA3 Mutant Achromatopsia Sheep.

    Science.gov (United States)

    Gootwine, Elisha; Ofri, Ron; Banin, Eyal; Obolensky, Alexey; Averbukh, Edward; Ezra-Elia, Raaya; Ross, Maya; Honig, Hen; Rosov, Alexander; Yamin, Esther; Ye, Guo-Jie; Knop, David R; Robinson, Paulette M; Chulay, Jeffrey D; Shearman, Mark S

    2017-06-01

    Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector expressing the human CNGA3 gene designated AGTC-402 (rAAV2tYF-PR1.7-hCNGA3) for the treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. The results are herein reported of a study evaluating safety and efficacy of AGTC-402 in CNGA3-deficient sheep. Thirteen day-blind sheep divided into three groups of four or five animals each received a subretinal injection of an AAV vector expressing a CNGA3 gene in a volume of 500 μL in the right eye. Two groups (n = 9) received either a lower or higher dose of the AGTC-402 vector, and one efficacy control group (n = 4) received a vector similar in design to one previously shown to rescue cone photoreceptor responses in the day-blind sheep model (rAAV5-PR2.1-hCNGA3). The left eye of each animal received a subretinal injection of 500 μL of vehicle (n = 4) or was untreated (n = 9). Subretinal injections were generally well tolerated and not associated with systemic toxicity. Most animals had mild to moderate conjunctival hyperemia, chemosis, and subconjunctival hemorrhage immediately after surgery that generally resolved by postoperative day 7. Two animals treated with the higher dose of AGTC-402 and three of the efficacy control group animals had microscopic findings of outer retinal atrophy with or without inflammatory cells in the retina and choroid that were procedural and/or test-article related. All vector-treated eyes showed improved cone-mediated electroretinography responses with no change in rod-mediated electroretinography responses. Behavioral maze testing under photopic conditions showed significantly improved navigation times and reduced numbers of obstacle collisions in all vector-treated eyes compared to their contralateral control eyes or pre-dose results in the treated eyes. These results support the use of AGTC-402 in clinical studies in patients with achromatopsia caused by CNGA3 mutations, with careful evaluation for possible inflammatory and/or toxic effects.

  20. Dynamic range majority data structures

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; He, Meng; Munro, J. Ian

    2011-01-01

    data structure for answering range α-majority queries on a dynamic set of points, where α ε (0,1). Our data structure uses O(n) space, supports queries in O((lg n)/α) time, and updates in O((lg n)/α) amortized time. If the coordinates of the points are integers, then the query time can be improved to O......((lg n/(α lglg n)). For constant values of α, this improved query time matches an existing lower bound, for any data structure with polylogarithmic update time. We also generalize our data structure to handle sets of points in d-dimensions, for d ≥ 2, as well as dynamic arrays, in which each entry...

  1. Tonopah test range - outpost of Sandia National Laboratories

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.

    1996-03-01

    Tonopah Test Range is a unique historic site. Established in 1957 by Sandia Corporation, Tonopah Test Range in Nevada provided an isolated place for the Atomic Energy Commission to test ballistics and non-nuclear features of atomic weapons. It served this and allied purposes well for nearly forty years, contributing immeasurably to a peaceful conclusion to the long arms race remembered as the Cold War. This report is a brief review of historical highlights at Tonopah Test Range. Sandia`s Los Lunas, Salton Sea, Kauai, and Edgewood testing ranges also receive abridged mention. Although Sandia`s test ranges are the subject, the central focus is on the people who managed and operated the range. Comments from historical figures are interspersed through the narrative to establish this perspective, and at the end a few observations concerning the range`s future are provided.

  2. Lead Poisoning at an Indoor Firing Range.

    Science.gov (United States)

    Kang, Kyung Wook; Park, Won Ju

    2017-10-01

    In March 2014, a 39-year-old Korean male presented with a 6-month history of various nonspecific symptoms including dizziness, fatigue, asthenia, irritability, elevated blood pressure, palpitation, eyestrain, and tinnitus. His occupational history revealed that he had been working as an indoor firing range manager for 13 months; therefore, he was subjected to a blood lead level (BLL) test. The test results showed a BLL of 64 μg/dL; hence, he was diagnosed with lead poisoning and immediately withdrawn from work. As evident from the workplace environmental monitoring, the level of lead exposure in the air exceeded its limit (0.015-0.387 mg/m³). He received chelation treatment with calcium-disodium ethylenediaminetetraacetic acid (1 g/day) for 5 days without any adverse effects. In the follow-up results after 2 months, the BLL had decreased to 9.7 μg/dL and the symptoms resolved. This report represents the first occupational case of lead poisoning in firing ranges in Korea, and this necessitates institutional management to prevent the recurrence of poisoning through this route. Workplace environmental monitoring should be implemented for indoor firing ranges, and the workers should undergo regularly scheduled special health examinations. In clinical practice, it is essential to question the patient about his occupational history. © 2017 The Korean Academy of Medical Sciences.

  3. Refuge narrative report : 1967 : Kenai National Moose Range

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Kenai National Moose Range outlines Refuge accomplishments during the 1967 calendar year. The report begins by summarizing the...

  4. National Bison Range, Ninepipe and Pablo Refuges: Narrative report - 1970

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for National Bison Range, Pablo NWR, and Ninepipe NWR outlines Refuge accomplishments during the 1970 calendar year. The report begins...

  5. The Geologic Story of Colorado's Sangre de Cristo Range

    Science.gov (United States)

    Lindsey, David A.

    2010-01-01

    There is no record of the beginning of time in the Sangre de Cristo Range. Almost 3 billion years of Earth history are missing, but the rest is on spectacular display in this rugged mountain landscape. This is the geologic story of the Sangre de Cristo Range.

  6. Managing interior Northwest rangelands: the Oregon Range Evaluation Project.

    Science.gov (United States)

    Thomas M. Quigley; H. Reed Sanderson; Arthur R. Tiedemann

    1989-01-01

    This report is a synthesis of results from an 11-year study of the effects of increasing intensities of range management strategies on herbage production, water resources, economics, and associated resources-such as wood fiber and recreation-in Grant County, Oregon. Four intensities of management were studied on Federal land (19 grazing allotments) ranging from no...

  7. The Ranges Of Subauroral Geomagnetic Field Elements | Rabiu ...

    African Journals Online (AJOL)

    Nigeria Journal of Pure and Applied Physics ... On quiet condition, the range in j season dominates over d- and e- seasons in all elements. ... Generally, the seasonal range in the D component for all the years as well as in H and Z components - apart from the anomaly - maintain the order e>j>d of seasonal variation which is ...

  8. Range management research, Fort Valley Experimental Forest (P-53)

    Science.gov (United States)

    Henry A. Pearson; Warren P. Clary; Margaret M. Moore; Carolyn Hull Sieg

    2008-01-01

    Range management research at the Fort Valley Experimental Forest during the past 100 years has provided scientific knowledge for managing ponderosa pine forests and forest-range grazing lands in the Southwest. Three research timeperiods are identified: 1908 to 1950, 1950 to 1978, and 1978 to 2008. Early research (1908-1950) addressed ecological effects of livestock...

  9. Are fish outside their usual ranges early indicators of climate-driven range shifts?

    Science.gov (United States)

    Fogarty, Hannah E; Burrows, Michael T; Pecl, Gretta T; Robinson, Lucy M; Poloczanska, Elvira S

    2017-05-01

    Shifts in species ranges are a global phenomenon, well known to occur in response to a changing climate. New species arriving in an area may become pest species, modify ecosystem structure, or represent challenges or opportunities for fisheries and recreation. Early detection of range shifts and prompt implementation of any appropriate management strategies is therefore crucial. This study investigates whether 'first sightings' of marine species outside their normal ranges could provide an early warning of impending climate-driven range shifts. We examine the relationships between first sightings and marine regions defined by patterns of local climate velocities (calculated on a 50-year timescale), while also considering the distribution of observational effort (i.e. number of sampling days recorded with biological observations in global databases). The marine trajectory regions include climate 'source' regions (areas lacking connections to warmer areas), 'corridor' regions (areas where moving isotherms converge), and 'sink' regions (areas where isotherms locally disappear). Additionally, we investigate the latitudinal band in which first sightings were recorded, and species' thermal affiliations. We found that first sightings are more likely to occur in climate sink and 'divergent' regions (areas where many rapid and diverging climate trajectories pass through) indicating a role of temperature in driving changes in marine species distributions. The majority of our fish first sightings appear to be tropical and subtropical species moving towards high latitudes, as would be expected in climate warming. Our results indicate that first sightings are likely related to longer-term climatic processes, and therefore have potential use to indicate likely climate-driven range shifts. The development of an approach to detect impending range shifts at an early stage will allow resource managers and researchers to better manage opportunities resulting from range

  10. Constitutional translocation t(1;17)(p36.31-p36.13;q11.2-q12.1) in a neuroblastoma patient. Establishment of somatic cell hybrids and identification of PND/A12M2 on chromosome 1 and NF1/SCYA7 on chromosome 17 as breakpoint flanking single copy markers

    NARCIS (Netherlands)

    Laureys, G.; Speleman, F.; Versteeg, R.; van der Drift, P.; Chan, A.; Leroy, J.; Francke, U.; Opdenakker, G.; van Roy, N.

    1995-01-01

    Cytogenetic and molecular studies in neuroblastoma suggest the presence of a tumor suppressor gene at the distal band p36 of human chromosome 1. We described a constitutional translocation t(1;17)(p36;q12-q21), involving the critical region 1p36, in a patient with neuroblastoma, and hypothesized

  11. Digital Surface and Terrain Models (DSM,DTM), 1.7 meter DSM in Urban Areas, 5 Meter DSM in National Forest, flown as part of the LAR-IAC project, Published in 2006, 1:600 (1in=50ft) scale, Los Angeles County Government.

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Digital Surface and Terrain Models (DSM,DTM) dataset current as of 2006. 1.7 meter DSM in Urban Areas, 5 Meter DSM in National Forest, flown as part of the LAR-IAC...

  12. Localization of the 17q breakpoint of a constitutional 1;17 translocation in a patient with neuroblastoma within a 25-kb segment located between the ACCN1 and TLK2 genes and near the distal breakpoints of two microdeletions in neurofibromatosis type 1 patients

    NARCIS (Netherlands)

    van Roy, Nadine; Vandesompele, Jo; Berx, Geert; Staes, Katrien; van Gele, Mireille; de Smet, Els; de Paepe, Anne; Laureys, Geneviève; van der Drift, Pauline; Versteeg, Rogier; van Roy, Frans; Speleman, Frank

    2002-01-01

    We have constructed a 1.4-Mb P1 artificial chromosome/bacterial artificial chromosome (PAC/BAC) contig spanning the 17q breakpoint of a constitutional translocation t(1;17)(p36.2;q11.2) in a patient with neuroblastoma. Three 17q breakpoint-overlapping cosmids were identified and sequenced. No coding

  13. Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves' orbitopathy: A five-year follow-up study.

    Science.gov (United States)

    Erdei, Annamaria; Paragh, Gyorgy; Kovacs, Peter; Karanyi, Zsolt; Berenyi, Ervin; Galuska, Laszlo; Lenkey, Agota; Szabados, Lajos; Gyory, Ferenc; Ujhelyi, Bernadett; Berta, Andras; Boda, Judit; Berta, Eszter; Bodor, Miklos; Gazdag, Annamaria; Nagy, Endre V

    2014-12-01

    Abstract The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves' orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), (99m)Tc-labeled diethylene triamine pentaacetic acid ((99m)Tc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m(2) body surface area for four weeks. The mean follow-up period was 67 (range 58-81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 ± 1.7 and decreased to 3.4 ± 1.6 by one month (p < 0.05) and remained unchanged (3.2 ± 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 ± 4.51 MBq/cm(3) and decreased to 11.97 ± 2.36 MBq/cm(3) at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 ± 17.61 ms and 84.29 ± 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 ± 3.4 U/L, 5.6 ± 4.5 U/L and 1.7 ± 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.

  14. Broader range of skills distinguishes successful CFOs.

    Science.gov (United States)

    Doody, M F

    2000-09-01

    In recent years, healthcare CFOs have seen their role expand significantly beyond traditional financial duties. A series of trended surveys on CFO roles and responsibilities reveals that today's healthcare CFO requires a broad new range of traits and skills in the areas of leadership, operations, and healthcare strategy. CFOs regard strategic thinking and the ability to communicate clearly as the most important of their essential leadership traits and skills, respectively. Among operational and strategic skills, CFOs most often cite the importance of being able to improve organizational performance and benchmark. Healthcare CFOs can enhance their chances of success by focusing self-improvement efforts on five key areas: implementing the organization's vision; developing tactics that stimulate change; enhancing communication skills; focusing on managing and leading; and strengthening relationships.

  15. Middle Range Theory: A Perspective on Development and Use.

    Science.gov (United States)

    Liehr, Patricia; Smith, Mary Jane

    This replication and critique addresses ongoing development and use of middle range theory since considering this body of nursing knowledge 18 years ago. Middle range theory is appreciated as essential to the structure of nursing knowledge. Nine middle range theories that demonstrate ongoing use by the theory authors are analyzed using the criteria of theory name, theory generation, disciplinary perspective, theory model, practice use and research use. Critique conclusions indicate the importance of staying with the theory over time, naming and development consistent with the disciplinary perspective, movement to an empirical level, and bringing middle range theory to the interdisciplinary table.

  16. Development of the seafloor acoustic ranging system

    Science.gov (United States)

    Osada, Y.; Kido, M.; Fujimoto, H.

    2007-12-01

    We have developed a seafloor acoustic ranging system, which simulates an operation with the DONET (Development of Dense Ocean-floor Network System for Earthquake and Tsunami) cable, to monitor seafloor crustal movement. The seafloor acoustic ranging system was based on the precise acoustic transponder (PXP). We have a few problems for the improvement of the resolution. One thing is the variation of sound speed. Another is the bending of ray path. A PXP measures horizontal distances on the seafloor from the round trip travel times of acoustic pulses between pairs of PXP. The PXP was equipped with the pressure, temperature gauge and tilt-meter. The variation of sound speed in seawater has a direct effect on the measurement. Therefore we collect the data of temperature and pressure. But we don't collect the data of salinity because of less influence than temperature and pressure. Accordingly a ray path of acoustic wave tends to be bent upward in the deep sea due to the Snell's law. As the acoustic transducer of each PXPs held about 3.0m above the seafloor, the baseline is too long for altitude from the seafloor. In this year we carried out the experiment for the seafloor acoustic ranging system. We deployed two PXPs at about 750m spacing on Kumano-nada. The water depth is about 2050m. We collected the 660 data in this experiment during one day. The round trip travel time show the variation with peak-to-peak amplitude of about 0.03msec. It was confirmed to explain the majority in this change by the change in sound speed according to the temperature and pressure. This results shows the resolution of acoustic measurements is +/-2mm. Acknowledgement This study is supported by 'DONET' of Ministry of Education, Culture, Sports, Science and Technology.

  17. Nocturnal Dry Cough in the First 7 Years of Life is Associated With Asthma at School Age

    NARCIS (Netherlands)

    Boudewijn, Ilse M.; Savenije, Olga E. M.; Koppelman, Gerard H.; Wijga, Alet H.; Smit, Henriette A.; de Jongste, Johan C.; Gehring, Ulrike; Postma, Dirkje S.; Kerkhof, Marjan

    Background: Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and

  18. Nocturnal dry cough in the first 7 years of life is associated with asthma at school age

    NARCIS (Netherlands)

    Boudewijn, Ilse M; Savenije, Olga E M; Koppelman, Gerard H; Wijga, Alet H; Smit, Henriëtte A; de Jongste, Johan C; Gehring, Ulrike; Postma, Dirkje S; Kerkhof, Marjan

    2015-01-01

    BACKGROUND: Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and

  19. Nocturnal dry cough in the first 7 years of life is associated with asthma at school age

    NARCIS (Netherlands)

    Boudewijn, Ilse M; Savenije, Olga E M; Koppelman, Gerard H; Wijga, Alet H; Smit, Henriëtte A|info:eu-repo/dai/nl/067730043; de Jongste, Johan C; Gehring, Ulrike; Postma, Dirkje S; Kerkhof, Marjan

    BACKGROUND: Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and

  20. Perceptual Contrast Enhancement with Dynamic Range Adjustment

    Science.gov (United States)

    Zhang, Hong; Li, Yuecheng; Chen, Hao; Yuan, Ding; Sun, Mingui

    2013-01-01

    Recent years, although great efforts have been made to improve its performance, few Histogram equalization (HE) methods take human visual perception (HVP) into account explicitly. The human visual system (HVS) is more sensitive to edges than brightness. This paper proposes to take use of this nature intuitively and develops a perceptual contrast enhancement approach with dynamic range adjustment through histogram modification. The use of perceptual contrast connects the image enhancement problem with the HVS. To pre-condition the input image before the HE procedure is implemented, a perceptual contrast map (PCM) is constructed based on the modified Difference of Gaussian (DOG) algorithm. As a result, the contrast of the image is sharpened and high frequency noise is suppressed. A modified Clipped Histogram Equalization (CHE) is also developed which improves visual quality by automatically detecting the dynamic range of the image with improved perceptual contrast. Experimental results show that the new HE algorithm outperforms several state-of-the-art algorithms in improving perceptual contrast and enhancing details. In addition, the new algorithm is simple to implement, making it suitable for real-time applications. PMID:24339452