WorldWideScience

Sample records for inches small active

  1. Production and cost of harvesting, processing, and transporting small-diameter (< 5 inches) trees for energy

    Science.gov (United States)

    Fei Pan; Han-Sup Han; Leonard R. Johnson; William J. Elliot

    2008-01-01

    Dense, small-diameter stands generally require thinning from below to improve fire-tolerance. The resulting forest biomass can be used for energy production. The cost of harvesting, processing, and transporting small-diameter trees often exceeds revenues due to high costs associated with harvesting and transportation and low market values for forest biomass....

  2. Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

    International Nuclear Information System (INIS)

    Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

    2011-01-01

    Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

  3. Electrocatalytic activation of small molecules

    OpenAIRE

    Liu, YuPing

    2017-01-01

    Electrochemsitry and electrocatalysis are useful techniques for energy conversion and energy storage applications. In this project, the electrocatalytic activation of small molecules, H₂O, methanol and ethanol, and CO₂, has been studied as potential methods for energy storage and conversion. A hexaniobate Lindqvist ion assisted Co and Ni nanostructure deposition method has been developed. Efficient catalytic activity towards water oxidation has been observed with high TOF values obtained ...

  4. 8-inch IBM floppy disk

    CERN Multimedia

    1971-01-01

    The 8-inch floppy disk was a magnetic storage disk for the data introduced commercially by IBM in 1971. It was designed by an IBM team as an inexpensive way to load data into the IBM System / 370. Plus it was a read-only bare disk containing 80 KB of data. The first read-write version was introduced in 1972 by Memorex and could contain 175 KB on 50 tracks (with 8 sectors per track). Other improvements have led to various coatings and increased capacities. Finally, it was surpassed by the mini diskette of 5.25 inches introduced in 1976.

  5. Ten inch Planar Optic Display

    Energy Technology Data Exchange (ETDEWEB)

    Beiser, L. [Beiser (Leo) Inc., Flushing, NY (United States); Veligdan, J. [Brookhaven National Lab., Upton, NY (United States)

    1996-04-01

    A Planar Optic Display (POD) is being built and tested for suitability as a high brightness replacement for the cathode ray tube, (CRT). The POD display technology utilizes a laminated optical waveguide structure which allows a projection type of display to be constructed in a thin (I to 2 inch) housing. Inherent in the optical waveguide is a black cladding matrix which gives the display a black appearance leading to very high contrast. A Digital Micromirror Device, (DMD) from Texas Instruments is used to create video images in conjunction with a 100 milliwatt green solid state laser. An anamorphic optical system is used to inject light into the POD to form a stigmatic image. In addition to the design of the POD screen, we discuss: image formation, image projection, and optical design constraints.

  6. 10-inch planar optic display

    Science.gov (United States)

    Beiser, Leo; Veligdan, James T.

    1996-05-01

    A planar optic display (POD) is being built and tested for suitability as a high brightness replacement for the cathode ray tube, (CRT). The POD display technology utilizes a laminated optical waveguide structure which allows a projection type of display to be constructed in a thin (1 to 2 inch) housing. Inherent in the optical waveguide is a black cladding matrix which gives the display a black appearance leading to very high contrast. A digital micromirror device, (DMD) from Texas Instruments is used to create video images in conjunction with a 100 milliwatt green solid state laser. An anamorphic optical system is used to inject light into the POD to form a stigmatic image. In addition to the design of the POD screen, we discuss: image formation, image projection, and optical design constraints.

  7. Environmental Education and Small Business Environmental Activity

    Science.gov (United States)

    Redmond, Janice; Walker, Beth

    2011-01-01

    Environmental education is seen as a key driver of small business environmental management, yet little is known about the activities small business owner-managers are undertaking to reduce their environmental impact or in what areas they may need education. Therefore, research that can identify environmental management activities being undertaken…

  8. Environmental assessment for the recycling of slightly activated copper coil windings from the 184-Inch Cyclotron at Lawrence Berkeley Laboratory, Berkeley, California

    Energy Technology Data Exchange (ETDEWEB)

    1993-08-02

    The proposed action is to recycle slightly activated copper that is currently stored in a warehouse leased by Lawrence Berkeley Laboratory (LBL) to a scrap metal dealer. Subsequent reutilization of the copper would be unrestricted. This document addresses the potential environmental effects of recycling and reutilizing the activated copper. In addition, the potential environmental effects of possible future uses by the dealer are addressed. Direct environmental effects from the proposed action are assessed, such as air emissions from reprocessing the activated copper, as well as indirect beneficial effects, such as averting air emissions that would result from mining and smelting an equivalent quantity of copper ore. Evaluation of the human health impacts of the proposed action focuses on the pertinent issues of radiological doses and protection of workers and the public. Five alternatives to the proposed action are considered, and their associated potential impacts are addressed. The no-action alternative is the continued storage of the activated copper at the LBL warehouse. Two recycling alternatives are considered: recycling the activated copper at the Scientific Ecology Group (SEG) facility for re-use at a DOE facility and selling or giving the activated copper to a foreign government. In addition, two disposal alternatives evaluate the impacts attributable to disposing of the activated copper either at a local sanitary landfill or at the Hanford Low-Level Waste Burial Site. The proposed project and alternatives include no new construction or development of new industry.

  9. Internal control activities in small Turkish companies

    Directory of Open Access Journals (Sweden)

    Ismail Bilgi

    2017-01-01

    Full Text Available The purpose of this paper is to present major outcomes from an empirical study concerning internal control activities in small Turkish companies, as to propose the improvement guidelines. Methods of analysis and synthesis, descriptive statistics, and statistical comparison were used. The collected data was processed with the help of the SPSS software. Тhe study is limited to organizations based in the European part of Turkey. Most of them operate in areas around large cities, such as Istanbul, Edirne, Kırklareli, and Tekirdağ. They employ on average 19-20 people and have a turnover of about TRY 3 million (≈€715,000, https://sdw.ecb.europa.eu on average. The survey concentrates mainly on small family businesses, which have been present on the market for more than ten years, with managers of good education and other characteristics that presuppose availability of internal control systems. The research results were used to compile main points of a SWOT analysis, as a part of the broader effort to help modernizing the internal control system in Turkish small businesses.

  10. Project W320 52-inch diameter equipment container load test: Test report

    International Nuclear Information System (INIS)

    Bellomy, J.R.

    1995-01-01

    This test report summarizes testing activities and documents the results of the load tests performed on-site and off-site to structural qualify the 52-inch equipment containers designed and fabricated under Project W-320

  11. Small business activity does not measure entrepreneurship

    Science.gov (United States)

    Henrekson, Magnus; Sanandaji, Tino

    2014-01-01

    Entrepreneurship policy mainly aims to promote innovative Schumpeterian entrepreneurship. However, the rate of entrepreneurship is commonly proxied using quantity-based metrics, such as small business activity, the self-employment rate, or the number of startups. We argue that those metrics give rise to misleading inferences regarding high-impact Schumpeterian entrepreneurship. To unambiguously identify high-impact entrepreneurs we focus on self-made billionaires (in US dollars) who appear on Forbes Magazine’s list and who became wealthy by founding new firms. We identify 996 such billionaire entrepreneurs in 50 countries in 1996–2010, a systematic cross-country study of billionaire entrepreneurs. The rate of billionaire entrepreneurs correlates negatively with self-employment, small business ownership, and firm startup rates. Countries with higher income, higher trust, lower taxes, more venture capital investment, and lower regulatory burdens have higher billionaire entrepreneurship rates but less self-employment. Despite its limitations, the number of billionaire entrepreneurs appears to be a plausible cross-country measure of Schumpeterian entrepreneurship. PMID:24449873

  12. Small business activity does not measure entrepreneurship.

    Science.gov (United States)

    Henrekson, Magnus; Sanandaji, Tino

    2014-02-04

    Entrepreneurship policy mainly aims to promote innovative Schumpeterian entrepreneurship. However, the rate of entrepreneurship is commonly proxied using quantity-based metrics, such as small business activity, the self-employment rate, or the number of startups. We argue that those metrics give rise to misleading inferences regarding high-impact Schumpeterian entrepreneurship. To unambiguously identify high-impact entrepreneurs we focus on self-made billionaires (in US dollars) who appear on Forbes Magazine's list and who became wealthy by founding new firms. We identify 996 such billionaire entrepreneurs in 50 countries in 1996-2010, a systematic cross-country study of billionaire entrepreneurs. The rate of billionaire entrepreneurs correlates negatively with self-employment, small business ownership, and firm startup rates. Countries with higher income, higher trust, lower taxes, more venture capital investment, and lower regulatory burdens have higher billionaire entrepreneurship rates but less self-employment. Despite its limitations, the number of billionaire entrepreneurs appears to be a plausible cross-country measure of Schumpeterian entrepreneurship.

  13. Broadband active electrically small superconductor antennas

    Science.gov (United States)

    Kornev, V. K.; Kolotinskiy, N. V.; Sharafiev, A. V.; Soloviev, I. I.; Mukhanov, O. A.

    2017-10-01

    A new type of broadband active electrically small antenna (ESA) based on superconducting quantum arrays (SQAs) has been proposed and developed. These antennas are capable of providing both sensing and amplification of broadband electromagnetic signals with a very high spurious-free dynamic range (SFDR)—up to 100 dB (and even more)—with high sensitivity. The frequency band can range up to tens of gigahertz, depending on Josephson junction characteristic frequency, set by fabrication. In this paper we review theoretical and experimental studies of SQAs and SQA-based antenna prototypes of both transformer and transformer-less types. The ESA prototypes evaluated were fabricated using a standard Nb process with critical current density 4.5 kA cm-2. Measured device characteristics, design issues and comparative analysis of various ESA types, as well as requirements for interfaces, are reviewed and discussed.

  14. Development and characterization of a CCD camera system for use on six-inch manipulator systems

    International Nuclear Information System (INIS)

    Logory, L.M.; Bell, P.M.; Conder, A.D.; Lee, F.D.

    1996-01-01

    The Lawrence Livermore National Laboratory has designed, constructed, and fielded a compact CCD camera system for use on the Six Inch Manipulator (SIM) at the Nova laser facility. The camera system has been designed to directly replace the 35 mm film packages on all active SIM-based diagnostics. The unit's electronic package is constructed for small size and high thermal conductivity using proprietary printed circuit board technology, thus reducing the size of the overall camera and improving its performance when operated within the vacuum environment of the Nova laser target chamber. The camera has been calibrated and found to yield a linear response, with superior dynamic range and signal-to-noise levels as compared to T-Max 3200 optic film, while providing real-time access to the data. Limiting factors related to fielding such devices on Nova will be discussed, in addition to planned improvements of the current design

  15. Small-molecule allosteric activators of sirtuins.

    Science.gov (United States)

    Sinclair, David A; Guarente, Leonard

    2014-01-01

    The mammalian sirtuins (SIRT1-7) are NAD(+)-dependent lysine deacylases that play central roles in cell survival, inflammation, energy metabolism, and aging. Members of this family of enzymes are considered promising pharmaceutical targets for the treatment of age-related diseases including cancer, type 2 diabetes, inflammatory disorders, and Alzheimer's disease. SIRT1-activating compounds (STACs), which have been identified from a variety of chemical classes, provide health benefits in animal disease models. Recent data point to a common mechanism of allosteric activation by natural and synthetic STACs that involves the binding of STACs to a conserved N-terminal domain in SIRT1. Compared with polyphenols such as resveratrol, the synthetic STACs show greater potency, solubility, and target selectivity. Although considerable progress has been made regarding SIRT1 allosteric activation, key questions remain, including how the molecular contacts facilitate SIRT1 activation, whether other sirtuin family members will be amenable to activation, and whether STACs will ultimately prove safe and efficacious in humans.

  16. Tax incentives for the economic activity of small businesses

    Directory of Open Access Journals (Sweden)

    Imanshapieva Mazika Musabekovna

    2012-08-01

    Full Text Available In article it is shown that the developed structure of the Russian small business doesn't answer problems of modernization of economy, taking into account features of subjects of small business necessity of strengthening of a role of a tax policy for regulation of their activity is given reason. The expediency of introduction in the Tax code of the Russian Federation of concepts «subjects of small business», «the small innovative enterprise» is proved. Necessity of specification of conditions and signs of reference of the organizations to subjects of small-scale business is revealed at application of the simplified system of the taxation. The expediency of change of existing approaches to formation of tax base at application of the general system of the taxation is established and recommendations about tax stimulation of economic activity of subjects of small business are offered.

  17. Small Spacecraft Active Thermal Control: Micro-Vascular Composites Enable Small Satellite Cooling

    Science.gov (United States)

    Ghosh, Alexander

    2016-01-01

    The Small Spacecraft Integrated Power System with Active Thermal Control project endeavors to achieve active thermal control for small spacecraft in a practical and lightweight structure by circulating a coolant through embedded micro-vascular channels in deployable composite panels. Typically, small spacecraft rely on small body mounted passive radiators to discard heat. This limits cooling capacity and leads to the necessity to design for limited mission operations. These restrictions severely limit the ability of the system to dissipate large amounts of heat from radios, propulsion systems, etc. An actively pumped cooling system combined with a large deployable radiator brings two key advantages over the state of the art for small spacecraft: capacity and flexibility. The use of a large deployable radiator increases the surface area of the spacecraft and allows the radiation surface to be pointed in a direction allowing the most cooling, drastically increasing cooling capacity. With active coolant circulation, throttling of the coolant flow can enable high heat transfer rates during periods of increased heat load, or isolate the radiator during periods of low heat dissipation.

  18. The Six-Inch Lunar Atlas A Pocket Field Guide

    CERN Document Server

    Spain, Don

    2009-01-01

    The Six-Inch Lunar Atlas has been designed specifically for use in the field by lunar observers so it’s perfect for fitting into an observer’s pocket! The author’s own lunar photographs were taken with a 6-inch (150mm) telescope and CCD camera, and closely match the visual appearance of the Moon when viewed through 3-inch to 8-inch telescopes. Each picture is shown oriented "as the Moon really is" when viewed from the northern hemisphere, and is supplemented by exquisite computer sketches that list the main features. Two separate computer sketches are provided to go with each photograph, one oriented to appear as seen through an SCT telescope (e.g. the Meade and Celestron ranges), the other oriented for Newtonian and refracting telescopes. Observers using the various types telescopes will find it extremely helpful to identify lunar features as the human brain is very poor at making "mirror-image" visual translations.

  19. Aerosol Research Branch (ARB) 48 inch Lidar Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The ARB_48_IN_LIDAR data set contains data collected from a 48-inch lidar system located at NASA Langley Research Center. Each granule consists of one year of data....

  20. 16 CFR 500.19 - Conversion of SI metric quantities to inch/pound quantities and inch/pound quantities to SI...

    Science.gov (United States)

    2010-01-01

    .../pound quantities and inch/pound quantities to SI metric quantities. 500.19 Section 500.19 Commercial... LABELING ACT § 500.19 Conversion of SI metric quantities to inch/pound quantities and inch/pound quantities to SI metric quantities. (a) For calculating the conversion of SI metric quantities to inch/pound...

  1. Development of 52 inches last stage blade for steam turbines

    International Nuclear Information System (INIS)

    Suzuki, Atsuhide; Hisa, Shoichi; Nagao, Shinichiro; Ogata, Hisao

    1986-01-01

    The last stage blades of steam turbines are the important component controlling the power output and performance of plants. In order to realize a unit of large capacity and high efficiency, the proper exhaust area and the last stage blades having good performance are indispensable. Toshiba Corp. has completed the development of the 52 inch last stage blades for 1500 and 1800 rpm steam turbines. The 52 inch last stage blades are the longest in the world, which have the annular exhaust area nearly 1.5 times as much as that of 41 inch blades used for 1100 MW, 1500 rpm turbines in nuclear power stations. By adopting these 52 inch blades, the large capacity nuclear power plants up to 1800 MW can be economically constructed, the rate of heat consumption of 1350 MW plants is improved by 3 ∼ 4 % as compared with 41 inch blades, and in the plants up to 1100 MW, LP turbines can be reduced from three sets to two. The features of 52 inch blades, the flow pattern and blade form design, the structural strength analysis and the erosion withstanding property, and the verification by the rotation test of the actual blades, the performance test using a test turbine, the vibration analysis of the actually loaded blades and the analysis of wet steam behavior are reported. (Kako, I.)

  2. High Performance Activity Practices in Small Firms in Romania

    Directory of Open Access Journals (Sweden)

    Gabriela ŢUŢUEANU

    2014-12-01

    Full Text Available High Performance Activity Practices in Small Firms in Romania Abstract: High performance activity practices (HPAPs are human resource management activities aimed at stimulating employee and organisational performance. The application of HPAPs is not widespread in small organisations. We examine whether the implementation of coherent bundles of HPAPs (aimed at employee ability, employee motivation or at the opportunity to perform depends on the scarcity of resources, as reflected in the size of the company, and on strategic decision-making in small firms related to the owner’s expertise and attitudes. In our research, a total of 224 employees from 50 small organisations were asked to rate the presence of HPAPs in their organisation. These averaged perceptions were linked to information provided by the owner–managers on the size of their firm and their own expertise and attitudes. The findings support that smaller but coherent bundles of HPAPs can be found in small organisations and that the implementation of these bundles depends on available resources, strategic decision-making and the combination of the two. These findings highlight the need to integrate the notions of resource poverty and strategic decision-making to understand the uptake of bundles of HPAPs within small firms.

  3. Tax Support of Small Enterprises Activity in Ukraine

    Directory of Open Access Journals (Sweden)

    Pronoza Pavlo V

    2015-03-01

    Full Text Available The purpose of the article is to evaluate the importance of small enterprises for the economic development of Ukraine and determine priorities of their stimulation. The analysis of quantitative indicators of small businesses and their comparison with the average level of all enterprises in Ukraine as a whole allowed evaluating their importance in the development of the country. There has been identified a special role of small enterprises in Ukraine’s economy and confirmed the expediency of using tax regulation instruments aimed at their development. There was identified an insufficient efficiency level of tax regulation of small businesses in Ukraine due to using a simplified system of taxation, accounting and reporting. The basic tools used in the framework of tax regulation of small enterprises activities in international practice have been determined. Additional analysis of performance of small enterprises by types of economic activity on the basis of an integrated assessment permitted to identify priorities of using tax regulation instruments in Ukraine.

  4. Relevant Factors of Innovative Activities of Small Business in Regions

    Directory of Open Access Journals (Sweden)

    Yelena Davidovna Vaysman

    2015-12-01

    Full Text Available The article discusses the system analysis aimed to identify the key reasons for the low innovation activity in the regions of the Russian Federation. The research is based on the hypothesis according to which the holism and systematic principles need to be applied for analyzing the reasons of the low innovative activity of small business in the regions,. To implement these principles, the authors have used the concept of «minimum number of descriptive levels of socio-economic system». In the research, the spiritual and cultural, cognitive, institutional, material and technological «layers» of the socio-economic system are investigated. The particular attention is paid to the cognitive and institutional segments. The methodological basis of the research is the methods of correlation and regression analysis, maps of positioning, integrated assessment, the author’s method of assessing the development of the knowledge-based economy and clustering. The quality of innovative small firms’ institutional environment is assessed using the resource approach. The authors have obtained the following results. The rate of demand growth for knowledge in the regions exceeded the growth rate of the regional offers of knowledge, including the innovative development of small businesses. A delayed reaction of the suppliers of innovative ideas to the corresponding demand is showed. The trend of differentiation increase of the Russian regions in terms of the knowledge-based economy’s development is revealed. A significant linear correlation of small firms’ innovative activities and the quality of institutional environment haven’t been discovered. It is shown that the regions are almost similar in the quality of basic socio-economic institutions, and more than 60 % of the regions have the intensity of small businesses’ innovation processes below the national average level. The obtained results allow to expand the scientific and methodological basis to

  5. The activation analysis of gold in small refractory pebbles

    International Nuclear Information System (INIS)

    Bibby, D.M.; Chaix, R.P.

    1975-08-01

    The gold content of a suite of small pebbles, residual to the milling and leach of a gold bearing ore, has been investigated by means of neutron activation analysis (NAA). An NAA technique presenting a sensitivity of 0.02μgm gold, was used as being appropriate to the samples under investigation. An alternative NAA technique developed with the same sample suite showed a sensitivity of the order of 10 -4 to 10 -5 μgm gold. The NAA techniques developed, are appropriate to the determination of gold in small samples of ore not normally amenable to milling and/or dissolution

  6. A synopsis of experimental activities on small-break LOCA

    International Nuclear Information System (INIS)

    Hein, D.

    1984-01-01

    Through reactor safety studies like WASH 1400 or the ''Deutsche Risiko-Studie'' the attention has turned from large break loss of coolant accidents to small breaks because of the high contribution of this type of accidents to core meltdown. But only after the TMI-2 accident were also the main activities in the experimental fields shifted world-wide to the small break LOCAs. Since TMI numerous research programs have either been finished or are underway. This review paper presents: a classification of the various types of transients according to break size; a discussion of major physical phenomena associated with a small break LOCA, and a description of a few selected research programs and the most important results achieved. (author)

  7. Health physics challenges involved with opening a "seventeen-inch" concrete waste vault.

    Science.gov (United States)

    Sullivan, Patrick T; Pizzulli, Michelle

    2005-05-01

    This paper describes the various activities involved with opening a sealed legacy "Seventeen-inch" concrete vault and the health physics challenges and solutions employed. As part of a legacy waste stream that was removed from the former Hazardous Waste Management Facility at Brookhaven National Laboratory, the "Seventeen-inch" concrete vault labeled 1-95 was moved to the new Waste Management Facility for ultimate disposal. Because the vault contained 239Pu foils with a total activity in excess of the transuranic waste limits, the foils needed to be removed and repackaged for disposal. Conventional diamond wire saws could not be used because of facility constraints, so this project relied mainly on manual techniques. The planning and engineering controls put in place enabled personnel to open the vault and remove the waste while keeping dose as low as reasonably achievable.

  8. A small-RNA enhancer of viral polymerase activity.

    Science.gov (United States)

    Perez, Jasmine T; Zlatev, Ivan; Aggarwal, Shilpa; Subramanian, Sailakshmi; Sachidanandam, Ravi; Kim, Baek; Manoharan, Muthiah; tenOever, Benjamin R

    2012-12-01

    Influenza A virus (IAV) is an unremitting virus that results in significant morbidity and mortality worldwide. Key to the viral life cycle is the RNA-dependent RNA polymerase (RdRp), a heterotrimeric complex responsible for both transcription and replication of the segmented genome. Here, we demonstrate that the viral polymerase utilizes a small RNA enhancer to regulate enzymatic activity and maintain stoichiometric balance of the viral genome. We demonstrate that IAV synthesizes small viral RNAs (svRNAs) that interact with the viral RdRp in order to promote genome replication in a segment-specific manner. svRNAs localize to the nucleus, the site of IAV replication, are synthesized from the positive-sense genomic intermediate, and interact within a novel RNA binding channel of the polymerase PA subunit. Synthetic svRNAs promote polymerase activity in vitro, while loss of svRNA inhibits viral RNA synthesis in a segment-specific manner. Taking these observations together, we mechanistically define svRNA as a small regulatory enhancer RNA, which functions to promote genome replication and maintain segment balance through allosteric modulation of polymerase activity.

  9. Active Learning on Large and Small Scales in Astronomy Courses

    Science.gov (United States)

    Craig, M. W.

    2005-05-01

    Experience using active learning techniques in astronomy courses of a range of scales will be described. They range from large (120 students per lecture) introductory astronomy courses on Solar System and Stellar astronomy to a small (10-15 students) course on cosmology. The primary audience of each course is non-science majors fulfilling a liberal studies requirement. In the large courses the use of Peer Instruction will be described. Several variations on the technique, which essentially involves asking students to respond to multiple choice questions during class by voting, will be presented. Assessment data based on pre- and post-testing of students using the Astronomy Diagnostic Test will be discussed. In the small cosmology course an overview will be given of a workshop approach to the course. The intent was to limit lecture and instead spend most class time doing activities. Representative activities and suggestions for future directions will be included. Some of the activities described in this poster were supported by a grant from the Minnesota State Colleges and Universities Center for Teaching and Learning.

  10. Small business support of youth physical activity opportunities.

    Science.gov (United States)

    Suminski, Richard R; Ding, Ding

    2012-01-01

    Describe small business support for youth physical activity opportunities (YPAO) and identify factors associated with this support. Cross-sectional analysis of quantitative data relating business characteristics and support for YPAO. Eight demographically heterogeneous, urban neighborhoods in a Midwest metropolitan area. Adult small business owners (n = 90; 65% response rate; mean age 48.4 years; 73.3% male; 45.2% minority). Neighborhood demographics from the 2000 U.S. Census and self-reported business and owner characteristics. Multivariate analysis of variance was used to contrast business and owner characteristics between businesses that did and did not support YPAO. Businesses supporting YPAO had larger annual operating (F = 7.6; p = .018) and advertising budgets (F = 8.5; p = .009) and had younger owners (F = 6.1; p = .034), with sports backgrounds (χ(2) = 5.6; p = .018) and who felt businesses should support YPAO (χ(2) = 3.8; p = .048). Of the 46 businesses not supporting YPAO, 82.6% felt small businesses should support YPAO. The major reasons for nonsupport were difficulty identifying YPAO to support and not being asked for support. Business (e.g., budgets) and business owner characteristics (e.g., age), owner connectedness with YPAO, and the approach used for garnering support (active solicitation, clearly defined support mechanism) were associated with supporting YPAO. Additional business (e.g., annual revenues), owner (e.g., perceptions of YPAO), and environmental (e.g., crime rate, land use) factors should be examined as potential correlates.

  11. Nanomanipulation of 2 inch wafer fabrication of vertically aligned carbon nanotube arrays by nanoimprint lithography

    DEFF Research Database (Denmark)

    Bu, Ian Y. Y.; Eichhorn, Volkmar; Carlson, Kenneth

    2011-01-01

    Carbon nanotube (CNT) arrays are typically defined by electron beam lithography (EBL), and hence limited to small areas due to the low throughput. To obtain wafer‐scale fabrication we propose large area thermal nanoimprint lithography (NIL). A 2‐inch stamp master is defined using EBL for subsequent......, efficient production of wafer‐scale/larger arrays of CNTs has been achieved. The CNTs have been deposited by wafer‐scale plasma enhanced chemical vapour deposition (PECVD) of C2H2/NH3. Substrates containing such nanotubes have been used to automate nanorobotic manipulation sequences of individual CNTs...

  12. Small Molecule Inhibitors Targeting Activator Protein 1 (AP-1)

    Science.gov (United States)

    2015-01-01

    Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases. PMID:24831826

  13. Small azobenzene derivatives active against bacteria and fungi.

    Science.gov (United States)

    Piotto, Stefano; Concilio, Simona; Sessa, Lucia; Porta, Amalia; Calabrese, Elena Concetta; Zanfardino, Anna; Varcamonti, Mario; Iannelli, Pio

    2013-10-01

    ATP synthase and protein kinase (PKs) are prime targets for drug discovery in a variety of diseases. It is well known that numerous stilbenes are capable to interact and inhibit ATP synthase and PKs. This work focuses on a series of azobenzene based molecules having high structural similarity with antimicrobial stilbenes. An investigation was carried out analyzing the potential toxicity of a large set of molecules by means of computational analysis. A small selection of potential low toxic molecules have been therefore synthesized, characterized and finally microbiologically tested. The synthesized compounds show potent bactericidal activity against Gram+ and a fungus, and are capable of inhibiting biofilm formation. Finally, the compounds demonstrated a thermal stability that makes them potential candidates for incorporation in polymer matrix for application as biomedical devices and food packaging. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Production of medical radioisotopes in ORNL 86-Inch Cyclotron

    International Nuclear Information System (INIS)

    Skidmore, M.R.

    1975-01-01

    Procedures, targets, and costs are discussed for the production of iodine-123 at the ORNL 86-Inch Cyclotron. The cyclotron is a fixed frequency machine producing 22-MeV proton beams with currents of 3 mA. Flat plate targets are used in the bombardment of readily fabricated metals when highest production rates are necessary, while capsule targets are used when flat plate coatings are difficult or when high production rates are not required. Window targets with metal foils or powders, inorganic compounds, or isotopically enriched materials are also used. (PMA)

  15. Synthesis of molecular complexes for small molecule activation

    International Nuclear Information System (INIS)

    Andrez, Julie

    2016-01-01

    The redox chemistry of f-elements is drawing the attention of inorganic chemists due to their unusual reaction pathways. Notably low-valent f-element complexes have been shown to be able to activate small molecules such as CO 2 and N 2 in mild conditions. Compared to d-block metals, f-elements present a coordination chemistry dominated by electrostatic interactions and steric constraints. Molecular complexes of f-elements could thus provide new catalytic routes to transform small molecules into valuable chemicals. However the redox chemistry of low valent f-elements is dominated by single-electron transfers while the reductions of CO 2 and N 2 require multi-electronic processes. Accordingly the first approach of this PhD work was the use of redox active ligands as electron reservoir to support f-element centres increasing the electron number available for reduction events. The coordination of uranium with tridentate Schiff base ligand was investigated and led to isolation of a dinuclear electron-rich species able to undertake up to eight-electron reduction combining the redox activity of the ligands and the uranium centres. In order to obtain electron-rich compounds potentially able to polarize the C=O bond of CO 2 , the synthesis of hetero-bimetallic species supported by salophen Schiff base ligand was also studied. In a second approach we have used bulky ligands with strong donor-character to tune the reducing abilities of low valent f-elements. In this case a bimolecular electron-transfer process is often observed. The reactivity of the U(III) siloxid complex [U(OSi(OtBu) 3 ) 4 K] was further investigated. Notably, reaction with Ph 3 PS led to the formation of a terminal U(IV) sulfide complex with multiple U-S bond which was analysed by DFT studies to better understand the bonding nature. Preliminary studies on the role of the counter-cation (M) in the system [U(OSi(OtBu) 3 ) 4 M] on the outcome of the reactivity with CS 2 and CO 2 have also been performed. The

  16. Kinetics of small particle activation in supersaturated vapors

    Energy Technology Data Exchange (ETDEWEB)

    McGraw, R.; Wang, J.

    2010-08-29

    We examine the nucleated (with barrier) activation of perfectly wetting (zero contact angle) particles ranging from bulk size down to one nanometer. Thermodynamic properties of the particles, coated with liquid layers of varying thickness and surrounded by vapor, are analyzed. Nano-size particles are predicted to activate at relative humidity below the Kelvin curve on crossing a nucleation barrier, located at a critical liquid layer thickness such that the total particle size (core + liquid layer) equals the Kelvin radius (Fig. 1). This barrier vanishes precisely as the critical layer thickness approaches the thin layer limit and the Kelvin radius equals the radius of the particle itself. These considerations are similar to those included in Fletcher's theory (Fletcher, 1958) however the present analysis differs in several important respects. Firstly, where Fletcher used the classical prefactor-exponent form for the nucleation rate, requiring separate estimation of the kinetic prefactor, we solve a diffusion-drift equation that is equivalent to including the full Becker-Doering (BD) multi-state kinetics of condensation/evaporation along the growth coordinate. We also determine the mean first passage time (MFPT) for barrier crossing (Wedekind et al., 2007), which is shown to provide a generalization of BD nucleation kinetics especially useful for barrier heights that are considerably lower than those typically encountered in homogeneous vapor-liquid nucleation, and make explicit comparisons between the MFPT and BD kinetic models. Barrier heights for heterogeneous nucleation are computed by a thermo-dynamic area construction introduced recently to model deliquescence and efflorescence of small particles (McGraw and Lewis, 2009). In addition to providing a graphical representation of the activation process that offers new insights, the area construction provides a molecular approach that avoids explicit use of the interfacial tension. Typical barrier profiles for

  17. Selecting Patients With Small Renal Masses For Active Surveillance.

    Science.gov (United States)

    Johnson, Michael H; Allaf, Mohamad E; Pierorazio, Phillip M

    2017-11-13

    The incidentally discovered, clinically-localized, small renal mass (clinical stage T1aN0M0, ≤4cm) is the most commonly diagnosed entity in renal cell carcinoma (RCC) - now accounting for at least 40% of newly diagnosed renal tumors. Given the above argument, active surveillance (AS) has emerged as a viable management strategy for SRM. This review will examine and discuss the existing literature regarding selection criteria for AS. AS of clinical T1a renal masses is emerging as a safe and effective management strategy in selected patients, yet appropriate patient selection and counseling remains an area of great interest. Long-term clinical outcomes are just beginning to be reported, thus much of the supporting evidence on AS and patient selection is based on retrospective data of heterogeneous quality. Nevertheless, there are certain conclusions that can be a made, despite these current limitations. First, appropriate selection of candidates should include a comprehensive evaluation of competing health risks, tumor characteristics, and patient preferences. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Studies Relevent to Catalytic Activation Co & other small Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Ford, Peter C

    2005-02-22

    Detailed annual and triannual reports describing the progress accomplished during the tenure of this grant were filed with the Program Manager for Catalysis at the Office of Basic Energy Sciences. To avoid unnecessary duplication, the present report will provide a brief overview of the research areas that were sponsored by this grant and list the resulting publications and theses based on this DOE supported research. The scientific personnel participating in (and trained by) this grant's research are also listed. Research carried out under this DOE grant was largely concerned with the mechanisms of the homogeneous catalytic and photocatalytic activation of small molecules such as carbon monoxide, dihydrogen and various hydrocarbons. Much of the more recent effort has focused on the dynamics and mechanisms of reactions relevant to substrate carbonylations by homogeneous organometallic catalysts. A wide range of modern investigative techniques were employed, including quantitative fast reaction methodologies such as time-resolved optical (TRO) and time-resolved infrared (TRIR) spectroscopy and stopped flow kinetics. Although somewhat diverse, this research falls within the scope of the long-term objective of applying quantitative techniques to elucidate the dynamics and understand the principles of mechanisms relevant to the selective and efficient catalytic conversions of fundamental feedstocks to higher value materials.

  19. Remote target removal for the Oak Ridge 86-inch Cyclotron

    International Nuclear Information System (INIS)

    Walls, A.A.

    1982-01-01

    A remotely operated target remover has been plaed in operation at the 86-Inch Cyclotron located in Oak Ridge. The system provides for the remote removal of a target from inside the cyclotron, loading it into a cask, and the removal of the cask from the 1.5 m (5-ft) shielding walls. The remote system consists of multiple electrical and pneumatically operated equipment which is designed for controlled step-by-step operation, operated with an electrical control panel, and monitored by a television system. The target remover has reduced the radiation exposures to operating personnel at the facility and has increased the effective operating time. The system is fast, requires a minimum of skill to operate, and has demonstrated both reliability and durability

  20. Seismic fragility test of a 6-inch diameter pipe system

    International Nuclear Information System (INIS)

    Chen, W.P.; Onesto, A.T.; DeVita, V.

    1987-02-01

    This report contains the test results and assessments of seismic fragility tests performed on a 6-inch diameter piping system. The test was funded by the US Nuclear Regulatory Commission (NRC) and conducted by ETEC. The objective of the test was to investigate the ability of a representative nuclear piping system to withstand high level dynamic seismic and other loadings. Levels of loadings achieved during seismic testing were 20 to 30 times larger than normal elastic design evaluations to ASME Level D limits would permit. Based on failure data obtained during seismic and other dynamic testing, it was concluded that nuclear piping systems are inherently able to withstand much larger dynamic seismic loadings than permitted by current design practice criteria or predicted by the probabilistic risk assessment (PRA) methods and several proposed nonlinear methods of failure analysis

  1. 78 FR 45051 - Small Business Size Standards; Support Activities for Mining; Correction

    Science.gov (United States)

    2013-07-26

    ... Industry Classification System (NAICS) Subsector 213, Support Activities for Mining, that are based on... SMALL BUSINESS ADMINISTRATION 13 CFR Part 121 RIN 3245-AG44 Small Business Size Standards; Support Activities for Mining; Correction AGENCY: U.S. Small Business Administration. ACTION: Final rule; correction...

  2. Posture manipulation for rescue activity via small traction robots

    International Nuclear Information System (INIS)

    Iwano, Yuki; Osuka, Koichi; Amano, Hisanori

    2006-01-01

    We discuss a conceptual design of rescue robots against nuclear-power plant accidents. We claim that the rescue robots in nuclear-power plants should have the following properties. (1) The size is small. (2) The structure is simple. (3) The number of the robots is large. This paper studies the rescue robots to rescue people in an area polluted with radioactive leakage in nuclear power institutions. In particular, we propose a rescue system which consists of a group of small mobile robots. First, small traction robots set the posture of the fainted victims to carry easily, and carry them to the safety space with the mobile robots for the stretcher composition. In this paper, we describe the produced small traction robots. And, we confirm that the robots can manipulate a 40 kg dummy doll's posture. We also examine the optimal number of robots from a perspective of working efficiency in the assumption spot. (author)

  3. Enhancing Leadership Abilities through Small-Group Activities.

    Science.gov (United States)

    Parise, James; Culp, William

    1988-01-01

    The article describes a 14-week program (one hour per week) of the Punxsutawney (Pennsylvania) schools in which 29 gifted high school students learned and practiced fundamentals of small group dynamics to enhance their leadership abilities. (DB)

  4. Small hydro takes stock of a dozen years of activity

    International Nuclear Information System (INIS)

    Leutwiler, H.

    2000-01-01

    This short article discusses a survey that takes stock of the investments made in small hydro schemes in Switzerland since 1985 and the structural changes in this area that have occurred. Typical figures are given for investments and the increase in energy production that have resulted. The various possibilities for the realisation of small hydro installations are discussed including pressure-reduction turbines, the use of turbines in drinking water and wastewater systems. The importance of the sale of the electricity thus generated as 'green' power is noted. The potential of this form of electricity generation in a liberalised electricity market and the obstacles placed in its way are discuss

  5. Advanced Power Technology Development Activities for Small Satellite Applications

    Science.gov (United States)

    Piszczor, Michael F.; Landis, Geoffrey A.; Miller, Thomas B.; Taylor, Linda M.; Hernandez-Lugo, Dionne; Raffaelle, Ryne; Landi, Brian; Hubbard, Seth; Schauerman, Christopher; Ganter, Mathew; hide

    2017-01-01

    NASA Glenn Research Center (GRC) has a long history related to the development of advanced power technology for space applications. This expertise covers the breadth of energy generation (photovoltaics, thermal energy conversion, etc.), energy storage (batteries, fuel cell technology, etc.), power management and distribution, and power systems architecture and analysis. Such advanced technology is now being developed for small satellite and cubesat applications and could have a significant impact on the longevity and capabilities of these missions. A presentation during the Pre-Conference Workshop will focus on various advanced power technologies being developed and demonstrated by NASA, and their possible application within the small satellite community.

  6. Experimental verification of the control mechanism of marketing activities of small consulting organization

    OpenAIRE

    Kirushkin, A. A.

    2013-01-01

    This article contains results of testing the new mechanism of managing marketing activity of a small consulting organization, proposed in the previous author’s article (see Journal Marketing MBA, 2013, issue 1). The testing was done with computer simulating the organization’s activity with several initial data. The simulations have given recommendations on managing marketing activity of small consulting organizations.

  7. Scaffolding of small groups’ metacognitive activities with an avatar

    NARCIS (Netherlands)

    Molenaar, I.; Chiu, M.M.; Sleegers, P.; van Boxtel, C.A.M.

    2011-01-01

    Metacognitive scaffolding in a computer-supported learning environment can influence students’ metacognitive activities, metacognitive knowledge and domain knowledge. In this study we analyze how metacognitive activities mediate the relationships between different avatar scaffolds on students’

  8. New small-size peptides possessing antifungal activity

    NARCIS (Netherlands)

    Garibotto, Francisco M.; Garro, Adriana D.; Masman, Marcelo F.; Rodriguez, Ana M.; Luiten, Paul G. M.; Raimondi, Marcela; Zacchino, Susana A.; Somlai, Csaba; Penke, Botond; Enriz, Ricardo D.

    2010-01-01

    The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using

  9. Small angle neutron scattering in surface-active agents mixtures

    Science.gov (United States)

    Bulavin, L. A.; Garamus, V. M.; Ostanevich, Yu. M.

    The method of study of micelle structure by small angle neutron scattering is studied. The determination of maximum size, radius of gyration, average scattering density of micelles is presented. The way of study of distribution of scattering density in micelle is described. The problem of micelles interaction is discussed.

  10. Development of 8-inch Key Processes for Insulated-Gate Bipolar Transistor

    Directory of Open Access Journals (Sweden)

    Guoyou Liu

    2015-09-01

    Full Text Available Based on the construction of the 8-inch fabrication line, advanced process technology of 8-inch wafer, as well as the fourth-generation high-voltage double-diffused metal-oxide semiconductor (DMOS+ insulated-gate bipolar transistor (IGBT technology and the fifth-generation trench gate IGBT technology, have been developed, realizing a great-leap forward technological development for the manufacturing of high-voltage IGBT from 6-inch to 8-inch. The 1600 A/1.7 kV and 1500 A/3.3 kV IGBT modules have been successfully fabricated, qualified, and applied in rail transportation traction system.

  11. Small Spacecraft Integrated Power System with Active Thermal Control

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop an integrated power generation and energy storage system with an active thermal management system. Carbon fiber solar panels will contain...

  12. Lowell Observatory's 24-inch Clark Refractor: Its History and Renovation

    Science.gov (United States)

    Schindler, Kevin; Nye, Ralph; Rosenthal, Peter

    2016-01-01

    In 1895, Percival Lowell hired eminent telescope maker Alvan G. Clark to build a 24-inch refractor. Lowell intended the telescope intitally for observing Mars in support of his controversial theories about life on that planet. Clark finished the telescope within a year and at a cost of $20,000. Lowell and his staff of assistants and astronomers began observing through it on July 23, 1896, setting off a long and productive career for the telescope.While Lowell's Mars studies dominated early work with the Clark, V.M. Slipher by the 1910s was using it to observe planetary rotations and atmospheric compositions. He soon revolutionized spectroscopic studies, gathering excruciatingly long spectra - some in excess of 40 hours - of the so-called white nebula and determining startling radial velocities, evidence of an expanding universe. In the 1960s, scientists and artists teamed up on the Clark and created detailed lunar maps in support of the Apollo program.In recent decades, the Clark has played a central role in the education programs at Lowell, with general public audiences, students, and private groups all taking advantage of this unique resource.With this nearly 120 years of contant use, the Clark had been wearing down in recent years. The telescope was becoming more difficult to move, old electrical wiring in the dome was a fire hazard, and many of the telescope's parts needed to be repaired or replaced.In 2013, Lowell Observatory began a fundraising campaign, collecting $291,000 to cover the cost of dome and telescope renovation. Workers removed the entire telescope mount and tube assembly from the dome, examining every part from tube sections to individuals screws. They also stabilized the dome, adding a water vapor barrier and new outer wall while reinforcing the upper dome. The project lasted from January, 2014 through August, 2015. The facility reopened for daytime tours in September, 2015 and evening viewing the following month.

  13. Modeling large scale cohesive sediment transport affected by small scale biological activity

    NARCIS (Netherlands)

    Borsje, Bastiaan Wijnand; de Vries, Mindert; Hulscher, Suzanne J.M.H.; de Boer, Gerben J.

    2008-01-01

    Biological activity on the bottom of the seabed is known to have significant influence on the dynamics of cohesive sediment on a small spatial and temporal scale. In this study, we aim to understand the large-scale effects of small-scale biological activity. Hereto, effects of biology are

  14. Methodological foundations of evaluation of effectiveness indicators of small-scale business activities

    Directory of Open Access Journals (Sweden)

    Ivanova T.

    2013-01-01

    Full Text Available The methodological approach to the measurement of financial indicators of small-scale enterprises has been developed. It enables to secure the comparability of financial condition indicators and the results of small-scale enterprise activities, and also to develop the methods of vertical integral estimate calculation at separate aspects of financial condition and the results of smallscale enterprise activities.

  15. FDG gamma camera PET equipped with one inch crystal and XCT. Assessment of myocardial viability

    Energy Technology Data Exchange (ETDEWEB)

    Beheshti, M. [Dept. of Nuclear Medicine, Medical Univ., General Hospital of Vienna (Austria); Dept. of Nuclear Medicine and Endocrinology, PET CT Centre, St. Vincent' s Hospital, Linz (Austria); Khorsand, A.; Graf, S. [Dept. of Cardiology, Medical Univ., General Hospital of Vienna (Austria); Dobrozemsky, G. [Dept. of Nuclear Medicine, Medical Univ. of Innsbruck (Austria); Oezer, S.; Kletter, K.; Dudczak, R. [Dept. of Nuclear Medicine, Medical Univ., General Hospital of Vienna (Austria); Pirich, C. [Dept. of Nuclear Medicine und Endocrinology, Paracelsus Private Medical Univ., SALK, Salzburg (Austria)

    2006-07-01

    Metabolic imaging with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) is actually considered as the best method to detect and quantitatively assess myocordial tissue viability. The aim of this study was to investigate the accuracy of FDG gamma camera positron emission tomography (GCPET) imaging equipped with one inch NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a ''gold standard'' in phantom and clinical studies. Patients, methods: nineteen patients with coronary artery disease (CAD) underwent both imaging modalities. Phantom and clinical GCPET imaging were performed with a dual-headed, coincidence based gamma camera equipped with 1 inch thick NaI crystals and an X-ray tube (XCT) for attenuation correction (AC), as well as with a dedicated PET scanner with AC. {sup 99m}Tc tetrofosmin single-photon emission tomography (SPET) studies were performed for assessment of myocardial perfusion, with AC. Results: phantom studies showed a significant relation in segmental activity between FDG imaging with AC using GCPET and dPET (r = 0.91, p < 0.001). In clinical studies with AC correlation coefficients of mean segmental FDG uptake and regional defect size were r = 0.87 (p < 0.0001) and r = 0.83 (p < 0.0001), respectively. In regional analysis close agreement was even found in the most attenuated regions of the heart if AC was used in GCPET imaging. The overall agreement for detection of viable myocardium was 81% between FDG-dPET (AC) and FDG-GCPET (AC) and 74% between FDG-dPET (AC) and FDG-GCPET (NC). Conclusions: suggests that the assessment of myocardial metabolism by means of FDG is feasible with a coincidence based gamma camera equipped with 1 inch thick NaI crystal if AC is performed. The results reveal a close concordance and agreement between FDG-dPET (AC) and FDG-GCPET (AC) as compared to FDG-GCPET (NC). (orig.)

  16. 16 CFR 460.20 - R-value per inch claims.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false R-value per inch claims. 460.20 Section 460.20 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.20 R-value per inch claims. In labels, fact sheets, ads, or other promotional...

  17. Orthopedic stretcher with average-sized person can pass through 18-inch opening

    Science.gov (United States)

    Lothschuetz, F. X.

    1966-01-01

    Modified Robinson stretcher for vertical lifting and carrying, will pass through an opening 18 inches in diameter, while containing a person of average height and weight. A subject 6 feet tall and weighing 200 pounds was lowered and raised out of an 18 inch diameter opening in a tank to test the stretcher.

  18. Torque expression of 0.018 and 0.022 inch conventional brackets

    NARCIS (Netherlands)

    Sifakakis, I.; Pandis, N.; Makou, M.; Eliades, T.; Katsaros, C.; Bourauel, C.

    2013-01-01

    The aim of this study was to assess the effect of the moments generated with low- and high-torque brackets. Four different bracket prescription-slot combinations of the same bracket type (Mini Diamond(R) Twin) were evaluated: high-torque 0.018 and 0.022 inch and low-torque 0.018 and 0.022 inch.

  19. Comparison of silicon strip tracker module size using large sensors from 6 inch wafers

    CERN Multimedia

    Honma, Alan

    1999-01-01

    Two large silicon strip sensor made from 6 inch wafers are placed next to each other to simulate the size of a CMS outer silicon tracker module. On the left is a prototype 2 sensor CMS inner endcap silicon tracker module made from 4 inch wafers.

  20. Test procedure for the Master-Lee and the modified Champion four inch hydraulic cutters

    International Nuclear Information System (INIS)

    Crystal, J.B.

    1995-01-01

    The Master-Lee and the modified Champion 4 Inch hydraulic cutters are being retested to gather and document information related to the following: determine if the Master-Lee cutters will cut the trunnions of an Aluminum fuel canister and a Stainless Steel fuel canister; determine if the Master-Lee cutters will cut 1 1/2 inch diameter fire hose; determine if the modified Champion 4 inch blade will cut sections of piping; and determine the effectiveness of the centering device for the Champion 4 Inch cutters. Determining the limitations of the hydraulic cutter will aid in the process of debris removal in the K-Basin. Based on a previous test, the cutters were returned to the manufacturer for modifications. The modifications to the Champion 4 Inch Cutter and further testing of the Master-Lee Cutter are the subjects of these feature tests

  1. Bank finance and export activities of Small and Medium Enterprises

    Directory of Open Access Journals (Sweden)

    Joshua Yindenaba Abor

    2014-12-01

    Full Text Available This study examines SMEs’ access to bank finance and how that affects their export activities. The study adopts a probit model to assess the empirical relations. The findings of the study suggest that SME access to bank finance improves their likelihood to export. Such finance is critical to cater for the high fixed costs of exporting, international marketing and branding, and meeting higher quality standards required for overseas markets. The results of the study also indicate that older firms, more productive firms, and larger firms are more likely to take the important step of entering into the export market. Policy interventions should therefore be directed at reducing the bottlenecks that prevent SMEs from accessing funding from the commercial banks.

  2. Low-cost activation analysis at small research reactors

    CERN Document Server

    Westphal, G P; Lemmel, H; Niedermaier, M R; Joestl, K; Schröder, P; Böck, H H; Schachner, H; Klapfer, E

    2003-01-01

    A software implementation of a loss-free counting multichannel analyzer, storing immediately into the multimegabyte memory of a low-cost 486 or Pentium type PC, enables the real-time control of a rabbit system as well as the collection of up to 1000 pairs of simultaneously recorded loss-corrected and non-corrected spectra of 16 k channels each, in a true sequence without time gaps in between, at throughput rates of up to 200 kc/s. Intended for activation analysis of short-lived isomeric transitions, the system renders possible peak to background optimizations and separations of lines with different half-lives without an a priori knowledge of sample composition by summing up appropriate numbers of spectra over appropriate intervals of time. By automatically adapting the noise filtering time to individual pulse intervals, the Preloaded Digital Filter (PLDF) combines low- to medium-rate resolutions comparable to those of high-quality Gaussian amplifiers with throughput rates of up to 100 kc/s, and high-rate reso...

  3. Environmental guidelines for small-scale activities in Africa: Environmentally sound design for planning and implementing development activities

    OpenAIRE

    USAID

    2007-01-01

    Metadata only record These guidelines were developed to help USAID and its partners meet the challenges posed by the need for environmentally sound design (ESD) in small-scale activities. Specifically, this book is:

  4. Small activating RNA restores the activity of the tumor suppressor HIC-1 on breast cancer.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available HIC-1 is a gene that is hypermethylated in cancer, and commonly downregulated in human breast cancer. However, the precise mechanisms and molecular pathways regulated by HIC-1 remain unclear. We assessed HIC-1 expression on a tissue microarray containing 80 cases of breast cancer. We also analyzed its biological function by restoring HIC-1 expression using 5-aza-2' deoxycytidine (5-CdR and small-activating RNAs for the reversal of HIC-1 tumor suppressive effects on MCF-7 and MDA-MB-231 cell lines. An Agilent Q44h global expressing microarray was probed after restoring the expression of HIC-1. Data demonstrated that HIC-1 expression was reduced significantly in breast cancer tissues. HIC-1 immunohistochemistry resulted in mean staining scores in cancer tissue and normal ductal epithelia of 3.54 and 8.2, respectively (p<0.01. 5-CdR partially reversed HIC-1 expression, and modulated cell growth and apoptosis. dsHIC1-2998, an saRNA, showed activating efficacy in breast cancer cells. A group of differentially expressed genes were characterized by cDNA microarray. Upon saRNA treatment, genes upregulated included those involved in immune activation, cell cycle interference, the induction of apoptosis, anti-metastasis, and cell differentiation. Downregulated genes included oncogenes and those that play roles in cell invasion, cell growth, and cell division. Our findings may provide valuable resources not only for gene functional studies, but also for potential clinical applications to develop novel drug targets.

  5. Closed Loop Control of Active Damped Small DC-link Capacitor Based Drive

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig

    2010-01-01

    A new method of active damping for small DC-link capacitor based drive system is implemented in stator flux oriented control for an induction machine. The active damping technique is based on a detailed model of the drive system which leads to a very simple implementation. The active damping can...

  6. Experimental performance of an internal resistance heater for Langley 6-inch expansion tube driver

    Science.gov (United States)

    Creel, T. R., Jr.

    1972-01-01

    An experimental investigation of the heating characteristics of an internal resistance heating element was conducted in the driver of the Langley 6-inch expansion tube to obtain actual operating conditions, to compare these results to theory, and to determine whether any modification need be made to the heater element. The heater was operated in pressurized helium from 138. MN/sq m to 62.1 MN/sq m. This investigation revealed large temperature variations within the heater element caused primarily by area reductions at insulator locations. These large temperature variations were reduced by welding small tabs over all grooves. Previous predictions of heater element and driver gas temperature were unacceptable so new equations were derived. These equations predict element and gas temperature within 10 percent of the test data when either the constant power cycle or the interrupted power cycle is used. Visual observation of the heater element, when exposed to the atmosphere with power on, resulted in a decision to limit the heater element to 815 K. Experimental shock Mach numbers are in good agreement with theory.

  7. MT. BIGELOW 61-INCH IMAGES OF 9P/TEMPEL 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains 6 images of 9P/Tempel 1 obtained on five nights in 1994 using a visual CCD mounted on the 61-inch Kuiper telescope of the Mt. Bigelow...

  8. Myogenic activation and calcium sensitivity of cannulated rat mesenteric small arteries

    NARCIS (Netherlands)

    VanBavel, E.; Wesselman, J. P.; Spaan, J. A.

    1998-01-01

    Pressure-induced activation of vascular smooth muscle may involve electromechanical as well as nonelectromechanical coupling mechanisms. We compared calcium-tone relations of cannulated rat mesenteric small arteries during pressure-induced activation, depolarization (16 to 46 mmol/L K+), and

  9. Taking It to the Classroom: Number Board Games as a Small Group Learning Activity

    Science.gov (United States)

    Ramani, Geetha B.; Siegler, Robert S.; Hitti, Aline

    2012-01-01

    We examined whether a theoretically based number board game could be translated into a practical classroom activity that improves Head Start children's numerical knowledge. Playing the number board game as a small group learning activity promoted low-income children's number line estimation, magnitude comparison, numeral identification, and…

  10. What Do We Want Small Group Activities For? Voices from EFL Teachers in Japan

    Science.gov (United States)

    Kato, Yoshitaka

    2016-01-01

    This paper discusses the fundamental issue of why small group activities are utilized in the language learning classroom. Although these activities have gained popularity in the field of Teaching English as a Second Language (TESL), supported by a sound theoretical base, few studies have so far examined the reasons why language teachers are…

  11. Unlocking the Potential of Time-Driven Activity-Based Costing for Small Logistics Companies

    NARCIS (Netherlands)

    Somapa, S.; Cools, M.; Dullaert, W.E.H.

    2012-01-01

    This paper reports on the development of a time-driven activity-based costing (TDABC) model in a small-sized road transport and logistics company. Activity-based costing (ABC) leads to increased accuracy benefiting decision-making, but the costs of implementation can be high. TDABC tries to overcome

  12. A small RNA activates CFA synthase by isoform-specific mRNA stabilization.

    Science.gov (United States)

    Fröhlich, Kathrin Sophie; Papenfort, Kai; Fekete, Agnes; Vogel, Jörg

    2013-11-13

    Small RNAs use a diversity of well-characterized mechanisms to repress mRNAs, but how they activate gene expression at the mRNA level remains not well understood. The predominant activation mechanism of Hfq-associated small RNAs has been translational control whereby base pairing with the target prevents the formation of an intrinsic inhibitory structure in the mRNA and promotes translation initiation. Here, we report a translation-independent mechanism whereby the small RNA RydC selectively activates the longer of two isoforms of cfa mRNA (encoding cyclopropane fatty acid synthase) in Salmonella enterica. Target activation is achieved through seed pairing of the pseudoknot-exposed, conserved 5' end of RydC to an upstream region of the cfa mRNA. The seed pairing stabilizes the messenger, likely by interfering directly with RNase E-mediated decay in the 5' untranslated region. Intriguingly, this mechanism is generic such that the activation is equally achieved by seed pairing of unrelated small RNAs, suggesting that this mechanism may be utilized in the design of RNA-controlled synthetic circuits. Physiologically, RydC is the first small RNA known to regulate membrane stability.

  13. Small group activities within academic communities improve the connectedness of students and faculty.

    Science.gov (United States)

    Brandl, Katharina; Schneid, Stephen D; Smith, Sunny; Winegarden, Babbi; Mandel, Jess; Kelly, Carolyn J

    2017-08-01

    The University of California, San Diego, School of Medicine implemented a curriculum change that included reduction of lectures, incorporation of problem-based learning and other small group activities. Six academic communities were introduced for teaching longitudinal curricular content and organizing extracurricular activities. Surveys were collected from 904 first- and second-year medical students over 6 years. Student satisfaction data with their sense of connectedness and community support were collected before and after the implementation of the new curriculum. In a follow-up survey, medical students rated factors that contributed to their sense of connectedness with faculty and students (n = 134). Students' perception of connectedness to faculty significantly increased following implementation of a curriculum change that included academic communities. Students ranked small group clinical skills activities within academic communities significantly higher than other activities concerning their sense of connectedness with faculty. Students' perception of connectedness among each other was high at baseline and did not significantly change. Small group activities scored higher than extracurricular activities regarding students' connectedness among themselves. The implementation of a new curriculum with more small group educational activities including academic communities enhanced connectedness between students and faculty and resulted in an increased sense of community.

  14. A review of the literature on preventive occupational health and safety activities in small enterprises

    DEFF Research Database (Denmark)

    Hasle, Peter; Limborg, Hans Jørgen

    2006-01-01

    The scientific literature regarding preventive occupational health and safety activities in small enterprises has been reviewed in order to identify effective preventive approaches and to develop a future research strategy. During the last couple of years, there has been a significant increase...... that employees of small enterprises are subject to higher risks than the employees of larger ones, and that small enterprises have difficulties in controlling risk. The most effective preventive approaches seem to be simple and low cost solutions, disseminated through personal contact. It is important to develop...

  15. Risk assessment of K Basin twelve-inch and four-inch drain valve failure from a postulated seismic initiating event

    Energy Technology Data Exchange (ETDEWEB)

    MORGAN, R.G.

    1999-06-23

    The Spent Nuclear Fuel (SNF) Project will transfer metallic SNF from the Hanford 105 K-East and 105 K-West Basins to safe interim storage in the Canister Storage Building in the 200 Area. The initial basis for design, fabrication, installation, and operation of the fuel removal systems was that the basin leak rate which could result from a postulated accident condition would not be excessive relative to reasonable recovery operations. However, an additional potential K Basin water leak path is through the K Basin drain valves. Three twelve-inch drain valves are located in the main basin bays along the north wall. Five four-inch drain valves are located in the north and south loadout pits (NLOP and SLOP), the weasel pit, the technical viewing pit, and the discharge chute pit. The sumps containing the valves are filled with concrete which covers the drain valve body. Visual observations indicate that only the valve's bonnet and stem are exposed above the basin concrete floor for the twelve-inch drain valve and that much less of the valve's bonnet and stem are exposed above the basin concrete floor for the five four-inch drain valves. It was recognized, however, that damage of the drain valve bonnet or stem during a seismic initiating event could provide a potential K Basin water leak path. The objectives of this analysis are to: (1) evaluate the likelihood of damaging the three twelve-inch drain valves located along the north wall of the main basin and the five four-inch drain valves located in the pits from a seismic initiating event, and (2) determine the likelihood of exceeding a specific consequence (initial leak rate) from a damaged valve. The analysis process is a risk-based uncertainty analysis where each variable is modeled using available information and engineering judgement. The uncertainty associated with each variable is represented by a probability distribution (probability density function). Uncertainty exists because of the inherent

  16. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    International Nuclear Information System (INIS)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-01-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[ 14 C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14 CO 2 excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an α 2 -adrenergic agonist

  17. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  18. Active damping technique for small DC-link capacitor based drive system

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Henriksen, Bjarne

    2010-01-01

    A detailed model of Adjustable Speed Drive (ASD) is discussed, which yield a general rule for active damping in a small DC link based drive. A desired value of input LC resonance damping coefficient can be achieved by changing gain parameters. The modified state space matrix due to active damping...... terms is also presented. The performance of the active damping is evaluated based on experimental results. A simple model is presented which can be used to measure the damping factor provided by the system parameters only.......A detailed model of Adjustable Speed Drive (ASD) is discussed, which yield a general rule for active damping in a small DC link based drive. A desired value of input LC resonance damping coefficient can be achieved by changing gain parameters. The modified state space matrix due to active damping...

  19. Complex of Key Instruments of Management of Operation Activity of a Small Business Trade Enterprise

    Directory of Open Access Journals (Sweden)

    Serdyuk Vira M.

    2013-11-01

    Full Text Available The article offers a complex of key instruments of management of operation activity of a small business trade enterprise, including: 1 budgeting of operation activity; 2 its accounting by norms and deviations from them; 3 monitoring of operational activity of an enterprise, which envisages analysis of revealed deviations. The article shows the most efficient way of realisation and practical use of the presented concept – application of the “standard-cost” scheme within the framework of which the following tasks are solved: 1 budgeting of income from operational activity; 2 establishment of standards of costs; 3 accumulation of data on factual income and expenditures; 4 analysis of deviations and reporting; and 5 introduction of necessary amendments. The article also offers an imitation model of analysis of dynamics of trade processes, which allows detection of key spheres of management of operation activity of a small trade enterprise and principles of carrying out an efficient and well thought over financial policy.

  20. Development of gamma spectroscopy employing NaI(Tl) detector 3 inch x 3 inch and readout electronic of flash-ADC/FPGA-based technology

    Energy Technology Data Exchange (ETDEWEB)

    Hai, Vo Hong [HCMC-National Univ., Hochiminh City (Viet Nam). Inst. of Nuclear Physics; Ton Duc Thang Univ., Ho Chi Minh City (Viet Nam). Div. of Nuclear Physics; Hung, Nguyen Quoc [HCMC-National Univ., Hochiminh City (Viet Nam). Inst. of Nuclear Physics; Khai, Bui Tuan [Osaka Univ. (Japan). Dept. of Physics

    2015-05-15

    n this article the development of a gamma spectroscopy system is described using a scintillation detector NaI(Tl) of 3 inch x 3 inch. The readout electronic for the spectroscopy is built from the fast analog-digital conversion of Flash Analog-Digital Converter (Flash-ADC) 250 MHz - 8 bits resolution, and the embedded Field-Programmable Gate Array (FPGA) technology. The embedded VHSIC Hardware Description Language (VHDL) code for FPGA is built in such a way that it works as a multi channel analyser (MCA) with 4096 Digital Charge Integration (DCI) channels. A pulse generator with frequency varying from Hz up to 12 kHz is used to evaluate the time response of the system. Two standard radioisotope sources of {sup 133}Ba and {sup 152}Eu with multi gamma energies ranging from several tens keV to MeV are used to evaluate the linearity and energy resolution of the system.

  1. The Small Protein SgrT Controls Transport Activity of the Glucose-Specific Phosphotransferase System.

    Science.gov (United States)

    Lloyd, Chelsea R; Park, Seongjin; Fei, Jingyi; Vanderpool, Carin K

    2017-06-01

    The bacterial small RNA (sRNA) SgrS has been a fruitful model for discovery of novel RNA-based regulatory mechanisms and new facets of bacterial physiology and metabolism. SgrS is one of only a few characterized dual-function sRNAs. SgrS can control gene expression posttranscriptionally via sRNA-mRNA base-pairing interactions. Its second function is coding for the small protein SgrT. Previous work demonstrated that both functions contribute to relief of growth inhibition caused by glucose-phosphate stress, a condition characterized by disrupted glycolytic flux and accumulation of sugar phosphates. The base-pairing activity of SgrS has been the subject of numerous studies, but the activity of SgrT is less well characterized. Here, we provide evidence that SgrT acts to specifically inhibit the transport activity of the major glucose permease PtsG. Superresolution microscopy demonstrated that SgrT localizes to the cell membrane in a PtsG-dependent manner. Mutational analysis determined that residues in the N-terminal domain of PtsG are important for conferring sensitivity to SgrT-mediated inhibition of transport activity. Growth assays support a model in which SgrT-mediated inhibition of PtsG transport activity reduces accumulation of nonmetabolizable sugar phosphates and promotes utilization of alternative carbon sources by modulating carbon catabolite repression. The results of this study expand our understanding of a basic and well-studied biological problem, namely, how cells coordinate carbohydrate transport and metabolism. Further, this work highlights the complex activities that can be carried out by sRNAs and small proteins in bacteria. IMPORTANCE Sequencing, annotation and investigation of hundreds of bacterial genomes have identified vast numbers of small RNAs and small proteins, the majority of which have no known function. In this study, we explore the function of a small protein that acts in tandem with a well-characterized small RNA during metabolic

  2. Am/Cm TTR testing - 3/8-inch glass beads evaluation in CIM5

    International Nuclear Information System (INIS)

    Witt, D. C.

    2000-01-01

    To facilitate the procurement and handling of the glass former for Am/Cm vitrification in the F-Canyon MPPF, 1/4 inch and 3/8 inch diameter glass beads were purchased from Corning for evaluation in the 5 inch Cylindrical Induction Melter (CIM5). Prior to evaluating the beads in the CIM5, tests were conducted in the Drain Tube Test Stand (DTTS) with 1/4 inch beads, 3/8 inch beads, and a 50/50 mixture to identify any process concerns. Results of the DTTS tests are summarized in Attachment 1. A somewhat larger volume expansion was experienced in all three DTTS runs as compared to a standard run using cullet. Further testing of the use of glass beads in the CIM5 was requested by the Design Authority as Task 1.02 of Technical Task Request 99-MNSS/SE-006. Since the Technical Task Plan was not yet approved, the completion of this task was conducted under an authorization request approved by the SRTC Laboratory Director, S. Wood. This request is included as Attachment 2

  3. Pomegranate peel extract decreases small intestine lipid peroxidation by enhancing activities of major antioxidant enzymes.

    Science.gov (United States)

    Al-Gubory, Kaïs H; Blachier, François; Faure, Patrice; Garrel, Catherine

    2016-08-01

    Pomegranate peel extract (PPE) contains several compounds with antioxidative properties. PPE added to foods may interact with endogenous antioxidants and promote health. However, little is known about the biochemical mechanisms by which PPE exerts their actions on tissues of biological systems in vivo. The purpose of this study was to determine the effects of PPE on activities of antioxidant enzymes. Mice were used to investigate the effects of PPE on plasma levels of malondialdehyde (MDA), tissue MDA content and activities of superoxide dismutase 1 (SOD1), SOD2 and glutathione peroxidase (GPX) in the small intestine, liver and skeletal muscle - different tissues involved in the digestion, absorption and metabolism of dietary nutrients. Control mice were fed a standard diet, whereas treated mice were fed for 40 days with the standard diet containing 5% or 10% PPE. Mice fed the 10% PPE diet exhibited lower plasma MDA concentrations, reduced content of MDA in the small intestine and liver and higher levels of SOD1 and GPX activities in the small intestine compared to mice fed the control diet. These findings demonstrate that intake of PPE in diet attenuates small intestine lipid peroxidation and strengthens the first line of small intestine antioxidant defense by enhancing enzymatic antioxidative pathways. PPE is worthy of further study as a therapeutic approach to prevent peroxidative stress-induced gut pathogenesis. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  4. Low lactase activity in a small-bowel biopsy specimen : Should dietary lactose intake be restricted in children with small intestinal mucosal damage?

    NARCIS (Netherlands)

    Koetse, HA; Vonk, RJ; Gonera-de Jong, GBC; Priebe, MG; Antoine, JM; Stellaard, F; Sauer, PJJ

    Objective. Small intestinal mucosal damage can result in decreased lactase activity (LA). When LA is low in a small-bowel biopsy (SBB) specimen, a reduction of dietary lactose intake is usually advised. This is often done by reducing dietary dairy products, which also reduces the intake of calcium,

  5. Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food

    International Nuclear Information System (INIS)

    Read, N.W.; Al-Janabi, M.N.; Edwards, C.A.; Barber, D.C.

    1984-01-01

    Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine

  6. The cyclopentyl group, as a small but bulky terminal group, allows rapid and efficient active transport.

    Science.gov (United States)

    Nishiyama, Junya; Makita, Yoshimasa; Kihara, Nobuhiro

    2015-01-02

    Secondary ammonium salts bearing a cyclopentyl terminal group rapidly formed pseudorotaxane with 1.5 equiv of DB24C8. Acylation of the pseudorotaxane with 50 equiv of benzoyl chloride in the presence of 50 equiv of triethylamine in toluene afforded rotaxane, the product of active transport, in 95% yield. The cyclopentyl group is small enough to allow rapid formation of pseudorotaxane, and bulky enough to facilitate the quantitative active transport by steric repulsion.

  7. The C-13/H-2-glucose test for determination of small intestinal lactase activity

    NARCIS (Netherlands)

    Vonk, RJ; Stellaard, F; Priebe, MG; Koetse, HA; Hagedoorn, RE; de Bruijn, S; Elzinga, H; Lenoir-Wijnkoop, [No Value; Antoine, JM

    Background To diagnose hypolactasia, determination of lactase enzyme activity in small intestinal biopsy material is considered to be the golden standard. Because of its strongly invasive character and the sampling problems, alternative methods have been looked for. Design We analysed the

  8. Comparative in vitro activity of ceftobiprole against staphylococci displaying normal and small-colony variant phenotypes

    NARCIS (Netherlands)

    von Eiff, Christof; Friedrich, Alexander W.; Becker, Karsten; Peters, Georg

    2005-01-01

    The antistaphylococcal activity of ceftobiprole was compared with those of cefuroxime, linezolid, and moxifloxacin by using the agar dilution method. Apart from three strains with small-colony variant phenotypes, all Staphylococcus aureus isolates tested were inhibited by < or =2 microg/ml of

  9. A review of the literature on preventive occupational health and safety activities in small enterprises

    DEFF Research Database (Denmark)

    Hasle, Peter; Limborg, Hans Jørgen

    2006-01-01

    The scientific literature regarding preventive occupational health and safety activities in small enterprises has been reviewed in order to identify effective preventive approaches and to develop a future research strategy. During the last couple of years, there has been a significant increase...

  10. Inhibition of small-conductance Ca2+-activated K+ channels terminates and protects against atrial fibrillation

    DEFF Research Database (Denmark)

    Diness, Jonas Goldin; Sørensen, Ulrik S; Nissen, Jakob Dahl

    2010-01-01

    Recently, evidence has emerged that small-conductance Ca(2+)-activated K(+) (SK) channels are predominantly expressed in the atria in a number of species including human. In rat, guinea pig, and rabbit ex vivo and in vivo models of atrial fibrillation (AF), we used 3 different SK channel inhibitors...

  11. An exploratory survey of small-scale off-farm economic activities and ...

    African Journals Online (AJOL)

    Small scale off-farm economic activities are believed to be a potential frontier for generating additional livelihoods support to sustain the farm household in rural Ghana. Despite this general belief, very little has been done to provide adequate information that might be utilized by policy makers and practitioners for possible ...

  12. Construction and genetic selection of small transmembrane proteins that activate the human erythropoietin receptor.

    Science.gov (United States)

    Cammett, Tobin J; Jun, Susan J; Cohen, Emily B; Barrera, Francisco N; Engelman, Donald M; Dimaio, Daniel

    2010-02-23

    This work describes a genetic approach to isolate small, artificial transmembrane (TM) proteins with biological activity. The bovine papillomavirus E5 protein is a dimeric, 44-amino acid TM protein that transforms cells by specifically binding and activating the platelet-derived growth factor beta receptor (PDGFbetaR). We used the E5 protein as a scaffold to construct a retrovirus library expressing approximately 500,000 unique 44-amino acid proteins with randomized TM domains. We screened this library to select small, dimeric TM proteins that were structurally unrelated to erythropoietin (EPO), but specifically activated the human EPO receptor (hEPOR). These proteins did not activate the murine EPOR or the PDGFbetaR. Genetic studies with one of these activators suggested that it interacted with the TM domain of the hEPOR. Furthermore, this TM activator supported erythroid differentiation of primary human hematopoietic progenitor cells in vitro in the absence of EPO. Thus, we have changed the specificity of a protein so that it no longer recognizes its natural target but, instead, modulates an entirely different protein. This represents a novel strategy to isolate small artificial proteins that affect diverse membrane proteins. We suggest the word "traptamer" for these transmembrane aptamers.

  13. Comparision of Incidental Reflection From Containerized Maintenance/Housekeeping Solutions and One Inch of Water

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Bryan Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); MacQuigg, Michael Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wysong, Andrew Russell [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-12-15

    This document addresses the incidental reflector reactivity worth of containerized maintenance/housekeeping fluids for use in PF-4 at Los Alamos National Laboratory (LANL). The intent of the document is to analyze containerized maintenance/housekeeping fluids which will be analyzed as water that may be present under normal conditions of an operation. The reactivity worth is compared to the reactivity worth due to I-inch of close-fitting 4n water reflection and I-inch of close-fitting radial water reflection. Both have been used to bound incidental reflection by 2-liter bottles in criticality safety evaluations. The conclusion is that, when the maintenance/housekeeping fluids are containerized the reactivity increase from a configuration which is bounding of normal conditions (up to eight bottles modeled with 2-liters of solution at varying diameter) is bound by I-inch of close fitting 4n water relection.

  14. Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

    Full Text Available Tsuneyuki Oku¹, Kenichi Tanabe¹, Shigeharu Ogawa², Naoki Sadamori¹, Sadako Nakamura¹¹Graduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; ²Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.9–3.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and

  15. Influence of small forms of active rest on intellection of students of agrarian higher institutes.

    Directory of Open Access Journals (Sweden)

    Prysjazhnuk S.I.

    2012-12-01

    Full Text Available Influence of facilities of active rest is considered on the increase of mental capacity of students. In research took part 105 students with the low level of physical preparedness. Progress of students is select the integral index of mental capacity. It is set that the most effective factors of diminishing of action of processes of fatigue and increase of mental capacity of students is the use of small forms of active rest during an educational day. It is suggested to utillize athletic pauses (minutes, micro pauses during the leadthrough of employments on theoretical disciplines. It is set that small forms of active rest in combination with a leadthrough independent health-improvement-trainings employments on physical self-perfection instrumental in the substantial improvement of the state of physical and mental capacity of student young people.

  16. Activation of catalase activity by a peroxisome-localized small heat shock protein Hsp17.6CII.

    Science.gov (United States)

    Li, Guannan; Li, Jing; Hao, Rong; Guo, Yan

    2017-08-20

    Plant catalases are important antioxidant enzymes and are indispensable for plant to cope with adverse environmental stresses. However, little is known how catalase activity is regulated especially at an organelle level. In this study, we identified that small heat shock protein Hsp17.6CII (AT5G12020) interacts with and activates catalases in the peroxisome of Arabidopsis thaliana. Although Hsp17.6CII is classified into the cytosol-located small heat shock protein subfamily, we found that Hsp17.6CII is located in the peroxisome. Moreover, Hsp17.6CII contains a novel non-canonical peroxisome targeting signal 1 (PTS1), QKL, 16 amino acids upstream from the C-terminus. The QKL signal peptide can partially locate GFP to peroxisome, and mutations in the tripeptide lead to the abolishment of this activity. In vitro catalase activity assay and holdase activity assay showed that Hsp17.6CII increases CAT2 activity and prevents it from thermal aggregation. These results indicate that Hsp17.6CII is a peroxisome-localized catalase chaperone. Overexpression of Hsp17.6CII conferred enhanced catalase activity and tolerance to abiotic stresses in Arabidopsis. Interestingly, overexpression of Hsp17.6CII in catalase-deficient mutants, nca1-3 and cat2 cat3, failed to rescue their stress-sensitive phenotypes and catalase activity, suggesting that Hsp17.6CII-mediated stress response is dependent on NCA1 and catalase activity. Overall, we identified a novel peroxisome-located catalase chaperone that is involved in plant abiotic stress resistance by activating catalase activity. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  17. The Natural History and Predictors for Intervention in Patients with Small Renal Mass Undergoing Active Surveillance

    Directory of Open Access Journals (Sweden)

    Zaher Bahouth

    2015-01-01

    Full Text Available Aim. To describe the natural history of small renal mass on active surveillance and identify parameters that could help in predicting the need for intervention in patients with small renal masses undergoing active surveillance. We also discuss the need for renal biopsy in the management of these patients. Methods. A retrospective analysis of 78 renal masses ≤4 cm diagnosed at our Urology Department at Bnai Zion Medical Center between September 2003 and March 2012. Results. Seventy patients with 78 small renal masses were analyzed. The mean age at diagnosis was 68 years (47–89. The mean follow-up period was 34 months (12–112. In 54 of 78 masses there was a growth of at least 2 mm between imaging on last available follow-up and diagnosis. Eight of the 54 (15% masses which grew in size underwent a nephron-sparing surgery, of which two were oncocytomas and six were renal cell carcinoma. Growth rate and mass diameter on diagnosis were significantly greater in the group of patients who underwent a surgery. Conclusions. Small renal masses might eventually be managed by active surveillance without compromising survival or surgical approach. All masses that were eventually excised underwent a nephron-sparing surgery. None of the patients developed metastases.

  18. An Active Damping Technique for Small DC-Link Capacitor Based Drive System

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Lu, Kaiyuan

    2013-01-01

    A small dc-link capacitor based drive system shows instability when it is operated with large input line inductance at operating points with high power. This paper presents a simple, new active damping technique that can stabilize effectively the drive system at unstable operating points, offering...... points. The stabilizing effect of the active damping terms is demonstrated for an induction machine based drive system. The effects of the added damping terms on the machine current and dc-link voltage are analyzed in detail. A design recommendation for the proposed active damping terms is given...

  19. A Small-Group Activity Introducing the Use and Interpretation of BLAST

    Directory of Open Access Journals (Sweden)

    Peter D. Newell

    2013-08-01

    Full Text Available As biological sequence data are generated at an ever increasing rate, the role of bioinformatics in biological research also grows. Students must be trained to complete and interpret bioinformatic searches to enable them to effectively utilize the trove of sequence data available. A key bioinformatic tool for sequence comparison and genome database searching is BLAST (Basic Local Alignment Search Tool. BLAST identifies sequences in a database that are similar to the entered query sequence, and ranks them based on the length and quality of the alignment. Our goal was to introduce sophomore and junior level undergraduate students to the basic functions and uses of BLAST with a small group activity lasting a single class period. The activity provides students an opportunity to perform a BLAST search, interpret the data output, and use the data to make inferences about bacterial cell envelope structure. The activity consists of two parts. Part 1 is a handout to be completed prior to class, complete with video tutorial, that reviews cell envelope structure, introduces key terms, and allows students to familiarize themselves with the mechanics of a BLAST search. Part 2 consists of a hands-on, web-based small group activity to be completed during the class period. Evaluation of the activity through student performance assessments suggests that students who complete the activity can better interpret the BLAST output parameters % query coverage and % max identity. While the topic of the activity is bacterial cell wall structure, it could be adapted to address other biological concepts.

  20. Sludge dewatering and disposal practices for small activated sludge wastewater treatment plants.

    Science.gov (United States)

    Hatziconstantinou, G J; Efstathiou, H

    2003-01-01

    Sludge dewatering is a decisive step in the reduction of waste sludge volume, thus considerably affecting total sludge treatment and disposal costs. The construction of sludge dewatering facilities in small WwTPs though, is generally not cost effective. In this paper some experimental evidence is presented, that waste sludge dewatering in small WwTPs of the activated sludge extended aeration type, can be effectively achieved by a centrifuge type of equipment withdrawing sludge directly from the aeration tank; an economic evaluation of the possibility to employ a transportable type of similar equipment mounted on a truck, to serve a number of small WwTPs located in remote or isolated areas is also presented and discussed.

  1. Effects of taurine on plasma glucose concentration and active glucose transport in the small intestine.

    Science.gov (United States)

    Tsuchiya, Yo; Kawamata, Koichi

    2017-11-01

    Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 (SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. © 2017 Japanese Society of Animal Science.

  2. Firing of antagonist small-diameter muscle afferents reduces voluntary activation and torque of elbow flexors.

    Science.gov (United States)

    Kennedy, David S; McNeil, Chris J; Gandevia, Simon C; Taylor, Janet L

    2013-07-15

    During muscle fatigue, firing of small-diameter muscle afferents can decrease voluntary activation of the fatigued muscle. However, these afferents may have a more widespread effect on other muscles in the exercising limb. We examined if the firing of fatigue-sensitive afferents from elbow extensor muscles in the same arm reduces torque production and voluntary activation of elbow flexors. In nine subjects we examined voluntary activation of elbow flexors by measuring changes in superimposed twitches evoked by transcranial magnetic stimulation of the motor cortex during brief (2-3 s) maximal voluntary contractions (MVC). Inflation of a blood pressure cuff following a 2-min sustained MVC blocked blood flow to the fatigued muscle and maintained firing of small-diameter afferents. After a fatiguing elbow flexion contraction, maximal flexion torque was lower (26.0 ± 4.4% versus 67.9 ± 5.2% of initial maximal torque; means ± s.d.; P torque was also reduced (82.2 ± 4.9% versus 91.4 ± 2.3% of initial maximal torque; P = 0.007), superimposed twitches were larger (2.7 ± 0.7% versus 1.3 ± 0.2% ongoing MVC; P = 0.02) and voluntary activation lower (81.6 ± 8.2% versus 95.5 ± 6.9%; P = 0.04) with than without ischaemia. After a fatiguing contraction, voluntary drive to the fatigued muscles is reduced with continued input from small-diameter muscle afferents. Furthermore, fatigue of the elbow extensor muscles decreases voluntary drive to unfatigued elbow flexors of the same arm. Therefore, firing of small-diameter muscle afferents from one muscle can affect voluntary activation and hence torque generation of another muscle in the same limb.

  3. How do Australian Small and Medium Enterprises Communicate their Environmental Improvement Activities Online?

    Directory of Open Access Journals (Sweden)

    Craig Parker

    2011-03-01

    Full Text Available There have been calls in the IS/eBusiness literature for research on "green" IS/IT in a Small and Medium Enterprises (SMEs context. The Corporate Social Responsibility (CSR literature has neglected the issue of how SMEs can use websites to communicate their environmental improvement activities. This paper links these two previously separate disciplines by reporting on a content analysis of 443 Australian SME websites from four industry sectors to identify if and how they use websites to communicate their environmental improvement activities. The study found that 47 websites were communicating such activities in some form. A detailed analysis was undertaken of these 47 websites to identify emergent themes relating to how these SMEs were communicating their environmental improvement activities. These themes resulted in a reconceptualisation of the traditional "4 Ps" of marketing for online communication of environmental improvement activities by SMEs: profile; product; process and prominence.

  4. Transcriptional tools: Small molecules for modulating CBP KIX-dependent transcriptional activators.

    Science.gov (United States)

    Bates, Caleb A; Pomerantz, William C; Mapp, Anna K

    2011-01-01

    Previously it was demonstrated that amphipathic isoxazolidines are able to functionally replace the transcriptional activation domains of endogenous transcriptional activators. In addition, in vitro binding studies suggested that a key binding partner of these molecules is the CREB Binding Protein (CBP), more specifically the KIX domain within this protein. Here we show that CBP plays an essential role in the ability of isoxazolidine transcriptional activation domains to activate transcription in cells. Consistent with this model, isoxazolidines are able to function as competitive inhibitors of the activators MLL and Jun, both of which utilize a binding interaction with KIX to up-regulate transcription. Further, modification of the N2 side chain produced three analogs with enhanced potency against Jun-mediated transcription, although increased cytotoxicity was also observed. Collectively these small KIX-binding molecules will be useful tools for dissecting the role of the KIX domain in a variety of pathological processes. 2010 Wiley Periodicals, Inc.

  5. Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering.

    Science.gov (United States)

    Peurois, François; Veyron, Simon; Ferrandez, Yann; Ladid, Ilham; Benabdi, Sarah; Zeghouf, Mahel; Peyroche, Gérald; Cherfils, Jacqueline

    2017-03-23

    Active, GTP-bound small GTPases need to be attached to membranes by post-translational lipid modifications in order to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by guanine nucleotide exchange factors (GEFs) and their termination by GTPase-activating proteins. Here, we replaced the lipid modification by a histidine tag in 11 full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid-containing membranes and characterize the kinetics of their activation by GEFs. Remarkably, this strategy uncovered large effects of membranes on the efficiency and/or specificity in all systems studied. Notably, it recapitulated the release of autoinhibition of Arf1, Arf3, Arf4, Arf5 and Arf6 GTPases by membranes and revealed that all isoforms are efficiently activated by two GEFs with different regulatory regimes, ARNO and Brag2. It demonstrated that membranes stimulate the GEF activity of Trio toward RhoG by ∼30 fold and Rac1 by ∼10 fold, and uncovered a previously unknown broader specificity toward RhoA and Cdc42 that was undetectable in solution. Finally, it demonstrated that the exceptional affinity of the bacterial RabGEF DrrA for the phosphoinositide PI(4)P delimits the activation of Rab1 to the immediate vicinity of the membrane-bound GEF. Our study thus validates the histidine-tag strategy as a potent and simple means to mimic small GTPase lipidation, which opens a variety of applications to uncover regulations brought about by membranes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  6. Evaluation of 3 Inch SN-219 Failure and S and SX Tank Farm Saltwell Piping

    International Nuclear Information System (INIS)

    ELSEN, J.J.

    2000-01-01

    Evaluation of direct buried piping currently in use or designated for future Saltwell pumping in S and SX Farms. Documented evaluation of failed S-103 saltwell pumping transfer line 3 inch SN-219. This evaluation is intended to reflect current status of Saltwell piping, when taken in context with referenced documents

  7. Full scale ambient water flow tests of a 10-inch emergency release coupling for LNG transfer

    NARCIS (Netherlands)

    Putte, L.J. van der; Webber, T.; Bokhorst, E. van; Revell, C.

    2016-01-01

    For LNG transfer in ship-to-ship and ship-to-shore configurations emergency release couplings (F.RC) in combination with loading arms and multi-composite hoses are applied In view of a demand for increasing transfer flow rates in offshore LNG applications a 10-inch ERC has been developed intended

  8. Interim results: fines recycle testing using the 4-inch diameter primary graphite burner

    International Nuclear Information System (INIS)

    Palmer, W.B.

    1975-05-01

    The results of twenty-two HTGR primary burner runs in which graphite fines were recycled pneumatically to the 4-inch diameter pilot-plant primary fluidized-bed burner are described. The result of the tests showed that zero fines accumulation can easily be achieved while operating at plant equivalent burn rates. (U.S.)

  9. Assessment of Crohn's disease activity in the small bowel with MR and conventional enteroclysis: preliminary results

    International Nuclear Information System (INIS)

    Gourtsoyiannis, Nicholas; Papanikolaou, Nickolas; Grammatikakis, John; Papamastorakis, George; Prassopoulos, Panos; Roussomoustakaki, Maria

    2004-01-01

    Every single imaging finding that can be disclosed on conventional and MR enteroclysis was correlated with the Crohn's disease activity index (CDAI). Nineteen consecutive patients with Crohn's disease underwent colon endoscopy and both conventional and MR enteroclysis examinations. Seventeen MR imaging findings and seven conventional enteroclysis findings were ranked on a four-point grading scale and correlated with CDAI, with a value of 150 considered as the threshold for disease activity. Six patients had active disease in the colon according to colon endoscopy. In the remaining 13 patients, the presence of deep ulcers (P=0.002), small bowel wall thickening (P=0.022) and gadolinium enhancement of mesenteric lymph nodes (P=0.014) identified on MR enteroclysis images were strongly correlated to disease activity. The product of deep ulcers and enhancement of lymph node ranks identified on MR enteroclysis were the optimum combination for discriminating active from non-active disease (F-test: 55.95, P<0.001). Additionally, the ranking of deep ulcers on conventional enteroclysis provided statistically significant differences between active and non-active patients (F-test: 14.12, P=0.004). Abnormalities strongly suggestive of active Crohn's disease can be disclosed on MR enteroclysis examinations and may provide pictorial information for local inflammatory activity. (orig.)

  10. Selective small-chemical inhibitors of protein arginine methyltransferase 5 with anti-lung cancer activity.

    Directory of Open Access Journals (Sweden)

    Gui-Mei Kong

    Full Text Available Protein arginine methyltransferase 5 (PRMT5 plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation. Oral administration of the inhibitor demonstrated antitumor activity in a lung tumor xenograft model. Thus, identified PRMT5-specific small-molecule inhibitors would help elucidate the biological roles of PRMT5 and serve as lead compounds for future drug development.

  11. A small-molecule activator of kinesin-1 drives remodeling of the microtubule network.

    Science.gov (United States)

    Randall, Thomas S; Yip, Yan Y; Wallock-Richards, Daynea J; Pfisterer, Karin; Sanger, Anneri; Ficek, Weronika; Steiner, Roberto A; Beavil, Andrew J; Parsons, Maddy; Dodding, Mark P

    2017-12-26

    The microtubule motor kinesin-1 interacts via its cargo-binding domain with both microtubules and organelles, and hence plays an important role in controlling organelle transport and microtubule dynamics. In the absence of cargo, kinesin-1 is found in an autoinhibited conformation. The molecular basis of how cargo engagement affects the balance between kinesin-1's active and inactive conformations and roles in microtubule dynamics and organelle transport is not well understood. Here we describe the discovery of kinesore, a small molecule that in vitro inhibits kinesin-1 interactions with short linear peptide motifs found in organelle-specific cargo adaptors, yet activates kinesin-1's function of controlling microtubule dynamics in cells, demonstrating that these functions are mechanistically coupled. We establish a proof-of-concept that a microtubule motor-cargo interface and associated autoregulatory mechanism can be manipulated using a small molecule, and define a target for the modulation of microtubule dynamics.

  12. Efficiency of state financial support of export activity of small and medium businesses

    Directory of Open Access Journals (Sweden)

    Timur R. Urumov

    2017-03-01

    Full Text Available Objective to assess the effectiveness and role of state financial support of export activities of small and medium enterprises. Methods regression analysis abstractlogical method method of comparison. Results the need is identified to evaluate the impact of state programs of export support on the results of export operations as a mechanism for assessing the efficiency of public spending in this area. The institutions are analyzed of state support of export of small and medium businesses production in the USA and India. It is revealed that in the US the main tool of support are export credits and guarantees while in India the emphasis is on the promotion of products to the world markets. To assess the effectiveness of public expenditure on export support the data were collected and systematized on the total volume of export and the costs of its support in the United States and India. The project revealed the presence of a time lag between these indices. When building a regression model the method of least squares was applied on the basis of which three hypotheses were investigated namely those taking into account and not taking into account the presence of the time lag between variables. As a result of constructing the model it was found that in the U.S. the increase in budget spending on export support to 1mln leads to an increase in export volume to 2mln. In India the corresponding figure was 10mln. The analysis of the Russian practice of the state support of export of the small and medium businesses production showed a lack of systematic approach and poor development of the small business sector compared to the studied countries. Scientific novelty the positive relationship was revealed between the costs of exports support and export sales in the United States and India. The necessity was grounded of state the financial support of export activities of small and medium enterprises in Russia as well as product promotion through sectoral

  13. Ablation of p120-Catenin Altering the Activity of Small GTPase in Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nan LIU

    2009-05-01

    Full Text Available Background and objective p120-catenin (p120ctn, a member of the Armadillo gene family, has emerged as an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis, whose mechanism are not well clarified yet. The aim of this study is to explore the roles of p120ctn on the regulation of small GTP family members in lung cancer and the effects to lung cancer invasions andmetastasis. Methods After p120ctn was knocked down by siRNA, in vivo and in vitro analysis was applied to investigate the role and possible mechanism of p120ctn in lung cancer, such as Western Blot, pull-down analysis, and nude mice models. Results p120ctn depletion inactivated RhoA, with the the activity of Cdc42 and Rac1 increased, the invasiveness of lung cancer cells was promoted both in vitro and in vivo . Conclusion p120ctn gene knockdown enhances the metastasis of lung cancer cells, probably by altering expression of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.

  14. Observations of Small-scale IRIS Bombs (Reconnection Events) in an Evolving Active Region

    Science.gov (United States)

    Madsen, C. A.; Tian, H.; DeLuca, E. E.

    2015-12-01

    We present the first Interface Region Imaging Spectrograph (IRIS) observations of small-scale bombs evolving with their host active region. Bombs appear most clearly in the IRIS 1330 Å and 1400 Å slit-jaw images as small (~1 arcsec), compact, intense brightenings at transition region temperatures. Their NUV/FUV emission spectra exhibit dramatic line splitting and strong absorption features indicative of bidirectional flows from magnetic reconnection embedded deep within the cool lower solar atmosphere. The bombs may contribute significantly to the heating of the solar atmosphere in active regions; however, it's unclear how prevalent the bombs are throughout the lifetime of an active region. Using a semi-automated detection method, we locate bombs within AR 11850 over the course of four observations from 06:00 UT on September 25, 2013 until 11:30 UT the next day. The active region is first observed in an emerging phase and rapidly grows into a mature active region with well-developed sunspots. The bomb occurrence rate drops dramatically as the active region fully emerges. We also find that the bombs fall into two distinct populations: one appears largely during active region emergence and contains a majority of the bombs, while the other population is present regardless of active region age. The first population of bombs is typically found embedded in the low-lying loops prominent in the young active region. Furthermore, we use Solar Dynamics Observatory/Helioseismic and Magnetic Imager (SDO/HMI) line-of-sight magnetograms to show that the bombs associated with the first population occur at the boundaries between the upward and downward flux of small, isolated bipolar regions. These regions dissipate as the active region emerges and reconfigures its magnetic field into two large network patches of upward and downward flux with a clear inversion line. The second, smaller population of bombs usually occurs far from the active region loop structures in the plage and

  15. Effect of control activity on blade fatigue damage rate for a small horizontal axis wind turbine

    Energy Technology Data Exchange (ETDEWEB)

    Riddle, A.F.; Freris, L.L.; Graham, J.M.R. [Imperial College, London (United Kingdom)

    1996-09-01

    An experiment into the effect of control activity on blade fatigue damage rate for a 5 kW, two bladed, teetered HAWT has been performed. It has been shown that control activity influences the distribution of strain in the blade but that in a high rotor speed, high cycle fatigue regime this has little influence on damage rate. The experiment was conducted on a small test turbine by implementing variable speed stall, pitch and yaw control strategies and measuring blade flapwise strain response at root and midspan locations. A full description of the investigation is provided. (au)

  16. Structural Basis for Selective Small Molecule Kinase Inhibition of Activated c-Met

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, Keith W.; Patel, Sangita B.; Allison, Timothy J.; Byrne, Noel J.; Darke, Paul L.; Ford, Rachael E.; Guerin, David J.; Hall, Dawn L.; Kornienko, Maria; Lu, Jun; Munshi, Sanjeev K.; Reid, John C.; Shipman, Jennifer M.; Stanton, Elizabeth F.; Wilson, Kevin J.; Young, Jonathon R.; Soisson, Stephen M.; Lumb, Kevin J. (Merck)

    2012-03-15

    The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix {alpha}C and the G loop to generate a viable active site. Helix {alpha}C adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

  17. Tracking small mountainous river derived terrestrial organic carbon across the active margin marine environment

    Science.gov (United States)

    Childress, L. B.; Blair, N. E.; Orpin, A. R.

    2015-12-01

    Active margins are particularly efficient in the burial of organic carbon due to the close proximity of highland sources to marine sediment sinks and high sediment transport rates. Compared with passive margins, active margins are dominated by small mountainous river systems, and play a unique role in marine and global carbon cycles. Small mountainous rivers drain only approximately 20% of land, but deliver approximately 40% of the fluvial sediment to the global ocean. Unlike large passive margin systems where riverine organic carbon is efficiently incinerated on continental shelves, small mountainous river dominated systems are highly effective in the burial and preservation of organic carbon due to the rapid and episodic delivery of organic carbon sourced from vegetation, soil, and rock. To investigate the erosion, transport, and burial of organic carbon in active margin small mountainous river systems we use the Waipaoa River, New Zealand. The Waipaoa River, and adjacent marine depositional environment, is a system of interest due to a large sediment yield (6800 tons km-2 yr-1) and extensive characterization. Previous studies have considered the biogeochemistry of the watershed and tracked the transport of terrestrially derived sediment and organics to the continental shelf and slope by biogeochemical proxies including stable carbon isotopes, lignin phenols, n-alkanes, and n-fatty acids. In this work we expand the spatial extent of investigation to include deep sea sediments of the Hikurangi Trough. Located in approximately 3000 m water depth 120 km from the mouth of the Waipaoa River, the Hikurangi Trough is the southern extension of the Tonga-Kermadec-Hikurangi subduction system. Piston core sediments collected by the National Institute of Water and Atmospheric Research (NIWA, NZ) in the Hikurangi Trough indicate the presence of terrestrially derived material (lignin phenols), and suggest a continuum of deposition, resuspension, and transport across the margin

  18. The nutrient stress-induced small GTPase Rab5 contributes to the activation of vesicle trafficking and vacuolar activity.

    Science.gov (United States)

    Nakatsukasa, Kunio; Kanada, Akira; Matsuzaki, Mariko; Byrne, Stuart D; Okumura, Fumihiko; Kamura, Takumi

    2014-07-25

    Rab family small GTPases regulate membrane trafficking by spatiotemporal recruitment of various effectors. However, it remains largely unclear how the expression and functions of Rab proteins are regulated in response to extracellular or intracellular stimuli. Here we show that Ypt53, one isoform of Rab5 in Saccharomyces cerevisiae, is up-regulated significantly under nutrient stress. Under non-stress conditions, Vps21, a constitutively expressed Rab5 isoform, is crucial to Golgi-vacuole trafficking and to vacuolar hydrolase activity. However, when cells are exposed to nutrient stress for an extended period of time, the up-regulated Ypt53 and the constitutive Vps21 function redundantly to maintain these activities, which, in turn, prevent the accumulation of reactive oxygen species and maintain mitochondrial respiration. Together, our results clarify the relative roles of these constitutive and nutrient stress-inducible Rab5 proteins that ensure adaptable vesicle trafficking and vacuolar hydrolase activity, thereby allowing cells to adapt to environmental changes.

  19. Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

    1997-01-01

    Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology....

  20. Novel direct AMPK activator suppresses non-small cell lung cancer through inhibition of lipid metabolism

    Science.gov (United States)

    Chen, Xi; Xie, Chun; Fan, Xing-Xing; Jiang, Ze-Bo; Wong, Vincent Kam-Wai; Xu, Jia-Hui; Yao, Xiao-Jun; Liu, Liang; Leung, Elaine Lai-Han

    2017-01-01

    Drug resistance is becoming an obstacle in anti-cancer therapies. For target-based therapy of lung cancer, gefitinib, as the first generation of tyrosine kinase inhibitors (TKIs), demonstrated good initial response to the non-small cell lung cancer (NSCLC) patients whom harbors epidermal growth factor receptor (EGFR) mutation. However, within one year, additional EGFR mutation occurred, leading to eventual gefitinib-resistance. Therefore, it is urgently to discover novel effective small molecule inhibitors for those patients. Abnormal energy metabolism is accepted as new cancer hallmark. Recently, a metabolism rate-limiting enzyme 5’-adenosine menophosphate-activated protein kinase (AMPK) has become a promising anti-cancer target. In this study, we have identified a novel direct AMPK agonist, D561-0775 from a compound library by using molecular docking screening technique. We demonstrated that D561-0775 exhibited significant inhibitory effect on gefitinib-resistant NSCLC cell lines but less cytotoxicity on normal cells. Furthermore, D561-0775 demonstrated a remarkable in vitro AMPK enzyme activation effect. Taken together, D561-0775 showed potential anti-cancer activity via inducing apoptosis, cell cycle arrest, suppressing glycolysis and cholesterol synthesis after activation of AMPK in gefitinib-resistant H1975 cells. D561-0775 has provided a new chemical structure that could be developed as cancer drug for gefitinib-resistant NSCLC patients through inhibition lipid metabolism by directly targeting at AMPK directly. PMID:29221189

  1. 75 FR 9431 - Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities...

    Science.gov (United States)

    2010-03-02

    ... Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities Experienced by U.S. Firms and Small.... General information concerning the Commission may also be obtained by accessing its Internet server ( http..., investigation No. 332-509, Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and...

  2. Intelligent landing strategy for the small bodies: from passive bounce to active trajectory control

    Science.gov (United States)

    Cui, Pingyuan; Liu, Yanjie; Yu, Zhengshi; Zhu, Shengying; Shao, Wei

    2017-08-01

    Landing exploration is an important way to improve the understanding of small bodies. Considering the weak gravity field as well as the strict attitude constraints which make bounce a common situation and a tough issue for safe landing on small bodies, a novel active trajectory control-based intelligent landing strategy is proposed to improve the safety and reliability of mission. The scenarios of intelligent landing strategy for both safe landing and hopping exploration are introduced in detail and a potential structure for autonomous navigation and control system is presented. Furthermore, a convex optimization-based control algorithm is developed, which is the key technology fulfilling the active trajectory control. Meanwhile a novel discretization method based on the fourth-order Runge-Kutta rule is proposed to improve the accuracy. A helpful adjustment process of time-to-landing is also introduced when the feasible trajectory does not exist. Comprehensive simulations about the proposed intelligent landing strategy are performed to demonstrate the improved safety and accuracy of both landing and hopping exploration on small bodies. Meanwhile, the performance and accuracy of the proposed convex optimization-based control algorithms is also compared and discussed thoroughly. Some useful conclusions for control system design are also obtained.

  3. Circadian phenomena and irradiation. Modifications of enzyme activity in the small intestine after sublethal exposure

    Energy Technology Data Exchange (ETDEWEB)

    Becciolini, A.; Giache, V.; Scubla, E.; D' Abbondio, D.

    1987-01-01

    Irradiation effects after a 3 Gy dose administered at four different times of a 24 h light/darkness cycle were studied: The modifications in the brush border enzyme activity of epithelial cells of the small intestine were determined. In controls the activity of these enzymes showed circadian oscillations with the maximum during the dark period and the minimum during the light period. The trend after irradiation in the various groups was very similar but some differences were present specially at the initial intervals when the effect appeared to be different depending on the enzyme level at the time of exposure. Lactase activity in animals irradiated at 0.00 and 18.00 o'clock returned to control levels later than in the other groups.

  4. ACTIVITY THEORY APPLIED AT CHANNEL EXPANSIONS IN SMALL AND MEDIUM ENTERPRISES

    Directory of Open Access Journals (Sweden)

    Siw Lundqvist

    2017-06-01

    Full Text Available Today’s commonly carried out channel expansions of commerce could be both costly and problematic to manage. Especially for small and medium-sized enterprises (SMEs that often suffer from a lack of digital competence, time and monetary resources in generally. Still, these transitions would be necessary to carry out because of customer demands and expectations concerning 24/7 availability, and access to digital commerce alternatives. Scarce resources are important reasons to search for how to carry out channel expansions with minimized problems. Activity theory (AT focuses on the whole in order to detect problems that hinder successful outcomes. Hence, this theory was applied to prior findings, from a project about SME’s channel expansions, highlighting several problems that could appear during these activities. Implications for research foremost involve issues connected to the use of AT; implications for practice particularly concern if and how AT could be used to support channel broadening activities.

  5. Small-conductance Ca2+-activated K+ channels: form and function.

    Science.gov (United States)

    Adelman, John P; Maylie, James; Sah, Pankaj

    2012-01-01

    Small-conductance Ca(2+)-activated K(+) channels (SK channels) are widely expressed throughout the central nervous system. These channels are activated solely by increases in intracellular Ca(2+). SK channels are stable macromolecular complexes of the ion pore-forming subunits with calmodulin, which serves as the intrinsic Ca(2+) gating subunit, as well as with protein kinase CK2 and protein phosphatase 2A, which modulate Ca(2+) sensitivity. Well-known for their roles in regulating somatic excitability in central neurons, SK channels are also expressed in the postsynaptic membrane of glutamatergic synapses, where their activation and regulated trafficking modulate synaptic transmission and the induction and expression of synaptic plasticity, thereby affecting learning and memory. In this review we discuss the molecular and functional properties of SK channels and their physiological roles in central neurons.

  6. [Progress of methodology for identifying target protein of natural active small molecules].

    Science.gov (United States)

    Tu, Peng-Fei; Zeng, Ke-Wu; Liao, Li-Xi; Song, Xiao-Min

    2016-01-01

    Drug targets are special molecules that can interact with drugs and exert pharmacological functions in human body. The natural active small molecules are the bioactive basis of traditional Chinese medicine, and the mechanism study is a hot topic now, especially for the identification of their target proteins. However, little progress has been made in this field until now. Here, we summarized the recent technologies and methods for the identification of target proteins of natural bioactive small molecules, and introduced the main research methods, principles and successful cases in this field. We also explored the applicability and discussed the advantages and disadvantages among different methods. We hope this review can be used as a reference for the researchers who engaged in natural pharmaceutical chemistry, pharmacology and chemical biology. Copyright© by the Chinese Pharmaceutical Association.

  7. Active Control of a Small-Scale Wind Turbine Blade Containing Magnetorheological Fluid

    Directory of Open Access Journals (Sweden)

    Fevzi Cakmak Bolat

    2018-02-01

    Full Text Available This research study proposes a new active control structure to suppress vibrations of a small-scale wind turbine blade filled with magnetorheological (MR fluid and actuated by an electromagnet. The aluminum blade structure is manufactured using the SH3055 (Bergey Windpower Co. Inc., Norman, OK, USA code numbered airfoil which is designed for use on small wind turbines. A dynamic interaction model between the MR fluid and the electromagnetic actuator is constructed to obtain a force relation. A detailed characterization study is presented for the proposed actuator to understand the nonlinear behavior of the electromagnetic force. A norm based multi-objective H2/H∞ controller is designed using the model of the elastic blade element. The H2/H∞ controller is experimentally implemented under the impact and steady state aerodynamic load conditions. The results of experiments show that the MR fluid- electromagnetic actuator is effective for suppressing vibrations of the blade structure.

  8. Supported gold catalysis: from small molecule activation to green chemical synthesis.

    Science.gov (United States)

    Liu, Xiang; He, Lin; Liu, Yong-Mei; Cao, Yong

    2014-03-18

    With diminishing natural resources, there is an ever-increasing demand for cost-effective and sustainable production of fine and commodity chemicals. For this purpose, there is a need for new catalytic methods that can permit efficient and targeted conversion of fossil and biorenewable feedstocks with lower energy requirements and environmental impact. A significant number of industrial catalytic processes are performed by platinum-group-metal (PGM)-based heterogeneous catalysts capable of activating a range of important small molecules, such as CO, O2, H2, and N2. In contrast, there is a general feeling that gold (Au) cannot act as an efficient catalyst because of its inability to activate most molecules, which is essential to any catalytic processes. As a consequence, researchers have long neglected the potential for use of gold as a catalyst. In recent years, however, chemists have put forth tremendous effort and progress in the use of supported gold catalysts to facilitate a variety of useful synthetic transformations. The seminal discovery by Haruta in 1987 that suitably prepared Au-based catalysts were surprisingly active for CO oxidation even at 200 K initiated rapid development of the field. Since then, researchers have widely employed Au-based catalysts in many types of mild chemical processes, with special focus on selective reactions involving small molecules (for example, CO, H2O, O2, or H2) as a reactant. That gold in the form of tiny nanoparticles (NPs, generally less than 5 nm in diameter) can subtly activate the reactant molecules under mild conditions has been evoked to explain the superior effectiveness of gold compared with conventional PGMs. In this context, Au-based catalysts are gaining great significance in developing new green processes with improved selectivity and energy minimization. In this Account, we describe our efforts toward the development of a range of green and selective processes largely through the appropriate choice of Au

  9. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo

    Directory of Open Access Journals (Sweden)

    Lavu Siva

    2009-03-01

    Full Text Available Abstract Background Calorie restriction (CR produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetylase SIRT1 has been implicated as one of the key downstream regulators of CR in yeast, rodents, and humans. Small molecule activators of SIRT1 have been identified that exhibit efficacy in animal models of diseases typically associated with aging including type 2 diabetes. To identify molecular processes induced in the liver of mice treated with two structurally distinct SIRT1 activators, SIRT501 (formulated resveratrol and SRT1720, for three days, we utilized a systems biology approach and applied Causal Network Modeling (CNM on gene expression data to elucidate downstream effects of SIRT1 activation. Results Here we demonstrate that SIRT1 activators recapitulate many of the molecular events downstream of CR in vivo, such as enhancing mitochondrial biogenesis, improving metabolic signaling pathways, and blunting pro-inflammatory pathways in mice fed a high fat, high calorie diet. Conclusion CNM of gene expression data from mice treated with SRT501 or SRT1720 in combination with supporting in vitro and in vivo data demonstrates that SRT501 and SRT1720 produce a signaling profile that mirrors CR, improves glucose and insulin homeostasis, and acts via SIRT1 activation in vivo. Taken together these results are encouraging regarding the use of small molecule activators of SIRT1 for therapeutic intervention into type 2 diabetes, a strategy which is currently being investigated in multiple clinical trials.

  10. Co-development of a Wiki for Tracking the Environmental Footprint of Small Business Activities

    Directory of Open Access Journals (Sweden)

    Helen Hasan

    2017-10-01

    Full Text Available Aim/Purpose: Climate change mitigation is a global challenge, in which academia and business have a role to play. This research explores ways to develop a freely-available information system that would enable small businesses to identify and reduce their environmental footprint. Background: While large organizations have the resources to track emissions and other pertinent data, small businesses may not, despite intentions to be more environmentally responsible. Freely available applications to track emissions focus on the carbon footprint of things, whereas activities are a more meaningful unit of analysis for business managers. Methodology: Using a design science research approach, we conducted a study of a collaborative project that investigated how a low-cost, freely-available online wiki could be developed by group of students, under the guidance of university scholars and business owners. In the project, different student groups were tasked to create the wiki, input content and design a dashboard interface for managers to find data relevant to their business. The research takes an information systems view of the project, relying on the holistic notion of activity from activity theory and taking a design science approach to the study. Contribution: The paper contributes to the practices of green information systems, climate change, and small business. Theoretically it provides new insights into the linear view of design science in resource poor, collaborative projects. Findings: The research demonstrates the viability of an online system to track the envi-ronmental footprint of business activities. It reveals the challenges from a design science perspective of attempts to create online systems using freely available products and labor. Recommendations for Practitioners: Meaningful information systems to assist small businesses to manage their environmental footprint should focus on activities not things, be low cost and easy to use

  11. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  12. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    International Nuclear Information System (INIS)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya; Nan, Fa-Jun; Li, Jia

    2013-01-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome

  13. Activity of small businesses in the process of building relationships in the supply chain

    Directory of Open Access Journals (Sweden)

    Waldemar Glabiszewski

    2016-09-01

    Full Text Available Background: Multilateral cooperation is an inherent part of any business and one of the most important factors in the success of modern enterprise. Therefore, in this paper the author addresses the problem of building relationships with partners in a supply chain and focuses on the development of relational abilities as well as inter-organizational ties, and his exploration and considerations are applied to small businesses. Methods: In the empirical part of the work the author aims to identify the scope and intensity of the involvement of small businesses in taking measures to build relationships with supply chain partners. The basic source of data is the results of empirical research conducted by the author in 2014 by means of mail and personal surveys. A questionnaire specially designed for this purpose was sent out to 500 randomly selected small businesses from the kujawsko-pomorskie region (Poland. Results: The author provides a positive verification of the formulated hypotheses, which imply that small businesses take action to develop both their ability to establish and maintain relationships and the actual relationships with partners in the supply chain. However, they take various activities into account, but not all, and this is mostly done in a manner that is not systematically, particularly in relation to those undertakings which require more sophisticated skills and tools. Conclusions: Propagating the theory of relational abilities among small businesses and the concepts indicating the forms of their development and use appears to be justified, even if these companies seem to be aware of the impact of the quality of relationships with supply chain partners on the effects of cooperation with them.

  14. Fabrication of 0.5-inch diameter FBR mixed oxide fuel pellets

    International Nuclear Information System (INIS)

    Rasmussen, D.E.; Benecke, M.W.; McCord, R.B.

    1979-01-01

    Large diameter (0.535 inch) mixed oxide fuel pellets for Fast Breeder Reactor application were successfully fabricated by the cold-press-and-sinter technique. Enriched UO 2 , PuO 2 -UO 2 , and PuO 2 -ThO 2 compositions were fabricated into nominally 90% theoretical density pellets for the UO 2 and PuO 2 -UO 2 compositions, and 88% and 93% T.D. for the PuO 2 -ThO 2 compositions. Some processing adjustments were required to achieve satisfactory pellet quality and density. Furnace heating rate was reduced from 200 to 50 0 C/h for the organic binder burnout cycle for the large, 0.535-inch diameter pellets to eliminate pellet cracking during sintering. Additional preslugging steps and die wall lubrication during pressing were used to eliminate pressing cracks in the PuO 2 -ThO 2 pellets

  15. Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

    1997-01-01

    Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... and the clinical parameters. This is the first report of a study using a quantitative method to compare levels of the components of the plasminogen activation system in tissue extracts from the two major lung cancer groups. The study shows that uPA, PAI-1 and uPAR are present in SCLC-tissue, suggesting...

  16. Discovery of novel small molecule activators of β-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Folkert Verkaar

    Full Text Available Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.

  17. Schlesinger's Telescope: A Brief History of the Yale 26-inch Refractor

    Science.gov (United States)

    van Altena, W. F.; Hoffleit, E. D.

    2003-08-01

    Frank Schlesinger began planning for the establishment of a southern observatory when he arrived at Yale in 1920. After discussing the possibility of a location in Auckland, New Zealand and gathering site survey observations for a four-month period, he decided to select a site in Johannesburg, South Africa. A large photographically corrected 26-inch objective was ground, polished and completed by James McDowell in 1923, while the telescope was built largely in the Yale shops in New Haven. Schlesinger left New Haven in 1924 with the lens, and the telescope followed shortly thereafter. Installation of the 26-inch refractor was completed in early June and dedicated by the Prince of Wales on June 22, 1924. The principal observational program for the 26-inch refractor was the determination of parallaxes of the bright stars and it was continued until 1952, when the telescope was moved to Mt. Stromlo due to the deteriorating sky conditions in Johannesburg. The parallax program continued at Mt. Stromlo until 1963 when the telescope was donated to the Commonwealth Observatory and the Yale-Columbia project moved to Argentina, Columbia having joined with Yale in 1943. Approximately 70,000 plates were taken with the refractor for the parallax programs and about 2,000 stellar parallaxes determined. The Schlesinger 26-inch refractor was destroyed by a firestorm on January 18, 2003, along with the other telescopes on Mount Stromlo, the workshop, library and many of the residences. This event was a sad ending to a telescope that played a major role in defining our knowledge of the distances, motions and masses of the brighter stars during the first half of the 20th century.

  18. Design of a 18F production system at ORNL 86-inch cyclotron

    International Nuclear Information System (INIS)

    Shaeffer, M.C.; Barreto, F.; Datesh, J.R.; Goldstein, B.R.

    1977-01-01

    A target system for the production of 18 F by proton bombardment of H 2 18 O was designed for the ORNL 86-inch cyclotron facility. The system consists of concentric titanium and aluminum cylinders. Oxygen-18-enriched H 2 O circulates through the inner titanium cylinder and through an external heat exchanger with cooling water flowing in the annulus. Yields of 5.0 curies are expected for a 250-μA proton beam current and 24-min irradiation time

  19. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Christine M. [Brandeis Univ., Waltham, MA (United States)

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  20. Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

    Directory of Open Access Journals (Sweden)

    Arne Bilet

    Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

  1. Using Thermogenic Beige Cells to Identify Biologically Active Small Molecules and Peptides.

    Science.gov (United States)

    Wu, Ling; Xu, Bin

    2017-01-01

    Incorporating molecular libraries in chemical biology screenings in cultured cells has been successfully used for gene discovery in many cellular processes. It has the unique potential to uncover novel mechanisms of complex cellular biology through the screening of small molecules and protein biologics in relevant cell-based assays. Recent development in the understanding and generation of thermogenic adipocytes provides opportunities for potential anti-obesity therapeutics discovery. In this chapter, we describe screening methods using thermogenic beige cells to identify novel compounds and peptides that activate adipocyte thermogenesis.

  2. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells

    OpenAIRE

    Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Kanterewicz, Beatriz; Balius, Trent; Belani, Chandra P.; Hershberger, Pamela A.

    2010-01-01

    We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel le...

  3. A small animal model of human Helicobacter pylori active chronic gastritis.

    Science.gov (United States)

    Lee, A; Fox, J G; Otto, G; Murphy, J

    1990-11-01

    Isolation of a spiral-shaped bacterium closely related to Helicobacter pylori from the cat stomach made it possible to investigate new small animal models of gastric infection. Pure cultures of this bacterium, provisionally named "Helicobacter felis," were fed to germ-free mice. The organism colonized the stomach in large numbers in mucus and deep in the gastric pits and showed the same gastric trophism found with H. pylori. Significant histopathology was seen in all H. felis-infected mice. At 2 weeks postinfection, an acute inflammatory response was seen composed primarily of eosinophils and neutrophils. At 3 weeks, the polymorphonuclear response was more pronounced with large numbers of neutrophils in some areas forming small microabscesses. Lymphocytes also increased in number. By 8 weeks, several relatively large lymphoid nodules were present in the submucosa. Multiple small microabscesses were still present in the pyloric mucosa. This is the first animal model of bacterial gastritis to be described that shows progression from acute inflammation to persistent acute on chronic inflammation (active chronic) as is seen in human infection with H. pylori.

  4. Photospheric Velocity Structures during the Emergence of Small Active Regions on the Sun

    Energy Technology Data Exchange (ETDEWEB)

    Khlystova, Anna [Institute of Solar-Terrestrial Physics SB RAS, Lermontov St., 126a, 664033 Irkutsk (Russian Federation); Toriumi, Shin, E-mail: hlystova@iszf.irk.ru, E-mail: shin.toriumi@nao.ac.jp [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan)

    2017-04-10

    We study the plasma flows in the solar photosphere during the emergence of two small active regions, NOAA 9021 and 10768. Using Solar and Heliospheric Observatory /Michelson Doppler Imager data, we find that the strong plasma upflows appear at the initial stage of active region formation, with maximum upflow velocities of −1650 and −1320 m s{sup −1}. The structures with enhanced upflows have size ∼8 Mm in diameter, and they exist for 1–2 hr. The parameters of the enhanced upflows are consistent with those of the large active region NOAA 10488, which may suggest the possibility that the elementary emerging magnetic loops that appear at the earliest phase of active region formation have similar properties, irrespective of scales of active regions. Comparison between the observations and a numerical simulation of magnetic flux emergence shows a striking consistency. We find that the driving force of the plasma upflow is at first the gas pressure gradient and later the magnetic pressure gradient.

  5. Small Molecule-Induced Allosteric Activation of the Vibrio Cholerae RTX Cysteine Protease Domain

    Energy Technology Data Exchange (ETDEWEB)

    Lupardus, P.J.; Shen, A.; Bogyo, M.; Garcia, K.C.

    2009-05-19

    Vibrio cholerae RTX (repeats in toxin) is an actin-disrupting toxin that is autoprocessed by an internal cysteine protease domain (CPD). The RTX CPD is efficiently activated by the eukaryote-specific small molecule inositol hexakisphosphate (InsP{sub 6}), and we present the 2.1 angstrom structure of the RTX CPD in complex with InsP{sub 6}. InsP{sub 6} binds to a conserved basic cleft that is distant from the protease active site. Biochemical and kinetic analyses of CPD mutants indicate that InsP{sub 6} binding induces an allosteric switch that leads to the autoprocessing and intracellular release of toxin-effector domains.

  6. Osculum dynamics and filtration activity in small single-osculum explants of the demosponge Halichondria panicea

    DEFF Research Database (Denmark)

    Kumala, Lars; Riisgård, Hans Ulrik; Canfield, Donald Eugene

    2017-01-01

    the clearance method. Osculum dynamics, as expressed by temporal variation of the OSA, including osculum contraction and expansion, correlated with variability in the explant filtration rate, and no water pumping was observed during periods of osculum closure. A linear relationship between filtration rate (FR......Contraction-inflation behavior, including the closure and opening of the exhalant opening (osculum), is common among sponges. This behavior may temporally affect filtration activity, making it difficult to study and understand sponge feeding biology. To examine the interplay between osculum...... dynamics and filtration activity, small (18 mm3) single-osculum explants of the demosponge Halichondria panicea were studied. Time-lapse video stereo-microscope recordings of the osculum cross-sectional area (OSA) were made simultaneously with measurements of the filtration rate (∼15°C, ∼20 PSU) using...

  7. Solid State Inflation Balloon Active Deorbiter: Scalable Low-Cost Deorbit System for Small Satellites

    Science.gov (United States)

    Huang, Adam

    2016-01-01

    The goal of the Solid State Inflation Balloon Active Deorbiter project is to develop and demonstrate a scalable, simple, reliable, and low-cost active deorbiting system capable of controlling the downrange point of impact for the full-range of small satellites from 1 kg to 180 kg. The key enabling technology being developed is the Solid State Gas Generator (SSGG) chip, generating pure nitrogen gas from sodium azide (NaN3) micro-crystals. Coupled with a metalized nonelastic drag balloon, the complete Solid State Inflation Balloon (SSIB) system is capable of repeated inflation/deflation cycles. The SSGG minimizes size, weight, electrical power, and cost when compared to the current state of the art.

  8. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment.

    Science.gov (United States)

    Hyer, Marc L; Milhollen, Michael A; Ciavarri, Jeff; Fleming, Paul; Traore, Tary; Sappal, Darshan; Huck, Jessica; Shi, Judy; Gavin, James; Brownell, Jim; Yang, Yu; Stringer, Bradley; Griffin, Robert; Bruzzese, Frank; Soucy, Teresa; Duffy, Jennifer; Rabino, Claudia; Riceberg, Jessica; Hoar, Kara; Lublinsky, Anya; Menon, Saurabh; Sintchak, Michael; Bump, Nancy; Pulukuri, Sai M; Langston, Steve; Tirrell, Stephen; Kuranda, Mike; Veiby, Petter; Newcomb, John; Li, Ping; Wu, Jing Tao; Powe, Josh; Dick, Lawrence R; Greenspan, Paul; Galvin, Katherine; Manfredi, Mark; Claiborne, Chris; Amidon, Benjamin S; Bence, Neil F

    2018-02-01

    The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment.

  9. Preparation of extra-small nisin nanoparticles for enhanced antibacterial activity after autoclave treatment.

    Science.gov (United States)

    Chang, Ranran; Lu, Hao; Li, Man; Zhang, Shuangling; Xiong, Liu; Sun, Qingjie

    2018-04-15

    Nisin is applied broadly in the food industry as an antimicrobial peptide. The objective of this study is to prepare nisin nanoparticles using free nisin by a facile nanoprecipitation technique and to investigate their antimicrobial activity after high-temperature processing. Transmission electron microscopic images showed that the size of extra-small nisin nanoparticles with different initial concentrations of nisin (0.1%, 0.3% and 0.5%) was 5, 10 and 15 nm, respectively. The nisin nanoparticles were stable at pH 5.0 with the smallest size. Moreover, nisin nanoparticles exhibited a higher antimicrobial activity than free nisin at a concentration below 2.0 mg/ml after autoclave treatment. These results suggested that nisin nanoparticles could serve as a potential food preservative. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium

    DEFF Research Database (Denmark)

    Rosenbaum, Sofia T; Svalø, Julie; Nielsen, Karsten

    2012-01-01

    Small-conductance calcium-activated potassium (SK3) channels have been detected in human myometrium and we have previously shown a functional role of SK channels in human myometrium in vitro. The aims of this study were to identify the precise localization of SK3 channels and to quantify SK3 m...... muscle cells, and that the molecular expression of SK3 channels is higher in non-pregnant compared to pregnant myometrium. On the basis of our previous study and the present findings, we propose that SK3 activators reduce contractility in human myometrium by modulating telocyte function....... This is the first report to provide evidence for a possible role of SK3 channels in human uterine telocytes....

  11. Start small, dream big: Experiences of physical activity in public spaces in Colombia.

    Science.gov (United States)

    Díaz Del Castillo, Adriana; González, Silvia Alejandra; Ríos, Ana Paola; Páez, Diana C; Torres, Andrea; Díaz, María Paula; Pratt, Michael; Sarmiento, Olga L

    2017-10-01

    Multi-sectoral strategies to promote active recreation and physical activity in public spaces are crucial to building a "culture of health". However, studies on the sustainability and scalability of these strategies are limited. This paper identifies the factors related to the sustainability and scaling up of two community-based programs offering physical activity classes in public spaces in Colombia: Bogotá's Recreovía and Colombia's "Healthy Habits and Lifestyles Program-HEVS". Both programs have been sustained for more than 10years, and have benefited 1455 communities. We used a mixed-methods approach including semi-structured interviews, document review and an analysis of data regarding the programs' history, characteristics, funding, capacity building and challenges. Interviews were conducted between May-October 2015. Based on the sustainability frameworks of Shediac-Rizkallah and Bone and Scheirer, we developed categories to independently code each interview. All information was independently analyzed by four of the authors and cross-compared between programs. Findings showed that these programs underwent adaptation processes to address the challenges that threatened their continuation and growth. The primary strategies included flexibility/adaptability, investing in the working conditions and training of instructors, allocating public funds and requesting accountability, diversifying resources, having community support and champions at different levels and positions, and carrying out continuous advocacy to include physical activity in public policies. Recreovía and HEVS illustrate sustainability as an incremental, multi-level process at different levels. Lessons learned for similar initiatives include the importance of individual actions and small events, a willingness to start small while dreaming big, being flexible, and prioritizing the human factor. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Membrane Active Small Molecules Show Selective Broad Spectrum Antibacterial Activity with No Detectable Resistance and Eradicate Biofilms.

    Science.gov (United States)

    Hoque, Jiaul; Konai, Mohini M; Gonuguntla, Spandhana; Manjunath, Goutham B; Samaddar, Sandip; Yarlagadda, Venkateswarlu; Haldar, Jayanta

    2015-07-23

    Treating bacterial biofilms with conventional antibiotics is limited due to ineffectiveness of the drugs and higher propensity to develop bacterial resistance. Development of new classes of antibacterial therapeutics with alternative mechanisms of action has become imperative. Herein, we report the design, synthesis, and biological evaluations of novel membrane-active small molecules featuring two positive charges, four nonpeptidic amide groups, and variable hydrophobic/hydrophilic (amphiphilic) character. The biocides synthesized via a facile methodology not only displayed good antibacterial activity against wild-type bacteria but also showed high activity against various drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and β-lactam-resistant Klebsiella pneumoniae. Further, these biocides not only inhibited the formation of biofilms but also disrupted the established S. aureus and E. coli biofilms. The membrane-active biocides hindered the propensity to develop bacterial resistance. Moreover, the biocides showed negligible toxicity against mammalian cells and thus bear potential to be used as therapeutic agents.

  13. Small-team active learning in an integrated pharmacokinetics course series.

    Science.gov (United States)

    Jones, Curtis E; Dyar, S Craig; McKeever, Andrea L

    2012-10-12

    To implement a pharmacokinetics curriculum that used small-team active learning and assess students' perceptions. The course design and delivery were based on delivery of Student Team lecture followed by concept reinforcement through problem-based learning sessions. Course faculty members facilitated classroom and problem-based learning discussions to promote an active-learning environment. An anonymous survey instrument was administered to students prior to and following completion of the pharmacokinetics course. Students reported a significant decrease in anxiety from 67% to 44% related to working in small teams upon completion of the course. However, students maintained negative perceptions related to peer teaching, with 80% of students reporting anxiety related to receipt of course information from peers. The course had a positive impact on students' ability to apply concepts to case-based scenarios, but little impact on their perceived ability to identify and critically evaluate new material and present that material to their peer team. The team-based structure defined herein for delivery of a pharmacokinetics curriculum offers students a tangible method to increase their comfort and confidence in the application of pharmacokinetic concepts in therapy.

  14. Anaphylaxis Imaging: Non-Invasive Measurement of Surface Body Temperature and Physical Activity in Small Animals.

    Directory of Open Access Journals (Sweden)

    Krisztina Manzano-Szalai

    Full Text Available In highly sensitized patients, the encounter with a specific allergen from food, insect stings or medications may rapidly induce systemic anaphylaxis with potentially lethal symptoms. Countless animal models of anaphylaxis, most often in BALB/c mice, were established to understand the pathophysiology and to prove the safety of different treatments. The most common symptoms during anaphylactic shock are drop of body temperature and reduced physical activity. To refine, improve and objectify the currently applied manual monitoring methods, we developed an imaging method for the automated, non-invasive measurement of the whole-body surface temperature and, at the same time, of the horizontal and vertical movement activity of small animals. We tested the anaphylaxis imaging in three in vivo allergy mouse models for i milk allergy, ii peanut allergy and iii egg allergy. These proof-of-principle experiments suggest that the imaging technology represents a reliable non-invasive method for the objective monitoring of small animals during anaphylaxis over time. We propose that the method will be useful for monitoring diseases associated with both, changes in body temperature and in physical behaviour.

  15. Physiological response and activity profile in recreational small-sided football

    DEFF Research Database (Denmark)

    Randers, Morten Bredsgaard; Nielsen, Jens J; Bangsbo, Jens

    2014-01-01

    We examined the effect of the number of players on the activity profile and physiological response to small-sided recreational football games with fixed relative pitch size. Twelve untrained men (age: 33.0 ± 6.4 (± standard deviation) years, fat%: 22.4 ± 6.1%, VO₂ max: 43.3 ± 5.2 mL/min/kg) compl......We examined the effect of the number of players on the activity profile and physiological response to small-sided recreational football games with fixed relative pitch size. Twelve untrained men (age: 33.0 ± 6.4 (± standard deviation) years, fat%: 22.4 ± 6.1%, VO₂ max: 43.3 ± 5.2 m...... observed during 3v3, 5v5, and 7v7, respectively, with no difference between formats. Similar total distance (3676 ± 478, 3524 ± 467, and 3577 ± 500 m), high-intensity distance (349 ± 145, 406 ± 134, and 409 ± 165 m), and RPE (4.7 ± 1.6, 4.9 ± 2.1, and 4.6 ± 1.8) were also observed. The number of intense...... accelerations (500 ± 139 vs 459 ± 143 and 396 ± 144) were higher (P responses for 6-14 players when pitch size is adapted, providing further evidence...

  16. The small neurotoxin apamin blocks not only small conductance Ca2+ activated K+ channels (SK type) but also the voltage dependent Kv1.3 channel.

    Science.gov (United States)

    Voos, Patrick; Yazar, Mehtap; Lautenschläger, René; Rauh, Oliver; Moroni, Anna; Thiel, Gerhard

    2017-09-01

    Apamin is frequently used as a specific blocker of small-conductance Ca 2+ -activated (SK type) K + channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC 50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool.

  17. The George C. Marshall Space Flight Center's 14 X 14-Inch Trisonic Wind Tunnel: A Historical Perspective

    Science.gov (United States)

    Springer, A.

    1994-01-01

    A history of the National Aeronautics and Space Administration (NASA) George C. Marshall Space Flight Center's (MSFC) 14 x 14-Inch Trisonic Wind Tunnel is presented. Its early and continuing role in the United States space program is shown through highlights of the tunnel's history and the major programs tested in the tunnel over the past 40 years. The 14-Inch Tunnel has its beginning with the Army in the late 1950's under the Army Ballistic Missile Agency (ABMA). Such programs as the Redstone, Jupiter, Pershing, and early Saturn were tested in the 14-Inch Tunnel in the late 1950's. America's first launch vehicle, the Jupiter C, was designed and developed using the 14-Inch Wind Tunnel. Under NASA, the 14-Inch Wind Tunnel has made large contributions to the Saturn, Space Transportation System, and future launch vehicle programs such as Shuttle-C and the National Launch System. A technical description of the tunnel is presented for background information on the type and capabilities of the 14-Inch Wind Tunnel. The report concludes in stating: the 14-Inch Wind Tunnel as in speed of sound; transonic, at or near the speed of sound the past, will continue to play a large but unseen role in he development of America's space program.

  18. Epidermal activation of the small GTPase Rac1 in psoriasis pathogenesis.

    Science.gov (United States)

    Winge, Mårten C G; Marinkovich, M Peter

    2017-01-05

    The small GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1) plays a central role in skin homeostasis, including barrier function, wound healing and inflammatory responses. Psoriasis is a common skin disease characterized by deregulation of these functions, and affected skin exhibit keratinocyte hyperproliferation, inflammation and immune cell infiltration. Although psoriasis is often triggered by environmental stimulus, there is a strong genetic association with genes expressed in both immune cells and keratinocytes, of which several are linked to Rac1 signaling. Rac1 is highly active in human psoriatic lesional skin and keratinocytes, and keratinocyte-specific overexpression of an activated mutant of Rac1, Rac1 V12 , in a transgenic mouse model closely mimics the presentation of human psoriasis. Both Rac1 activation in keratinocytes and immune derived stimulus are required to drive psoriasiform signaling in transgenic mouse and human xenograft models of psoriasis. Therefore, understanding how increased Rac1 activation in psoriatic epidermis is regulated is central to understanding how the abnormal crosstalk between keratinocytes and immune cells is maintained.

  19. Fishing activity in Northern Rio de Janeiro State (Brazil and its relation with small cetaceans

    Directory of Open Access Journals (Sweden)

    Ana Paula Madeira Di Beneditto

    1998-01-01

    Full Text Available Research on fishing activity at Atafona village, in Northern Rio de Janeiro, Brazil (21°35'S, was carried out between 1987-96 for the purpose of relating it to the accidental capture of small cetaceans and of estimating the relationship between fishing activity and the diet of small cetaceans. Data on fishing operations were obtained at the cold storage plants management, from interviews with fishermen and personal observations. The most representative fishing resources were Xyphopenaeus kroyeri, Micropogonias furnieri, Carcharhinus plumbeus, C. acronotus,and Rhizoprionodon porosus. Gillnets are responsible for the accidental capture of small cetaceans in the region, mainly Pontoporia blainvillei and Sotalia fluviatilis (marine form. Four types of gillnets that are used on the region ("minjuada", "sarda", "caçoá" and "pescadinha" were dangerous to these species because they are placed in their preferred habitat. There is no competition between fishermen and small cetaceans due to the selection in the capture of commercialized fishesInvestigação sobre a atividade pesqueira na localidade de Atafona, Norte do Rio de Janeiro, Brasil (21º25`S, foi conduzida entre 1987-96 com o objetivo de relacioná-la com a captura acidental e a dieta dos pequenos cetáceos. Dados sobre as operações pesqueiras foram obtidos na administração dos entrepostos de pesca, através de entrevistas com pescadores e observações pessoais. Os recursos pesqueiros mais representativos foram Xyphopenaeus kroyeri, Micropogonias furnieri, Carcharhinus plumbeus, C. acronotus, and Rhizoprionodon porosus. As redes de espera são responsáveis pela captura acidental de pequenos cetáceos na região, principalmente de Pontoporia blainvillei e Sotalia fluviatilis (forma marinha. Quatro tipos de redes de espera que são usadas na região ("minjuada", "sarda", "caçoá" and "pescadinha" foram mais perigosas para essas espécies pois são colocadas no seu hábitat preferencial

  20. In vitro and in vivo activity of a novel antifungal small molecule against Candida infections.

    Directory of Open Access Journals (Sweden)

    Sarah Sze Wah Wong

    Full Text Available Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC 0.2-1.6 µg/ml. In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use.

  1. Screening of pharmacologically active small molecule compounds identifies antifungal agents against Candida biofilms

    Directory of Open Access Journals (Sweden)

    Takao eWatamoto

    2015-12-01

    Full Text Available Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using C. albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM using an antifungal susceptibility test (AST. To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and 9 compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration.Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal

  2. The Nutrient Stress-induced Small GTPase Rab5 Contributes to the Activation of Vesicle Trafficking and Vacuolar Activity*

    Science.gov (United States)

    Nakatsukasa, Kunio; Kanada, Akira; Matsuzaki, Mariko; Byrne, Stuart D.; Okumura, Fumihiko; Kamura, Takumi

    2014-01-01

    Rab family small GTPases regulate membrane trafficking by spatiotemporal recruitment of various effectors. However, it remains largely unclear how the expression and functions of Rab proteins are regulated in response to extracellular or intracellular stimuli. Here we show that Ypt53, one isoform of Rab5 in Saccharomyces cerevisiae, is up-regulated significantly under nutrient stress. Under non-stress conditions, Vps21, a constitutively expressed Rab5 isoform, is crucial to Golgi-vacuole trafficking and to vacuolar hydrolase activity. However, when cells are exposed to nutrient stress for an extended period of time, the up-regulated Ypt53 and the constitutive Vps21 function redundantly to maintain these activities, which, in turn, prevent the accumulation of reactive oxygen species and maintain mitochondrial respiration. Together, our results clarify the relative roles of these constitutive and nutrient stress-inducible Rab5 proteins that ensure adaptable vesicle trafficking and vacuolar hydrolase activity, thereby allowing cells to adapt to environmental changes. PMID:24923442

  3. The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte E; Drivsholm, Lars; Pappot, Helle

    2013-01-01

    The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our...

  4. Assessment of RELAP/MOD3 using BETHSY 6.2TC 6-inch cold leg side break comparative test

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Young-Jong; Jeong, Jae-Jun; Chang, Won-Pyo; Kim, Dong-Su [Korea Atomic Energy Research Institute, Yusung, Taejon (Korea, Republic of)] [and others

    1996-10-01

    This report presents the results of the RELAP5/MOD3 Version 7j assessment on BETHSY 6.2TC. BETHSY 6.2TC test corresponding to a six inch cold leg break LOCA of the Pressurizer Water Reactor(PWR). The primary objective of the test was to provide reference data of two facilities of different scales (BETHSY and LSTF facility). On the other hand, the present calculation aims at analysis of RELAP5/N4OD3 capability on the small break LOCA simulation, The results of calculation have shown that the RELAP5/MOD3 reasonably predicts occurrences as well as trends of the major phenomena such as primary pressure, timing of loop seal clearing, liquid hold up, etc. However, some disagreements also have been found in the predictions of loop seal clearing, collapsed core water level after loop seal clearing, and accumulator injection behaviors. For better understanding of discrepancies in same predictions, several sensitivity calculations have been performed as well. These include the changes of two-phase discharge coefficient at the break junction and some corrections of the interphase drag term. As result, change of a single parameter has not improved the overall predictions and it has been found that the interphase drag model has still large uncertainties.

  5. Assessment of RELAP/MOD3 using BETHSY 6.2TC 6-inch cold leg side break comparative test

    International Nuclear Information System (INIS)

    Chung, Young-Jong; Jeong, Jae-Jun; Chang, Won-Pyo; Kim, Dong-Su

    1996-10-01

    This report presents the results of the RELAP5/MOD3 Version 7j assessment on BETHSY 6.2TC. BETHSY 6.2TC test corresponding to a six inch cold leg break LOCA of the Pressurizer Water Reactor(PWR). The primary objective of the test was to provide reference data of two facilities of different scales (BETHSY and LSTF facility). On the other hand, the present calculation aims at analysis of RELAP5/N4OD3 capability on the small break LOCA simulation, The results of calculation have shown that the RELAP5/MOD3 reasonably predicts occurrences as well as trends of the major phenomena such as primary pressure, timing of loop seal clearing, liquid hold up, etc. However, some disagreements also have been found in the predictions of loop seal clearing, collapsed core water level after loop seal clearing, and accumulator injection behaviors. For better understanding of discrepancies in same predictions, several sensitivity calculations have been performed as well. These include the changes of two-phase discharge coefficient at the break junction and some corrections of the interphase drag term. As result, change of a single parameter has not improved the overall predictions and it has been found that the interphase drag model has still large uncertainties

  6. Technical and Physical Activities of Small-Sided Games in Young Korean Soccer Players.

    Science.gov (United States)

    Joo, Chang H; Hwang-Bo, Kwan; Jee, Haemi

    2016-08-01

    Joo, CH, Hwang-Bo, K, and Jee, H. Technical and physical activities of small-sided games in young Korean soccer players. J Strength Cond Res 30(8): 2164-2173, 2016-The aim of this study was to examine the technical aspects and physical demands during small-sided games (SSGs) with different sized pitches in young Korean soccer players. Participants were randomly selected during a nationally held youth competition. Three different game formats were used: SSG8 (8 vs. 8 played on a small-sized field [68 × 47 m]), RSG8 (8 vs. 8 played on a regular-sized field [75 × 47 m]), and RSG11 (11 vs. 11 played on a regular-sized field). Eleven technical (ball touches, passes, and shots) and 6 physical demand variables (exercise frequency by intensity) were observed and analyzed. Same variables were also analyzed for the goalkeepers. As a result, SSG8 and RSG8 showed significantly greater numbers of technical plays in 5 and 4 variables in comparison to RSG11, respectively. In addition, although the exercise intensities increased slightly in both SSG formats, the amount was within the similar range as previous reports. In conclusion, the SSGs with reduced number of players may be referred in young players to effectively train them in technical aspects of the game by allowing greater ball exposure time without excessive physical demands. Various confounding factors such as pitch dimension should be carefully considered for training specific technical and physical variables in young Korean players.

  7. Autaptic pacemaker mediated propagation of weak rhythmic activity across small-world neuronal networks

    Science.gov (United States)

    Yilmaz, Ergin; Baysal, Veli; Ozer, Mahmut; Perc, Matjaž

    2016-02-01

    We study the effects of an autapse, which is mathematically described as a self-feedback loop, on the propagation of weak, localized pacemaker activity across a Newman-Watts small-world network consisting of stochastic Hodgkin-Huxley neurons. We consider that only the pacemaker neuron, which is stimulated by a subthreshold periodic signal, has an electrical autapse that is characterized by a coupling strength and a delay time. We focus on the impact of the coupling strength, the network structure, the properties of the weak periodic stimulus, and the properties of the autapse on the transmission of localized pacemaker activity. Obtained results indicate the existence of optimal channel noise intensity for the propagation of the localized rhythm. Under optimal conditions, the autapse can significantly improve the propagation of pacemaker activity, but only for a specific range of the autaptic coupling strength. Moreover, the autaptic delay time has to be equal to the intrinsic oscillation period of the Hodgkin-Huxley neuron or its integer multiples. We analyze the inter-spike interval histogram and show that the autapse enhances or suppresses the propagation of the localized rhythm by increasing or decreasing the phase locking between the spiking of the pacemaker neuron and the weak periodic signal. In particular, when the autaptic delay time is equal to the intrinsic period of oscillations an optimal phase locking takes place, resulting in a dominant time scale of the spiking activity. We also investigate the effects of the network structure and the coupling strength on the propagation of pacemaker activity. We find that there exist an optimal coupling strength and an optimal network structure that together warrant an optimal propagation of the localized rhythm.

  8. Crystallographic structure of a small molecule SIRT1 activator-enzyme complex

    Science.gov (United States)

    Dai, Han; Case, April W.; Riera, Thomas V.; Considine, Thomas; Lee, Jessica E.; Hamuro, Yoshitomo; Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M.; Pietrak, Beth; Schwartz, Benjamin; Blum, Charles A.; Disch, Jeremy S.; Caldwell, Richard; Szczepankiewicz, Bruce; Oalmann, Christopher; Yee Ng, Pui; White, Brian H.; Casaubon, Rebecca; Narayan, Radha; Koppetsch, Karsten; Bourbonais, Francis; Wu, Bo; Wang, Junfeng; Qian, Dongming; Jiang, Fan; Mao, Cheney; Wang, Minghui; Hu, Erding; Wu, Joe C.; Perni, Robert B.; Vlasuk, George P.; Ellis, James L.

    2015-07-01

    SIRT1, the founding member of the mammalian family of seven NAD+-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation and catalytic activation by small molecule sirtuin-activating compounds (STACs). Using this construct, we solved the crystal structure of a mini-hSIRT1-STAC complex, which revealed the STAC-binding site within the N-terminal domain of hSIRT1. Together with hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis using full-length hSIRT1, these data establish a specific STAC-binding site and identify key intermolecular interactions with hSIRT1. The determination of the interface governing the binding of STACs with human SIRT1 facilitates greater understanding of STAC activation of this enzyme, which holds significant promise as a therapeutic target for multiple human diseases.

  9. Inducing gene expression by targeting promoter sequences using small activating RNAs

    Directory of Open Access Journals (Sweden)

    Ji Wang

    2015-02-01

    Full Text Available Vector-based systems comprised of exogenous nucleic acid sequences remain the standard for ectopic expression of a particular gene. Such systems offer robust overexpression, but have inherent drawbacks such the tedious process of construction, excluding sequences (e.g. introns and untranslated regions important for gene function and potential insertional mutagenesis of host genome associated with the use of viral vectors. We and others have recently reported that short double-stranded RNAs (dsRNAs can induce endogenous gene expression by targeting promoter sequences in a phenomenon referred to as RNA activation (RNAa and such dsRNAs are termed small activating RNAs (saRNAs. To date, RNAa has been successfully utilized to induce the expression of different genes such as tumor suppressor genes. Here, we describe a detailed protocol for target selection and dsRNA design with associated experiments to facilitate RNAa in cultured cells. This technique may be applied to selectively activate endogenous gene expression for studying gene function, interrogating molecular pathways and reprogramming cell fate.

  10. The influence of small mammal burrowing activity on water storage at the Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Landeen, D.S.

    1994-09-01

    The amount and rate at which water may penetrate a protective barrier and come into contact with buried radioactive waste is a major concern. Because burrowing animals eventually will reside on the surface of any protective barrier, the effect these burrow systems may have on the loss or retention of water needs to be determined. The first section of this document summarizes the known literature relative to small mammals and the effects that burrowing activities have on water distribution, infiltration, and the overall impact of burrows on the ecosystem. Topics that are summarized include burrow air pressures, airflow, burrow humidity, microtopography, mounding, infiltration, climate, soil evaporation, and discussions of large pores relative to water distribution. The second section of this document provides the results of the study that was conducted at the Hanford Site to determine what effect small mammal burrows have on water storage. This Biointrusion task is identified in the Permanent Isolation Surface Barrier Development Plan in support of protective barriers. This particular animal intrusion task is one part of the overall animal intrusion task identified in Animal Intrusion Test Plan.

  11. Determine small and medium enterprise social media activities: A community engagement project in the Tshwane community

    Directory of Open Access Journals (Sweden)

    Louise van Scheers

    2015-09-01

    Full Text Available The aim of this paper is to determine small and medium enterprise (SME social media activities and promote CE scholarship engagement. It is a community engagement project conducted in the Tshwane community. Community engagement (CE as a planned process with the specific purpose of working with identified groups of people in the community to address issues affecting their well-being. The CE project SME skills transfer workshops are aimed at expanding involvement with the community. The benefits of social media seem to be ignored by most SMEs however; challenges prevent SME owners from using the tool effectively. A survey study method of research design has been selected for the research. The sample for the study comprised 200 SME owners who currently manage small businesses in the Tshwane area. The conducted research recommends that social media can be cost effective if the SMEs make use of their social networks and use best practises that enable them to get their adverts or posts shared across social networks. The conducted research also recommends that SMEs with limited resources start with social media and YouTube as a marketing tool, as the learning curve is low and cost involved is almost nil.

  12. The influence of small mammal burrowing activity on water storage at the Hanford Site

    International Nuclear Information System (INIS)

    Landeen, D.S.

    1994-09-01

    The amount and rate at which water may penetrate a protective barrier and come into contact with buried radioactive waste is a major concern. Because burrowing animals eventually will reside on the surface of any protective barrier, the effect these burrow systems may have on the loss or retention of water needs to be determined. The first section of this document summarizes the known literature relative to small mammals and the effects that burrowing activities have on water distribution, infiltration, and the overall impact of burrows on the ecosystem. Topics that are summarized include burrow air pressures, airflow, burrow humidity, microtopography, mounding, infiltration, climate, soil evaporation, and discussions of large pores relative to water distribution. The second section of this document provides the results of the study that was conducted at the Hanford Site to determine what effect small mammal burrows have on water storage. This Biointrusion task is identified in the Permanent Isolation Surface Barrier Development Plan in support of protective barriers. This particular animal intrusion task is one part of the overall animal intrusion task identified in Animal Intrusion Test Plan

  13. Properties of 8-inch photomultiplier tubes for a large volume imaging water Cerenkov detector

    International Nuclear Information System (INIS)

    Oehler, Ch.

    1996-01-01

    In the Institut fuer Kernphysik I conceptional studies for a possible succession project for the KARMEN-ν-detector are performed. This design studies propose to build a large volume 1300 t imaging water Cerenkov detector. The main goal of this experiment will be the investigation of ν-e - -scattering in the medium energy range up to 50 MeV. The sensitive surface of this detector will be instrumented with about 3000 8-inch photomultiplier tubes (PMT) providing a coverage of 20%. In the framework of this detector design, studies of the properties of hemispherical 8-inch phototubes have been investigated in this work. The topic was to optimise the quality of the important PMT properties like time- and energy-resolution which are crucial to achieve the required spatial and angular resolutions. A second task of this work was to construct a test facility for the PMT, with the possibility to test large quantities. Monte Carlo calculations show that the required detector resolutions of σ E /E(E e ≤50 MeV)=5.2%+47%/√E, σ t (E e ∼30 MeV)=0.6 ns, σ x (E e ∼30 MeV)=13 cm, σ Θ (E e ∼30 MeV)=20 , can be achieved if the phototubes have a transit-time spread less than 1 ns. Up to now, two different 8-inch tubes are available and have been tested, the HAMAMATSU R5912 and the EMI 9353. (orig.)

  14. A comparison of ARMS and mutation specific IHC for common activating EGFR mutations analysis in small biopsy and cytology specimens of advanced non small cell lung cancer

    OpenAIRE

    Wang, Xueqing; Wang, Guoqing; Hao, Yueyue; Xu, Yinhong; Zhang, Lihua

    2014-01-01

    We have compared mutation analysis by Amplification Refractory Mutation System (ARMS) and epidermal growth factor receptor (EGFR) mutant-specific antibodies for their ability to detect two common activating EGFR mutations in a cohort of 115 advanced non-small cell lung cancer (NSCLC), including cytology material, core biopsy, and bronchoscopic biopsies. Assessment of EGFR mutation status was performed by using antibodies and ARMS assay specific to the two major forms of mutant EGFR, exon 19 d...

  15. Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

    Directory of Open Access Journals (Sweden)

    Jessica A. Cottrell

    2010-01-01

    Full Text Available The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts.

  16. De novo activating epidermal growth factor mutations (EGFR) in small-cell lung cancer.

    Science.gov (United States)

    Thai, Alesha; Chia, Puey L; Russell, Prudence A; Do, Hongdo; Dobrovic, Alex; Mitchell, Paul; John, Thomas

    2017-09-01

    In Australia, mutations in epidermal growth factor mutations (EGFR) occur in 15% of patients diagnosed with non-small-cell lung cancer and are found with higher frequency in female, non-smokers of Asian ethnicity. Activating mutations in the EGFR gene are rarely described in SCLC. We present two cases of de novo EGFR mutations in patients with SCLC detected in tissue and in plasma cell free DNA, both of whom were of Asian ethnicity and never-smokers. These two cases add to the growing body of evidence suggesting that screening for EGFR mutations in SCLC should be considered in patients with specific clinical features. © 2017 Royal Australasian College of Physicians.

  17. Photometric Typing Analyses of Three Young Supernovae with the Robotic Palomar 60-Inch Telescope

    OpenAIRE

    Rajala, Anne M.; Fox, Derek B.; Gal-Yam, Avishay; Leonard, Douglas C.; Soderberg, Alicia M.; Kulkarni, S. R.; Cenko, S. Bradley; Moon, Dae-Sik; Harrison, Fiona A.

    2004-01-01

    We present photometric typing analyses of three young supernovae observed with the Robotic 60-inch Telescope at Palomar Observatory (P60). This represents the first time that such photo-typing has been attempted, in a blind fashion, on newly-discovered supernovae. For one of the target supernovae, SN2004cs, our photometry provided the first constraint on the SN type, which we predicted would be type Ia. To the contrary, however, our subsequent Keck spectroscopy shows it to be an unusual type ...

  18. First thin AC-coupled silicon strip sensors on 8-inch wafers

    Energy Technology Data Exchange (ETDEWEB)

    Bergauer, T., E-mail: thomas.bergauer@oeaw.ac.at [Institute of High Energy Physics of the Austrian Academy of Sciences, Nikolsdorfer Gasse 18, 1050 Wien (Vienna) (Austria); Dragicevic, M.; König, A. [Institute of High Energy Physics of the Austrian Academy of Sciences, Nikolsdorfer Gasse 18, 1050 Wien (Vienna) (Austria); Hacker, J.; Bartl, U. [Infineon Technologies Austria AG, Siemensstrasse 2, 9500 Villach (Austria)

    2016-09-11

    The Institute of High Energy Physics (HEPHY) in Vienna and the semiconductor manufacturer Infineon Technologies Austria AG developed a production process for planar AC-coupled silicon strip sensors manufactured on 200 μm thick 8-inch p-type wafers. In late 2015, the first wafers were delivered featuring the world's largest AC-coupled silicon strip sensors. Detailed electrical measurements were carried out at HEPHY, where single strip and global parameters were measured. Mechanical studies were conducted and the long-term behavior was investigated using a climate chamber. Furthermore, the electrical properties of various test structures were investigated to validate the quality of the manufacturing process.

  19. Elemental Water Impact Test: Phase 2 36-Inch Aluminum Tank Head

    Science.gov (United States)

    Vassilakos, Gregory J.

    2014-01-01

    Spacecraft are being designed based on LS-DYNA simulations of water landing impacts. The Elemental Water Impact Test (EWIT) series was undertaken to assess the accuracy of LS-DYNA water impact simulations. EWIT Phase 2 featured a 36-inch aluminum tank head. The tank head was outfitted with one accelerometer, twelve pressure transducers, three string potentiometers, and four strain gages. The tank head was dropped from heights of 1 foot and 2 feet. The focus of this report is the correlation of analytical models against test data. As a measure of prediction accuracy, peak responses from the baseline LS-DYNA model were compared to peak responses from the tests.

  20. The 88-Inch Cyclotron: A One-Stop Facility for Electronics Radiation and Detector Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kireeff Covo, M.; Albright, R. A.; Ninemire, B. F.; Johnson, M. B.; Hodgkinson, A.; Loew, T.; Benitez, J. Y.; Todd, D. S.; Xie, D. Z.; Perry, T.; Phair, L.; Bernsteiny, L. A.; Bevins, J.; Brown, J. A.; Goldblum, B. L.; Harasty, M.; Harrig, K. P.; Laplace, T. A.; Matthews, E. F.; Bushmaker, A.; Walker, D.; Oklejas, V.; Hopkins, A. R.; Bleuel, D. L.; Chen, J.; Cronin, S. B.

    2017-10-01

    In outer space down to the altitudes routinely flown by larger aircrafts, radiation can pose serious issues for microelectronics circuits. The 88-Inch Cyclotron at Lawrence Berkeley National Laboratory is a sector-focused cyclotron and home of the Berkeley Accelerator Space Effects Facility, where the effects of energetic particles on sensitive microelectronics are studied with the goal of designing electronic systems for the space community. This paper describes the flexibility of the facility and its capabilities for testing the bombardment of electronics by heavy ions, light ions, and neutrons. Experimental capabilities for the generation of neutron beams from deuteron breakups and radiation testing of carbon nanotube field effect transistor will be discussed.

  1. ORION: A Small, General Purpose, Low Earth Orbit Satellite Bus Design

    OpenAIRE

    Fuhs, A.E.; Mosier, M.R.

    1987-01-01

    Publication: AIAA/USU Conference on Small Satellites Technical Session IV: Small Satellites - Systems/Buses A low cost general purpose mini-satellite bus has been designed to support a wide variety of small scientific and commercial payloads. The design provides a number of launch options, including the new NASA extended Get-A way-Special (GAS) canister and several small expendable launch vehicles. The satellite is 19 inches in diameter, 35 inches high and weighs approximately 270 lbs. ...

  2. High-Volume Production of Lightweight, Multi-Junction Solar Cells Using 6-inch GaAs, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In the proposed Phase II program, we will transition MicroLink's 6-inch epitaxial lift-off (ELO) solar cell fabrication process into a manufacturing platform capable...

  3. Development of small intestinal enzyme activities and their relationship with some gut regulatory peptides in grazing sheep.

    Science.gov (United States)

    Wang, C L; Lang, X; Wu, P J; Casper, D P; Li, F D

    2017-08-01

    Growth depends on an animal's capacity to digest and assimilate ingested nutrients, and insufficient supply and impairment will constrain lamb growth. Eight groups of Alpine Finewool lambs were harvested on 0, 3, 7, 14, 21, 28, 42, and 56 d to measure pH and enzymatic activities in the duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum mucosa or digesta. From the duodenum to the ileum the pH of intestinal mucosa and digesta increased, whereas pH changed very little with age. The trypsin, chymotrypsin, lipase, lactase, and α-amylase activities observed at birth decreased by d 3, followed by a nonuniform enzymatic response in the small intestine. The trypsin activity increased from d 3 to peak, at d 21, followed by a decline. Chymotrypsin activity followed the same general trend but with smaller responses in activities. Trypsin demonstrated greater enzymatic activity than chymotrypsin at the same age. The lipase activity of small intestinal mucosa and digesta changed little with age. The lactase activity was high at birth, decreased by d 3, and then increased, followed by a decrease as lambs approached weaning. α-Amylase activity was similar in the small intestinal mucosa and digesta at birth but increased with age for the duodenum and proximal jejunum. Plasma concentrations of cholecystokinin (CCK), secretin, and gastrin were positively correlated ( 0.05). Small intestinal enzymatic activities exist and may be sufficient to enhance lamb growth via appropriate nutrient supplementation.

  4. Small Renal Masses Progressing to Metastases under Active Surveillance: A Systematic Review and Pooled Analysis

    Science.gov (United States)

    Smaldone, Marc C.; Kutikov, Alexander; Egleston, Brian L.; Canter, Daniel J.; Viterbo, Rosalia; Chen, David Y.T.; Jewett, Michael A.; Greenberg, Richard E.; Uzzo, Robert G.

    2012-01-01

    Purpose We conducted a systematic review and pooled analysis of small renal masses under active surveillance to identify progression risk and characteristics associated with metastases. Materials and Methods A MEDLINE search was performed to identify all clinical series reporting surveillance of localized renal masses. For studies reporting individual level data, clinical and radiographic characteristics of tumors without progression were compared to those progressing to metastases. Results 18 series (880 patients, 936 masses) met screening criteria from which 18 patients progressing to metastasis were identified (mean 40.2 months). Six studies (259 patients, 284 masses) provided individual level data for pooled analysis. With a mean follow up of 33.5±22.6 months, mean initial tumor diameter was 2.3±1.3 cm and mean linear growth rate was 0.31±0.38 cm/year. 65 masses (23%) exhibited zero net growth under surveillance; of which none progressed to metastasis. Pooled analysis revealed increased age (75.1±9.1 vs. 66.6±12.3 years, p=0.03), initial tumor diameter (4.1±2.1 vs. 2.3±1.3 cm, p<0.0001), initial estimated tumor volume (66.3±100.0 vs. 15.1±60.3 cm3, p<0.0001), linear growth rate (0.8±0.65 vs. 0.3±0.4 cm/yr, p=0.0001), and volumetric growth rate (27.1±24.9 vs. 6.2±27.5 cm3/yr, p<0.0001) in the progression cohort. Conclusions A substantial proportion of small renal masses remain radiographically static following an initial period of active surveillance. Progression to metastases occurs in a small percentage of patients and is generally a late event. These results indicate that in patients with competing health risks, radiographic surveillance may be an acceptable initial approach with delayed intervention reserved for those exhibiting significant linear or volumetric growth. PMID:21766302

  5. Heavy section steel technology program. Technical report No. 36. The irradiated fracture toughness of ASTM A533, Grade B, Class 1 steel measured with a four inch thick compact tension specimen

    International Nuclear Information System (INIS)

    Williams, J.A.

    1975-01-01

    The fracture toughness of an ASTM A533-B four inch thick compact tension specimen irradiated to approximately 3.8 x 10 19 n/cm 2 (E greater than 1 MeV) at 550 0 F was determined to be 80 ksi √in at a test temperature of 200 0 F. Smaller 0.394 inch thick fracture specimens were tested prior to the large specimen test to aid in establishing the test temperature and to compare the fracture transition of large and small irradiated specimens. The K/sub Ic.394/ toughness transition as measured at 100 ksi √in was observed at a temperature of 210 0 F; plate RW and WR orientations were comparable. Fracture toughness behavior of the small specimens closely predicts the large specimen behavior in the transition region. 23 references. (U.S.)

  6. Stand Development 25 Years after a 9.0-inch Diameter-Limit First Cutting In Appalachian Hardwoods

    Science.gov (United States)

    H. Clay Smith; N. I. Lamson

    1977-01-01

    This report is a case history of stand development 25 years after a 9.0-inch diameter-limit cutting in a primarily second growth 40- to 45-year-old Appalachian hardwood stand. Some old residual trees from the early 1900 logging era were scattered throughout the stand. In 1950, a 9.0-inch diameter-limit cutting removed 8,650 board feet per acre and reduced the basal...

  7. Workplace activities to promote small attempts for safety. Toward development of safety culture in a nuclear power plant

    International Nuclear Information System (INIS)

    Fukui, Hirokazu; Sugiman, Toshio

    2007-01-01

    Activities that could possibly grow into learning activities for developing safety culture were explored by intensive fieldwork in a nuclear power plant depending on Engestroem's activity theory. As a first step to achieve this goal, workers' small attempts that might contribute to nurturing a safety culture were investigated. Eight kinds of activity were observed and interpreted as having the possibility to facilitate small recognition and small practice, i.e., activities including (1) workgroup as community, (2) other workgroups and other departments as community, (3) meeting drawing remarks as mediating artifacts, (4) study session and Off-the-Job-Training as mediating artifact, (5) award as mediating artifact, (6) extended leave as mediating artifact, (7) check sheet as mediating artifact, and (8) skill-transfer system as mediating artifact. (author)

  8. Development of a 55 μm pitch 8 inch CMOS image sensor for the high resolution NDT application

    Science.gov (United States)

    Kim, M. S.; Kim, G.; Cho, G.; Kim, D.

    2016-11-01

    A CMOS image sensor (CIS) with a large area for the high resolution X-ray imaging was designed. The sensor has an active area of 125 × 125 mm2 comprised with 2304 × 2304 pixels and a pixel size of 55 × 55 μm2. First batch samples were fabricated by using an 8 inch silicon CMOS image sensor process with a stitching method. In order to evaluate the performance of the first batch samples, the electro-optical test and the X-ray test after coupling with an image intensifier screen were performed. The primary results showed that the performance of the manufactured sensors was limited by a large stray capacitance from the long path length between the analog multiplexer on the chip and the bank ADC on the data acquisition board. The measured speed and dynamic range were limited up to 12 frame per sec and 55 dB respectively, but other parameters such as the MTF, NNPS and DQE showed a good result as designed. Based on this study, the new X-ray CIS with ~ 50 μm pitch and ~ 150 cm2 active area are going to be designed for the high resolution X-ray NDT equipment for semiconductor and PCB inspections etc.

  9. Recommendations for protecting against failure by brittle fracture: Category II and III ferritic steel shipping containers with wall thickness greater than four inches

    International Nuclear Information System (INIS)

    Schwartz, M.W.; Fischer, L.E.

    1996-08-01

    This report provides criteria for selecting ferritic steels that would prevent brittle fracture in Category II and III shipping containers with wall thickness greater than 4 inches. These methods are extensions of those previously used for Category II and III containers less than 4 inches thick and Category I containers more than 4 inches thick

  10. Discovery of Novel Small Molecules that Activate Satellite Cell Proliferation and Enhance Repair of Damaged Muscle.

    Science.gov (United States)

    Billin, Andrew N; Bantscheff, Marcus; Drewes, Gerard; Ghidelli-Disse, Sonja; Holt, Jason A; Kramer, Henning F; McDougal, Alan J; Smalley, Terry L; Wells, Carrow I; Zuercher, William J; Henke, Brad R

    2016-02-19

    Skeletal muscle progenitor stem cells (referred to as satellite cells) represent the primary pool of stem cells in adult skeletal muscle responsible for the generation of new skeletal muscle in response to injury. Satellite cells derived from aged muscle display a significant reduction in regenerative capacity to form functional muscle. This decrease in functional recovery has been attributed to a decrease in proliferative capacity of satellite cells. Hence, agents that enhance the proliferative abilities of satellite cells may hold promise as therapies for a variety of pathological settings, including repair of injured muscle and age- or disease-associated muscle wasting. Through phenotypic screening of isolated murine satellite cells, we identified a series of 2,4-diaminopyrimidines (e.g., 2) that increased satellite cell proliferation. Importantly, compound 2 was effective in accelerating repair of damaged skeletal muscle in an in vivo mouse model of skeletal muscle injury. While these compounds were originally prepared as c-Jun N-terminal kinase 1 (JNK-1) inhibitors, structure-activity analyses indicated JNK-1 inhibition does not correlate with satellite cell activity. Screening against a broad panel of kinases did not result in identification of an obvious molecular target, so we conducted cell-based proteomics experiments in an attempt to identify the molecular target(s) responsible for the potentiation of the satellite cell proliferation. These data provide the foundation for future efforts to design improved small molecules as potential therapeutics for muscle repair and regeneration.

  11. Dung biomass smoke activates inflammatory signaling pathways in human small airway epithelial cells.

    Science.gov (United States)

    McCarthy, Claire E; Duffney, Parker F; Gelein, Robert; Thatcher, Thomas H; Elder, Alison; Phipps, Richard P; Sime, Patricia J

    2016-12-01

    Animal dung is a biomass fuel burned by vulnerable populations who cannot afford cleaner sources of energy, such as wood and gas, for cooking and heating their homes. Exposure to biomass smoke is the leading environmental risk for mortality, with over 4,000,000 deaths each year worldwide attributed to indoor air pollution from biomass smoke. Biomass smoke inhalation is epidemiologically associated with pulmonary diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, and respiratory infections, especially in low and middle-income countries. Yet, few studies have examined the mechanisms of dung biomass smoke-induced inflammatory responses in human lung cells. Here, we tested the hypothesis that dung biomass smoke causes inflammatory responses in human lung cells through signaling pathways involved in acute and chronic lung inflammation. Primary human small airway epithelial cells (SAECs) were exposed to dung smoke at the air-liquid interface using a newly developed, automated, and reproducible dung biomass smoke generation system. The examination of inflammatory signaling showed that dung biomass smoke increased the production of several proinflammatory cytokines and enzymes in SAECs through activation of the activator protein (AP)-1 and arylhydrocarbon receptor (AhR) but not nuclear factor-κB (NF-κB) pathways. We propose that the inflammatory responses of lung cells exposed to dung biomass smoke contribute to the development of respiratory diseases. Copyright © 2016 the American Physiological Society.

  12. Small-Scale Activity Above the Penumbra of a Fast-Rotating Sunspot

    Science.gov (United States)

    Bharti, L.; Quintero Noda, C.; Rakesh, S.; Sobha, B.; Pandya, A.; Joshi, C.

    2018-03-01

    High-resolution observations of small-scale activity above the filamentary structure of a fast-rotating sunspot of NOAA Active Region 10930 are presented. The penumbral filament that intrudes into the umbra shows a central dark core and substructures. It almost approached another end of the umbra, like a light bridge. The chromospheric Ca ii H images show many jet-like structures with a bright leading edge above it. These bright jets move across the filament tips and show coordinated up and down motions. Transition region images also show brightening at the same location above the intrusion. Coronal 195 Å images suggest that one end of the bright coronal loop footpoints resides in this structure. The intrusion has opposite polarity with respect to the umbra. Strong downflows are observed at the edges along the length of the intrusion where the opposite-polarity field is enhanced. We also observe a counter-Evershed flow in the filamentary structure that also displays brightening and energy dissipation in the upper atmosphere. This scenario suggests that the jets and brightenings are caused by low-altitude reconnection driven by opposite-polarity fields and convective downflows above such structures.

  13. Chaperone activity of human small heat shock protein-GST fusion proteins.

    Science.gov (United States)

    Arbach, Hannah; Butler, Caley; McMenimen, Kathryn A

    2017-07-01

    Small heat shock proteins (sHsps) are a ubiquitous part of the machinery that maintains cellular protein homeostasis by acting as molecular chaperones. sHsps bind to and prevent the aggregation of partially folded substrate proteins in an ATP-independent manner. sHsps are dynamic, forming an ensemble of structures from dimers to large oligomers through concentration-dependent equilibrium dissociation. Based on structural studies and mutagenesis experiments, it is proposed that the dimer is the smallest active chaperone unit, while larger oligomers may act as storage depots for sHsps or play additional roles in chaperone function. The complexity and dynamic nature of their structural organization has made elucidation of their chaperone function challenging. HspB1 and HspB5 are two canonical human sHsps that vary in sequence and are expressed in a wide variety of tissues. In order to determine the role of the dimer in chaperone activity, glutathione-S-transferase (GST) was genetically linked as a fusion protein to the N-terminus regions of both HspB1 and HspB5 (also known as Hsp27 and αB-crystallin, respectively) proteins in order to constrain oligomer formation of HspB1 and HspB5, by using GST, since it readily forms a dimeric structure. We monitored the chaperone activity of these fusion proteins, which suggest they primarily form dimers and monomers and function as active molecular chaperones. Furthermore, the two different fusion proteins exhibit different chaperone activity for two model substrate proteins, citrate synthase (CS) and malate dehydrogenase (MDH). GST-HspB1 prevents more aggregation of MDH compared to GST-HspB5 and wild type HspB1. However, when CS is the substrate, both GST-HspB1 and GST-HspB5 are equally effective chaperones. Furthermore, wild type proteins do not display equal activity toward the substrates, suggesting that each sHsp exhibits different substrate specificity. Thus, substrate specificity, as described here for full-length GST

  14. A new alignment procedure for the South African Astronomical Observatory's 74-inch telescope

    Science.gov (United States)

    Crause, Lisa A.; Booth, John A.; Doss, David; Loubser, Egan; O'Connor, James E.; Sass, Craig; Sickafoose, Amanda A.; Worters, Hannah L.

    2016-07-01

    Considerable effort has gone into improving the performance and reliability of the SAAO's 74-inch telescope. This included replacing the telescope encoders, refining the pointing model and increasing the telescope throughput. The latter involved re-aluminising the primary and formulating a procedure to ensure optimal alignment of the telescope mirrors. To this end, we developed the necessary hardware and techniques to ensure that such alignment is achieved and maintained, particularly following re-aluminising of the mirrors. In essence, the procedure involves: placing a Taylor Hobson Alignment Telescope on the mechanical rotation axis of the 74-inch (which we define to be the optical axis, since the Cassegrain instruments attach to the associated turntable), then adjusting the tip/tilt of the secondary mirror to get it onto that axis and, lastly, adjusting the tip/tilt of the primary mirror to eliminate coma. An eyepiece (or wavefront camera) is installed at the Cassegrain port for this final step since comatic star images indicate the need to tip/tilt the primary mirror to align it to the secondary. Tuning out any brightness gradients seen in an out-of-focus image of a bright star may also be used for feedback when adjusting the tip/tilt of the primary mirror to null coma.

  15. A PROTOTYPE FOUR INCH SHORT HYDRIDE (FISH) BED AS A REPLACEMENT TRITIUM STORAGE BED

    Energy Technology Data Exchange (ETDEWEB)

    Klein, J.; Estochen, E.; Shanahan, K.; Heung, L.

    2011-02-23

    The Savannah River Site (SRS) tritium facilities have used 1st generation (Gen1) metal hydride storage bed assemblies with process vessels (PVs) fabricated from 3 inch nominal pipe size (NPS) pipe to hold up to 12.6 kg of LaNi{sub 4.25}Al{sub 0.75} metal hydride for tritium gas absorption, storage, and desorption for over 15 years. The 2nd generation (Gen2) of the bed design used the same NPS for the PV, but the added internal components produced a bed nominally 1.2 m long, and presented a significant challenge for heater cartridge replacement in a footprint limited glove-box. A prototype 3rd generation (Gen3) metal hydride storage bed has been designed and fabricated as a replacement candidate for the Gen2 storage bed. The prototype Gen3 bed uses a PV pipe diameter of 4 inch NPS so the bed length can be reduced below 0.7 m to facilitate heater cartridge replacement. For the Gen3 prototype bed, modeling results show increased absorption rates when using hydrides with lower absorption pressures. To improve absorption performance compared to the Gen2 beds, a LaNi{sub 4.15}Al{sub 0.85} material was procured and processed to obtain the desired pressure-composition-temperature (PCT) properties. Other bed design improvements are also presented.

  16. Artist autonomy in a digital era: The case of Nine Inch Nails

    Directory of Open Access Journals (Sweden)

    Steven C. Brown

    2012-09-01

    Full Text Available A 2009 presentation by Michael Masnick (CEO and founder of insight company Floor64 entitled ‘How Trent Reznor and Nine Inch Nails represent the Future of the Music Business’ brought the success of the business models employed by Reznor in distributing Nine Inch Nails’ music into the spotlight. The present review provides a comprehensive timeline of the band circa 2005-2010, evaluating the success of the distribution methods employed in accordance with Masnick’s (2009 proposed business model of connecting with fans and providing them with a reason to buy. The model is conceptualised in the wider context in which Reznor’s distribution methods take place (including a brief consideration of Radiohead’s much cited pay-what-you- want model, addressing the perceived gaps in the model by exploring the involvement of musical preferences; age and consumer purchasing behavior and fan worship. Implications are discussed concerning the applicability of the model for new and emerging bands.

  17. Separation Efficiency of Nagar Parker China Clay Using Two Inch Hydrocyclone

    Directory of Open Access Journals (Sweden)

    Abdul Ghani Pathan

    2013-01-01

    Full Text Available Performance efficiency of two inch hydrocyclone has been investigated, using the Nagar Parker china clay. Raw china clay was initially washed with tap water and -75 ?m size fraction was separated through wet sieving. Washed china clay of -75 ?m was used as feed sample in hydrocyclone tests. Solids concentration in slurry was kept as 2.5%. 45 tests were conducted with different combinations of pressure, vortex finder and spigot. Three sizes of spigot viz. 3.2, 2.2 and 1.5mm and three sizes of vortex finder viz. 7.00, 5.5 and 3.00mm were used. Hydrocyclone rig was operated at five different pressures viz. 20, 30, 40, 50 and 60 psi in conjunction with various combinations of vortex finder and spigot. Laser light scattering technique was used for particle size analysis of O/F (Overflow and U/F (Underflow products. Separation efficiency of the hydrocyclone, for various combinations of Vortex Finder, Spigot and operating pressure, was determined for two size fractions, i.e. less than ten micron and less than twenty micron, present in O/F and U/F products. From the results it was concluded that the best separation efficiency of 2 inch hydrocyclone is achieved by using the vortex finder of 7.0mm size and spigot of 1.5mm size. It was also concluded that the separation efficiency of the hydrocyclone decreases by increasing the pressure.

  18. Antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Perry

    Full Text Available Ubiquitin (Ub is a vital regulatory component in various cellular processes, including cellular responses to viral infection. As obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (Ub cycle to their advantage by encoding Ub-modifying proteins including deubiquitinases (DUBs. However, how cellular DUBs modulate specific viral infections, such as norovirus, is poorly understood. To examine the role of DUBs during norovirus infection, we used WP1130, a small molecule inhibitor of a subset of cellular DUBs. Replication of murine norovirus in murine macrophages and the human norovirus Norwalk virus in a replicon system were significantly inhibited by WP1130. Chemical proteomics identified the cellular DUB USP14 as a target of WP1130 in murine macrophages, and pharmacologic inhibition or siRNA-mediated knockdown of USP14 inhibited murine norovirus infection. USP14 is a proteasome-associated DUB that also binds to inositol-requiring enzyme 1 (IRE1, a critical mediator of the unfolded protein response (UPR. WP1130 treatment of murine macrophages did not alter proteasome activity but activated the X-box binding protein-1 (XBP-1 through an IRE1-dependent mechanism. In addition, WP1130 treatment or induction of the UPR also reduced infection of other RNA viruses including encephalomyocarditis virus, Sindbis virus, and La Crosse virus but not vesicular stomatitis virus. Pharmacologic inhibition of the IRE1 endonuclease activity partially rescued the antiviral effect of WP1130. Taken together, our studies support a model whereby induction of the UPR through cellular DUB inhibition blocks specific viral infections, and suggest that cellular DUBs and the UPR represent novel targets for future development of broad spectrum antiviral therapies.

  19. Small Coronal Holes Near Active Regions as Sources of Slow Solar Wind

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.-M., E-mail: yi.wang@nrl.navy.mil [Space Science Division, Naval Research Laboratory, Washington, DC 20375 (United States)

    2017-06-01

    We discuss the nature of the small areas of rapidly diverging, open magnetic flux that form in the strong unipolar fields at the peripheries of active regions (ARs), according to coronal extrapolations of photospheric field measurements. Because such regions usually have dark counterparts in extreme-ultraviolet (EUV) images, we refer to them as coronal holes, even when they appear as narrow lanes or contain sunspots. Revisiting previously identified “AR sources” of slow solar wind from 1998 and 1999, we find that they are all associated with EUV coronal holes; the absence of well-defined He i 1083.0 nm counterparts to some of these holes is attributed to the large flux of photoionizing radiation from neighboring AR loops. Examining a number of AR-associated EUV holes during the 2014 activity maximum, we confirm that they are characterized by wind speeds of ∼300–450 km s{sup −1}, O{sup 7+}/O{sup 6+} ratios of ∼0.05–0.4, and footpoint field strengths typically of order 30 G. The close spacing between ARs at sunspot maximum limits the widths of unipolar regions and their embedded holes, while the continual emergence of new flux leads to rapid changes in the hole boundaries. Because of the highly nonradial nature of AR fields, the smaller EUV holes are often masked by the overlying canopy of loops, and may be more visible toward one solar limb than at central meridian. As sunspot activity declines, the AR remnants merge to form much larger, weaker, and longer-lived unipolar regions, which harbor the “classical” coronal holes that produce recurrent high-speed streams.

  20. Resting-state oscillatory activity in children born small for gestational age: a magnetoencephalographic study

    Directory of Open Access Journals (Sweden)

    Maria eBoersma

    2013-09-01

    Full Text Available Growth restriction in utero during a period that is critical for normal growth of the brain, has previously been associated with deviations in cognitive abilities and brain anatomical and functional changes. We measured magnetoencephalography (MEG in 4-7 year old children to test if children born small for gestational age (SGA show deviations in resting-state brain oscillatory activity. Children born SGA children with postnatally spontaneous catch-up growth (SGA+; 6 boys, 7 girls; mean age 6.3 y (SD=0.9 and children born appropriate for gestational age (AGA; 7 boys, 3 girls; mean age 6.0 y (SD=1.2 participated in a resting-state MEG study. We calculated absolute and relative power spectra and used nonparametric statistics to test for group differences. SGA+ and AGA born children showed no significant differences in absolute and relative power except for reduced absolute gamma band power in SGA children. At time of MEG investigation, SGA+ children showed was significantly lower head circumference (HC and a trend toward lower IQ, however there was no association of HC or IQ with absolute or relative power. Except for reduced absolute gamma band power, our findings suggest normal brain activity patterns at school age in a group of children born SGA in which spontaneous catch-up growth of bodily length after birth occurred. Although previous findings suggest that being born SGA alters brain oscillatory activity early in neonatal life, we show that these neonatal alterations do not persist at early school age when spontaneous postnatal catch-up growth occurs after birth.

  1. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Carrie L. Shaffer

    2016-04-01

    Full Text Available Bacteria utilize complex type IV secretion systems (T4SSs to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85 that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA and peptidoglycan into gastric epithelial cells. In H. pylori, KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori, we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs.

  2. 78 FR 77139 - Agency Information Collection Activities: Small Vessel Reporting System

    Science.gov (United States)

    2013-12-20

    ... Reporting System AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: 30-Day... approval in accordance with the Paperwork Reduction Act: Small Vessel Reporting System (SVRS). This is a...: Small Vessel Reporting System. OMB Number: 1651-0137. Form Number: None. Abstract: The Small Vessel...

  3. A Kinetic Model to Explain the Maximum in alpha-Amylase Activity Measurements in the Presence of Small Carbohydrates

    NARCIS (Netherlands)

    Baks, T.; Janssen, A.E.M.; Boom, R.M.

    2006-01-01

    The effect of the presence of several small carbohydrates on the measurement of the -amylase activity was determined over a broad concentration range. At low carbohydrate concentrations, a distinct maximum in the -amylase activity versus concentration curves was observed in several cases. At higher

  4. Application of Optical Biosensors in Small-Molecule Screening Activities

    Directory of Open Access Journals (Sweden)

    Wolfgang Knecht

    2012-03-01

    Full Text Available The last two decades have seen remarkable progress and improvements in optical biosensor systems such that those are currently seen as an important and value-adding component of modern drug screening activities. In particular the introduction of microplate-based biosensor systems holds the promise to match the required throughput without compromising on data quality thus representing a sought-after complement to traditional fluidic systems. This article aims to highlight the application of the two most prominent optical biosensor technologies, namely surface plasmon resonance (SPR and optical waveguide grating (OWG, in small-molecule screening and will present, review and discuss the advantages and disadvantages of different assay formats on these platforms. A particular focus will be on the specific advantages of the inhibition in solution assay (ISA format in contrast to traditional direct binding assays (DBA. Furthermore we will discuss different application areas for both fluidic as well as plate-based biosensor systems by considering the individual strength of the platforms.

  5. Differential IL-13 Production by Small Intestinal Leukocytes in Active Coeliac Disease versus Refractory Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Sascha Gross

    2013-01-01

    Full Text Available A small fraction of coeliac disease (CD patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII. Pathogenesis of active CD (ACD has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of the TH2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs isolated from RCDII patients as compared to LPL from ACD patients (P=0.05. In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P=0.02. IL-13 secretion correlated with other TH2 as well as TH1 cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

  6. Dimeric aluminum-phosphorus compounds as masked frustrated Lewis pairs for small molecule activation.

    Science.gov (United States)

    Roters, Steffi; Appelt, Christian; Westenberg, Hauke; Hepp, Alexander; Slootweg, J Chris; Lammertsma, Koop; Uhl, Werner

    2012-08-14

    Hydroalumination of aryldialkynylphosphines RP(C≡C-(t)Bu)(2) (R = Ph, Mes) with equimolar quantities of diethylaluminum hydride afforded mixed alkenyl-alkynyl cyclic dimers in which the dative aluminum-phosphorus bonds are geminal to the exocyclic alkenyl groups. Addition of triethylaluminum to isolated 1 (R = Ph) or to the in situ generated species (R = Mes) caused diethylaluminum ethynide elimination to yield the arylethylphosphorus dimers 2 and 3. These possess a chair-like Al(2)C(2)P(2) heterocycle with intermolecular Al-P interactions. The boat conformation (4) was obtained by the reaction of (t)Bu-P(C≡C-(t)Bu)(2) with di(tert-butyl)aluminum hydride. Despite being dimeric, 2 behaves as a frustrated Lewis pair and activates small molecules. The reaction with carbon dioxide gave cis/trans isomeric AlPC(2)O heterocycles that differ only by the configuration of the exocyclic alkenyl unit. Four isomers resulted from the reaction with phenyl isocyanate. This is caused by cis/trans isomerization of the initial C=O adduct and subsequent rearrangement to the AlPC(2)N heterocycle, being the C=N adduct.

  7. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation

    Science.gov (United States)

    Chakravarty, Debyani; Santos, Elmer; Ryder, Mabel; Knauf, Jeffrey A.; Liao, Xiao-Hui; West, Brian L.; Bollag, Gideon; Kolesnick, Richard; Thin, Tin Htwe; Rosen, Neal; Zanzonico, Pat; Larson, Steven M.; Refetoff, Samuel; Ghossein, Ronald; Fagin, James A.

    2011-01-01

    Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAFV600E) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAFV600E, the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAFV600E expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAFV600E rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAFV600E mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications. PMID:22105174

  8. Identification of an antioxidant small-molecule with broad-spectrum antiviral activity.

    Science.gov (United States)

    Panchal, Rekha G; Reid, St Patrick; Tran, Julie P; Bergeron, Alison A; Wells, Jay; Kota, Krishna P; Aman, Javad; Bavari, Sina

    2012-01-01

    The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets. Published by Elsevier B.V.

  9. Fungi Treated with Small Chemicals Exhibit Increased Antimicrobial Activity against Facultative Bacterial and Yeast Pathogens

    Directory of Open Access Journals (Sweden)

    Christoph Zutz

    2014-01-01

    Full Text Available For decades, fungi have been the main source for the discovery of novel antimicrobial drugs. Recent sequencing efforts revealed a still high number of so far unknown “cryptic” secondary metabolites. The production of these metabolites is presumably epigenetically silenced under standard laboratory conditions. In this study, we investigated the effect of six small mass chemicals, of which some are known to act as epigenetic modulators, on the production of antimicrobial compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples was tested against clinically facultative pathogens and multiresistant clinical isolates. In total, 30 samples of treated fungi belonging to six different genera reduced significantly growth of different test organisms compared to the untreated fungal sample (growth log reduction 0.3–4.3. For instance, the pellet of Penicillium restrictum grown in the presence of butyrate revealed significant higher antimicrobial activity against Staphylococcus (S. aureus and multiresistant S. aureus strains and displayed no cytotoxicity against human cells, thus making it an ideal candidate for antimicrobial compound discovery. Our study shows that every presumable fungus, even well described fungi, has the potential to produce novel antimicrobial compounds and that our approach is capable of rapidly filling the pipeline for yet undiscovered antimicrobial substances.

  10. Fungi treated with small chemicals exhibit increased antimicrobial activity against facultative bacterial and yeast pathogens.

    Science.gov (United States)

    Zutz, Christoph; Bandian, Dragana; Neumayer, Bernhard; Speringer, Franz; Gorfer, Markus; Wagner, Martin; Strauss, Joseph; Rychli, Kathrin

    2014-01-01

    For decades, fungi have been the main source for the discovery of novel antimicrobial drugs. Recent sequencing efforts revealed a still high number of so far unknown "cryptic" secondary metabolites. The production of these metabolites is presumably epigenetically silenced under standard laboratory conditions. In this study, we investigated the effect of six small mass chemicals, of which some are known to act as epigenetic modulators, on the production of antimicrobial compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples was tested against clinically facultative pathogens and multiresistant clinical isolates. In total, 30 samples of treated fungi belonging to six different genera reduced significantly growth of different test organisms compared to the untreated fungal sample (growth log reduction 0.3-4.3). For instance, the pellet of Penicillium restrictum grown in the presence of butyrate revealed significant higher antimicrobial activity against Staphylococcus (S.) aureus and multiresistant S. aureus strains and displayed no cytotoxicity against human cells, thus making it an ideal candidate for antimicrobial compound discovery. Our study shows that every presumable fungus, even well described fungi, has the potential to produce novel antimicrobial compounds and that our approach is capable of rapidly filling the pipeline for yet undiscovered antimicrobial substances.

  11. Testing of one-inch UF{sub 6} cylinder valves under simulated fire conditions

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, P.G. [Martin Marietta Energy Systems, Inc., Paducah, KY (United States)

    1991-12-31

    Accurate computational models which predict the behavior of UF{sub 6} cylinders exposed to fires are required to validate existing firefighting and emergency response procedures. Since the cylinder valve is a factor in the containment provided by the UF{sub 6} cylinder, its behavior under fire conditions has been a necessary assumption in the development of such models. Consequently, test data is needed to substantiate these assumptions. Several studies cited in this document provide data related to the behavior of a 1-inch UF{sub 6} cylinder valve in fire situations. To acquire additional data, a series of tests were conducted at the Paducah Gaseous Diffusion Plant (PGDP) under a unique set of test conditions. This document describes this testing and the resulting data.

  12. Recent developments in high charge state heavy ion beams at the LBL 88-inch Cyclotron

    International Nuclear Information System (INIS)

    Gough, R.A.; Clark, D.J.; Glasgow, L.R.

    1978-01-01

    Recent advances in design and operation of the internal PIG sources at the LBL 88-Inch Cyclotron have led to the development of high charge state (0.4 16 O 8+ . Total external intensities of these beams range from 10 12 particles/s for 6 Li 3+ to 0.1 particles/s for 16 O 8+ . Techniques have been developed for routine tune-out of the low intensity beams. These include use of model beams and reliance on the large systematic data base of cyclotron parameters which has been developed over many years of operation. Techniques for delivery of these weak beams to the experimental target areas are presented. Source design and operation, including special problems associated with Li, Be, and B beams are discussed

  13. LOFT transient thermal analysis for 10 inch primary coolant blowdown piping weld

    International Nuclear Information System (INIS)

    Howell, S.K.

    1978-01-01

    A flaw in a weld in the 10 inch primary coolant blowdown piping was discovered by LOFT personnel. As a result of this, a thermal analysis and fracture mechanics analysis was requested by LOFT personnel. The weld and pipe section were analyzed for a complete thermal cycle, heatup and Loss of Coolant Experiment (LOCE), using COUPLE/MOD2, a two-dimensional finite element heat conduction code. The finite element representation used in this analysis was generated by the Applied Mechanics Branch. The record of nodal temperatures for the entire transient was written on tape VSN=T9N054, and has been forwarded to the Applied Mechanics Branch for use in their mechanical analysis. Specific details and assumptions used in this analysis are found in appropriate sections of this report

  14. Transient flows of the solar wind associated with small-scale solar activity in solar minimum

    Science.gov (United States)

    Slemzin, Vladimir; Veselovsky, Igor; Kuzin, Sergey; Gburek, Szymon; Ulyanov, Artyom; Kirichenko, Alexey; Shugay, Yulia; Goryaev, Farid

    The data obtained by the modern high sensitive EUV-XUV telescopes and photometers such as CORONAS-Photon/TESIS and SPHINX, STEREO/EUVI, PROBA2/SWAP, SDO/AIA provide good possibilities for studying small-scale solar activity (SSA), which is supposed to play an important role in heating of the corona and producing transient flows of the solar wind. During the recent unusually weak solar minimum, a large number of SSA events, such as week solar flares, small CMEs and CME-like flows were observed and recorded in the databases of flares (STEREO, SWAP, SPHINX) and CMEs (LASCO, CACTUS). On the other hand, the solar wind data obtained in this period by ACE, Wind, STEREO contain signatures of transient ICME-like structures which have shorter duration (<10h), weaker magnetic field strength (<10 nT) and lower proton temperature than usual ICMEs. To verify the assumption that ICME-like transients may be associated with the SSA events we investigated the number of weak flares of C-class and lower detected by SPHINX in 2009 and STEREO/EUVI in 2010. The flares were classified on temperature and emission measure using the diagnostic means of SPHINX and Hinode/EIS and were confronted with the parameters of the solar wind (velocity, density, ion composition and temperature, magnetic field, pitch angle distribution of the suprathermal electrons). The outflows of plasma associated with the flares were identified by their coronal signatures - CMEs (only in few cases) and dimmings. It was found that the mean parameters of the solar wind projected to the source surface for the times of the studied flares were typical for the ICME-like transients. The results support the suggestion that weak flares can be indicators of sources of transient plasma flows contributing to the slow solar wind at solar minimum, although these flows may be too weak to be considered as separate CMEs and ICMEs. The research leading to these results has received funding from the European Union’s Seventh Programme

  15. The effects of a physical activity intervention on employees in small and medium enterprises: a mixed methods study.

    Science.gov (United States)

    Edmunds, Sarah; Stephenson, Duncan; Clow, Angela

    2013-01-01

    Workplaces have potential as a setting for physical activity promotion but evidence of the effectiveness of intervention programmes in small and medium sized enterprises is limited. This paper reports the impact of an intervention which trained existing employees to promote physical activity to their colleagues. Eighty-nine previously low-active employees from 17 small and medium sized organisations participated. A mixed methods evaluation design was used. Quantitative data were collected at baseline and 6 months later using an online questionnaire. Qualitative data from a series of 6 focus groups were analysed. Repeated measures t-tests showed significant increases over time in physical activity, general health rating, satisfaction with life and positive mood states. There were significant decreases in body mass index (BMI), perceived stress, negative mood states and presenteeism. There was no change in absenteeism. Analysis of focus group data provided further insight into the impact of the intervention. Five major themes emerged: awareness of physical activity; sustaining physical activity behaviour change; improved health and well-being; enhanced social networks; and embedding physical activity in the workplace culture. This study shows it is feasible and effective to train employees in small and medium sized enterprises to support their colleagues in physical activity behaviour change.

  16. Spatio-temporal manipulation of small GTPase activity at subcellular level and on timescale of seconds in living cells.

    Science.gov (United States)

    DeRose, Robert; Pohlmeyer, Christopher; Umeda, Nobuhiro; Ueno, Tasuku; Nagano, Tetsuo; Kuo, Scot; Inoue, Takanari

    2012-03-09

    Dynamic regulation of the Rho family of small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events(1, 2). Their spatiotemporally dynamic nature has been revealed by visualization of their activity and localization in real time(3). In order to gain deeper understanding of their roles in diverse cellular functions at the molecular level, the next step should be perturbation of protein activities at a precise subcellular location and timing. To achieve this goal, we have developed a method for light-induced, spatio-temporally controlled activation of small GTPases by combining two techniques: (1) rapamycin-induced FKBP-FRB heterodimerization and (2) a photo-caging method of rapamycin. With the use of rapamycin-mediated FKBP-FRB heterodimerization, we have developed a method for rapidly inducible activation or inactivation of small GTPases including Rac(4), Cdc42(4), RhoA(4) and Ras(5), in which rapamycin induces translocation of FKBP-fused GTPases, or their activators, to the plasma membrane where FRB is anchored. For coupling with this heterodimerization system, we have also developed a photo-caging system of rapamycin analogs. A photo-caged compound is a small molecule whose activity is suppressed with a photocleavable protecting group known as a caging group. To suppress heterodimerization activity completely, we designed a caged rapamycin that is tethered to a macromolecule such that the resulting large complex cannot cross the plasma membrane, leading to virtually no background activity as a chemical dimerizer inside cells(6). Figure 1 illustrates a scheme of our system. With the combination of these two systems, we locally recruited a Rac activator to the plasma membrane on a timescale of seconds and achieved light-induced Rac activation at the subcellular level(6).

  17. 76 FR 82314 - Agency Information Collection Activities: Small Vessel Reporting System

    Science.gov (United States)

    2011-12-30

    ... Reporting System AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: 30-Day... accordance with the Paperwork Reduction Act: the Small Vessel Reporting System (SVRS). CBP is proposing that.... Title: Small Vessel Reporting System. OMB Number: Will be assigned upon approval. Form Number: None...

  18. 78 FR 19217 - Small Takes of Marine Mammals Incidental to Specified Activities; Cape Wind's High Resolution...

    Science.gov (United States)

    2013-03-29

    ... conjunction with seismic surveys. The pseudo-random noise stimulus and tactical sonar-like signals that were..., but not intentional, taking of small numbers of marine mammals by U.S. citizens who engage in a... small numbers of marine mammals by harassment, provided that there is no potential for serious injury or...

  19. 76 FR 80891 - Small Takes of Marine Mammals Incidental to Specified Activities; Cape Wind's High Resolution...

    Science.gov (United States)

    2011-12-27

    ... to non-tactical sonar sources used in conjunction with seismic surveys. The pseudo-random noise... request, the incidental, but not intentional, taking of small numbers of marine mammals by U.S. citizens... authorization to incidentally take small numbers of marine mammals by harassment. Section 101(a)(5)(D...

  20. The role of imaging in the active surveillance of small renal masses

    NARCIS (Netherlands)

    Wagstaff, P. G. K.; Zondervan, P. J.; de la Rosette, J. J. M. C. H.; Laguna, M. P.

    2014-01-01

    Up to 66 % of renal cell carcinomas are detected as small renal masses before the presence of clinical symptoms. Small renal mass treatment has evolved from the exclusive use of radical nephrectomy to the use of nephron sparing procedures where possible. An increase in elderly and comorbid patients,

  1. Consequences of actively managing a small Bull Trout population in a fragmented landscape

    Science.gov (United States)

    Al-Chokhachy, Robert K.; Moran, Sean; McHugh, Peter; Bernall, Shana; Fredenberg, Wade; DosSantos, Joseph M.

    2015-01-01

    Habitat fragmentation, which affects many native salmonid species, is one of the major factors contributing to the declines in distribution and abundance of Bull Trout Salvelinus confluentus. Increasingly, managers are considering options to maintain and enhance the persistence of isolated local populations through active management strategies. Understanding the ecological consequences of such actions is a necessary step in conservation planning. We used an individual-based model to evaluate the consequences of an ongoing management program aimed at mitigating the anthropogenic fragmentation of the lower Clark Fork River in Montana. Under this program juvenile Bull Trout are trapped and transported from small, headwater source populations to Lake Pend Oreille, Idaho, for rearing, and adults are subsequently recaptured in their upstream migration and returned to the natal population for spawning. We examined one of these populations and integrated empirical estimates of demographic parameters to simulate different management scenarios where moderate (n = 4) and high (n = 8) numbers of age-2, age-3, or age-4 Bull Trout were removed for transport with variable return rates under both demographic stochasticity and environmental perturbations. Our results indicated the risks from removal with no returns increased substantially when removal totals and age of Bull Trout removed from the simulated population increased. Specifically, removing eight age-3 or age-4 individuals resulted in 26% and 62% reductions in average adult population size, respectively, across simulations. We found the risks of transport were not likely alleviated with low (3%) or moderate (6%) return rates, and there were considerable risks of declines for the source population even when return rates were extremely high (>12%). Our simulations indicated little risk of declines for the source population with removals of age-2 Bull Trout, and any risks were alleviated with low return rates. However, we

  2. On the relation between the small world structure and scientific activities.

    Science.gov (United States)

    Ebadi, Ashkan; Schiffauerova, Andrea

    2015-01-01

    The modern science has become more complex and interdisciplinary in its nature which might encourage researchers to be more collaborative and get engaged in larger collaboration networks. Various aspects of collaboration networks have been examined so far to detect the most determinant factors in knowledge creation and scientific production. One of the network structures that recently attracted much theoretical attention is called small world. It has been suggested that small world can improve the information transmission among the network actors. In this paper, using the data on 12 periods of journal publications of Canadian researchers in natural sciences and engineering, the co-authorship networks of the researchers are created. Through measuring small world indicators, the small worldiness of the mentioned network and its relation with researchers' productivity, quality of their publications, and scientific team size are assessed. Our results show that the examined co-authorship network strictly exhibits the small world properties. In addition, it is suggested that in a small world network researchers expand their team size through getting connected to other experts of the field. This team size expansion may result in higher productivity of the whole team as a result of getting access to new resources, benefitting from the internal referring, and exchanging ideas among the team members. Moreover, although small world network is positively correlated with the quality of the articles in terms of both citation count and journal impact factor, it is negatively related with the average productivity of researchers in terms of the number of their publications.

  3. Activity of crizotinib over choroidal metastases in non-small-cell lung cancer (NSCLC)-ALK rearranged: a case report.

    Science.gov (United States)

    Bearz, Alessandra; Santarossa, Sandra; Manfrè, Antonio; Beltrame, Giorgio; Urbani, Martina; Sartor, Ivana; Da Ros, Valentina; Tirelli, Umberto

    2014-09-02

    Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib. Despite the concerns about the efficacy of crizotinib over cerebral metastases, some reports have described its activity, although always after local treatment with radiotherapy. Recently it has been reported activity of crizotinib over choroidal metastases, again after radiotherapy. Herein we report a case of activity of crizotinib over choroidal metastases not previously treated with radiotherapy. We suggest crizotinib may be active over choroidal metastases in a patient harboring ALK translocation with no need of radiotherapy.

  4. A STUDY REGARDING THE USE OF THE INFORMATION TECHNOLOGY AND COMMUNICATIONS IN THE LOGISTIC ACTIVITY OF SMALL AND MEDIUM ENTERPRISES

    Directory of Open Access Journals (Sweden)

    NAIANA ŢARCĂ

    2010-01-01

    Full Text Available This paper presents the results of a study regarding the necessary means for small and medium enterprises to effectively interact and cooperate in terms of obtaining a maximum profit from transport infrastructures and communications using available and predictable information technology and communications means. The diversity of structures among enterprises has led to the development of new software products, which are more competitive and efficient and are covering a wider domain of application. As the majority of logistics activities are focused on planning, realizing and tracking cargo, managing vehicles and afferent activities, specific software products were designed and developed, generically called TMS. An analysis of current situation shows that small and medium enterprises are using just a small part of available software. They are treat customers individually and does not enable collaboration between customers to reduce transportation costs or sharing the transport resources.

  5. Development of Small Molecule Activators of Protein Phosphotase 2A (SMAPs) for the Treatment of Castration Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    recently developed a series of small molecules that activate PP2A and thereby exert anticancer effects in cell culture and xenograft models. This...molecules that activate PP2A and thereby exert anticancer effects in cell culture and xenograft models. This proposal focuses on a third generation...months. 9 Changes that had a significant impact on expenditures Significant changes in use or care of human subjects, vertebrate animals

  6. Activity of crizotinib over choroidal metastases in Non-Small-Cell Lung Cancer (NSCLC)-ALK rearranged: a case report

    OpenAIRE

    Bearz, Alessandra; Santarossa, Sandra; Manfrè, Antonio; Beltrame, Giorgio; Urbani, Martina; Sartor, Ivana; Da Ros, Valentina; Tirelli, Umberto

    2014-01-01

    Background Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib. Despite the concerns about the efficacy of crizotinib over cerebral metastases, some reports have described its activity, although always after local treatment with radiotherapy. Recently it has been reported activity of crizotinib over choroidal metastases, again after radiotherapy. Case presentation Herei...

  7. Risk analysis and assessment of vertical and incline small winder systems and peripheral activities.

    CSIR Research Space (South Africa)

    Moss, PS

    2000-01-01

    Full Text Available operations. It is important, therefore, that any investigation of small winders incorporating an analysis and assessment of risk should also include a review of the potential for human error. 3 2. Methodology Accident and incident information held...

  8. Small Entrepreneurship and Entrepreneurial Activity of Population in Russia in the Context of the Economic Transformation

    NARCIS (Netherlands)

    Chepurenko, Alexander

    2010-01-01

    "Kleinunternehmen und Grundungsaktivitaten in Russland im Zuge des Transformationsprozesses". The paper deals with the main stages of private (small) entrepreneurship (SME) development and changing approaches to the SME policy in Russia under the systemic transition. The author argues that the

  9. An enzymatic deconjugation method for the analysis of small molecule active drugs on antibody-drug conjugates.

    Science.gov (United States)

    Li, Yi; Gu, Christine; Gruenhagen, Jason; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

    2016-01-01

    Antibody-drug conjugates (ADCs) are complex therapeutic agents that use the specific targeting properties of antibodies and the highly potent cytotoxicity of small molecule drugs to selectively eliminate tumor cells while limiting the toxicity to normal healthy tissues. Two critical quality attributes of ADCs are the purity and stability of the active small molecule drug linked to the ADC, but these are difficult to assess once the drug is conjugated to the antibody. In this study, we report a enzyme deconjugation approach to cleave small molecule drugs from ADCs, which allows the drugs to be subsequently characterized by reversed-phase high performance liquid chromatography. The model ADC we used in this study utilizes a valine-citrulline linker that is designed to be sensitive to endoproteases after internalization by tumor cells. We screened several proteases to determine the most effective enzyme. Among the 3 cysteine proteases evaluated, papain had the best efficiency in cleaving the small molecule drug from the model ADC. The deconjugation conditions were further optimized to achieve complete cleavage of the small molecule drug. This papain deconjugation approach demonstrated excellent specificity and precision. The purity and stability of the active drug on an ADC drug product was evaluated and the major degradation products of the active drug were identified. The papain deconjugation method was also applied to several other ADCs, with the results suggesting it could be applied generally to ADCs containing a valine-citrulline linker. Our results indicate that the papain deconjugation method is a powerful tool for characterizing the active small molecule drug conjugated to an ADC, and may be useful in ensuring the product quality, efficacy and the safety of ADCs.

  10. Activities of occupational physicians for occupational health services in small-scale enterprises in Japan and in the Netherlands

    NARCIS (Netherlands)

    Moriguchi, J.; Ikeda, M.; Sakuragi, S.; Takeda, K.; Muto, T.; Higashi, T.; Weel, A.N.H.; Van Dijk, F.J.

    2010-01-01

    Occupational health service (OHS) for small-scale enterprises (SSEs) is still limited in many countries. Both Japan and the Netherlands have universal OHS systems for all employees. The objective of this survey was to examine the activities of occupational physicians (OPs) in the two countries for

  11. The Application of Video Clips with Small Group and Individual Activities to Improve Young Learners' Speaking Performance

    Science.gov (United States)

    Muslem, Asnawi; Mustafa, Faisal; Usman, Bustami; Rahman, Aulia

    2017-01-01

    This study investigated whether the application of video clips with small groups or with individual teaching-learning activities improved the speaking skills of young EFL learners the most; accordingly a quasi-experimental study with a pre-test, post-test design was done. The instrument used in this study was a test in the form of an oral test or…

  12. Exploring corporate sustainability integration into business activities. Experiences from 18 small and medium sized enterprises in the Netherlands

    NARCIS (Netherlands)

    Witjes, S.; Vermeulen, W.J.V.; Cramer, J.M.

    Although companies have shown a growing awareness of the importance of Corporate Sustainability (CS), integration of CS into their business activities is still problematic. Most of the CS research focuses on large corporations, with limited discussions of Small and Medium Sized Enterprises (SMEs).

  13. Teaching with the Case Study Method to Promote Active Learning in a Small Molecule Crystallography Course for Chemistry Students

    Science.gov (United States)

    Campbell, Michael G.; Powers, Tamara M.; Zheng, Shao-Liang

    2016-01-01

    Implementing the case study method in a practical X-ray crystallography course designed for graduate or upper-level undergraduate chemistry students is described. Compared with a traditional lecture format, assigning small groups of students to examine literature case studies encourages more active engagement with the course material and…

  14. Occupational activities associated with a reported history of malaria among women working in small-scale agriculture in South Africa

    NARCIS (Netherlands)

    S. Naidoo (Steven); L. London (Leslie); A. Burdorf (Alex); S. Naidoo (Steven); H. Kromhout (Hans)

    2011-01-01

    textabstractMalaria-endemic agricultural communities are at risk for this disease because of crop and agricultural activities. A cross-sectional survey among women in small-scale agriculture on irrigated and dryland areas in Makhatini Flats, KwaZulu-Natal South Africa explored associations with

  15. Double Stimulation in Strategic Concept Formation: An Activity-Theoretical Analysis of Business Planning in a Small Technology Firm

    Science.gov (United States)

    Virkkunen, Jaakko; Ristimaki, Paivi

    2012-01-01

    In this article, we study the relationships between culturally existing general strategy concepts and a small information and communication technology firm's specific strategic challenge in its management team's search for a new strategy concept. We apply three theoretical ideas of cultural historical activity theory: (a) the idea of double…

  16. Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs

    DEFF Research Database (Denmark)

    Diness, Jonas Goldin; Skibsbye, Lasse; Simó-Vicens, Rafel

    2017-01-01

    Background Evidence has emerged that small-conductance Ca2+-activated K+ (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK channels are predominantly expressed in the atria as compared with the ventricles. Various marketed antiarrhythmic drugs are limited......-resistant porcine model of AF. These results suggest SK channel blockers as potentially interesting anti-AF drugs....

  17. Intercultural Interactions of Mono-Cultural, Mono-Lingual Local Students in Small Group Learning Activities: A Bourdieusian Analysis

    Science.gov (United States)

    Colvin, Cassandra; Fozdar, Farida; Volet, Simone

    2015-01-01

    This research examines the understandings and experiences of mono-cultural, mono-lingual local students in relation to intercultural interactions within small group learning activities at university. Bourdieu's concepts of field, habitus and capital are employed to illuminate a number of barriers to intercultural interaction. Using qualitative…

  18. Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue

    DEFF Research Database (Denmark)

    Jakobsen, Ann-Katrine; Lauridsen, Kristina Lystlund; Samuel, Evelyn Benuja

    2015-01-01

    of the camptothecin family (CPT). TDP1 has in cell line based assays been shown to counteract the effect of CPT. We have quantified the enzymatic activities of TOP1 and TDP1 in paired (tumor and adjacent non-tumor) samples from non-small cell lung cancer (NSCLC) patients and show that in NSCLC TOP1 and TDP1...

  19. Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke

    2009-01-01

    PURPOSE: Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK...

  20. An active electrode for biopotential recording from small localized bio-sources

    Directory of Open Access Journals (Sweden)

    Pallikarakis Nicolas E

    2004-07-01

    Full Text Available Abstract Background Laser bio-stimulation is a well-established procedure in Medical Acupuncture. Nevertheless there is still a confusion as to whether it works or the effect is just placebo. Although a plethora of scientific papers published, showing positive clinical results, there is still a lack of objective scientific proofs about the bio-stimulation effect of lasers used in Acupuncture. The objective of this work was to design and build a body surface electrode and an amplifier for biopotential recording from acupuncture points, considered here as small localized bio-sources (SLB. The design is aimed for studying SLB potentials provoked by laser stimulus, in search for objective proofs of the bio-stimulation effect of lasers used in Medical Acupuncture. Methods The active electrode presented features a new adjustable anchoring system and fractionation of the biopotential amplifier between the electrode and the cabinet's location. The new adjustable electrode anchoring system is designed to reduce the electrode-skin contact impedance, its variation and motion artifacts. That is achieved by increasing the electrode-skin tension and decreasing its relative movement. Additionally the sensing element provides local constant skin stretching thus eliminating the contribution of the skin potential artifact. The electrode is attached to the skin by a double-sided adhesive pad, where the sensing element is a stainless steel, 4 mm in diameter. The fractionation of the biopotential amplifier is done by incorporating the amplifier's front-end op-amps at the electrodes, thus avoiding the use of extra buffers. The biopotential amplifier features two selectable modes of operation: semi-AC-mode with a -3 dB bandwidth of 0.32–1000 Hz and AC-mode with a bandwidth of 0.16–1000 Hz. Results The average measured DC electrode-skin contact impedance of the proposed electrode was 450 kΩ, with electrode tension of 0.3 kg/cm2 on an unprepared skin of the inner

  1. On the relation between the small world structure and scientific activities.

    Directory of Open Access Journals (Sweden)

    Ashkan Ebadi

    Full Text Available The modern science has become more complex and interdisciplinary in its nature which might encourage researchers to be more collaborative and get engaged in larger collaboration networks. Various aspects of collaboration networks have been examined so far to detect the most determinant factors in knowledge creation and scientific production. One of the network structures that recently attracted much theoretical attention is called small world. It has been suggested that small world can improve the information transmission among the network actors. In this paper, using the data on 12 periods of journal publications of Canadian researchers in natural sciences and engineering, the co-authorship networks of the researchers are created. Through measuring small world indicators, the small worldiness of the mentioned network and its relation with researchers' productivity, quality of their publications, and scientific team size are assessed. Our results show that the examined co-authorship network strictly exhibits the small world properties. In addition, it is suggested that in a small world network researchers expand their team size through getting connected to other experts of the field. This team size expansion may result in higher productivity of the whole team as a result of getting access to new resources, benefitting from the internal referring, and exchanging ideas among the team members. Moreover, although small world network is positively correlated with the quality of the articles in terms of both citation count and journal impact factor, it is negatively related with the average productivity of researchers in terms of the number of their publications.

  2. The influence of daily variation in foraging cost on the activity of small carnivores

    Science.gov (United States)

    William J. Zielinski

    1988-01-01

    The daily activity of some predators is correlated with the activity pattern of their prey. If capture efficiency varies as a function of prey activity, a predator that synchronizes its foraging activity with the time of day that prey are most vulnerable should capture more prey, and at lower cost, than a predator that initiates foraging at random. Mink, ...

  3. Neutron Reference Benchmark Field Specification: ACRR 44 Inch Lead-Boron (LB44) Bucket Environment (ACRR-LB44-CC-32-CL).

    Energy Technology Data Exchange (ETDEWEB)

    Vega, Richard Manuel [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Parma, Edward J. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Griffin, Patrick J. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Vehar, David W. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-07-01

    This report was put together to support the International Atomic Energy Agency (IAEA) REAL- 2016 activity to validate the dosimetry community’s ability to use a consistent set of activation data and to derive consistent spectral characterizations. The report captures details of integral measurements taken in the Annular Core Research Reactor (ACRR) central cavity with the 44 inch Lead-Boron (LB44) bucket, reference neutron benchmark field. The field is described and an “a priori” calculated neutron spectrum is reported, based on MCNP6 calculations, and a subject matter expert (SME) based covariance matrix is given for this “a priori” spectrum. The results of 31 integral dosimetry measurements in the neutron field are reported.

  4. Occupational activities associated with a reported history of malaria among women working in small-scale agriculture in South Africa.

    Science.gov (United States)

    Naidoo, Saloshni; London, Leslie; Burdorf, Alex; Naidoo, Rajen N; Kromhout, Hans

    2011-11-01

    Malaria-endemic agricultural communities are at risk for this disease because of crop and agricultural activities. A cross-sectional survey among women in small-scale agriculture on irrigated and dryland areas in Makhatini Flats, KwaZulu-Natal South Africa explored associations with self-reported history of malaria, including demographics, crop production, and specific agricultural activities. Ninety-eight (15.2%) of 644 women reported malaria while working in agriculture. More women working in drylands than women working in irrigation scheme reported disease (18.4% versus 10.9%; P agriculture. This study suggests that certain agricultural activities and types of crop production may increase the risk for malaria among women working in small-scale agriculture.

  5. Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats

    OpenAIRE

    Gui, Le; LaGrange, Lila P.; Larson, Robert A.; Gu, Mingjun; Zhu, Jianhua; Chen, Qing-Hui

    2012-01-01

    Small conductance Ca2+-activated K+ (SK) channels regulate membrane properties of rostral ventrolateral medulla (RVLM) projecting hypothalamic paraventricular nucleus (PVN) neurons and inhibition of SK channels increases in vitro excitability. Here, we determined in vivo the role of PVN SK channels in regulating sympathetic nerve activity (SNA) and mean arterial pressure (MAP). In anesthetized rats, bilateral PVN microinjection of SK channel blocker with peptide apamin (0, 0.125, 1.25, 3.75, ...

  6. The Berkeley accelerator space effects facility (BASE) - A newmission for the 88-inch cyclotron at LBNL

    Energy Technology Data Exchange (ETDEWEB)

    McMahan, M.A.

    2005-09-06

    In FY04, the 88-Inch Cyclotron began a new operating mode that supports a local research program in nuclear science, R&D in accelerator technology and a test facility for the National Security Space (NSS) community (the U.S. Air Force and NRO). The NSS community (and others on a cost recovery basis) can take advantage of both the light- and heavy-ion capabilities of the Cyclotron to simulate the space radiation environment. A significant portion of this work involves the testing of microcircuits for single event effects. The experimental areas within the building that are used for the radiation effects testing are now called the Berkeley Accelerator and Space Effects (BASE) facility. Improvements to the facility to provide increased reliability, quality assurance and new capabilities are underway and will be discussed. These include a 16 AMeV ''cocktail'' of beams for heavy ion testing, a neutron beam, more robust dosimetry, and other upgrades.

  7. Design evaluation of the 20-cm (8-inch) secondary burner system

    Energy Technology Data Exchange (ETDEWEB)

    Rode, J.S.

    1977-08-01

    This report describes an evaluation of the design of the existing 20-cm (8-inch) engineering-scale secondary burner system in the HTGR reprocessing cold pilot plant at General Atomic Co. The purpose of this evaluation is to assess the suitability of the existing design as a prototype of the HTGR Recycle Demonstration Facility (HRDF) secondary burner system and to recommend alternatives where the existing design is thought to be unsuitable as a prototype. This evaluation has led to recommendations for the parallel development of two integrated design concepts for a prototype secondary burner system. One concept utilizes the existing burner heating and cooling subsystems in order to minimize development risk, but simplifies a number of other features associated with remote maintenance and burner operation. The other concept, which offers maximum cost reduction, utilizes internal gas cooling of the burner, retains the existing heating subsystem for design compatibility, but requires considerable development to reduce the risk to acceptable limits. These concepts, as well as other design alternatives, are described and evaluated.

  8. Performance and Flowfield Measurements on a 10-inch Ducted Rotor VTOL UAV

    Science.gov (United States)

    Martin, Preston; Tung, Chee

    2004-01-01

    A ducted fan VTOL UAV with a 10-inch diameter rotor was tested in the US Army 7-by 10-Foot Wind Tunnel. The test conditions covered a range of angle of attack from 0 to 110 degrees to the freestream. The tunnel velocity was varied from 0 (simulating a hover condition) to 128 ft/sec in propeller mode. A six-component internal balance measured the aerodynamic loads for a range of model configurations. including the isolated rotor, the isolated duct, and the full configuration of the duct and rotor. For some conditions, hotwire velocity surveys were conducted along the inner and outer surface of the duct and across the downstream wake. In addition, fluorescent oil flow visualization allowed the flow separation patterns inside and outside of the duct to be mapped for a few test conditions. Two different duct shapes were tested to determine the performance effects of leading edge radius. For each duct, a range of rotor tip gap from 1%R to 4.5%R was tested to determine the performance penalty in hover and axial flight. Measured results are presented in terms of hover performance, hover performance in a crosswind, and high angle of attack performance in propeller mode. In each case, the effects of both tip gap and duct leading edge radius are illustrated using measurements. Some of the hover performance issues were also studied using a simple analytical method, and the results agreed with the measurements.

  9. Summary of LaRC 2-inch Erectable Joint Hardware Heritage Test Data

    Science.gov (United States)

    Dorsey, John T.; Watson, Judith J.

    2016-01-01

    As the National Space Transportation System (STS, also known as the Space Shuttle) went into service during the early 1980's, NASA envisioned many missions of exploration and discovery that could take advantage of the STS capabilities. These missions included: large orbiting space stations, large space science telescopes and large spacecraft for manned missions to the Moon and Mars. The missions required structures that were significantly larger than the payload volume available on the STS. NASA Langley Research Center (LaRC) conducted studies to design and develop the technology needed to assemble the large space structures in orbit. LaRC focused on technology for erectable truss structures, in particular, the joint that connects the truss struts at the truss nodes. When the NASA research in large erectable space structures ended in the early 1990's, a significant amount of structural testing had been performed on the LaRC 2-inch erectable joint that was never published. An extensive set of historical information and data has been reviewed and the joint structural testing results from this historical data are compiled and summarized in this report.

  10. Design evaluation of the 20-cm (8-inch) secondary burner system

    International Nuclear Information System (INIS)

    Rode, J.S.

    1977-08-01

    This report describes an evaluation of the design of the existing 20-cm (8-inch) engineering-scale secondary burner system in the HTGR reprocessing cold pilot plant at General Atomic Co. The purpose of this evaluation is to assess the suitability of the existing design as a prototype of the HTGR Recycle Demonstration Facility (HRDF) secondary burner system and to recommend alternatives where the existing design is thought to be unsuitable as a prototype. This evaluation has led to recommendations for the parallel development of two integrated design concepts for a prototype secondary burner system. One concept utilizes the existing burner heating and cooling subsystems in order to minimize development risk, but simplifies a number of other features associated with remote maintenance and burner operation. The other concept, which offers maximum cost reduction, utilizes internal gas cooling of the burner, retains the existing heating subsystem for design compatibility, but requires considerable development to reduce the risk to acceptable limits. These concepts, as well as other design alternatives, are described and evaluated

  11. Development of the Software for 30 inch Telescope Control System at KHAO

    Science.gov (United States)

    Mun, B.-S.; Kim, S.-J.; Jang, M.; Min, S.-W.; Seol, K.-H.; Moon, K.-S.

    2006-12-01

    Even though 30inch optical telescope at Kyung Hee Astronomy Observatory has been used to produce a series of scientific achievements since its first light in 1992, numerous difficulties in the operation of the telescope have hindered the precise observations needed for further researches. Since the currently used PC-TCS (Personal Computer based Telescope Control system) software based on ISA-bus type is outdated, it doesn't have a user friendly interface and make it impossible to scale. Also accumulated errors which are generated by discordance from input and output signals into a motion controller required new control system. Thus we have improved the telescope control system by updating software and modifying mechanical parts. We applied a new BLDC (brushless DC) servo motor system to the mechanical parts of the telescope and developed a control software using Visual Basic 6.0. As a result, we could achieve a high accuracy in controlling of the telescope and use the userfriendly GUI (Graphic User Interface).

  12. Activation of endothelial and epithelial K(Ca) 2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Nielsen, Gorm

    2012-01-01

    BACKGROUND AND PURPOSE: Small (K(Ca) 2) and intermediate (K(Ca) 3.1) conductance calcium-activated potassium channels (K(Ca) ) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we inv...... targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease....

  13. Just-in-Time Online Professional Development Activities for an Innovation in Small Rural Schools

    Science.gov (United States)

    Hamel, Christine; Allaire, Stephane; Turcotte, Sandrine

    2012-01-01

    This article describes the just-in-time online professional development offered to teachers in the Remote Networked Schools (RNS), a systemic initiative funded by the Quebec Ministry of Education (Canada), which aims at enriching the learning environment of small rural schools with the use of information and communication technologies (ICTs). The…

  14. 76 FR 65206 - Agency Information Collection Activities: Small Vessel Reporting System

    Science.gov (United States)

    2011-10-20

    ... Reporting System AGENCY: U.S. Customs and Border Protection (CBP), Department of Homeland Security. ACTION... Vessel Reporting System (SVRS). This request for comment is being made pursuant to the Paperwork... concerning the following information collection: Title: Small Vessel Reporting System. OMB Number: Will be...

  15. 78 FR 61378 - Agency Information Collection Activities: Small Vessel Reporting System

    Science.gov (United States)

    2013-10-03

    ... Reporting System AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: 60-Day... Reporting System (SVRS). This request for comment is being made pursuant to the Paperwork Reduction Act of... Reporting System. OMB Number: 1651-0137. Form Number: None. Abstract: The Small Vessel Reporting System...

  16. Invented Spelling Activities in Small Groups and Early Spelling and Reading

    Science.gov (United States)

    Martins, Margarida Alves; Salvador, Liliana; Albuquerque, Ana; Silva, Cristina

    2016-01-01

    Our aim was to assess the impact of an invented spelling programme conducted in small groups on children's written language acquisition in Portuguese. We expected the experimental group to have better post-test results than the control group in spelling and reading. Participants were 160 preschool-age children who were randomly divided into an…

  17. 78 FR 37404 - Small Business Size Standards: Support Activities for Mining

    Science.gov (United States)

    2013-06-20

    ... Support Activities for Coal Mining $7.0 $19.0 213114 Support Activities for Metal Mining $7.0 $19.0 SBA is... million in net income after income taxes) for business concerns that do not meet the size standards for... Oil and Gas Operations.. $35.5 213113 Support Activities for Coal Mining $19.0 213114 Support...

  18. The capsule endoscopy "suspected blood indicator" (SBI) for detection of active small bowel bleeding: no active bleeding in case of negative SBI.

    Science.gov (United States)

    Tal, Andrea Oliver; Filmann, Natalie; Makhlin, Konstantin; Hausmann, Johannes; Friedrich-Rust, Mireen; Herrmann, Eva; Zeuzem, Stefan; Albert, Jörg G

    2014-09-01

    Capsule endoscopy (CE) is the gold standard to diagnose small bowel bleeding. The "suspected blood indicator" (SBI) offers an automated detection of active small bowel bleeding but validity of this technique is unknown. The objective was to analyze specificity and sensitivity of the SBI using the second small bowel capsule generation for the detection of active bleeding. This is a retrospective analysis of all patients (199) who attended our clinic for CE from June 2008 through March 2013. The second-generation PillCam SB 2 capsule was used for detection of (1) luminal blood content and (2) potentially responsible small bowel lesions. The findings of an independent investigator were correlated to SBI findings and a number of SBI markings were analyzed by a receiver operating characteristic (ROC). In 157/199 cases, no sign of active bleeding or altered blood was detected. One hundred and thirty-seven of these 157 cases provided at least one SBI marking and a mean of 18.4 positive SBI markings per record were found. In 20 cases, neither SBI nor the human investigator detected abnormalities. Thirteen patients showed investigator-detected minor bleeding with mean SBI findings of 36 positive screenshots per record. When major bleeding was diagnosed by the investigator (n = 29), SBI detected a mean of 46.6 SBI-positive markings. SBI turned positive in 179 patients, whereas the investigator detected active bleeding in 42 cases. All patients with active bleeding were detected by SBI (sensitivity 100%, specificity 13%). ROC analysis revealed 51.0 SBI markings being the optimal cutoff for active versus no bleeding (sensitivity 79.1%, specificity 90.4%, misclassification of 15.3%). The new SBI software is a reliable tool to exclude active bleeding and/or major lesions but analysis of the CE video by a trained investigator is still important for the detection of lesions responsible for past bleeding.

  19. Differentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations — Initial experience

    International Nuclear Information System (INIS)

    Bickelhaupt, S.; Froehlich, J.M.; Cattin, R.; Patuto, N.; Tutuian, R.; Wentz, K.U.; Culmann, J.L.; Raible, S.; Bouquet, H.; Bill, U.; Patak, M.A.

    2013-01-01

    Aim: To evaluate the influence of locally active Crohn's disease on systemic small-bowel motility in patients with chronic Crohn's disease compared to healthy individuals. Material and methods: Fifteen healthy individuals (11 men, four women; mean age 37 years) and 20 patients with histopathologically proven active (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one man; mean age 48 years) Crohn's disease were included in this institutional review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5 T) was performed after standardized preparation. Two-dimensional (2D) cine sequences for motility acquisition were performed in apnoea (27 s). Motility assessment was performed using dedicated software in three randomly chosen areas of the small-bowel outside known Crohn's disease-affected hotspots. The main quantitative characteristics (frequency, amplitude, occlusion rate) were compared using Student's t-test and one-way analysis of variance (ANOVA). Results: Three randomly chosen segments were analysed in each participant. Patients with active Crohn's disease had significantly (p < 0.05) reduced contraction frequencies (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to healthy individuals and patients with chronic Crohn's disease. Contraction amplitudes were significantly reduced during active Crohn's disease (6.71 mm) compared to healthy participants (10.14 mm), but this only reached borderline significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen diameter was significantly (p = 0.04) higher in patients with active Crohn's disease (16.91 mm) compared to healthy participants (14.79 mm) but not in comparison to patients with chronic Crohn's disease (13.68). Conclusion: The findings of the present study suggest that local inflammatory activity of small-bowel segments in patients with

  20. Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity.

    Science.gov (United States)

    Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E; Briars, Emma; Sauer, Uwe; Segrè, Daniel; Noor, Elad

    2017-09-12

    Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurements and the SMRN to make inferences on the sensitivity of enzymes to their regulators. Generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Transmembrane α-Helix 2 and 7 Are Important for Small Molecule-Mediated Activation of the GLP-1 Receptor

    DEFF Research Database (Denmark)

    Underwood, Christina Rye; Møller Knudsen, Sanne; Schjellerup Wulff, Birgitte

    2011-01-01

    Glucagon-like peptide-1 (GLP-1) activates the GLP-1 receptor (GLP-1R), which belongs to family B of the G-protein-coupled receptors. We previously identified a selective small molecule ligand, compound 2, that acted as a full agonist and allosteric modulator of GLP-1R. In this study......, the structurally related small molecule, compound 3, stimulated cAMP production from GLP-1R, but not from the homologous glucagon receptor (GluR). The receptor selectivity encouraged a chimeric receptor approach to identify domains important for compound 3-mediated activation of GLP-1R. A subsegment of the GLP-1R...... transmembrane domain containing TM2 to TM5 was sufficient to transfer compound 3 responsiveness to GluR. Therefore, divergent residues in this subsegment of GLP-1R and GluR are responsible for the receptor selectivity of compound 3. Functional analyses of other chimeric receptors suggested that the existence...

  2. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine

    DEFF Research Database (Denmark)

    Christensen, Louise Wulff; Kuhre, Rune Ehrenreich; Janus, Charlotte

    2015-01-01

    -protein-cou- pled receptor, FFAR1 (previously GPR40), expressed on L cells and activated by long-chain fatty acids (LCFAs) is a potential target. A link between FFAR1 activation and GLP-1 secretion has been demonstrated in cellular models and small-molecule FFAR1 agonists have been developed. In this study, we exam....../L LA, all significantly increased GLP-1 secretion compared to basal levels (Pagonists was ineffective. Thus, both natural and small-mole- cule agonists of the FFAR1 receptor appear to require absorption prior to stimulating GLP-1 secretion......Glucagon-like peptide 1 (GLP-1) plays a central role in modern treatment of type 2 diabetes (T2DM) in the form of GLP-1 enhancers and GLP-1 mimetics. An alternative treatment strategy is to stimulate endogenous GLP-1 secretion from enteroendocrine L cells using a targeted approach. The G...

  3. Activation of CO2 and Related Small Molecules by Neopentyl-Derivatized Uranium Complexes

    OpenAIRE

    Schmidt, Anna-Corina

    2015-01-01

    The world´s concern about the environment has continued to intensify as the effects of greenhouse gases or complicated work-up and disposal of radioactive substances become more obvious and profound. Unsurprisingly, the number of publications related to the solution of these issues has greatly increased in the last 15 years. Thus, a basic understanding of the specific properties and behavior of small molecules is crucial for the reduction of greenhouse gases, which may be realized through act...

  4. Small-molecule inhibitors of SREBP activation – potential for new treatment of metabolic disorders

    OpenAIRE

    Watanabe, Mizuki; Uesugi, Motonari

    2013-01-01

    Sterol regulatory element-binding proteins (SREBPs) are transcriptional factors that control lipid and cholesterol metabolism. Activation of SREBPs in response to a decrease in cellular sterols results in acceleration of the synthesis of fatty acids, triglycerides, and cholesterol. Aberrant SREBP activity has been linked to metabolic disease states, such as obesity, fatty liver, insulin resistance, hyperlipidemia, and atherosclerosis. Thus, inhibition of SREBP activation is a potential therap...

  5. Unbundling the retail gas market: Current activities and guidance for serving residential and small customers

    Energy Technology Data Exchange (ETDEWEB)

    Costello, K.W.; Lemon, J.R.

    1996-05-01

    The restructuring of retail gas services has followed a typical pattern for previously heavily regulated industries: large customers are initially given rights to purchase unbundled services from different entities, with the same rights dispersed over time to smaller customers. For about ten years now industrial customers in most states have been able to {open_quotes}play the market{close_quotes}. Since the passage of the Federal Energy Regulatory Commission (FERC) Order 636 in 1992, interest has centered on expanding service unbundling to small retail customers, including residential customers. Importantly, the Order prohibited pipelines from providing bundled sales service. This is not surprising - in the telecommunications industry, for example, the unbundling of wholesale services was a strong stimulant for developing competition in the local exchange market. The push for small-customer service unbundling has derived from the basic but politically attractive idea that all retail customers should directly benefit from competitive forces in the natural gas industry. When one looks at the movement of prices since 1985, it is easy to see that large retail customers have enjoyed more favorable prices than other retail customers. For example, over the period 1985 to 1994 gas prices to industrial customers and electric utilities fell around 23 percent and 36 percent, respectively. In comparison, gas prices to residential customers increased by around 5 percent while gas prices to commercial customers decreased slightly by about 1 percent. This report examines various aspects of unbundling to small retail gas customers, with special emphasis on residential customers.

  6. Unbundling the retail gas market: Current activities and guidance for serving residential and small customers

    International Nuclear Information System (INIS)

    Costello, K.W.; Lemon, J.R.

    1996-05-01

    The restructuring of retail gas services has followed a typical pattern for previously heavily regulated industries: large customers are initially given rights to purchase unbundled services from different entities, with the same rights dispersed over time to smaller customers. For about ten years now industrial customers in most states have been able to open-quotes play the marketclose quotes. Since the passage of the Federal Energy Regulatory Commission (FERC) Order 636 in 1992, interest has centered on expanding service unbundling to small retail customers, including residential customers. Importantly, the Order prohibited pipelines from providing bundled sales service. This is not surprising - in the telecommunications industry, for example, the unbundling of wholesale services was a strong stimulant for developing competition in the local exchange market. The push for small-customer service unbundling has derived from the basic but politically attractive idea that all retail customers should directly benefit from competitive forces in the natural gas industry. When one looks at the movement of prices since 1985, it is easy to see that large retail customers have enjoyed more favorable prices than other retail customers. For example, over the period 1985 to 1994 gas prices to industrial customers and electric utilities fell around 23 percent and 36 percent, respectively. In comparison, gas prices to residential customers increased by around 5 percent while gas prices to commercial customers decreased slightly by about 1 percent. This report examines various aspects of unbundling to small retail gas customers, with special emphasis on residential customers

  7. Inhibitory Activity of (+-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility.

    Directory of Open Access Journals (Sweden)

    Yi Yang

    Full Text Available Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+-usnic acid and cetuximab. These results implied that (+-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.

  8. Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility

    Science.gov (United States)

    Yang, Yi; Nguyen, Thanh Thi; Jeong, Min-Hye; Crişan, Florin; Yu, Young Hyun; Ha, Hyung-Ho; Choi, Kyung Hee; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2016-01-01

    Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action. PMID:26751081

  9. Computational fluid dynamics analysis of space shuttle main propulsion feed line 17-inch disconnect valves

    Science.gov (United States)

    Kandula, Max; Pearce, Daniel

    1989-01-01

    A steady incompressible three-dimensional (3-D) viscous flow analysis was conducted for the Space Shuttle Main Propulsion External Tank (ET)/Orbiter (ORB) propellant feed line quick separable 17-inch disconnect flapper valves for liquid oxygen (LO2) and liquid hydrogen (LH2). The main objectives of the analysis were to predict and correlate the hydrodynamic stability of the flappers and pressure drop with available water test data. Computational Fluid Dynamics (CFD) computer codes were procured at no cost from the public domain, and were modified and extended to carry out the disconnect flow analysis. The grid generator codes SVTGD3D and INGRID were obtained. NASA Ames Research Center supplied the flow solution code INS3D, and the color graphics code PLOT3D. A driver routine was developed to automate the grid generation process. Components such as pipes, elbows, and flappers can be generated with simple commands, and flapper angles can be varied easily. The flow solver INS3D code was modified to treat interior flappers, and other interfacing routines were developed, which include a turbulence model, a force/moment routine, a time-step routine, and initial and boundary conditions. In particular, an under-relaxation scheme was implemented to enhance the solution stability. Major physical assumptions and simplifications made in the analysis include the neglect of linkages, slightly reduced flapper diameter, and smooth solid surfaces. A grid size of 54 x 21 x 25 was employed for both the LO2 and LH2 units. Mixing length theory applied to turbulent shear flow in pipes formed the basis for the simple turbulence model. Results of the analysis are presented for LO2 and LH2 disconnects.

  10. [160 activities analyzed by the risk of biomechanical overload on the upper limbs in small industry, handicrafts, services and agriculture].

    Science.gov (United States)

    Caselli, Ugo; Breschi, Chiara; Compagnonil, Raffaella; De Filippo, Laura; Gogliettino, Maria Angela; Guerrera, Elena; Mameli, Marina; Mastrominico, Eleonora; Mochi, Silvia; Sarto, Daniela

    2014-01-01

    We analyzed 160 work activities in the sectors of small industries, handicrafts, services and agriculture to evaluate the risk of biomnechanical overload of the upper limbs with the OCRA Checklist. The aim was to provide a tool available for the risk assessment in activities generally underestimnated for this risk and typical of the Italian production. The information was provided in the form of cards containing easily accessible data, risk scenarios in different timing, along with some of the key prevention interventions that can be realized.

  11. Small Scale High Speed Turbomachinery

    Science.gov (United States)

    London, Adam P. (Inventor); Droppers, Lloyd J. (Inventor); Lehman, Matthew K. (Inventor); Mehra, Amitav (Inventor)

    2015-01-01

    A small scale, high speed turbomachine is described, as well as a process for manufacturing the turbomachine. The turbomachine is manufactured by diffusion bonding stacked sheets of metal foil, each of which has been pre-formed to correspond to a cross section of the turbomachine structure. The turbomachines include rotating elements as well as static structures. Using this process, turbomachines may be manufactured with rotating elements that have outer diameters of less than four inches in size, and/or blading heights of less than 0.1 inches. The rotating elements of the turbomachines are capable of rotating at speeds in excess of 150 feet per second. In addition, cooling features may be added internally to blading to facilitate cooling in high temperature operations.

  12. How Do Small Things Make a Big Difference? Activities to Teach about Human-Microbe Interactions

    Science.gov (United States)

    Jasti, Chandana; Hug, Barbara; Waters, Jillian L.; Whitaker, Rachel J.

    2014-01-01

    Recent scientific studies are providing increasing evidence for how microbes living in and on us are essential to our good health. However, many students still think of microbes only as germs that harm us. The classroom activities presented here are designed to shift student thinking on this topic. In these guided inquiry activities, students…

  13. Small increase of actual physical activity 6 months after total hip or knee arthroplasty

    NARCIS (Netherlands)

    I.B. de Groot (Ingrid); J.B.J. Bussmann (Hans); H.J. Stam (Henk); J.A.N. Verhaar (Jan)

    2008-01-01

    textabstractLimitation in daily physical activity is one of the reasons for total hip arthroplasty (THA) or total knee arthroplasty (TKA). However, studies of the effects of THA or TKA generally do not determine actual daily activity as part of physical functioning. We determined the effect of THA

  14. Relationships between activators and inhibitors of plasminogen, and the progression of small abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Jørgensen, B; Shi, G-P

    2003-01-01

    plasmin is a common activator of the known proteolytic systems involved in the aneurysmal degradation, and is reported to be associated with the expansion of abdominal aortic aneurysms (AAA). The aim of this study was to study the activating pathways of plasminogen as predictors of the progression...

  15. Innovation activities by small and medium-sized manufacturing enterprises in Tanzania

    NARCIS (Netherlands)

    Mahemba, Christopher M.; de Bruijn, E.J.

    2003-01-01

    The primary aim of this research is to explore innovation activities and ascertain the relationships between these activities and growth performance of SMEs in the Tanzanian manufacturing sector. The applied model has been derived from international studies of innovation. A survey of SMEs combined

  16. High quality, small molecule-activity datasets for kinase research [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rajan Sharma

    2016-10-01

    Full Text Available Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease. The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR data. Bioactivity databases such as the Kinase Knowledgebase (KKB, WOMBAT, GOSTAR, and ChEMBL provide researchers with quantitative data characterizing the activity of compounds across many biological assays. The KKB, for example, contains over 1.8M kinase structure-activity data points reported in peer-reviewed journals and patents. In the spirit of fostering methods development and validation worldwide, we have extracted and have made available from the KKB 258K structure activity data points and 76K associated unique chemical structures across eight kinase targets. These data are freely available for download within this data note.

  17. High quality, small molecule-activity datasets for kinase research [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rajan Sharma

    2016-06-01

    Full Text Available Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease. The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR data. Bioactivity databases such as the Kinase Knowledgebase (KKB, WOMBAT, GOSTAR, and ChEMBL provide researchers with quantitative data characterizing the activity of compounds across many biological assays. The KKB, for example, contains over 1.8M kinase structure-activity data points reported in peer-reviewed journals and patents. In the spirit of fostering methods development and validation worldwide, we have extracted and have made available from the KKB 258K structure activity data points and 76K associated unique chemical structures across eight kinase targets. These data are freely available for download within this data note.

  18. High quality, small molecule-activity datasets for kinase research [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rajan Sharma

    2016-07-01

    Full Text Available Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease. The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR data. Bioactivity databases such as the Kinase Knowledgebase (KKB, WOMBAT, GOSTAR, and ChEMBL provide researchers with quantitative data characterizing the activity of compounds across many biological assays. The KKB, for example, contains over 1.8M kinase structure-activity data points reported in peer-reviewed journals and patents. In the spirit of fostering methods development and validation worldwide, we have extracted and have made available from the KKB 258K structure activity data points and 76K associated unique chemical structures across eight kinase targets. These data are freely available for download within this data note.

  19. Intracellular calcium promotes radioresistance of non-small cell lung cancer A549 cells through activating Akt signaling.

    Science.gov (United States)

    Wang, Yiling; He, Jiantao; Zhang, Shenghui; Yang, Qingbo

    2017-03-01

    Radiotherapy is a major therapeutic approach in non-small cell lung cancer but is restricted by radioresistance. Although Akt signaling promotes radioresistance in non-small cell lung cancer, it is not well understood how Akt signaling is activated. Since intracellular calcium (Ca 2+ ) could activate Akt in A549 cells, we investigated the relationship between intracellular calcium (Ca 2+ ) and Akt signaling in radioresistant A549 cells by establishing radioresistant non-small cell lung cancer A549 cells. The radioresistant cell line A549 was generated by dose-gradient irradiation of the parental A549 cells. The cell viability, proliferation, and apoptosis were, respectively, assessed using the cell counting kit-8, EdU labeling, and flow cytometry analysis. The phosphorylation of Akt was evaluated by Western blotting, and the intracellular Ca 2+ concentration was assessed by Fluo 4-AM. The radioresistant A549 cells displayed mesenchymal morphology. After additional irradiation, the radioresistant A549 cells showed decreased cell viability and proliferation but increased apoptosis. Moreover, the intracellular Ca 2+ concentration and the phosphorylation level on the Akt473 site in radioresistant A549 cells were higher than those in original cells, whereas the percentage of apoptosis in radioresistant A549 cells was less. All these results could be reversed by verapamil. In conclusion, our study found that intracellular Ca 2+ could promote radioresistance of non-small cell lung cancer cells through phosphorylating of Akt on the 473 site, which contributes to a better understanding on the non-small cell lung cancer radioresistance, and may provide a new target for radioresistance management.

  20. A bioassay-guided fractionation system to identify endogenous small molecules that activate plasma membrane H+-ATPase activity in Arabidopsis.

    Science.gov (United States)

    Han, Xiuli; Yang, Yongqing; Wu, Yujiao; Liu, Xiaohui; Lei, Xiaoguang; Guo, Yan

    2017-05-17

    Plasma membrane (PM) H+-ATPase is essential for plant growth and development. Various environmental stimuli regulate its activity, a process that involves many protein cofactors. However, whether endogenous small molecules play a role in this regulation remains unknown. Here, we describe a bio-guided isolation method to identify endogenous small molecules that regulate PM H+-ATPase activity. We obtained crude extracts from Arabidopsis seedlings with or without salt treatment and then purified them into fractions based on polarity and molecular mass by repeated column chromatography. By evaluating the effect of each fraction on PM H+-ATPase activity, we found that fractions containing the endogenous, free unsaturated fatty acids oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) extracted from salt-treated seedlings stimulate PM H+-ATPase activity. These results were further confirmed by the addition of exogenous C18:1, C18:2, or C18:3 in the activity assay. The ssi2 mutant, with reduced levels of C18:1, C18:2, and C18:3, displayed reduced PM H+-ATPase activity. Furthermore, C18:1, C18:2, and C18:3 directly bound to the C-terminus of the PM H+-ATPase AHA2. Collectively, our results demonstrate that the binding of free unsaturated fatty acids to the C-terminus of PM H+-ATPase is required for its activation under salt stress. The bio-guided isolation model described in this study could enable the identification of new endogenous small molecules that modulate essential protein functions, as well as signal transduction, in plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Siloxides as supporting ligands in uranium(III)-mediated small-molecule activation

    Energy Technology Data Exchange (ETDEWEB)

    Mougel, Victor; Camp, Clement; Pecaut, Jacques; Mazzanti, Marinella [Laboratoire de Reconnaissance Ionique et Chimie de Coordination, SCIB, UMR-E3 CEA-UJF, INAC, CEA-Grenoble (France); Coperet, Christophe [Laboratory of Inorganic Chemistry, ETH Zurich (Switzerland); Maron, Laurent; Kefalidis, Christos E. [LPCNO, CNRS and INSA, UPS, Universite de Toulouse (France)

    2012-12-03

    Siloxides can support U..in the reduction of small molecules with uranium complexes. The treatment of [U{N(SiMe_3)_2}{sub 3}] with HOSi(OtBu){sub 3} (3 equiv) yielded a novel homoleptic uranium(III) siloxide complex 1, which acted as a two-electron reducing agent toward CS{sub 2} and CO{sub 2}. Complex 1 also reduced toluene to afford a diuranium inverted-sandwich complex. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Singularities of marketing activities of small businesses: attracting and retaining customers

    Directory of Open Access Journals (Sweden)

    Roshchak Dmitrii Aleksandrovich

    2013-04-01

    Full Text Available The article deals with the use of internet marketing in general, and tools such as blogging, in particular with a view to establishing a system of customer relationship management: recruitment and retention. The article describes the most effective techniques to enhance the customer base. Common errors and the use of this tool by other companies of small and medium businesses are specified. Particular attention is paid to low-budget methods of "guerrilla" techniques by which these companies can achieve their goals and build an effective marketing strategy.

  3. Activity Based Costing knowledge: empirical study on small and mediumsize enterprises

    Directory of Open Access Journals (Sweden)

    Maria João Cardoso Vieira Machado

    2012-01-01

    Full Text Available The objective of this paper is to analyze the percentage rate of use and knowledge of activitybased costing (ABC in small and medium-sized Portuguese enterprises and at the same time searching for the existence of any factors that might explain why this method is not is used among most companies. The collected data allow us to conclude that none of these enterprises uses the ABC and that the majority of respondents did not have any knowledge on the subject. Hierarchical level, age and academic qualifications are the reasons why the knowledge of the ABC is associated to the individual characteristics of people responsible for management accounting.

  4. How Do Small Things Make a Big Difference? Activities to Teach about Human-Microbe Interactions.

    Science.gov (United States)

    Jasti, Chandana; Hug, Barbara; Waters, Jillian L; Whitaker, Rachel J

    2014-11-01

    Recent scientific studies are providing increasing evidence for how microbes living in and on us are essential to our good health. However, many students still think of microbes only as germs that harm us. The classroom activities presented here are designed to shift student thinking on this topic. In these guided inquiry activities, students investigate human-microbe interactions as they work together to interpret and analyze authentic data from published articles and develop scientific models. Through the activities, students learn and apply ecological concepts as they come to see the human body as a fascinatingly complex ecosystem.

  5. How Do Small Things Make a Big Difference? Activities to Teach about Human–Microbe Interactions

    Science.gov (United States)

    JASTI, CHANDANA; HUG, BARBARA; WATERS, JILLIAN L.; WHITAKER, RACHEL J.

    2014-01-01

    Recent scientific studies are providing increasing evidence for how microbes living in and on us are essential to our good health. However, many students still think of microbes only as germs that harm us. The classroom activities presented here are designed to shift student thinking on this topic. In these guided inquiry activities, students investigate human–microbe interactions as they work together to interpret and analyze authentic data from published articles and develop scientific models. Through the activities, students learn and apply ecological concepts as they come to see the human body as a fascinatingly complex ecosystem. PMID:25520526

  6. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction

    Science.gov (United States)

    Namkung, Wan; Yao, Zhen; Finkbeiner, Walter E.; Verkman, A. S.

    2011-01-01

    TMEM16A (ANO1) is a calcium-activated chloride channel (CaCC) expressed in secretory epithelia, smooth muscle, and other tissues. Cell-based functional screening of ∼110,000 compounds revealed compounds that activated TMEM16A CaCC conductance without increasing cytoplasmic Ca2+. By patch-clamp, N-aroylaminothiazole “activators” (Eact) strongly increased Cl− current at 0 Ca2+, whereas tetrazolylbenzamide “potentiators” (Fact) were not active at 0 Ca2+ but reduced the EC50 for Ca2+-dependent TMEM16A activation. Of 682 analogs tested, the most potent activator (Eact) and potentiator (Fact) produced large and more sustained CaCC Cl− currents than general agonists of Ca2+ signaling, with EC50 3–6 μM and Cl− conductance comparable to that induced transiently by Ca2+-elevating purinergic agonists. Analogs of activators were identified that fully inhibited TMEM16A Cl− conductance, providing further evidence for direct TMEM16A binding. The TMEM16A activators increased CaCC conductance in human salivary and airway submucosal gland epithelial cells, and IL-4 treated bronchial cells, and stimulated submucosal gland secretion in human bronchi and smooth muscle contraction in mouse intestine. Small-molecule, TMEM16A-targeted activators may be useful for drug therapy of cystic fibrosis, dry mouth, and gastrointestinal hypomotility disorders, and for pharmacological dissection of TMEM16A function.—Namkung, W., Yao, Z., Finkbeiner, W. E., Verkman, A. S. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. PMID:21836025

  7. Small molecule SIRT1 activators for the treatment of aging and age-related diseases.

    Science.gov (United States)

    Hubbard, Basil P; Sinclair, David A

    2014-03-01

    Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD⁺-dependent deacylases that are central to the body's response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A Novel High Gain Active Reflect Array Antenna Architecture for Small Spacecraft, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this Phase I SBIR effort is to develop and demonstrate an advanced, deployable, high gain, active reflect array antenna for use in high data rate...

  9. 77 FR 72766 - Small Business Size Standards: Support Activities for Mining

    Science.gov (United States)

    2012-12-06

    ....9 $3,246.0 0.892 $35.5 $7.0 Operations 35.5 35.5 35.5 $35.5 213113 Support Activities for Coal... taxes (excluding any carry-over losses) for the 2 full fiscal years before the date of the application... Oil and Gas $7.0 $35.5 Operations. 213113 Support Activities for Coal Mining...... 7.0 19.0 213114...

  10. Profile of epidermal metabolic activity in autosomal dominant ichthyosis and small bowel disorders

    International Nuclear Information System (INIS)

    Dykes, P.J.; Marks, R.; Smith, P.

    1978-01-01

    The in vitro incorporation of 14 C acetate by the epidermis has been studied in patients with autosomal dominant ichthyosis and in patients with a dry, itchy, slightly scaly skin associated with a disorder of the small bowel. Analysis of 14 C acetate containing lipid moieties by thin layer chromatography has indicated that there are both quantitative and qualitative differences in the uptake of 14 C acetate between autosomal dominant ichthyosis and normal. In particular an increased incorporation into the triglyceride and phosphatidyl choline fractions was noted. No such differences were apparent in those patients with disorders of the small bowel. In addition the in vitro incorporation of radioactively labelled thymidine, proline and histidine has been studied in these patients. In both groups of patients the rate of incorporation of tritiated thymidine and histidine into epidermal macromolecules was found not to differ significantly from normal. On the other hand the rate of incorporation of tritiated proline was increased in both groups of patients. (author)

  11. Identification of small-molecule antagonists that inhibit an activator: coactivator interaction.

    Science.gov (United States)

    Best, Jennifer L; Amezcua, Carlos A; Mayr, Bernhard; Flechner, Lawrence; Murawsky, Christopher M; Emerson, Beverly; Zor, Tsaffrir; Gardner, Kevin H; Montminy, Marc

    2004-12-21

    Phosphorylation of the cAMP response element binding protein (CREB) at Ser-133 in response to hormonal stimuli triggers cellular gene expression via the recruitment of the histone acetylase coactivator paralogs CREB binding protein (CBP) and p300 to the promoter. The NMR structure of the CREB:CBP complex, using relevant interaction domains called KID and KIX, respectively, reveals a shallow hydrophobic groove on the surface of KIX that accommodates an amphipathic helix in phospho (Ser-133) KID. Using an NMR-based screening approach on a preselected small-molecule library, we identified several compounds that bind to different surfaces on KIX. One of these, KG-501 (2-naphthol-AS-E-phosphate), targeted a surface distal to the CREB binding groove that includes Arg-600, a residue that is required for the CREB:CBP interaction. When added to live cells, KG-501 disrupted the CREB: CBP complex and attenuated target gene induction in response to cAMP agonist. These results demonstrate the ability of small molecules to interfere with second-messenger signaling cascades by inhibiting specific protein-protein interactions in the nucleus.

  12. Development of active learning modules in pharmacology for small group teaching.

    Science.gov (United States)

    Tripathi, Raakhi K; Sarkate, Pankaj V; Jalgaonkar, Sharmila V; Rege, Nirmala N

    2015-01-01

    Current teaching in pharmacology in undergraduate medical curriculum in India is primarily drug centered and stresses imparting factual knowledge rather than on pharmacotherapeutic skills. These skills would be better developed through active learning by the students. Hence modules that will encourage active learning were developed and compared with traditional methods within the Seth GS Medical College, Mumbai. After Institutional Review Board approval, 90 second year undergraduate medical students who consented were randomized into six sub-groups, each with 15 students. Pre-test was administered. The three sub-groups were taught a topic using active learning modules (active learning groups), which included problems on case scenarios, critical appraisal of prescriptions and drug identification. The remaining three sub-groups were taught the same topic in a conventional tutorial mode (tutorial learning groups). There was crossover for the second topic. Performance was assessed using post-test. Questionnaires with Likert-scaled items were used to assess feedback on teaching technique, student interaction and group dynamics. The active and tutorial learning groups differed significantly in their post-test scores (11.3 ± 1.9 and 15.9 ± 2.7, respectively, P active learning session as interactive (vs. 37/90 students in tutorial group) and enhanced their understanding vs. 56/90 in tutorial group), aroused intellectual curiosity (47/90 students of active learning group vs. 30/90 in tutorial group) and provoked self-learning (41/90 active learning group vs. 14/90 in tutorial group). Sixty-four students in the active learning group felt that questioning each other helped in understanding the topic, which was the experience of 25/90 students in tutorial group. Nevertheless, students (55/90) preferred tutorial mode of learning to help them score better in their examinations. In this study, students preferred an active learning environment, though to pass examinations, they

  13. Structures of Clostridium Botulinum Neurotoxin Serotype A Light Chain Complexed with Small-Molecule Inhibitors Highlight Active-Site Flexibility

    Energy Technology Data Exchange (ETDEWEB)

    Silvaggi,N.; Boldt, G.; Hixon, M.; Kennedy, J.; Tzipori, S.; Janda, K.; Allen, K.

    2007-01-01

    The potential for the use of Clostridial neurotoxins as bioweapons makes the development of small-molecule inhibitors of these deadly toxins a top priority. Recently, screening of a random hydroxamate library identified a small-molecule inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (BoNT/A-LC), 4-chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo efficacy in mice and no toxicity. We describe the X-ray crystal structures of BoNT/A-LC in complexes with two potent small-molecule inhibitors. The structures of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic hydroxamate bound are compared to the structure of the enzyme complexed with L-arginine hydroxamate, an inhibitor with modest affinity. Taken together, this suite of structures provides surprising insights into the BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket. Information gained from these structures will inform the design and optimization of more effective small-molecule inhibitors of BoNT/A-LC.

  14. Coamorphous Active Pharmaceutical Ingredient-Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability.

    Science.gov (United States)

    Newman, Ann; Reutzel-Edens, Susan M; Zografi, George

    2018-01-01

    In the recent years, coamorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule coformer have appeared as alternatives to the use of either amorphous solid dispersions containing polymer or cocrystals of API and small molecule coformers, to improve the dissolution and oral bioavailability of poorly soluble crystalline API. This Commentary article considers the relative properties of amorphous solid dispersions and coamorphous systems in terms of methods of preparation; miscibility; glass transition temperature; physical stability; hygroscopicity; and aqueous dissolution. It also considers important questions concerning the fundamental criteria to be used for the proper selection of a small molecule coformer regarding its ability to form either coamorphous or cocrystal systems. Finally, we consider various aspects of product development that are specifically associated with the formulation of commercial coamorphous systems as solid oral dosage forms. These include coformer selection; screening; methods of preparation; preformulation; physical stability; bioavailability; and final formulation. Through such an analysis of coamorphous API-small molecule coformer systems, against the more widely studied API-polymer dispersions and cocrystals, it is believed that the strengths and weaknesses of coamorphous systems can be better understood, leading to more efficient formulation and manufacture of such systems for enhancing oral bioavailability. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Phenotypic plasticity of post-fire activity and thermal biology of a free-ranging small mammal.

    Science.gov (United States)

    Stawski, Clare; Körtner, Gerhard; Nowack, Julia; Geiser, Fritz

    2016-05-15

    Ecosystems can change rapidly and sometimes irreversibly due to a number of anthropogenic and natural factors, such as deforestation and fire. How individual animals exposed to such changes respond behaviourally and physiologically is poorly understood. We quantified the phenotypic plasticity of activity patterns and torpor use - a highly efficient energy conservation mechanism - in brown antechinus (Antechinus stuartii), a small Australian marsupial mammal. We compared groups in densely vegetated forest areas (pre-fire and control) with a group in a burned, open habitat (post-fire). Activity and torpor patterns differed among groups and sexes. Females in the post-fire group spent significantly less time active than the other groups, both during the day and night. However, in males only daytime activity declined in the post-fire group, although overall activity was also reduced on cold days in males for all groups. The reduction in total or diurnal activity in the post-fire group was made energetically possible by a ~3.4-fold and ~2.2-fold increase in the proportion of time females and males, respectively, used torpor in comparison to that in the pre-fire and control groups. Overall, likely due to reproductive needs, torpor was more pronounced in females than in males, but low ambient temperatures increased torpor bout duration in both sexes. Importantly, for both male and female antechinus and likely other small mammals, predator avoidance and energy conservation - achieved by reduced activity and increased torpor use - appear to be vital for post-fire survival where ground cover and refuges have been obliterated. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A Rapid Review of the Factors Affecting Healthcare Students' Satisfaction with Small-Group, Active Learning Methods.

    Science.gov (United States)

    Kilgour, James M; Grundy, Lisa; Monrouxe, Lynn V

    2016-01-01

    PHENOMENON: Problem-based learning (PBL) and other small-group, active learning methodologies have been widely adopted into undergraduate and postgraduate healthcare curricula across the world. Although much research has examined student perceptions of these innovative teaching pedagogies, there are still questions over which factors influence these views. This article aims to identify these key elements that affect healthcare student satisfaction with PBL and other small-group learning methods, including case-based and team-based learning. A systematic rapid review method was used to identify high-quality original research papers from the healthcare education literature from between 2009 and 2014. All papers were critically appraised before inclusion in line with published guidelines. Narrative synthesis was achieved using an inductively developed, thematic framework approach. Fifty-four papers were included in the narrative synthesis. The evidence suggests that, despite an initial period of negative emotion and anxiety, the perspectives of healthcare students toward small-group, active learning methods are generally positive. The key factors influencing this satisfaction level include (a) the facilitator role, (b) tutorial structure, (c) individual student factors, (d) case authenticity, (e) increased feedback, (f) group harmony, and (g) resource availability. Insights: Student satisfaction is an important determinant of healthcare education quality, and the findings of this review may be of value in future curriculum design. The evidence described here suggests that an ideal curriculum may be based on an expert-led, hybrid PBL model.

  17. Abba promotes PDGF-mediated membrane ruffling through activation of the small GTPase Rac1.

    Science.gov (United States)

    Zheng, Datong; Niu, Shuqiong; Yu, Dan; Zhan, Xiaoguo H; Zeng, Xianchun; Cui, Bota; Chen, Yanping; Yoon, Jennifer; Martin, Stuart S; Lu, Xiang; Zhan, Xi

    2010-10-29

    Abba is a member of the I-BAR-domain protein family that is characterized by a convex-shaped membrane-binding motif. Overexpression of GFP-tagged Abba in murine fibroblasts potentiated PDGF-mediated formation of membrane ruffles and lamellipodia. Immunofluorescent microscopy and pull-down analysis revealed that GFP-Abba colocalized with an active form of Rac1 in the membrane ruffles and enhanced the Rac GTPase activity in response to PDGF stimulation. Further immunoprecipitation assays demonstrated that GFP-Abba bound to both wild-type and constitutively active Rac1 and that the binding to either of the Rac1 forms was significantly enhanced upon PDGF stimulation. On the other hand, an Abba mutant deficient in Rac1 binding failed to promote membrane ruffling and Rac1 activation in response to PDGF. However, the cells overexpressing a truncated mutant carrying the I-BAR domain alone displayed numerous filopodia-like microspikes in a manner independent of growth factors. Also, the Rac-binding activity of the mutant was not affected by PDGF treatment. Our data indicates that the interaction between full-length Abba and Rac1 is implicated in membrane deformation and subjected to a growth factor-mediated regulation through the C-terminal sequence. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Distribution of physical activity facilities in Scotland by small area measures of deprivation and urbanicity

    Directory of Open Access Journals (Sweden)

    Ogilvie David

    2010-10-01

    Full Text Available Abstract Background The aim of this study was to examine the distribution of physical activity facilities by area-level deprivation in Scotland, adjusting for differences in urbanicity, and exploring differences between and within the four largest Scottish cities. Methods We obtained a list of all recreational physical activity facilities in Scotland. These were mapped and assigned to datazones. Poisson and negative binomial regression models were used to investigate associations between the number of physical activity facilities relative to population size and quintile of area-level deprivation. Results The results showed that prior to adjustment for urbanicity, the density of all facilities lessened with increasing deprivation from quintiles 2 to 5. After adjustment for urbanicity and local authority, the effect of deprivation remained significant but the pattern altered, with datazones in quintile 3 having the highest estimated mean density of facilities. Within-city associations were identified between the number of physical activity facilities and area-level deprivation in Aberdeen and Dundee, but not in Edinburgh or Glasgow. Conclusions In conclusion, area-level deprivation appears to have a significant association with the density of physical activity facilities and although overall no clear pattern was observed, affluent areas had fewer publicly owned facilities than more deprived areas but a greater number of privately owned facilities.

  19. Siloxides as supporting ligands in uranium(III)-mediated small-molecule activation

    Energy Technology Data Exchange (ETDEWEB)

    Mougel, Victor; Camp, Clement; Pecaut, Jacques; Mazzanti, Marinella [CEA-Grenoble (France). Lab. de Reconnaissance Ionique et Chimie de Coordination; Coperet, Christophe [ETH Zuerich (Switzerland). Lab. of Inorganic Chemistry; Maron, Laurent; Kefalidis, Christos E. [Toulouse Univ. (France). LPCNO, CNRS et INSA, UPS

    2012-12-03

    Siloxides support the reduction of small molecules with uranium complexes. The treatment of [U{N(SiMe_3)_2}{sub 3}] with HOSi(OtBu){sub 3} (3 equiv.) yielded a novel homoleptic uranium(III) siloxide complex 1, which acted as a two-electron reducing agent toward CS{sub 2} and CO{sub 2}. Uranium(III) siloxide complex 1 also reduced toluene to afford a diuranium inverted-sandwich complex. [German] Siloxide unterstuetzen die Reduktion kleiner Molekuele durch Uran-Komplexe. Die Behandlung von [U{N(SiMe_3)_2}{sub 3}] mit HOSi(OtBu){sub 3} (3 Aequiv.) liefert den neuartigen homoleptischen Uran(III)-Siloxid-Komplex 1, der als Zwei-Elektronen-Reduktionsmittel fuer CS{sub 2} und CO{sub 2} (siehe Schema) wirkt. Komplex 1 reduziert ausserdem Toluol und bildet einen invertierten Diuran-Sandwichkomplex.

  20. Effect of antiarrhythmic drugs on small conductance calcium –activated potassium channels

    DEFF Research Database (Denmark)

    Simo Vicens, Rafel; Sauter, Daniel Rafael Peter; Grunnet, Morten

    2017-01-01

    Atrial fibrillation (AF) is the most common type of arrhythmia. Current pharmacological treatment for AF is moderately effective and/or increases the risk of serious ventricular adverse effects. To avoid ventricular adverse effects, a new target has been considered, the small conductance calcium....... Whether antiarrhythmic drugs (AADs) recommended for treating AF target KCa2.X channels is unknown. To this end, we tested a large number of AADs on the human KCa2.2 and KCa2.3 channels to assess their effect on this new target using automated whole-cell patch clamp. Of the AADs recommended for treatment...... for their antiarrhythmic effect is unlikely, as the calculated IC50 values are very high compared to the effective free therapeutic plasma concentration of the drugs when used for AF treatment, 40,000-fold for dofetilide and 140- fold higher for propafenone....

  1. Activation of CO{sub 2} and related small molecules by neopentyl-derivatized uranium complexes

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Anna-Corina

    2015-06-18

    This work reports the newly synthesized neopentyl derivatized tris(aryloxide) U{sup III} complex [(({sup nP,Me}ArO){sub 3}tacn)U{sup III}] (1) and its reactivity with small molecules like nitrous oxide (N{sub 2}O), carbon dioxide (CO{sub 2}), and sulfur dioxide (SO{sub 2}). Additionally, a deeper insight into covalency of U-R bonds with R = O, N and the participation of the f-orbitals to bonding are discussed. For this purpose, a large number of characterization methods were used, such as X-ray diffraction analysis, U{sup V}/vis/NIR, IR vibrational, Raman, X-ray absorption, EPR, and {sup 1}H, {sup 15}N, {sup 13}C and {sup 19}F NMR spectroscopy, cyclic voltammetry, SQUID magnetization measurements and DFT calculations. Moreover, all compounds were checked for purity by elemental analysis.

  2. Small, Continual Lightning Activity in the Overshooting Turret of Supercell Storms

    Science.gov (United States)

    Macgorman, D.; Kuhlman, K.; Bruning, E.; Rust, D.; Krehbiel, P.; Rison, B.

    2007-12-01

    Several supercell storms have occurred within the region in which the Oklahoma Lightning Mapping Array (OKLMA) maps all three spatial dimensions of lightning. These storms span much of the supercell spectrum -- from non-tornadic storms to storms that produced strong tornadoes and from low-precipitation to heavy- precipitation morphologies. As noted by several studies, supercell storms tend to have much larger flash rates than ordinary isolated thunderstorms; maximum rates are typically hundreds of flashes per minute, even when considering only flashes that produce at least ten mapped points per flash. However, the OKLMA indicates that most of the flashes occurring within the main body of the storm during periods of high flash rates have quite small spatial extents, many with a long dimension of 3-10 km. Not usually included in these flash rates are a large number that appear to be isolated points (sometimes called singletons), each failing criteria of distance or time for associating it with other points in a flash. Often determining whether these isolated points are artifacts of the OKLMA is difficult, but in the overshooting top, they present a coherent pattern that appears plausible. They are distributed throughout a cap having horizontal dimensions comparable to that of the overshooting top and sitting near or on the upper surface. They occur continually, though they are too far apart in time or space to be associated in a flash with each other. A comparison with high-resolution reflectivity data for one storm observed by the two mobile 5-cm wavelength SMART-R radars shows that these isolated points were most concentrated near the top of the 40 dBZ echo in the overshooting turret, but some occurred higher, in regions of small reflectivity or just above the overshooting top. These points may be similar to the continual lightning noted by Bill Taylor in the upper region of a severe storm in the early 1980s.

  3. Effects of fractionated doses of ionizing radiation on small intestinal motor activity

    International Nuclear Information System (INIS)

    Otterson, M.F.; Sarna, S.K.; Moulder, J.E.

    1988-01-01

    The small intestinal motor effects of fractionated doses of ionizing radiation were studied in 6 conscious dogs. Eight strain-gauge transducers were implanted on the small intestine and a single gauge on the ascending colon, of each dog. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for 3 successive weeks (total dose, 2250 cGy). Recordings were then made for 4 wk of follow-up. Giant migrating contractions occurred 11 times in 520 h of control recordings in the fasted and fed state, with a mean distance of origin of 55 +/- 16 cm from the ileocolonic junction. Abdominal field irradiation significantly increased the incidence and distance of origin of these giant contractions to 438 in 745 recording hours and 158 +/- 7 cm from the ileocolonic junction, respectively. The incidence of giant migrating contractions peaked after the second dose of radiation. The amplitude ratio of radiation-induced giant migrating contractions to phase III contractions, and their duration and velocity of migration, were similar to the control state. The dogs developed diarrhea and vomiting as early as the first fraction of radiation. Irradiation also increased the incidence of retrograde giant contractions from 8 in 520 h of control recording to 42 in 745 h of recording during the radiation schedule. The radiation-induced retrograde giant contractions peaked in incidence on the day of the first fraction of radiation and were more likely to be associated with a vomiting episode than those occurring in the control period. Migrating motor complex cycling persisted during radiation and its cycle length was not different from the control or postradiation values

  4. MLEP-Fail calibration for 1/8 inch thick cast plate of 17-4 steel.

    Energy Technology Data Exchange (ETDEWEB)

    Corona, Edmundo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2018-02-01

    The purpose of the work presented in this memo was to calibrate the Sierra material model Multilinear Elastic-Plastic Hardening Model with Failure (MLEP-Fail) for 1/8 inch thick cast plate of 17-4 steel. The calibration approach is essentially the same as that recently used in a previous memo using data from smooth and notched tensile specimens. The notched specimens were manufactured with three notch radii R = 1=8, 1/32 and 1/64 inches. The dimensions of the smooth and notched specimens are given in the prints in Appendix A. Two cast plates, Plate 3 and Plate 4, with nominally identical properties were considered.

  5. Performance analysis of active damped small DC-link capacitor based drive for unbalanced input voltage supply

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig

    2011-01-01

    A small DC-link capacitor based drive is presented in this paper. The drive shows negative impedance instability at operating points with high power load. A phase portrait is presented for input filter states which exhibit a limit cycle. When the drive is operated with unbalanced input supply...... voltages, the rectified voltage contains all even harmonics frequencies. However, it is shown that the dominant harmonic component of the DC-link voltage is decided by the limit cycle instead of the input filter resonance frequency. An active damping technique is used to stabilize the operating point....... The responses of the DC-link voltage with and without active damping are presented. The low order harmonics components are reduced with the increase in the gain of the active damping term. The experimental results for the DC-link voltage, input phase currents, and machine phase current are presented....

  6. Anticancer and antimetastatic activities of Renieramycin M, a marine tetrahydroisoquinoline alkaloid, in human non-small cell lung cancer cells.

    Science.gov (United States)

    Halim, Hasseri; Chunhacha, Preedakorn; Suwanborirux, Khanit; Chanvorachote, Pithi

    2011-01-01

    Renieramycin M, has been shown to exhibit promising anticancer activity against some cancer cell lines; however, the underlying mechanism remains unknown. Renieramycin M was isolated from the blue sponge Xestospongia sp. Anticancer and antimetastatic activities of renieramycin M were investigated in human non-small cell lung cancer cells. Renieramycin M treatment caused p53 activation, which subsequently down-regulated anti-apoptotic MCL-1 and BCL-2 proteins, while the level of pro-apoptotic BAX protein was not altered. The subtoxic concentrations of renieramycin M significantly decreased invasion and migration abilities of cancer cells. In addition, this compound showed a strong inhibitory effect on anchorage-independent growth of the cells. These results reveal that renieramycin M induced lung cancer cells apoptosis through p53-dependent pathway and the compound may inhibit progression and metastasis of lung cancer cells.

  7. Small-Pore Molecular Sieves SAPO-34 with Chabazite Structure: Theoretical Study of Silicon Incorporation and Interrelated Catalytic Activity

    Science.gov (United States)

    Wang, Hong; Lewis, James; Liu, Zhongmin

    2011-03-01

    The catalytic conversion of methonal to olefin (MTO) has attracted attention both in industrial and academic fields. Strong evidence shows that small-pore molecular sieves with certain amount silicon incorporated (SAPO) present promising high catalytic activity in MTO conversion. Using DFT, we study the structural and electronic properties of chabazite SAPO-34. Although there are extensively experimental results show that silicon incorporation does not change the overall structure as the original AlPO structure, local structural changes are still created by silicon substitution, which probably accounted for the high catalytic activity. It is noted that the catalytic activity of SAPO-34 presents increasing trend along with the silicon incorporation amount increasing and maintain a flat peak even with more silicon incorporated. Hence, there is an optimal silicon incorporation amount which possibly yields the highest catalytic MTO conversion.

  8. The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Nardi, Antonio; Calloe, Kirstine

    2007-01-01

    Large-conductance Ca(2+)- and voltage-activated K(+) channels (Kca1.1/BK/MaxiK) are widely expressed ion channels. They provide a Ca(2+)-dependent feedback mechanism for the regulation of various body functions such as blood flow, neurotransmitter release, uresis, and immunity. In addition......, a mitochondrial K(+) channel with KCa1.1-resembling properties has been found in the heart, where it may be involved in regulation of energy consumption. In the present study, the effect of a novel NeuroSearch compound, 1-(3,5-bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea (NS11021......), was investigated on cloned KCa1.1 expressed in Xenopus laevis oocytes and mammalian cells using electrophysiological methods. NS11021 at concentrations above 0.3 microM activated KCa1.1 in a concentration-dependent manner by parallel-shifting the channel activation curves to more negative potentials. Single-channel...

  9. Analysis of voltage modulation based active damping techniques for small DC-link drive system

    DEFF Research Database (Denmark)

    Wang, Dong; Lu, Kaiyuan; Rasmussen, Peter Omand

    2015-01-01

    without the requirements of the information of system parameters and operating conditions. Finally, active damping techniques with minimized current magnitude and total duty cycle are discussed, in order to fit various operating conditions. Simulation and experimental results are presented to verify...

  10. Need for Cognition and Active Information Search in Small Student Groups

    Science.gov (United States)

    Curseu, Petru Lucian

    2011-01-01

    In a sample of 213 students organized in 44 groups this study tests the impact of need for cognition on active information search by using a multilevel analysis. The results show that group members with high need for cognition seek more advice in task related issues than those with low need for cognition and this pattern of information exchange is…

  11. 75 FR 13498 - Small Takes of Marine Mammals Incidental to Specified Activities; Dumbarton Bridge Seismic...

    Science.gov (United States)

    2010-03-22

    ... of Marine Mammals Incidental to Specified Activities; Dumbarton Bridge Seismic Retrofit Project... pile driving associated with the Dumbarton Bridge Seismic Retrofit Project. DATES: Effective August 15... request from Caltrans to harass marine mammals incidental to the Dumbarton Bridge Seismic Retrofit Project...

  12. Evaluation of Antioxidant Activities of Some Small Fruits Containing Anthocyanins Using Electrochemical and Chemical Methods

    Directory of Open Access Journals (Sweden)

    Adina Căta

    2016-06-01

    Full Text Available The objective of this work was to estimate the antioxidant capacity of some fruits extracts containing anthocyanins (strawberry, raspberry, elderberry, mulberry, blackberry, bilberry, black and red currant using an electrochemical technique and three classical chemical methods based on reaction between antioxidants and a chromogen compound. evaluation of antioxidant activities of extracts was performed by using FRAP (ferric reducing/antioxidant capacity, ABTS (2,2’-azinobis[3-ethylbenzothiazoline-6-sulphonate] and DPPH (2,2-diphenyl-1-picrylhydrazyl assays. Antioxidant activities of the extracts were correlated with their content of monomeric anthocyanins and total phenolics. Good correlations were obtained especially between antioxidant activities and total phenolics content. Cyclic voltammetry was used for the evaluation of overall reducing capacity of the extracts using a glassy carbon electrode. Reducing capacity of selected fruits extracts was assessed based on the half-peak potential (E1/2 of the first oxidation peak. The oxidation potentials characterized by E1/2 value were not correlated with the antioxidant activities evaluated by the classical methods. This work is licensed under a Creative Commons Attribution 4.0 International License.

  13. Becoming a Runner: Big, Middle and Small Stories about Physical Activity Participation in Later Life

    Science.gov (United States)

    Griffin, Meridith; Phoenix, Cassandra

    2016-01-01

    How do older adults learn to tell a "new" story about, through, and with the body? We know that narratives are embodied, lived and central to the process of meaning-making--and as such, they do not lie in the waiting for telling, but are an active part of everyday interaction. Telling stories about ourselves to others is one way in which…

  14. Lactic acid bacteria active during the fermentation of wheat silage in small scale silos

    Energy Technology Data Exchange (ETDEWEB)

    Moon, N.J.; Parker, J.A.; Moon, L.C.; Ely, L.O.

    1981-01-01

    Wheat was ensiled and periodically analyzed for lactic acid bacteria present. Initially Lactobacillus plantarum, Leuconostoc mesenteroides, Lactobacillus cellobiosus and Streptococcus lactis predominated. After two to four days enterococci including S. faecium and S. bovis were present in high populations as well as Lactobacillus plantarum. It was concluded that mixed populations of enterococci and L. plantarum are active in the successful fermentation of wheat silage.

  15. Real astronomy with small telescopes step-by-step activities for discovery

    CERN Document Server

    Gainer, Michael

    2010-01-01

    This book demonstrates the use of an 80mm refractor and shows how it can be used as a real scientific instrument. Users will find many activities and projects suitable for an 80mm refractor or 90mm reflector or Maksutov that have not been published elsewhere.

  16. Optimizing Facility Configurations and Operating Conditions for Improved Performance in the NASA Ames 24 Inch Shock Tube

    Science.gov (United States)

    Bogdanoff, David W.; Cruden, Brett A.

    2016-01-01

    The Ames Electric Arc Shock Tube (EAST) is a shock tube wherein the driver gas can be heated by an electric arc discharge. The electrical energy is stored in a 1.2 MJ capacitor bank. Four inch and 24 inch diameter driven tubes are available. The facility is described and the need for testing in the 24 inch tube to better simulate low density NASA mission profiles is discussed. Three test entries, 53, 53B and 59, are discussed. Tests are done with air or Mars gas (95.7% CO2/2.7% N2/1.6% Ar) at pressures of 0.01 to 0.14 Torr. Velocities spanned 6.3-9.2 km/s, with a nominal center of 7 km/s. Many facility configurations are studied in an effort to improve data quality. Various driver and driven tube configurations and the use of a buffer section between the driver and the driven tube are studied. Diagnostics include test times, time histories of the shock light pulses and tilts of the shock wave off the plane normal to the tube axis. The report will detail the results of the various trials, give the best configuration/operating conditions found to date and provide recommendations for further improvements. Finally, diaphragm performance is discussed.

  17. Four inches and seven pounds | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... new options for diagnosing celiac disease, including capsule endoscopy, which involves patients swallowing a capsule containing a tiny video camera that records images of the small intestine. Several drug treatments ...

  18. Stabilization of the activated alphaMbeta2 integrin by a small molecule inhibits leukocyte migration and recruitment.

    Science.gov (United States)

    Björklund, Mikael; Aitio, Olli; Stefanidakis, Michael; Suojanen, Juho; Salo, Tuula; Sorsa, Timo; Koivunen, Erkki

    2006-03-07

    Integrins are potential targets for the development of antiinflammatory agents. Here we develop a novel high-throughput assay by allowing a chemical library to compete with phage display peptide binding and identify a novel small-molecule ligand to the leukocyte-specific alpha(M)beta(2) integrin. The identified thioxothiazolidine-containing compound, IMB-10, had an unexpected activity in that it stabilized binding of alpha(M)beta(2) to its endogenous ligands proMMP-9 and fibrinogen. Single amino acid substitutions in the activity-regulating C-terminal helix and the underlying region in the ligand-binding I domain of the integrin suppressed the effect of IMB-10. A computational model indicated that IMB-10 occupies a distinct cavity present only in the activated form of the integrin I domain. IMB-10 inhibited alpha(M)beta(2)-dependent migration in vitro and inflammation-induced neutrophil emigration in vivo. Stabilization of integrin-mediated adhesion by a small molecule is a novel means to inhibit cell migration and may have a utility in treatment of inflammatory diseases involving leukocyte recruitment.

  19. Visualization of the Activity of Rac1 Small GTPase in a Cell

    International Nuclear Information System (INIS)

    Higashi, Morihiro; Yu, Jianyong; Tsuchiya, Hiroshi; Saito, Teruyoshi; Oyama, Toshinao; Kawana, Hidetada; Kitagawa, Motoo; Tamaru, Jun-ichi; Harigaya, Kenichi

    2010-01-01

    Rho family G proteins including Rac regulate a variety of cellular functions, such as morphology, motility, and gene expression. Here we developed a fluorescence resonance energy transfer-based analysis in which we could monitor the activity of Rac1. To detect fluorescence resonance energy transfer, yellow fluorescent protein fused Rac1 and cyan fluorescent protein fused Cdc42-Rac1-interaction-binding domain of Pak1 protein were used as intermolecular probes of FRET. The fluorophores were separated with linear unmixing method. The fluorescence resonance energy transfer efficiency was measured by acceptor photobleaching assisted assay. With these methods, the Rac1 activity was visualized in a cell. The present findings indicate that this approach is sensitive enough to achieve results similar to those from ratiometric fluorescence resonance energy transfer analysis

  20. Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41.

    Science.gov (United States)

    Zhou, Guangyan; Sofiyev, Vladimir; Kaur, Hardeep; Snyder, Beth A; Mankowski, Marie K; Hogan, Priscilla A; Ptak, Roger G; Gochin, Miriam

    2014-06-26

    We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure-activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and molecular properties. Thirty new compounds were evaluated in binding, cell-cell fusion, and viral replication assays. Below a 1 μM threshold, correlation between binding and biological activity was diminished, indicating an amphipathic requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 μM binding affinity and 0.2 μM EC50 against cell-cell fusion and live virus replication and was active against T20 resistant strains. Twenty-two compounds with the same connectivity displayed a consensus pose in docking calculations, with rank order matching the biological activity. The work provides insight into requirements for small molecule inhibition of HIV-1 fusion and demonstrates a potent low molecular weight fusion inhibitor.

  1. Structure–Activity Relationship Studies of Indole-Based Compounds as Small Molecule HIV-1 Fusion Inhibitors Targeting Glycoprotein 41

    Science.gov (United States)

    2015-01-01

    We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure–activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and molecular properties. Thirty new compounds were evaluated in binding, cell–cell fusion, and viral replication assays. Below a 1 μM threshold, correlation between binding and biological activity was diminished, indicating an amphipathic requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 μM binding affinity and 0.2 μM EC50 against cell–cell fusion and live virus replication and was active against T20 resistant strains. Twenty-two compounds with the same connectivity displayed a consensus pose in docking calculations, with rank order matching the biological activity. The work provides insight into requirements for small molecule inhibition of HIV-1 fusion and demonstrates a potent low molecular weight fusion inhibitor. PMID:24856833

  2. Bioanalytical characterisation of multiple endocrine- and dioxin-like activities in sediments from reference and impacted small rivers

    Energy Technology Data Exchange (ETDEWEB)

    Kinani, Said, E-mail: said@dcmr.polytechnique.f [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France); Departement de Chimie des Mecanismes Reactionnels, Ecole Polytechnique, 91128 Palaiseau Cedex (France); Bouchonnet, Stephane, E-mail: stephane.bouchonnet@dcmr.polytechnique.f [Departement de Chimie des Mecanismes Reactionnels, Ecole Polytechnique, 91128 Palaiseau Cedex (France); Creusot, Nicolas [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France); Bourcier, Sophie [Departement de Chimie des Mecanismes Reactionnels, Ecole Polytechnique, 91128 Palaiseau Cedex (France); Balaguer, Patrick [Institut National de la Sante et de la Recherche Medicale (INSERM), U896, Montpellier, F-34298 (France); Porcher, Jean-Marc [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France); Ait-Aissa, Selim, E-mail: selim.ait-aissa@ineris.f [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France)

    2010-01-15

    A comprehensive evaluation of organic contamination was performed in sediments sampled in two reference and three impacted small streams where endocrine disruptive (ED) effects in fish have been evidenced. The approach combined quantitative chemical analyses of more than 50 ED chemicals (EDCs) and a battery of in vitro bioassays allowing the quantification of receptor-mediated activities, namely estrogen (ER), androgen (AR), dioxin (AhR) and pregnane X (PXR) receptors. At the most impacted sites, chemical analyses showed the presence of natural estrogens, organochlorine pesticides, parabens, polycyclic aromatic hydrocarbons (16 PAHs), bisphenol A and alkylphenols, while synthetic steroids, myco-estrogens and phyto-estrogens were not detected. Determination of toxic-equivalent amounts showed that 28-96% of estrogenic activities in bioassays (0.2-6.3 ng/g 17beta-estradiol equivalents) were explained by 17beta-estradiol and estrone. PAHs were major contributors (20-60%) to the total dioxin-like activities. Interestingly, high PXR and (anti)AR activities were detected; however, the targeted analysed compounds could not explain the measured biological activities. This study highlighted the presence of multiple organic EDCs in French river sediments subjected to mixed diffuse pollution, and argues for the need to further identify AR and PXR active compounds in the aquatic environment. - Multiple endocrine disrupting chemicals (ER, AR, AhR and PXR ligands) are detected in French river sediments using a panel of in vitro bioassays and analytical methods.

  3. Lactic acid bacteria active during the fermentation of wheat silage in small scale silos

    Energy Technology Data Exchange (ETDEWEB)

    Moon, N.J.; Moon, L.C.; Ely, L.O.; Parker, J.A.

    1981-01-01

    Wheat was ensiled and periodically analyzed for lactic acid bacteria present. Initially Lactobacillus plantarum, Leuconostoc mesenteroides, Lactobacillus cellobiosus and Streptococcus lactis predominated. After two to four days enterococci including S. faecium and S. bovis were present in high populations as well as Lactobacillus plantarum. It was concluded that mixed populations of enterococci and L. plantarum are active in the successful fermentation of wheat silage. (Refs. 5).

  4. Impact of Catchment Area Activities on Water Quality in Small Retention Reservoirs

    Directory of Open Access Journals (Sweden)

    Oszczapińska Katarzyna

    2018-01-01

    Full Text Available The aim of the study was to evaluate catchment area impact on small water reservoirs condition in Podlasie. The researches were conducted in two different catchment areas. Topiło reservoir, located in Podlasie area in the south-east of Białowieża Forest, has typical sylvan catchment. Second reservoir, Dojlidy, is located also in Podlasie, in the south-east of Białystok as a part of Dojlidy Ponds. In contrast to Topiło, Dojlidy has agricultural catchment. Water samples collected from five sites along each reservoir were analysed for the presence of total nitrogen and phosphorus, chlorophyll “a”, reaction, turbidity and conductivity. Researches took place in spring, summer and autumn 2013 (Topiło Lake and 2014/2015 (Dojlidy. The lowest trophic state was observed in autumn and the highest in summer. Because of the high loads of phosphorus received by the reservoirs, this element did not limit primary production. Calculated TSI values based on total phosphorus were always markedly higher than calculated on chlorophyll-a and total nitrogen. Both reservoirs demonstrated TSI indexes specific to hypertrophic lakes due to large amount of total phosphorus.

  5. Impact of Catchment Area Activities on Water Quality in Small Retention Reservoirs

    Science.gov (United States)

    Oszczapińska, Katarzyna; Skoczko, Iwona; Szczykowska, Joanna

    2018-02-01

    The aim of the study was to evaluate catchment area impact on small water reservoirs condition in Podlasie. The researches were conducted in two different catchment areas. Topiło reservoir, located in Podlasie area in the south-east of Białowieża Forest, has typical sylvan catchment. Second reservoir, Dojlidy, is located also in Podlasie, in the south-east of Białystok as a part of Dojlidy Ponds. In contrast to Topiło, Dojlidy has agricultural catchment. Water samples collected from five sites along each reservoir were analysed for the presence of total nitrogen and phosphorus, chlorophyll "a", reaction, turbidity and conductivity. Researches took place in spring, summer and autumn 2013 (Topiło Lake) and 2014/2015 (Dojlidy). The lowest trophic state was observed in autumn and the highest in summer. Because of the high loads of phosphorus received by the reservoirs, this element did not limit primary production. Calculated TSI values based on total phosphorus were always markedly higher than calculated on chlorophyll-a and total nitrogen. Both reservoirs demonstrated TSI indexes specific to hypertrophic lakes due to large amount of total phosphorus.

  6. Monitoring the Spatiotemporal Activities of miRNAs in Small Animal Models Using Molecular Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Patrick Baril

    2015-03-01

    Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under physiopathological conditions. Recent evidence indicates that miRNA expression is more complex than simple regulation at the transcriptional level. MiRNAs undergo complex post-transcriptional regulations such miRNA processing, editing, accumulation and re-cycling within P-bodies. They are dynamically regulated and have a well-orchestrated spatiotemporal localization pattern. Real-time and spatio-temporal analyses of miRNA expression are difficult to evaluate and often underestimated. Therefore, important information connecting miRNA expression and function can be lost. Conventional miRNA profiling methods such as Northern blot, real-time PCR, microarray, in situ hybridization and deep sequencing continue to contribute to our knowledge of miRNA biology. However, these methods can seldom shed light on the spatiotemporal organization and function of miRNAs in real-time. Non-invasive molecular imaging methods have the potential to address these issues and are thus attracting increasing attention. This paper reviews the state-of-the-art of methods used to detect miRNAs and discusses their contribution in the emerging field of miRNA biology and therapy.

  7. Active acoustic leak detection for LMFBR steam generators. Pt. 7. Potential for small leak detection

    International Nuclear Information System (INIS)

    Kumagai, Hiromichi; Yoshida, Kazuo

    1998-01-01

    In order to prevent the expansion of tube damage and to maintain structural integrity in the steam generators (SGs) of fast breeder reactors (FBR), it is necessary to detect precisely and immediately the leakage of water from heat transfer tubes. Therefore, an active acoustic method, which detects the sound attenuation due to bubbles generated in the sodium-water reactions, is being developed. Previous studies have revealed that the active acoustic method can detect bubbles of 10 l/s (equivalence water leak rate about 10 g/s) within 10 seconds in practical steam generators. In order to prevent the expansion of damage to neighboring tubes, however, it is necessary to detect smaller leakage of water from heat transfer tubes. In this study, in order to evaluate the detection sensitivity of the active method, the signal processing methods for emitter and receiver sound and the detection method for leakage within 1 g/s are investigated experimentally, using an SG full-sector model that simulates the actual SGs. A typical result shows that detection of 0.4 l/s air bubbles (equivalent water leak rate about 0.4 g/s) takes about 80 seconds, which is shorter than the propagation time of damage to neighboring tubes. (author)

  8. Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.

    Science.gov (United States)

    Zeng, Canjun; Goodluck, Helen; Qin, Xuezhong; Liu, Bo; Mohan, Subburaman; Xing, Weirong

    2016-10-01

    Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment. Overexpression of constitutively active Q61L RAC1 partially rescued the resorptive function of Lrrk1-deficient osteoclasts. Furthermore, lack of Lrrk1 in osteoclasts led to reduced autophosphorylation of p21 protein-activated kinase-1 at Ser 144 , catalyzed by RAC1/Cdc42 binding and activation. Our data indicate that Lrrk1 regulates osteoclast function by directly modulating phosphorylation and activation of small GTPase RAC1/Cdc42 and that its function depends on ANK, ROC, WD40, and kinase domains. Copyright © 2016 the American Physiological Society.

  9. The Clinical Outcomes of Transcatheter Microcoil Embolization in Patients with Active Lower Gastrointestinal Bleeding in the Small Bowel

    International Nuclear Information System (INIS)

    Kwak, Hyo Sung; Han, Young Min; Lee, Soo Teik

    2009-01-01

    To assess the clinical outcomes of the transcatheter microcoil embolization in patients with active lower gastrointestinal (LGI) bleeding in the small bowel, as well as to compare the mortality rates between the two groups based on the visualization or non-visualization of the bleeding focus determined by an angiography. We retrospectively evaluated all of the consecutive patients who underwent an angiography for treatment of acute LGI bleeding between January 2003 and October 2007. In total, the study included 36 patients who underwent a colonoscopy and were diagnosed to have an active bleeding in the LGI tracts. Based on the visualization or non-visualization of the bleeding focus, determined by an angiography, the patients were classified into two groups. The clinical outcomes included technical success, clinical success (no rebleeding within 30 days), delayed rebleeding (> 30 days), as well as the major and minor complication rates. Of the 36 patients, 17 had angiography-proven bleeding that was distal to the marginal artery. The remaining 19 patients did not have a bleeding focus based on the angiography results. The technical and clinical success rates of performing transcatheter microcoil embolizations in patients with active bleeding were 100% and 88%, respectively (15 of 17). One patient died from continued LGI bleeding and one patient received surgery to treat the continued bleeding. There was no note made on the delayed bleeding or on the major or minor complications. Of the 19 patients without active bleeding, 16 (84%) did not have recurrent bleeding. One patient died due to continuous bleeding and multi-organ failure. The superselective microcoil embolization can help successfully treat patients with active LGI bleeding in the small bowel, identified by the results of an angiography. The mortality rate is not significantly different between the patients of the visualization and non-visualization groups on angiography

  10. Small activating RNA induces myogenic differentiation of rat adipose-derived stem cells by upregulating MyoD

    Directory of Open Access Journals (Sweden)

    Chenghe Wang

    2015-08-01

    Full Text Available ABSTRACTPurpose:RNA activation (RNAa is a mechanism of gene activation triggered by promoter-targeted small double stranded RNAs (dsRNAs, also known as small activating RNAs (saRNAs. Myogenic regulatory factor MyoD is regarded as the master activator of myogenic differentiation cascade by binding to enhancer of muscle specific genes. Stress urinary incontinence (SUI is a condition primarily resulted from urethral sphincter deficiency. It is thus expected that by promoting differentiation of adipose-derived stem cells (ADSCs into myoblasts by activating MyoD gene through RNAa may offer benefits to SUI.Materials and Methods:Rats ADSCs were isolated, proliferated in vitro, and identified by flow cytometry. Purified ADSCs were then transfected with a MyoD saRNA or control transfected. Real-time polymerase chain reaction (RT-PCR and western blotting were used to detect MyoD mRNA and protein expression, respectively. Immunocytochemical staining was applied to determine the expression of desmin protein in transfected cells. Cell viability was measured by using CellTiter 96® AQueous One Solution Cell Proliferation Assay kit.Results:Transfection of a MyoD saRNA (dsMyoD into ADSCs significantly induced the expression of MyoD at both the mRNA and protein levels, and inhibited cell proliferation. Desmin protein expression was detected in dsMyoD treated ADSCs 2 weeks later.Conclusion:Our findings show that RNAa mediated overexpression of MyoD can promote transdifferentiation of ADSCs into myoblasts and may help treat stress urinary incontinence (SUI–a condition primarily resulted from urethral sphincter deficiency.

  11. Modeling post-transcriptional regulation activity of small non-coding RNAs in Escherichia coli.

    Science.gov (United States)

    Wang, Rui-Sheng; Jin, Guangxu; Zhang, Xiang-Sun; Chen, Luonan

    2009-04-29

    Transcriptional regulation is a fundamental process in biological systems, where transcription factors (TFs) have been revealed to play crucial roles. In recent years, in addition to TFs, an increasing number of non-coding RNAs (ncRNAs) have been shown to mediate post-transcriptional processes and regulate many critical pathways in both prokaryotes and eukaryotes. On the other hand, with more and more high-throughput biological data becoming available, it is possible and imperative to quantitatively study gene regulation in a systematic and detailed manner. Most existing studies for inferring transcriptional regulatory interactions and the activity of TFs ignore the possible post-transcriptional effects of ncRNAs. In this work, we propose a novel framework to infer the activity of regulators including both TFs and ncRNAs by exploring the expression profiles of target genes and (post)transcriptional regulatory relationships. We model the integrated regulatory system by a set of biochemical reactions which lead to a log-bilinear problem. The inference process is achieved by an iterative algorithm, in which two linear programming models are efficiently solved. In contrast to available related studies, the effects of ncRNAs on transcription process are considered in this work, and thus more reasonable and accurate reconstruction can be expected. In addition, the approach is suitable for large-scale problems from the viewpoint of computation. Experiments on two synthesized data sets and a model system of Escherichia coli (E. coli) carbon source transition from glucose to acetate illustrate the effectiveness of our model and algorithm. Our results show that incorporating the post-transcriptional regulation of ncRNAs into system model can mine the hidden effects from the regulation activity of TFs in transcription processes and thus can uncover the biological mechanisms in gene regulation in a more accurate manner. The software for the algorithm in this paper is available

  12. Small surfactant-like peptides can drive soluble proteins into active aggregates

    Directory of Open Access Journals (Sweden)

    Zhou Bihong

    2012-01-01

    Full Text Available Abstract Background Inactive protein inclusion bodies occur commonly in Escherichia coli (E. coli cells expressing heterologous proteins. Previously several independent groups have found that active protein aggregates or pseudo inclusion bodies can be induced by a fusion partner such as a cellulose binding domain from Clostridium cellulovorans (CBDclos when expressed in E. coli. More recently we further showed that a short amphipathic helical octadecapeptide 18A (EWLKAFYEKVLEKLKELF and a short beta structure peptide ELK16 (LELELKLKLELELKLK have a similar property. Results In this work, we explored a third type of peptides, surfactant-like peptides, for performing such a "pulling-down" function. One or more of three such peptides (L6KD, L6K2, DKL6 were fused to the carboxyl termini of model proteins including Aspergillus fumigatus amadoriase II (AMA, all three peptides were used, Bacillus subtilis lipase A (LipA, only L6KD was used, hereinafter the same, Bacillus pumilus xylosidase (XynB, and green fluorescent protein (GFP, and expressed in E. coli. All fusions were found to predominantly accumulate in the insoluble fractions, with specific activities ranging from 25% to 92% of the native counterparts. Transmission electron microscopic (TEM and confocal fluorescence microscopic analyses confirmed the formation of protein aggregates in the cell. Furthermore, binding assays with amyloid-specific dyes (thioflavin T and Cong red to the AMA-L6KD aggregate and the TEM analysis of the aggregate following digestion with protease K suggested that the AMA-L6KD aggregate may contain structures reminiscent of amyloids, including a fibril-like structure core. Conclusions This study shows that the surfactant-like peptides L6KD and it derivatives can act as a pull-down handler for converting soluble proteins into active aggregates, much like 18A and ELK16. These peptide-mediated protein aggregations might have important implications for protein aggregation in

  13. Determination of very small activities of radioiodine and plutonium in air

    International Nuclear Information System (INIS)

    Irlweck, K.; Karg, V.; Schoenfeld, T.; Sorantin, H.; Steger, F.

    1982-01-01

    A mobile high volume sampler with the following characteristics was developed: air flow rate 5000 m 3 .h - 1 , total cross section of the seven activated charcoal filter units 0.6 m 2 , diameter of each filter unit 33 cm, thickness of charcoal layer 4 - 7 cm. The sorbed radioiodine is eluted from the charcoal in a circulation unit by a circulating solution (sodium hydroxide/hydrazine) and is transfered into a sorbent containing silver (ion exchange resin with colloidal silver), thereby bringing about a reduction in volume by a factor of approximately 1000. The radioiodine activity is then determined by gamma spectrometric measurement of the silver containing sorbent. The overall radioiodine yield measured with 123 I spike (sorption on charcoal and transfer to the silver containing sorbent) is 75 (+- 7)%. A detection limit of 0.02 mBq.m - 3 is achieved for 131 I. If the sampler is operated with the standard throughput of 5000 m 3 .h - 1 , this limit applies to one hour average concentration values. Results of environmental monitorings for the period 1979 - 1982 at the Research Center Seibersdorf for 131 I (up to 2,6 mBq/m 3 ) and for plutonium (up to 4 μBq/m 3 ) are given. (Author)

  14. Gain-of-function mutant p53 activates small GTPase Rac1 through SUMOylation to promote tumor progression.

    Science.gov (United States)

    Yue, Xuetian; Zhang, Cen; Zhao, Yuhan; Liu, Juan; Lin, Alan W; Tan, Victor M; Drake, Justin M; Liu, Lianxin; Boateng, Michael N; Li, Jun; Feng, Zhaohui; Hu, Wenwei

    2017-08-15

    Tumor suppressor p53 is frequently mutated in human cancer. Mutant p53 often promotes tumor progression through gain-of-function (GOF) mechanisms. However, the mechanisms underlying mutant p53 GOF are not well understood. In this study, we found that mutant p53 activates small GTPase Rac1 as a critical mechanism for mutant p53 GOF to promote tumor progression. Mechanistically, mutant p53 interacts with Rac1 and inhibits its interaction with SUMO-specific protease 1 (SENP1), which in turn inhibits SENP1-mediated de-SUMOylation of Rac1 to activate Rac1. Targeting Rac1 signaling by RNAi, expression of the dominant-negative Rac1 (Rac1 DN), or the specific Rac1 inhibitor NSC23766 greatly inhibits mutant p53 GOF in promoting tumor growth and metastasis. Furthermore, mutant p53 expression is associated with enhanced Rac1 activity in clinical tumor samples. These results uncover a new mechanism for Rac1 activation in tumors and, most importantly, reveal that activation of Rac1 is an unidentified and critical mechanism for mutant p53 GOF in tumorigenesis, which could be targeted for therapy in tumors containing mutant p53. © 2017 Yue et al.; Published by Cold Spring Harbor Laboratory Press.

  15. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation.

    Science.gov (United States)

    Fazzini, F; Peri, G; Doni, A; Dell'Antonio, G; Dal Cin, E; Bozzolo, E; D'Auria, F; Praderio, L; Ciboddo, G; Sabbadini, M G; Manfredi, A A; Mantovani, A; Querini, P R

    2001-12-01

    To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.

  16. Proposal for the CEA/DRN activity on small and medium size reactors research on threshold effects

    International Nuclear Information System (INIS)

    Fiorini, G.L.

    1998-01-01

    The discussion on Small and Medium Size Reactors - SMR is difficult considering the presumptions, justified or not, that affect the debate. Nevertheless, within this context, the CEA/DRN/DER generic objective is the achievement of an exhaustive identification and assessment of the problems that are specific for the SMR. The paper shows the proposals for the activities that are actually under discussion at the CEA/DRN. Among these activities, the research on threshold effects is an essential stage in the assessment of the choices in innovative concepts. This research, as well as the assessment itself, must cover, in an exploratory way, the aspects of operation, safety, economy, fuel cycle, etc. Before starting or, in some cases, continuing this research work, it seems interesting to define a general outline which, by systematising the approach, provides a helpful tool to the designer. The document is a potential starting point (among others) for the discussions. (author)

  17. Modeling the nucleophilic reactivity of small organochlorine electrophiles: A mechanistically based quantitative structure-activity relationship

    Energy Technology Data Exchange (ETDEWEB)

    Verhaar, H.J.M.; Seinen, W.; Hermens, J.L.M. [Utrecht Univ. (Netherlands); Rorije, E. [Dutch Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Borkent, H. [Univ. of Nijmegen (Netherlands)

    1996-06-01

    Environmental pollutants can be divided into four broad categories, narcosis-type chemicals, less inert (polar narcosis) chemicals, reactive chemicals, and specifically acting chemicals. For narcosis-type, or baseline, chemicals and for less inert chemicals, adequate quantitative structure-activity relationships (QSARs) are available for estimation of toxicity to aquatic species. This is not the case for reactive chemicals and specifically acting chemicals. A possible approach to develop aquatic toxicity QSARs for reactive chemicals based on simple considerations regarding their reactivity is given. It is shown that quantum chemical calculations on reaction transition states can be used to quantitatively predict the reactivity of sets of reactive chemicals. These predictions can then be used to develop aquatic toxicity QSARs.

  18. Intestinal myoelectric activity and contractile motility in dogs with a reversed jejunal segment after extensive small bowel resection.

    Science.gov (United States)

    Uchiyama, M; Iwafuchi, M; Ohsawa, Y; Yagi, M; Iinuma, Y; Ohtani, S

    1992-06-01

    To evaluate the functioning and effectiveness of a reversed jejunal segment after extensive small bowel resection, we continuously measured the postoperative bowel motility (using bipolar electrodes and/or contractile strain gage force transducers) in interdigestive and postprandial conscious dogs at 2 to 5 weeks after surgery. The fasting duodenal migrating myoelectric (or motor) complex (MMC) occurred at markedly longer intervals in dogs with a 20-cm reversed jejunal segment created after 75% to 80% extensive small bowel resection (group 3) than in dogs that received extensive resection alone (group 2) or dogs that underwent construction of a reversed jejunal segment without bowel resection (group 1). The MMC arising from the duodenum was often interrupted at the jejunum above the proximal anastomosis and did not migrate smoothly to the reversed segment or terminal ileum in group 3. In addition, brief small discordant contractions were frequent in the reversed segment and the jejunum above the proximal anastomosis in group 3. The duration of the postprandial period without duodenal MMC activity was significantly prolonged in groups 2 and 3. These results suggest that the transit time and passage of intestinal contents were delayed and that the periodical MMC was disturbed in group 3. The delay of transit time was due to prolongation of the interval between duodenal MMCs, the interruption of MMC propagation at the jejunum above the proximal anastomosis, the dominance of MMCs that followed the inherent anatomical continuity of the bowel, and discordant movements across the proximal anastomosis. Functional obstruction could be a potential problem in a 20-cm reversed jejunal segment inserted after extensive small bowel resection.

  19. A New Negative Allosteric Modulator AP14145 for the Study of Small Conductance Calcium-Activated Potassium Channels

    DEFF Research Database (Denmark)

    Simo Vicens, Rafel; Kirchhoff, Jeppe Egedal; Dolce, Bernardo

    2017-01-01

    Background and purpose: Small conductance Ca2+-activated K+ (KCa2) channels represent a promising atrial-selective target for treatment of atrial fibrillation (AF). Here, we establish the mechanism of KCa2 inhibition by the new compound AP14145. Experimental approach: Using site directed mutagene......Background and purpose: Small conductance Ca2+-activated K+ (KCa2) channels represent a promising atrial-selective target for treatment of atrial fibrillation (AF). Here, we establish the mechanism of KCa2 inhibition by the new compound AP14145. Experimental approach: Using site directed...... mutagenesis binding determinants for AP14145 inhibition were explored. AP14145 selectivity and mechanism of action were investigated by patch clamp recordings of heterologously expressed KCa2 channels. The biological efficacy of AP14145 was assessed by measuring atrial effective refractory period (AERP......) prolongation in anaesthetised rats and a beam walk test was performed in mice to determine acute CNS related effects of the drug. Key results: AP14145 was found to be an equipotent negative allosteric modulator of KCa2.2 and KCa2.3 channels (IC50 = 1.1 ± 0.3 μM L-1). The presence of AP14145 (10 μM L-1...

  20. A New Negative Allosteric Modulator AP14145 for the Study of Small Conductance Calcium-Activated Potassium Channels

    DEFF Research Database (Denmark)

    Simo Vicens, Rafel; Kirchhoff, Jeppe Egedal; Dolce, Bernardo

    2017-01-01

    Background and purpose: Small conductance Ca2+-activated K+ (KCa2) channels represent a promising atrial-selective target for treatment of atrial fibrillation (AF). Here, we establish the mechanism of KCa2 inhibition by the new compound AP14145. Experimental approach: Using site directed mutagene......Background and purpose: Small conductance Ca2+-activated K+ (KCa2) channels represent a promising atrial-selective target for treatment of atrial fibrillation (AF). Here, we establish the mechanism of KCa2 inhibition by the new compound AP14145. Experimental approach: Using site directed......) prolongation in anaesthetised rats and a beam walk test was performed in mice to determine acute CNS related effects of the drug. Key results: AP14145 was found to be an equipotent negative allosteric modulator of KCa2.2 and KCa2.3 channels (IC50 = 1.1 ± 0.3 μM L-1). The presence of AP14145 (10 μM L-1...... inhibition is accomplished at the molecular level will help future development of drugs targeting KCa2 channels....

  1. Exercise modulates redox-sensitive small GTPase activity in the brain microvasculature in a model of brain metastasis formation.

    Directory of Open Access Journals (Sweden)

    Gretchen Wolff

    Full Text Available Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB. There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0 ± 0.3 km/day. Mice were then infused with 1.0 × 10(6 D122 (murine Lewis lung carcinoma cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies or 2-3 weeks (in long-term studies post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals.

  2. Synthesis of Ultra-Small Platinum, Palladium and Gold Nanoparticles by Shewanella loihica PV-4 Electrochemically Active Biofilm and Their Enhanced Catalytic Activities

    KAUST Repository

    Ahmed, Elaf

    2018-02-21

    Ultra-small nanoparticles (USNPs) of noble metals have a great potential in a variety of applications due to their high surface areas and high reactivity. This works employed electrochemically active biofilms (EABs) composed of a single bacterium strain of Shewanella loihica PV-4 and successfully synthesized USNPs of noble metal Au, Pd, and Pt. The synthesized USNPs had a size range between 2 and 7 nm and exhibited excellent catalytic performance in dye decomposition. The results of this work shine lights on the use of EABs in nanoparticle synthesis.

  3. Evaluation and comparison of capsule endoscopy scores for assessment of inflammatory activity of small-bowel in Crohn's disease.

    Science.gov (United States)

    Ponte, Ana; Pinho, Rolando; Rodrigues, Adélia; Silva, Joana; Rodrigues, Jaime; Sousa, Mafalda; Carvalho, João

    2018-04-01

    Capsule endoscopy (CE) has the highest sensitivity in the evaluation of small-bowel mucosa in Crohn's disease (CD). Recent guidelines recommend the use of validated CE scores to assess small-bowel inflammatory activity in CD. Lewis score (LS) and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are the currently available validated scores, but comparative studies are scarce. Moreover, correlation of these endoscopic scores with biomarkers and clinical activity is lacking. This study aims to compare LS with CECDAI, to determine cutoff values for CECDAI similar to those of LS (135-790), and to correlate LS and CECDAI with biomarkers and symptoms. All patients with CD who underwent CE between March/2010 and February/2016 were included. LS and CECDAI were determined after analysis of each CE. In patients with small-bowel CD, C-reactive protein (CRP) and Harvey-Bradshaw index (HBI) were evaluated. descriptive statistics, Spearman's correlation coefficient and linear regression analysis. p<0.05. Fifty-three patients were included and the mean values obtained for LS were 1147±1453, CECDAI 11.3±6.9, CRP 0.92±1.5mg/dL and HBI 2.4±2.8. There was a very strong correlation between LS and CECDAI (r s =0.878; p<0.0001) and thresholds values of 135-790 in LS corresponded to 7.7-10.3 cutoff values in CECDAI, respectively. Neither CRP correlated with LS (r s =0.068; p=0.72) or CECDAI (r s =-0.004; p=0.98), nor HBI with LS (r s =-0.15; p=0.40) or CECDAI (r s =-0.10; p=0.23). Correlation between the two CE activity scores was very strong, with LS thresholds of 135-790 corresponding to CECDAI values of 7.7-10.3. HBI and CRP had no correlation with CECDAI and LS. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. Ghrelin upregulates PepT1 activity in the small intestine epithelium of rats with sepsis.

    Science.gov (United States)

    Liu, Jingquan; Shi, Bin; Shi, Kai; Ma, Guoguang; Zhang, Hongze; Lou, Xiaoli; Liu, Hongxiang; Wan, Shengxia; Liang, Dongyu

    2017-02-01

    Sepsis causes nutritional substrate malabsorption; hence, preventing gut barrier problems and improving the nutritional status in sepsis is a compelling issue. We tested whether ghrelin administration affects peptide transporter 1 (PepT1) activity in the intestinal epithelium of rats with sepsis. Sixty male Sprague-Dawley rats were randomly divided into sham-operated, sepsis, and ghrelin-treated groups. The cecum of sham-operated rats was separated after laparotomy without ligation and perforation. Sepsis group rats underwent cecal ligation and puncture (CLP). Mucosal specimens were used for immunohistochemstry, real-time PCR, and western blotting to detect PepT1 distribution, and mRNA and protein expression levels, respectively. TNF-α, IL-1β, and ghrelin levels were estimated in serum and intestinal mucosal tissue by ELISA. High-performance liquid chromatography was used to measure PepT1 uptake by the epithelial cells. Moreover, survival, body weight, and food intake of the rats were recorded during the 7-day treatment period. All rats in the sham-operated group survived, and 80% of rats in the sepsis group died within 7d of CLP. Treatment with ghrelin attenuated the CLP-induced body weight loss, intestine mucosa damage, and the survival rate was better. In addition, ghrelin attenuated increases in TNF-α and IL-1β production. The expressions of PepT1 mRNA and protein were higher in ghrelin-treated group rats than in sepsis rats. Moreover, the uptake function of PepT1 was better in ghrelin-treated group rats. Ghrelin treatment can reduce the inflammatory response and greatly upregulate the physiological function of PepT1 in intestinal epithelial cells of rats with sepsis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. The Structure of Urease Activation Complexes Examined by Flexibility Analysis, Mutagenesis, and Small-angle X-ray Scattering Approaches

    International Nuclear Information System (INIS)

    Quiroz, Soledad; Sukuru, Sai Chetan K.; Hausinger, Robert P.; Kuhn, Leslie A.; Heller, William T

    2008-01-01

    Conformational changes of Klebsiella aerogenes urease apoprotein (UreABC) 3 induced upon binding of the UreD and UreF accessory proteins were examined by a combination of flexibility analysis, mutagenesis, and small-angle X-ray scattering (SAXS). ProFlex analysis of urease provided evidence that the major domain of UreB can move in a hinge-like motion to account for prior chemical cross-linking results. Rigidification of the UreB hinge region, accomplished through a G11P mutation, reduced the extent of urease activation, in part by decreasing the nickel content of the mutant enzyme, and by sequestering a portion of the urease apoprotein in a novel activation complex that includes all of the accessory proteins. SAXS analyses of urease, (UreABC-UreD) 3 , and (UreABC-UreDF) 3 confirm that UreD and UreF bind near UreB at the periphery of the (UreAC) 3 structure. This study supports an activation model in which a domain-shifted UreB conformation in (UreABC-UreDF) 3 allows CO 2 and nickel ions to gain access to the nascent active site

  6. The Development of Steady-State Activation Hubs between Adult LTi ILC3s and Primed Macrophages in Small Intestine.

    Science.gov (United States)

    Savage, Adam K; Liang, Hong-Erh; Locksley, Richard M

    2017-09-01

    Group 3 innate lymphoid cells (ILC3s) are important for intestinal health, particularly in controlling inflammation in response to epithelial dysregulation, but their role during homeostasis remains less well understood. We generated IL-22 reporter mice to assess production of this key cytokine by ILC3s in the small intestine during development and under basal conditions. Although IL-22 is produced by a variety of lymphocyte populations, constitutively high IL-22 expression was limited to lymphoid-tissue inducer (LTi) cells residing in lymph node-like structures in the gut called solitary intestinal lymphoid tissues (SILT). Constitutive IL-22 expression was dependent on the microbiota and MyD88 signaling, appeared upon weaning, and was present across the spectrum of SILT, including in cryptopatches. Activated SILT LTi cells colocalized with a rare subpopulation of activated macrophages constitutively positive for IL-12/23 p40 and capable of activating neonatal LTi cells in response to TLR stimulus. Thus, weaning leads to the organization of innate immune activation hubs at SILT that mature and are continuously sustained by signals from the microbiota. This functional and anatomic organization constitutes a significant portion of the steady-state IL-23/IL-22 axis. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. Small angle neutron scattering reveals pH-dependent conformational changes in Trichoderma reesei cellobiohydrolase I: implications for enzymatic activity.

    Science.gov (United States)

    Pingali, Sai Venkatesh; O'Neill, Hugh M; McGaughey, Joseph; Urban, Volker S; Rempe, Caroline S; Petridis, Loukas; Smith, Jeremy C; Evans, Barbara R; Heller, William T

    2011-09-16

    Cellobiohydrolase I (Cel7A) of the fungus Trichoderma reesei (now classified as an anamorph of Hypocrea jecorina) hydrolyzes crystalline cellulose to soluble sugars, making it of key interest for producing fermentable sugars from biomass for biofuel production. The activity of the enzyme is pH-dependent, with its highest activity occurring at pH 4-5. To probe the response of the solution structure of Cel7A to changes in pH, we measured small angle neutron scattering of it in a series of solutions having pH values of 7.0, 6.0, 5.3, and 4.2. As the pH decreases from 7.0 to 5.3, the enzyme structure remains well defined, possessing a spatial differentiation between the cellulose binding domain and the catalytic core that only changes subtly. At pH 4.2, the solution conformation of the enzyme changes to a structure that is intermediate between a properly folded enzyme and a denatured, unfolded state, yet the secondary structure of the enzyme is essentially unaltered. The results indicate that at the pH of optimal activity, the catalytic core of the enzyme adopts a structure in which the compact packing typical of a fully folded polypeptide chain is disrupted and suggest that the increased range of structures afforded by this disordered state plays an important role in the increased activity of Cel7A through conformational selection.

  8. High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors

    Science.gov (United States)

    Siles, Samuel A.; Srinivasan, Anand; Pierce, Christopher G.

    2013-01-01

    Candida albicans is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against C. albicans biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors of C. albicans biofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibit C. albicans biofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed. PMID:23689719

  9. Hydrogen test of a small, low specific speed centrifugal pump stage

    Science.gov (United States)

    1991-01-01

    A small, low specific speed centrifugal pump stage with a 2 inch tip diameter, .030 inch tip width shrouded impeller and volute collector was tested with liquid hydrogen as the pumped fluid. The hydrodynamic design of the pump stage is summarized and the noncavitating and cavitating performance results are presented. Test speeds were 60 and 80 percent of the 77,000 rpm design speed. Liquid hydrogen test results are compared with data from previous tests of the stage in water.

  10. MiRNA-135a regulates the expression of small conductance calcium-activated potassium (SK3) channels in epilepsy-like conditions

    NARCIS (Netherlands)

    Honrath, Birgit; Norwood, Braxton; Tanrioever, Gaye; Kuter, Katarzyna; Henshall, David C; Aksel-Aksoy, Ayla; Schratt, Gerhard; Pasterkamp, Jeroen; Dencher, Norbert A.; Nieweg, Katja; Culmsee, Carsten; Dolga, Amalia Mihalea

    2017-01-01

    Background Excessive and hypersynchronous neuronal discharges are key characteristics in the pathophysiology of neurological disorders such as epilepsy. Owing to their ability of regulating neuronal excitability, small conductance calcium-activated potassium (SK) channels have been implicated in

  11. Low-Cost, Manufacturable, 6-Inch Wafer Bonding Process for Next-Generation 5-Junction IMM+Ge Photovoltaic Devices Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the development of a 6-inch wafer bonding process to allow bonding of a multi-junction inverted metamorphic (IMM) tandem solar cell structure to an...

  12. MRIR/Nimbus-2 Images of Daytime Brightness Temperature on 4 x 5 inch Film Sheets V001 (MRIRN2IM) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — MRIRN2IM is the Nimbus-2 Medium Resolution Infrared Radiometer (MRIR) data product consisting of 4 x 5 inch photographic film sheets. Each film sheet contains an...

  13. MRIR/Nimbus-3 Images of Daytime Brightness Temperature on 4 x 5 inch Film Sheets V001 (MRIRN3IM) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — MRIRN3IM is the Nimbus-3 Medium Resolution Infrared Radiometer (MRIR) data product consisting of 4 x 5 inch photographic film sheets. Each film sheet contains an...

  14. NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease-Implications for Prevention.

    Science.gov (United States)

    McCarty, Mark F

    2015-04-15

    Cerebral small vessel disease (SVD), a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS) activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways-exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea), and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine-which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine-mediate this benefit. Ameliorating the risk factors for SVD-including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine-also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

  15. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    Science.gov (United States)

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-06-01

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Non-Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases.

    Science.gov (United States)

    Isozaki, Hideko; Ichihara, Eiki; Takigawa, Nagio; Ohashi, Kadoaki; Ochi, Nobuaki; Yasugi, Masayuki; Ninomiya, Takashi; Yamane, Hiromichi; Hotta, Katsuyuki; Sakai, Katsuya; Matsumoto, Kunio; Hosokawa, Shinobu; Bessho, Akihiro; Sendo, Toshiaki; Tanimoto, Mitsune; Kiura, Katsuyuki

    2016-03-15

    Crizotinib is the standard of care for advanced non-small cell lung cancer (NSCLC) patients harboring the anaplastic lymphoma kinase (ALK) fusion gene, but resistance invariably develops. Unlike crizotinib, alectinib is a selective ALK tyrosine kinase inhibitor (TKI) with more potent antitumor effects and a favorable toxicity profile, even in crizotinib-resistant cases. However, acquired resistance to alectinib, as for other TKIs, remains a limitation of its efficacy. Therefore, we investigated the mechanisms by which human NSCLC cells acquire resistance to alectinib. We established two alectinib-resistant cell lines that did not harbor the secondary ALK mutations frequently occurring in crizotinib-resistant cells. One cell line lost the EML4-ALK fusion gene, but exhibited increased activation of insulin-like growth factor-1 receptor (IGF1R) and human epidermal growth factor receptor 3 (HER3), and overexpressed the HER3 ligand neuregulin 1. Accordingly, pharmacologic inhibition of IGF1R and HER3 signaling overcame resistance to alectinib in this cell line. The second alectinib-resistant cell line displayed stimulated HGF autocrine signaling that promoted MET activation and remained sensitive to crizotinib treatment. Taken together, our findings reveal two novel mechanisms underlying alectinib resistance that are caused by the activation of alternative tyrosine kinase receptors rather than by secondary ALK mutations. These studies may guide the development of comprehensive treatment strategies that take into consideration the various approaches ALK-positive lung tumors use to withstand therapeutic insult. ©2015 American Association for Cancer Research.

  17. Magnetic resonance imaging of the small bowel in children with idiopathic inflammatory bowel disease: evaluation of disease activity

    Energy Technology Data Exchange (ETDEWEB)

    Alexopoulou, Efthymia; Loggitsi, Dimitra; Economopoulos, Nikos; Papakonstantinou, Olympia; Kelekis, Nikolaos L. [National and Kapodistrian University of Athens, General University Hospital, Second Department of Radiology, Athens (Greece); Roma, Eleftheria; Panagiotou, Ioanna; Pahoula, Ioanna [National and Kapodistrian University of Athens, Aghia Sofia Children' s Hospital, First Department of Paediatrics, Athens (Greece)

    2009-08-15

    Examinations using ionizing radiation are frequently used in the evaluation of disease activity in children affected by idiopathic inflammatory bowel disease (IBD). To develop an MR imaging protocol without the need for fluoroscopic insertion of an enteral tube and to assess the disease activity in children with IBD. Included in the study were 37 children (22 girls and 15 boys; age range 7-15 years, mean 11.67 years) with IBD who underwent MR imaging of the small bowel. Of these 37 children, 32 had Crohn disease and 5 had indeterminate colitis. A water solution containing herbal fibres was administered orally or through a nasogastric tube. Patients were imaged on a 1.5-T MR scanner with T1-weighted and {tau}2-weighted sequences followed by a dynamic study using 3-D T1-W images after intravenous administration of gadolinium. The percentage enhancement of the bowel wall was significantly increased in patients with abnormal C-reactive protein (CRP) values compared to patients with CRP values in the normal range (P<0.001). A relatively weak but significant correlation between percentage enhancement of the bowel wall and CRP values was noted during all phases of enhancement. This MR imaging protocol is a safe and well-tolerated method for evaluating disease activity and extraintestinal manifestations of IBD in children. (orig.)

  18. Activation of PI3-kinase/Akt induced small bowel cell apoptosis during laparoscopic ischaemia-reperfusion of swine jejunum.

    Science.gov (United States)

    Puglisi, F; Lacitigniola, L; Loverre, A; Capuano, P; Martines, G; Staffieri, F; Rossi, G; Crovace, A

    2009-01-01

    This study aimed to detect small bowel cell apoptosis by evaluating the nuclear activation of transcription factors, nuclear factor-kappaB (NF-kappaB) and Akt pathways as well as detecting apoptotic cells by TUNEL assay, during ischaemia-reperfusion (I/R) injury by Arterio-Venous Occlusion (AVO) of ajejunal loop in swine, using a laparoscopic procedure. A jejunal loop was isolated and a biopsy sample (T0) obtained. Biopsies were obtained at 30 minutes (T30I) and 60 minutes (T60I) after clamping and again during reperfusion (R), T30R and T60R. Standard H&E stains and immunohistochemical study for infiltrating polymorphonuclear leukocytes and TUNEL assays were performed. The activation of Akt and NF-kappaB in the animal model was evaluated by indirect immunofluorescence and confocal microscopy. Our results confirmed that I/R injury of the jejunum did not only cause epithelial damage, but also activated the molecular pathways triggering an apoptotic reaction (by pro-inflammatory cytokines) and an anti-apoptotic mechanism that can lead to the regeneration of injured tissue.

  19. TRAIN (Transcription of Repeats Activates INterferon) in response to chromatin destabilization induced by small molecules in mammalian cells.

    Science.gov (United States)

    Leonova, Katerina; Safina, Alfiya; Nesher, Elimelech; Sandlesh, Poorva; Pratt, Rachel; Burkhart, Catherine; Lipchick, Brittany; Gitlin, Ilya; Frangou, Costakis; Koman, Igor; Wang, Jianmin; Kirsanov, Kirill; Yakubovskaya, Marianna G; Gudkov, Andrei V; Gurova, Katerina

    2018-02-05

    Cellular responses to the loss of genomic stability are well-established, while how mammalian cells respond to chromatin destabilization is largely unknown. We previously found that DNA demethylation on p53-deficient background leads to transcription of repetitive heterochromatin elements, followed by an interferon response, a phenomenon we named TRAIN (Transcription of Repeats Activates INterferon). Here, we report that curaxin, an anticancer small molecule, destabilizing nucleosomes via disruption of histone/DNA interactions, also induces TRAIN. Furthermore, curaxin inhibits oncogene-induced transformation and tumor growth in mice in an interferon-dependent manner, suggesting that anticancer activity of curaxin, previously attributed to p53-activation and NF-kappaB-inhibition, may also involve induction of interferon response to epigenetic derepression of the cellular 'repeatome'. Moreover, we observed that another type of drugs decondensing chromatin, HDAC inhibitor, also induces TRAIN. Thus, we proposed that TRAIN may be one of the mechanisms ensuring epigenetic integrity of mammalian cells via elimination of cells with desilenced chromatin. © 2018, Leonova et al.

  20. Combined of Lyapunov-stable and active disturbance rejection control for the path following of a small unmanned aerial vehicle

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2017-03-01

    Full Text Available This article proposes a composite path following controller that allows the small fixed-wing unmanned aerial vehicle to follow a predefined path. Assuming that the vehicle is equipped with an autopilot for altitude and airspeed maintained well, the controller design adopts the hierarchical control structure. With the inner-loop controller design based on the notion of active disturbance rejection control which will respond to the desired roll angle command, the core part of the outer-loop controller is designed based on Lyapunov stability theorem to generate the desired course rate for the straight-line paths. The bank to turn maneuver is used to transform the desired course rate to the desired roll angle command. Both the hardware-in-the-loop simulation in the X-Plane simulator and actual experimental flight tests have been successfully achieved, which verified the effectiveness of the proposed method.

  1. Is the activity based costing system a viable instrument for small and medium enterprises? The case of Mexico

    Directory of Open Access Journals (Sweden)

    Martha Ríos-Manríquez

    2014-07-01

    Full Text Available Small and medium-sized firms (SMEs face serious challenges in order to be competitive, and they need to develop strategies enabling them to control their costs. This work aims to analyze and evaluate the impact, penetration and characteristics of Activity-Based Costs (ABC. This research is of a quantitative type descriptive design, with a sample of 180 SMEs. The results show low penetration of the ABC in SMEs using traditional systems, due to the lack of knowledge, and that there are enterprises that do not use any costing system at all. Finally the Mexican SMEs recognize the compatibility and usefulness of ABC, and that the most important fact is to understand the possible application of different costing methodologies for different purposes.

  2. Dynamic Characteristics of Area Variations of Small and Large Sunspots and Quasi-Biennial Oscillations in Solar Activity

    Science.gov (United States)

    Kostyuchenko, I. G.

    2017-12-01

    The spatiotemporal and chaotic dynamics of variations in area of sunspot groups related conventionally to small (area 50 Msh) populations is analyzed. The Greenwich Observatory-Marshall Space Flight Center data were used. The results show that both sunspot populations have a single initial source, which is a magnetic flux generated by the dynamo process (presumably at the bottom of the convective zone) and is responsible for the 11—22-year periodicity of solar activity. A possible explanation of the revealed different behavior of the considered populations is that the magnetic flux is partially involved in another process responsible for the shaping of primarily very large sunspot groups. This process develops presumably in the upper layer of the convective zone with an unstable amplitude and a period varying within 1-2 years. The analysis of power spectrum of the Wolf number time series has indicated the difference between dynamic characteristics of the two studied processes.

  3. Analysis of the pore structure of activated carbons produced from paper mill sludge using small angle neutron scattering data

    Energy Technology Data Exchange (ETDEWEB)

    Sandi, G.; Khalil, N. R.; Littrell, K.; Thiyagarajan, P.

    1999-12-13

    A novel, cost-effective, and environmentally benign process was developed to produce highly efficient carbon-based adsorbents (CBAs) from paper mill sludge. The production process required chemical activation of sludge using zinc chloride and pyrolysis at 750 C in N{sub 2} gas. The produced CBAs were characterized according to their surface area and pore size distribution using N{sub 2}-BET adsorption isotherm data. Further characterization of the surface and pore structure was conducted using a unified exponential/power law approach applied to small angle neutron scattering (SANS) data. The structural features analyzed by SANS revealed the dependence of porosity with zinc chloride concentration. The presence of inaccessible pores was also determined by contrast-match experiments.

  4. Two members of the CERN HPD team present their babies. André Braem (left) holds in his hands a 5-inch glass HPD, while a ceramic HPD for medical applications is shown by Christian Joram. The large detector in the middle is a 10-inch HPD developed for an astrophysics experiment.

    CERN Multimedia

    Maximilien Brice

    2004-01-01

    Two members of the CERN HPD team present their babies. André Braem (left) holds in his hands a 5-inch glass HPD, while a ceramic HPD for medical applications is shown by Christian Joram. The large detector in the middle is a 10-inch HPD developed for an astrophysics experiment.

  5. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Sharlow

    2010-04-01

    Full Text Available The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK, an enzyme essential to the parasite that transfers the gamma-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay.Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were approximately 20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03activity. None of the compounds displayed structural similarity to known hexokinase inhibitors or human African trypanosomiasis therapeutics.The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  6. Particulate matter pollution from aviation-related activity at a small airport of the Aegean Sea Insular Region.

    Science.gov (United States)

    Psanis, C; Triantafyllou, E; Giamarelou, M; Manousakas, M; Eleftheriadis, K; Biskos, G

    2017-10-15

    The unprecedented growth in aviation during the last years has resulted in a notable increase of local air pollution related to airports. The impacts of aviation on air quality can be extremely high particularly around airports serving remote insular regions with pristine atmospheric environments. Here we report measurements that show how the atmospheric aerosol is affected by the activity at a small airport in a remote region. More specifically, we provide measurements performed at the airport of Mytilene, Greece, a regional yet international airport that serves the entire island of Lesvos; the third largest island of the country. The measurements show that the activity during landing, taxiing and take-off of the aircrafts accounted for up to a 10-fold increase in particulate matter (PM) mass concentration in the vicinity of the airport. The number concentration of particles having diameters from 10 to 500nm also increased from ca. 4×10 2 to 8×10 5 particlescm -3 , while the mean particle diameter decreased to 20nm when aircrafts were present at the airport. Elemental analysis on particle samples collected simultaneously at the airport and at a remote site 3km away, showed that the former were significantly influenced by combustion sources, and specifically from the engines of the aircrafts. Our results show that despite their small size, local airports serving remote insular regions should be considered as important air pollution hotspots, raising concerns for the exposure of the people working and leaving in their vicinities to hazardous pollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Radiation Characterization Summary: ACRR Cadmium-Polyethylene (CdPoly) Bucket Located in the Central Cavity on the 32-Inch Pedestal at the Core Centerline

    Energy Technology Data Exchange (ETDEWEB)

    Parma, Edward J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Naranjo, Gerald E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kaiser, Krista Irene [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Arnold, James F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lippert, Lance L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Clovis, Ralph D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martin, Lonnie E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Quirk, Thomas J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vehar, David W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-10-01

    This document presents the facility-recommended characterization of the neutron, prompt gamma-ray, and delayed gamma-ray radiation fields in the Annular Core Research Reactor (ACRR) for the cadmium-polyethylene (CdPoly) bucket in the central cavity on the 32-inch pedestal at the core centerline. The designation for this environment is ACRR-CdPoly-CC-32-cl. The neutron, prompt gamma-ray, and delayed gamma-ray energy spectra, uncertainties, and covariance matrices are presented as well as radial and axial neutron and gamma-ray fluence profiles within the experiment area of the bucket. Recommended constants are given to facilitate the conversion of various dosimetry readings into radiation metrics desired by experimenters. Representative pulse operations are presented with conversion examples. Acknowledgements The authors wish to thank the Annular Core Research Reactor staff and the Radiation Metrology Laboratory staff for their support of this work. Also thanks to Drew Tonigan for helping field the activation experiments in ACRR, David Samuel for helping to finalize the drawings and get the parts fabricated, and Elliot Pelfrey for preparing the active dosimetry plots.

  8. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Zejun [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Gong, Chaoju [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058 (China); Liu, Hong [Zhejiang Normal University – Jinhua People' s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004 (China); Zhang, Xiaomin; Mei, Lingming [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Song, Mintao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005 (China); Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Chen, Xiang, E-mail: sychenxiang@126.com [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China)

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  9. Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.

    Science.gov (United States)

    Chan, Yi-Hsin; Tsai, Wei-Chung; Ko, Jum-Suk; Yin, Dechun; Chang, Po-Cheng; Rubart, Michael; Weiss, James N; Everett, Thomas H; Lin, Shien-Fong; Chen, Peng-Sheng

    2015-10-13

    Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038). Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction. © 2015 American Heart Association, Inc.

  10. The effects of Earth's magnetic field on 3-inch diameter photomultipliers used in KM3NeT neutrino telescope

    Science.gov (United States)

    Giordano, V.; Aiello, S.; Leonora, E.; Randazzo, N.

    2016-04-01

    The KM3NeT neutrino telescope will be the largest underwater neutrino telescope and will be located in the abyss of the Mediterranean Sea. In neutrino telescopes the key element of the detector is the optical module and for KM3NeT it consists of 31 PMTs stored inside a transparent pressure-resistant glass sphere of 17-inch that serves as mechanical protection while ensuring good light transmission. Since the PMTs installed into an underwater neutrino telescope can change their orientation because of movements of the detector structure due to sea currents, the influence of Earth's magnetic field has been investigated. Magnetic shielding by means of a mu-metal cage is used to reduce magnetic effects and to make the response of the PMT sufficiently orientation independent. In order to quantify the effect on magnetic field, we compared measurements on variation of gain, transit time spread and detection efficiency for a 3-inch PMT in shielded and unshielded condition at 3 PMT inclinations. Data shows that variations are sufficiently low especially for timing properties.

  11. Application of Derrick Corporation's stack sizer technology for slimes reduction in 6 inch clean coal hydrocyclone circuits

    Energy Technology Data Exchange (ETDEWEB)

    Brodzik, P.

    2009-04-15

    The article discusses the successful introduction of Derrick Corporation's Stack Sizer technology for removing minus 200 mesh slimes from 6-inch coal hydrocyclone underflow prior to froth flotation or dewatering by screen bowl centrifuges. In 2006, the James River Coal Company selected the Stack Sizer fitted with Derrick 150 micron and 100 micron urethane screen panels for removal of the minus 100 mesh high ash clay fraction from the clean coal spiral product circuits. After this application proved successful, Derrick Corporation introduced new 75 micron urethane screen panels for use on the Stack Sizer. Evaluation of feed slurry to flotation cells and screen bowl centrifuges showed significant amounts of minus 75 micron that could potentially be removed by efficient screening technology. Removal of the minus 75 micron fraction was sought to reduce ash and moisture content of the final clean coal product. Full-scale lab tests confirmed that the Stack Sizer fitted with Derrick 75 micron urethane screen panels consistently reduced the minus 75 micron percentage in coal slurry from 6-inch clean coal hydrocyclone underflow that is approximately 15 to 20% solid by-weight and 30 to 60% minus 75 micron to a clean coal fraction that is approximately 13 to 16% minus 75 micron. As a result total ash is reduced from approximately 36 to 38% in the hydrocyclone underflow to 14 to 16% in the oversize product fraction form the Stack Sizers. 1 fig., 2 tabs., 5 photos.

  12. Experimental Investigation of Project Orion Crew Exploration Vehicle Aeroheating: LaRC 20-Inch Mach 6 Air Tunnel Test 6931

    Science.gov (United States)

    Hollis, Brian R.

    2009-01-01

    An investigation of the aeroheating environment of the Project Orion Crew Entry Vehicle has been performed in the Langley Research Center 20-Inch Mach 6 Air Tunnel. Data were measured on a approx.3.5% scale model (0.1778-m/7-inch diameter) of the vehicle using coaxial thermocouples at free stream Reynolds numbers of 2.0 10(exp 6)/ft to 7.30 10(exp 6)/ft and computational predictions were generated for all test conditions. The primary goals of this test were to obtain convective heating data for use in assessing the accuracy of the computational technique and to validate test methodology and heating data from a test of the same wind tunnel model in the Arnold Engineering Development Center Tunnel 9. Secondary goals were to determine the extent of transitional/turbulent data which could be produced on a CEV model in this facility, either with or without boundary-layer trips, and to demonstrate continuous pitch-sweep operation in this tunnel for heat transfer testing.

  13. Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Bravo, Dawn T; Yang, Yi-Lin; Kuchenbecker, Kristopher; Hung, Ming-Szu; Xu, Zhidong; Jablons, David M; You, Liang

    2013-01-01

    Wnt-2 plays an oncogenic role in cancer, but which Frizzled receptor(s) mediates the Wnt-2 signaling pathway in lung cancer remains unclear. We sought to (1) identify and evaluate the activation of Wnt-2 signaling through Frizzled-8 in non-small cell lung cancer, and (2) test whether a novel expression construct dominant negative Wnt-2 (dnhWnt-2) reduces tumor growth in a colony formation assay and in a xenograft mouse model. Semi-quantitative RT-PCR was used to identify the expression of Wnt-2 and Frizzled-8 in 50 lung cancer tissues from patients. The TCF reporter assay (TOP/FOP) was used to detect the activation of the Wnt canonical pathway in vitro. A novel dnhWnt-2 construct was designed and used to inhibit activation of Wnt-2 signaling through Frizzled-8 in 293T, 293, A549 and A427 cells and in a xenograft mouse model. Statistical comparisons were made using Student’s t-test. Among the 50 lung cancer samples, we identified a 91% correlation between the transcriptional increase of Wnt-2 and Frizzled-8 (p<0.05). The Wnt canonical pathway was activated when both Wnt-2 and Frizzled-8 were co-expressed in 293T, 293, A549 and A427 cells. The dnhWnt-2 construct we used inhibited the activation of Wnt-2 signaling in 293T, 293, A549 and A427 cells, and reduced the colony formation of NSCLC cells when β-catenin was present (p<0.05). Inhibition of Wnt-2 activation by the dnhWnt-2 construct further reduced the size and mass of tumors in the xenograft mouse model (p<0.05). The inhibition also decreased the expression of target genes of Wnt signaling in these tumors. We demonstrated an activation of Wnt-2 signaling via the Frizzled-8 receptor in NSCLC cells. A novel dnhWnt-2 construct significantly inhibits Wnt-2 signaling, reduces colony formation of NSCLC cells in vitro and tumor growth in a xenograft mouse model. The dnhWnt-2 construct may provide a new therapeutic avenue for targeting the Wnt pathway in lung cancer

  14. Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

    DEFF Research Database (Denmark)

    Stankevicius, Edgaras; Dalsgaard, Thomas; Kroigaard, Christel

    2011-01-01

    This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolar......This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium...... in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (∼1093 μm) and small mesenteric (∼300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior....... In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases in calcium, outward...

  15. Activation of signal transducer and activator of transcription 3 (STAT3) signaling in EGFR mutant non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Codony-Servat, Carles; Codony-Servat, Jordi; Karachaliou, Niki; Molina, Miguel Angel; Chaib, Imane; Ramirez, Jose Luis; de Los Llanos Gil, Maria; Solca, Flavio; Bivona, Trever G; Rosell, Rafael

    2017-07-18

    Gefitinib, erlotinib or afatinib are the current treatment for non-small-cell lung cancer (NSCLC) harboring an activating mutation of the epidermal growth factor receptor (EGFR), but less than 5% of patients achieve a complete response and the median progression-free survival is no longer than 12 months. Early adaptive resistance can occur as soon as two hours after starting treatment by activating signal transducer and activation of transcription 3 (STAT3) signaling. We investigated the activation of STAT3 in a panel of gefitinib-sensitive EGFR mutant cell lines, and gefitinib-resistant PC9 cell lines developed in our laboratory. Afatinib has great activity in gefitinib-sensitive as well as in gefitinib-resistant EGFR mutant NSCLC cell lines. However, afatinib therapy causes phosphorylation of STAT3 tyrosine 705 (pSTAT3Tyr705) and elevation of STAT3 and RANTES mRNA levels. The combination of afatinib with TPCA-1 (a STAT3 inhibitor) ablated pSTAT3Tyr705 and down-regulated STAT3 and RANTES mRNA levels with significant growth inhibitory effect in both gefitinib-sensitive and gefitinib-resistant EGFR mutant NSCLC cell lines. Aldehyde dehydrogenase positive (ALDH+) cells were still observed with the combination at the time that Hairy and Enhancer of Split 1 (HES1) mRNA expression was elevated following therapy. Although the combination of afatinib with STAT3 inhibition cannot eliminate the potential problem of a remnant cancer stem cell population, it represents a substantial advantage and opportunity to further prolong progression free survival and probably could increase the response rate in comparison to the current standard of single therapy.

  16. Activation of Relaxin Family Receptor 1 from different mammalian species by relaxin peptide and small molecule agonist ML290

    Directory of Open Access Journals (Sweden)

    Zaohua eHuang

    2015-08-01

    Full Text Available Relaxin peptide (RLN, which signals through the relaxin family peptide 1 (RXFP1 GPCR receptor, has shown therapeutic effects in an acute heart failure clinical trial. We have identified a small molecule agonist of human RXFP1, ML290; however, it does not activate the mouse receptor. To find a suitable animal model for ML290 testing and to gain mechanistic insights into the interaction of various ligands with RXFP1, we have cloned rhesus macaque, pig, rabbit, and guinea pig RXFP1s and analyzed their activation by RLN and ML290. HEK293T cells expressing macaque or pig RXFP1 responded to relaxin and ML290 treatment as measured by an increase of cAMP production. Guinea pig RXFP1 responded to relaxin but had very low response to ML290 treatment only at highest concentrations used. The rabbit RXFP1 amino acid sequence was the most divergent, with a number of unique substitutions within the ectodomain and the 7-transmembrane domain (7TM. Two splice variants of rabbit RXFP1 derived through alternative splicing of the forth exon were identified. In contrast to the other species, rabbit RXFP1s were activated by ML290, but not with human, pig, mouse, or rabbit relaxins. Using FLAG-tagged constructs, we have shown that both rabbit RXFP1 variants are expressed on the cell surface. No binding of human Eu-labeled relaxin to rabbit RXFP1 was detected, suggesting that in this species RXFP1 might be non-functional. We used chimeric rabbit-human and guinea pig-human constructs to identify regions important for RLN or ML290 receptor activation. Chimeras with the human ectodomain and rabbit 7TM domain were activated by RLN, whereas substitution of part of the guinea pig 7TM domain with the human sequence only partially restored ML290 activation, confirming the allosteric mode of action for the two ligands. Our data demonstrate that macaque and pig models can be used for ML290 testing.

  17. Concomitant active tuberculosis prolongs survival in non-small cell lung cancer: a study in a tuberculosis-endemic country.

    Directory of Open Access Journals (Sweden)

    Chih-Hsi Kuo

    Full Text Available BACKGROUND: Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. METHODS: Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. RESULTS: A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01. Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48 ~ 0.97. Squamous cell carcinoma (SCC (55.8 vs. 31.7%, p<0.01 is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05. Active tuberculosis in SCC increases the expression of CD3 (46.4 ± 24.8 vs. 24.0 ± 16.0, p<0.05, CXCR3 (35.1 ± 16.4 vs. 19.2 ± 13.3, p<0.01 and IP-10 (63.5 ± 21.9 vs. 35.5 ± 21.0, p<0.01, while expression of FOXP3 is decreased (3.5 ± 0.5 vs. 13.3 ± 3.7 p<0.05, p<0.05. Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05 and CXCR3 (12.1 vs. 4.4 month, p<0.05 is longer than that with low expression. CONCLUSIONS: Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches.

  18. Small-angle neutron scattering study of activated carbon cloth and ammonium persulfate-modified activated carbon cloth: Effect of oxygen content

    International Nuclear Information System (INIS)

    Pendleton, Phillip; Chen Lin

    2006-01-01

    Small-angle neutron scattering (SANS) patterns of as-received, oxidized, and thermally reduced FM1/250 activated carbon cloth (ACC) samples are compared to determine the effects of surface chemistry on scattering. Porosity analyses show minimal effect on pore size distribution from oxidation, but an increase in micropore volume on heat treatment. SANS suggests an increase in localized order within the treated samples when compared with graphite cloth patterns. The ACC exhibits Porod scattering at q-ranges -1 ; the graphite cloth exhibits the same at q-ranges>1.0 nm -1 . A cylindrical model reproduces the scattering patterns in the micropore equivalent dimensions, q>0.5 nm -1

  19. Experimental evidence for the effect of small wind turbine proximity and operation on bird and bat activity.

    Directory of Open Access Journals (Sweden)

    Jeroen Minderman

    Full Text Available The development of renewable energy technologies such as wind turbines forms a vital part of strategies to reduce greenhouse gas emissions worldwide. Although large wind farms generate the majority of wind energy, the small wind turbine (SWT, units generating <50 kW sector is growing rapidly. In spite of evidence of effects of large wind farms on birds and bats, effects of SWTs on wildlife have not been studied and are likely to be different due to their potential siting in a wider range of habitats. We present the first study to quantify the effects of SWTs on birds and bats. Using a field experiment, we show that bird activity is similar in two distance bands surrounding a sample of SWTs (between 6-18 m hub height and is not affected by SWT operation at the fine scale studied. At shorter distances from operating turbines (0-5 m, bat activity (measured as the probability of a bat "pass" per hour decreases from 84% (71-91% to 28% (11-54% as wind speed increases from 0 to 14 m/s. This effect is weaker at greater distances (20-25 m from operating turbines (activity decreases from 80% (65-89% to 59% (32-81%, and absent when they are braked. We conclude that bats avoid operating SWTs but that this effect diminishes within 20 m. Such displacement effects may have important consequences especially in landscapes where suitable habitat is limiting. Planning guidance for SWTs is currently lacking. Based on our results we recommend that they are sited at least 20 m away from potentially valuable bat habitat.

  20. Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth

    Science.gov (United States)

    Wang, Lu-Lu; Guo, Hui-Hui; Zhan, Yun; Feng, Chen-Lin; Huang, Shuai; Han, Yan-Xing; Zheng, Wen-Sheng; Jiang, Jian-Dong

    2017-01-01

    The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53–/−) and HT-29 were transfected with the p21-saRNA-322. The expression of P21 protein and p21 mRNA were measured using the Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). The effect of p21-saRNA-322 on cancer cells was evaluated in vitro; and furthermore, a xenograft colorectal tumor mode in mice was established to estimate the tumor suppressing ability of p21-saRNA-322 in vivo. The results showed that in all three colorectal cancer cell lines, the expression of p21 mRNA and P21 protein were dramatically elevated after p21-saRNA-322 transfection. Transfection of p21-saRNA-322 caused apoptosis and cell cycle arrest at the G0/G1. Furthermore, anti-proliferation effect, reduction of colonies formation and cell senescence were observed in p21-saRNA-322 treated cells. Animal studies showed that p21-saRNA-322 treatment significantly inhibited the HT-29 tumor growth and facilitated p21 activation in vivo. These results indicated that, p21-saRNA-322-induceded up-regulation of p21 might be a promising therapeutic option for the treatment of colorectal cancer. PMID:28445988

  1. Induction of Activating Transcription Factor 3 Is Associated with Cisplatin Responsiveness in Non–Small Cell Lung Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Jair Bar

    2016-09-01

    Full Text Available Non–small cell lung carcinoma (NSCLC is the most common cause of cancer deaths, with platin-based combination chemotherapy the most efficacious therapies. Gains in overall survival are modest, highlighting the need for novel therapeutic approaches including the development of next-generation platin combination regimens. The goal of this study was to identify novel regulators of platin-induced cytotoxicity as potential therapeutic targets to further enhance platin cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their cisplatin-resistant sublines, Calu6cisR1 and H23cisR1, activating transcription factor 3 (ATF3 was robustly induced in cisplatin-treated parental sensitive cell lines but not their resistant sublines, and in three of six tumors evaluated, but not in their corresponding normal adjacent lung tissue (0/6. Cisplatin-induced JNK activation was a key regulator of this ATF3 induction. Interestingly, in both resistant sublines, this JNK induction was abrogated, and the expression of an activated JNK construct in these cells enhanced both cisplatin-induced cytotoxicity and ATF3 induction. An FDA-approved drug compound screen was employed to identify enhancers of cisplatin cytotoxicity that were dependent on ATF3 gene expression. Vorinostat, a histone deacetylase inhibitor, was identified in this screen and demonstrated synergistic cytotoxicity with cisplatin in both the parental Calu6 and H23 cell lines and importantly in their resistant sublines as well that was dependent on ATF3 expression. Thus, we have identified ATF3 as an important regulator of cisplatin cytotoxicity and that ATF3 inducers in combination with platins are a potential novel therapeutic approach for NSCLC.

  2. The Use of the Active Breathing Coordinator Throughout Radical Non-Small-Cell Lung Cancer (NSCLC) Radiotherapy

    International Nuclear Information System (INIS)

    Brock, Juliet; McNair, Helen A.; Panakis, Niki; Symonds-Tayler, Richard; Evans, Phil M.; Brada, Michael

    2011-01-01

    Purpose: To assess feasibility and reproducibility of an Active Breathing Coordinator (ABC) used throughout radical radiotherapy for non-small-cell lung cancer, and compare lung dosimetric parameters between free-breathing and ABC plans. Methods and Materials: A total of 18 patients, recruited into an approved study, had free-breathing and ABC breath-hold treatment plans generated. Lung volume, the percentage volume of lung treated to a dose of ≥20 Gy (V 20 ), and mean lung dose (MLD) were compared. Treatment (64 Gy in 32 fractions, 5 days/week) was delivered in breath-hold. Repeat breath-hold computed tomography scans were used to assess change in gross tumor volume (GTV) size and position. Setup error was also measured and potential GTV-planning target volume (PTV) margins calculated. Results: Seventeen of 18 patients completed radiotherapy using ABC daily. Intrafraction tumor position was consistent, but interfraction variation had mean (range) values of 5.1 (0-25), 3.6 (0-9.7), and 3.5 (0-16.6) mm in the superoinferior (SI), right-left (RL), and anteroposterior (AP) directions, respectively. Tumor moved partially outside the PTV in 5 patients. Mean reduction in GTV from planning to end of treatment was 25% (p = 0.003). Potentially required PTV margins were 18.1, 11.9, and 11.9 mm in SI, RL, and AP directions. ABC reduced V 20 by 13% (p = 0.0001), V 13 by 12% (p = 0.001), and MLD by 13% (p < 0.001) compared with free-breathing; lung volume increased by 41% (p < 0.001). Conclusions: Clinically significant movements of GTV were seen during radiotherapy for non-small-cell lung cancer using ABC. Image guidance is recommended with ABC. The use of ABC can reduce dose volume parameters determining lung toxicity, and might allow for equitoxic radiotherapy dose escalation.

  3. Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study

    NARCIS (Netherlands)

    Zuurbier, L.A.; Ikram, M.A.; Luik, A.I.; Hofman, A.; van Someren, E.J.W.; Vernooij, M.W.; Tiemeier, H.

    2015-01-01

    Background and purpose: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to

  4. Activity of retinene palmitasynthetase and retinene palmitatehydrolase in the small intestine mucosa and membranes of its cells in white rats affected by A-avitaminosis and irradiation

    International Nuclear Information System (INIS)

    Leutskij, K.M.; Sovtysik, D.D.

    1977-01-01

    A combined action of A-avitaminosis and ionizing radiation on the activity of retinenepalmitatesynthetase and retinenepalmitatehydrolase in the small intestine mucosa and cell membranes of white rats has been investigated. The activity of retinenepalmitatehydrolase has been shown to decrease in the irradiated animals deficient in vitamin A as compared to the control nonirradiated animals. The activity of retinenepalmitatesynthetase affected by a combination of A-avitaminosis and irradiation increases as compared to the control nonirradiated rats both in the small intestine mucosa and its cell membranes

  5. Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Coffey Matthew C

    2009-07-01

    Full Text Available Abstract Background Reovirus type 3 Dearing strain (ReoT3D has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safety and potential efficacy are currently being investigated in early clinical trials. In this study, we investigated the in vitro combination effects of ReoT3D and chemotherapeutic agents against human non-small cell lung cancer (NSCLC. Results ReoT3D alone exerted significant cytolytic activity in 7 of 9 NSCLC cell lines examined, with the 50% effective dose, defined as the initial virus dose to achieve 50% cell killing after 48 hours of infection, ranging from 1.46 ± 0.12 ~2.68 ± 0.25 (mean ± SD log10 pfu/cell. Chou-Talalay analysis of the combination of ReoT3D with cisplatin, gemcitabine, or vinblastine demonstrated strong synergistic effects on cell killing, but only in cell lines that were sensitive to these compounds. In contrast, the combination of ReoT3D and paclitaxel was invariably synergistic in all cell lines tested, regardless of their levels of sensitivity to either agent. Treatment of NSCLC cell lines with the ReoT3D-paclitaxel combination resulted in increased poly (ADP-ribose polymerase cleavage and caspase activity compared to single therapy, indicating enhanced apoptosis induction in dually treated NSCLC cells. NSCLC cells treated with the ReoT3D-paclitaxel combination showed increased proportions of mitotic and apoptotic cells, and a more pronounced level of caspase-3 activation was demonstrated in mitotically arrested cells. Conclusion These data suggest that the oncolytic activity of ReoT3D can be potentiated by taxanes and other chemotherapeutic agents, and that the ReoT3D-taxane combination most effectively achieves synergy through accelerated apoptosis triggered by prolonged mitotic arrest.

  6. Characterization of the first double-sided 3D radiation sensors fabricated at FBK on 6-inch silicon wafers

    International Nuclear Information System (INIS)

    Sultan, D.M.S.; Mendicino, R.; Betta, G.-F. Dalla; Boscardin, M.; Ronchin, S.; Zorzi, N.

    2015-01-01

    Following 3D pixel sensor production for the ATLAS Insertable B-Layer, Fondazione Bruno Kessler (FBK) fabrication facility has recently been upgraded to process 6-inch wafers. In 2014, a test batch was fabricated to check for possible issues relevant to this upgrade. While maintaining a double-sided fabrication technology, some process modifications have been investigated. We report here on the technology and the design of this batch, and present selected results from the electrical characterization of sensors and test structures. Notably, the breakdown voltage is shown to exceed 200 V before irradiation, much higher than in earlier productions, demonstrating robustness in terms of radiation hardness for forthcoming productions aimed at High Luminosity LHC upgrades

  7. Two inch large area patterning on a vertical light-emitting diode by nano-imprinting technology

    International Nuclear Information System (INIS)

    Byeon, Kyeong-Jae; Hong, Eun-Ju; Park, Hyoungwon; Yoon, Kyung-Min; Lee, Heon; Song, Hyun Don; Lee, Jin Wook; Kim, Sun-Kyung; Cho, Hyun Kyong; Kwon, Ho Ki

    2010-01-01

    A vertical light-emitting diode (LED) with a chip size of 500 × 500 µm 2 was fabricated by the laser lift-off (LLO) process of an InGaN-based blue LED wafer. After the LLO process, photonic crystal patterns by UV nano-imprint lithography were formed on the n-GaN top layer of the vertical LED over the entire area with a diameter of 2 inches. As the result of n-GaN patterning, light output power of the vertical LED with photonic crystals was increased by up to 44% compared to that of the vertical LED without a photonic crystal at a driving current of 1000 mA

  8. Modeling the effects of repeated systemic administrations of small activity amounts In radionuclide therapy with beta emitters

    International Nuclear Information System (INIS)

    Calderon, Carlos; Gonzalez, Joaquin; Cepero, Janet; Colom, Camila; Rodriguez, Juan C.

    2008-01-01

    Full text: Good results for radionuclide therapy treatments where repeated short time spaced systemic injection of small activity amounts are given have been reported. Bone marrow and kidneys are usually considered as dose-limiting organs in radionuclide therapy. The treatments in radionuclide therapy with repeated administration could be optimized if irradiation effects in those one might be estimated. Xeno-grafted mice is the often biological model used during the evaluation of candidates for radionuclide therapy. A mathematical model of tumor cell kinetics was combined with another one reported for marrow cell kinetics which allows the calculation of marrow cell survival and proliferation in response to different irradiation schemes. Radionuclide therapy treatment with repeated administrations with radiopharmaceuticals labeled with beta emitters were simulated. The effects on fast-growing and slow-growing tumors were evaluated, as well as radiosensitive and radioresistant tumors. For more realistic estimation of absorbed dose in mice organs the cross-irradiation due to high energy beta particles was included into the MIRD's formula. Tumor and kidneys responses to the irradiation were estimated on the linear-quadratic model framework which was adapted for a multi-exponential dose rate function describing radionuclide therapy treatments with repeated administrations. Published values for murine tumors kinetics, marrows cellular turnover rates and radiosensitivities were used during the calculations. Iso-effective schemes were also determined varying the interval between fractions and the number of administration. For a given tolerated level of thrombocytopenia and absorbed dose in kidneys an optimal regime of radionuclide therapy with repeated administration could be found. The mathematical model presented here allows the prediction of the nadir and duration of thrombocytopenia, the effects on kidneys and the tumor cell response to various treatment schemes

  9. The development of 8 inch roll-to-plate nanoimprint lithography (8-R2P-NIL) system

    Science.gov (United States)

    Lee, Lai Seng; Mohamed, Khairudin; Ooi, Su Guan

    2017-07-01

    Growth in semiconductor and integrated circuit industry was observed in the past decennium of years for industrial technology which followed Moore's law. The line width of nanostructure to be exposed was influenced by the essential technology of photolithography. Thus, it is crucial to have a low cost and high throughput manufacturing process for nanostructures. Nanoimprint Lithography technique invented by Stephen Y. Chou was considered as major nanolithography process to be used in future integrated circuit and integrated optics. The drawbacks of high imprint pressure, high imprint temperature, air bubbles formation, resist sticking to mold and low throughput of thermal nanoimprint lithography on silicon wafer have yet to be solved. Thus, the objectives of this work is to develop a high throughput, low imprint force, room temperature UV assisted 8 inch roll to plate nanoimprint lithography system capable of imprinting nanostructures on 200 mm silicon wafer using roller imprint with flexible mold. A piece of resist spin coated silicon wafer was placed onto vacuum chuck drives forward by a stepper motor. A quartz roller wrapped with a piece of transparent flexible mold was used as imprint roller. The imprinted nanostructures were cured by 10 W, 365 nm UV LED which situated inside the quartz roller. Heat generated by UV LED was dissipated by micro heat pipe. The flexible mold detaches from imprinted nanostructures in a 'line peeling' pattern and imprint pressure was measured by ultra-thin force sensors. This system has imprinting speed capability ranging from 0.19 mm/s to 5.65 mm/s, equivalent to imprinting capability of 3 to 20 pieces of 8 inch wafers per hour. Speed synchronization between imprint roller and vacuum chuck was achieved by controlling pulse rate supplied to stepper motor which drive the vacuum chuck. The speed different ranging from 2 nm/s to 98 nm/s is achievable. Vacuum chuck height was controlled by stepper motor with displacement of 5 nm/step.

  10. Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium.

    Science.gov (United States)

    Noble, Karen; Floyd, Rachel; Shmygol, Andre; Shmygol, Anatoly; Mobasheri, A; Wray, Susan

    2010-01-01

    Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels. 2009 Elsevier Ltd. All rights reserved.

  11. COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo.

    Science.gov (United States)

    Salim, Kowthar Y; Maleki Vareki, Saman; Danter, Wayne R; Koropatnick, James

    2016-07-05

    Identification of novel anti-cancer compounds with high efficacy and low toxicity is critical in drug development. High-throughput screening and other such strategies are generally resource-intensive. Therefore, in silico computer-aided drug design has gained rapid acceptance and popularity. We employed our proprietary computational platform (CHEMSAS®), which uses a unique combination of traditional and modern pharmacology principles, statistical modeling, medicinal chemistry, and machine-learning technologies to discover and optimize novel compounds that could target various cancers. COTI-2 is a small molecule candidate anti-cancer drug identified using CHEMSAS. This study describes the in vitro and in vivo evaluation of COTI-2. Our data demonstrate that COTI-2 is effective against a diverse group of human cancer cell lines regardless of their tissue of origin or genetic makeup. Most treated cancer cell lines were sensitive to COTI-2 at nanomolar concentrations. When compared to traditional chemotherapy or targeted-therapy agents, COTI-2 showed superior activity against tumor cells, in vitro and in vivo. Despite its potent anti-tumor efficacy, COTI-2 was safe and well-tolerated in vivo. Although the mechanism of action of COTI-2 is still under investigation, preliminary results indicate that it is not a traditional kinase or an Hsp90 inhibitor.

  12. Pollution control activities for waste-water treatment plants: planning, integrated approach, functionality controls and small plants

    International Nuclear Information System (INIS)

    Serena, F.; Tomiato, L.; Ostoich, M.; Falletti, L.

    2009-01-01

    The work presents the problem of the Wastewater Treatment Plants' (WWTPs) controls and the organization of the consequential activities with reference to the priorities of the Environmental Agencies through a hierarchy assessment according to the environmental importance of the pressure sources. The European Recommendation 2001/331/EC bases the environmental controls of industrial sites and also of WWTPs on an integrated approach overtaking the simple analytic control; the integrated approach requires documentary, technical, management and analytic controls. The Veneto Regional Environmental Prevention and Protection Agency (ARPAV) has recently developed and applied a check-list for the implementation of the European Recommendation for WWTPs. The check-list includes the functionality assessment of the WWTP in case of discharge control delegation to the plant manager as consented with Annex 5 third part Italian Decree 3/04/2006 n. 152. In the paper the general framework of environmental controls on public WWTPs in the Veneto region is described. Particular importance for the numerousness and for the required control typology is referred to the small WWTP ( [it

  13. Tests of small X-ray Active Matrix Pixel Sensor prototypes at the National Synchrotron Light Source

    Science.gov (United States)

    Carini, G. A.; Chen, W.; Dragone, A.; Fried, J.; Jakoncic, J.; Kuczweski, A.; Li, Z.; Mead, J.; Michta, R.; Pratte, J.-F.; Rehak, P.; Siddons, D. P.

    2009-03-01

    X-ray Active Matrix Pixel Sensors (XAMPS) were designed and fabricated at Brookhaven National Laboratory. Devices based on J-FET technology were produced on 100 mm high-resistivity silicon, typically 400 μm-thick. The prototypes are square matrices with n rows and n columns with n = 16, 32, 64, 128, 256, 512. Each pixel of the matrix is 90 × 90 μm2 and contains a JFET switch to control the charge readout. The XAMPS is a position sensitive ionization detector made on high resistivity silicon. It consists of a pixel array detector with integrated switches. Pixels are isolated from each other by a potential barrier and the device is fully depleted by applying a high voltage bias to the junction on the entrance window of the sensor. The small features of the design presented some technological challenges fully addressed during this production. The first prototypes were tested at the National Synchrotron Light Source (NSLS) with a monochromatic beam of 8 keV and millisecond readout and exhibit good performances at room temperature.

  14. Tests of small X-ray Active Matrix Pixel Sensor prototypes at the National Synchrotron Light Source

    Energy Technology Data Exchange (ETDEWEB)

    Carini, G A; Chen, W; Fried, J; Jakoncic, J; Kuczweski, A; Li, Z; Mead, J; Michta, R; Pratte, J-F; Rehak, P; Siddons, D P [Brookhaven National Laboratory, Upton, 11973 NY (United States); Dragone, A [SLAC National Accelerator Center, Menlo Park, 94025 CA (United States)], E-mail: carini@bnl.gov

    2009-03-15

    X-ray Active Matrix Pixel Sensors (XAMPS) were designed and fabricated at Brookhaven National Laboratory. Devices based on J-FET technology were produced on 100 mm high-resistivity silicon, typically 400 {mu}m-thick. The prototypes are square matrices with n rows and n columns with n = 16, 32, 64, 128, 256, 512. Each pixel of the matrix is 90 x 90 {mu}m{sup 2} and contains a JFET switch to control the charge readout. The XAMPS is a position sensitive ionization detector made on high resistivity silicon. It consists of a pixel array detector with integrated switches. Pixels are isolated from each other by a potential barrier and the device is fully depleted by applying a high voltage bias to the junction on the entrance window of the sensor. The small features of the design presented some technological challenges fully addressed during this production. The first prototypes were tested at the National Synchrotron Light Source (NSLS) with a monochromatic beam of 8 keV and millisecond readout and exhibit good performances at room temperature.

  15. p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

    Science.gov (United States)

    Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

    2016-07-25

    We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

  16. Devising of the method for the determination of small and very small amounts of cadmium in biological materials by radiochemical version of neutron activation analysis

    International Nuclear Information System (INIS)

    Dybczynski, R.; Samczynski, Z.

    1996-01-01

    The newly modified version of the method for the determination of cadmium in biological materials by radiochemical NAA based on selective post irradiation separation of Cd using ion exchange rasin Retardion 11A8 is presented. The conditions necessary for the selective retaining of Cd on the column exploiting both anionic and cationic ion exchange function of the resin have been discussed. Depending on the composition of the external solution, cadmium existing in the form of either anionic chloride complexes or cationic amine species is taken up by quaternary ammonium or carboxylate functional groups, respectively while accompanying elements are eluted. The elaborated method was further verified by determine Cd content in several certified biological reference materials using neutron activation analysis. The ion exchange separation procedure assures very high radiochemical purity of the cadmium fraction. Decontamination factors obtained for Mo, Sb, Na, Zn, Co, Sc amounted to 10 3 - 10 6 . Detection limit for Cd was 0.5 μg kg -1 . Analytical results show good agreement with the certified values. (author). 10 refs, 7 figs, 1 tab

  17. The impact of small-scale mining activities on the levels of mercury in the environment. The case of Prestea and its environs

    International Nuclear Information System (INIS)

    Serfor-Armah, Y.; Adotey, D.K.; Nyarko, B.J.B.; Akaho, E.H.K.; Adomako, D.

    2004-01-01

    To obtain the baseline information of mercury pollution due to gold mining activities in Prestea and its environs total mercury (T-Hg) concentrations were measured in water and stream sediment. The samples were analyzed by instrumental neutron activation analysis (INAA). They were irradiated and counted without any preconcentration. Higher levels of T-Hg concentration were found in samples at the sites with extensive small-scale 'galamsey' gold mining activities than at the sites with low small-scale 'galamsey' activities. Concentrations varied between 6.80-19.82 mg/l for water and 28.90-84.30 mg/kg in sediment at sites with extensive small-scale mining activities. At low small-scale mining sites concentration levels for T-Hg varied between 0.50-9.10 mg/l and 1.20-22.75 mg/kg in water and sediment, respectively. The concentration levels of T-Hg in water from all the sampling sites are in excess of the WHO tolerable limit of 0.001 mg/l for drinking water. (author)

  18. Small-conductance Ca2+-activated potassium type 2 channels regulate the formation of contextual fear memory.

    Directory of Open Access Journals (Sweden)

    Saravana R K Murthy

    Full Text Available Small-conductance, Ca2+ activated K+ channels (SK channels are expressed at high levels in brain regions responsible for learning and memory. In the current study we characterized the contribution of SK2 channels to synaptic plasticity and to different phases of hippocampal memory formation. Selective SK2 antisense-treatment facilitated basal synaptic transmission and theta-burst induced LTP in hippocampal brain slices. Using the selective SK2 antagonist Lei-Dab7 or SK2 antisense probes, we found that hippocampal SK2 channels are critical during two different time windows: 1 blockade of SK2 channels before the training impaired fear memory, whereas, 2 blockade of SK2 channels immediately after the training enhanced contextual fear memory. We provided the evidence that the post-training cleavage of the SK2 channels was responsible for the observed bidirectional effect of SK2 channel blockade on memory consolidation. Thus, Lei-Dab7-injection before training impaired the C-terminal cleavage of SK2 channels, while Lei-Dab7 given immediately after training facilitated the C-terminal cleavage. Application of the synthetic peptide comprising a leucine-zipper domain of the C-terminal fragment to Jurkat cells impaired SK2 channel-mediated currents, indicating that the endogenously cleaved fragment might exert its effects on memory formation by blocking SK2 channel-mediated currents. Our present findings suggest that SK2 channel proteins contribute to synaptic plasticity and memory not only as ion channels but also by additionally generating a SK2 C-terminal fragment, involved in both processes. The modulation of fear memory by down-regulating SK2 C-terminal cleavage might have applicability in the treatment of anxiety disorders in which fear conditioning is enhanced.

  19. Viscosity and not biological mechanisms often controls the effects of temperature on ciliary activity and swimming velocity of small aquatic organisms

    DEFF Research Database (Denmark)

    Larsen, Poul Scheel; Riisgård, H. U.

    2009-01-01

    A number of studies have shown that temperature-dependent viscosity of the ambient water controls or strongly affects bio-mechanical activity such as beat frequency of water-pumping cilia in mussels and ascidians, swimming velocity of sperm cells, ciliates and small (micro- and meso-scale) aquatic...... organisms using cilia or small appendages for propulsion. Here we summarize results from the literature and from own studies on bio-mechanical activities in response to changing temperature or manipulated viscosity at constant temperature, both having the same change in kinematic viscosity. The survey......-law regressions for viscosity manipulation (by means of an additive) and/or temperature we suggest that viscosity and not biological mechanisms often control the response. This knowledge enhances our basic understanding of the effect of temperature not only on the swimming and feeding behaviour of small aquatic...

  20. Effect of weight and frontal area of external telemetry packages on the kinematics, activity levels and swimming performance of small-bodied sharks.

    Science.gov (United States)

    Bouyoucos, I A; Suski, C D; Mandelman, J W; Brooks, E J

    2017-05-01

    This study sought to observe the effects of submerged weight and frontal cross-sectional area of external telemetry packages on the kinematics, activity levels and swimming performance of small-bodied juvenile sharks, using lemon sharks Negaprion brevirostris (60-80 cm total length, L T ) as a model species. Juveniles were observed free-swimming in a mesocosm untagged and with small and large external accelerometer packages that increased frontal cross-sectional area of the animals and their submerged weight. Despite adhering to widely used standards for tag mass, the presence of an external telemetry package altered swimming kinematics, activity levels and swimming performance of juvenile N. brevirostris relative to untagged individuals, suggesting that tag mass is not a suitable standalone metric of device suitability. Changes in swimming performance could not be detected from tail-beat frequency, which suggests that tail-beat frequency is an unsuitable standalone metric of swimming performance for small N. brevirostris. Lastly, sharks experienced treatment-specific changes in activity level and swimming kinematics from morning to afternoon observation. Therefore, the presence of external telemetry packages altered the kinematics, activity levels and swimming performance of small young-of-the-year N. brevirostris and these data may therefore be relevant to other similar-sized juveniles of other shark species. © 2017 The Fisheries Society of the British Isles.

  1. Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum

    NARCIS (Netherlands)

    Chen, Mao Xiang; Gorman, Shelby A.; Benson, Bill; Singh, Kuljit; Hieble, J. Paul; Michel, Martin C.; Tate, Simon N.; Trezise, Derek J.

    2004-01-01

    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in

  2. Automated patch-clamp technique: increased throughput in functional characterization and in pharmacological screening of small-conductance Ca2+ release-activated Ca2+ channels

    DEFF Research Database (Denmark)

    Schrøder, Rikke L; Friis, Søren; Sunesen, Morten

    2008-01-01

    The suitability of an automated patch clamp for the characterization and pharmacological screening of calcium release-activated calcium (CRAC) channels endogenously expressed in RBL-2H3 cells was explored with the QPatch system. CRAC currents (I( CRAC)) are small, and thus precise recordings requ...

  3. Expression of the Small Conductance Ca(2+)-Activated Potassium Channel Subtype 3 (SK3) in Rat Uterus after Stimulation with 17β-Estradiol

    DEFF Research Database (Denmark)

    Rahbek, Mette; Nazemi, Sasan; Odum, Lars

    2014-01-01

    of the myometrium. The small conductance Ca(2+)-activated potassium channel subtype 3 (SK3) has been identified in the myometrium of several species including humans, mice and rats, but with great inter species variation of the expression pattern and regulation. The aim of this study was to investigate...

  4. Smart dynamic rotor control using active flaps on a small-scale wind turbine: aeroelastic modeling and comparison with wind tunnel measurements

    DEFF Research Database (Denmark)

    Barlas, Thanasis K.; van Wingerden, W.; Hulskamp, A.W.

    2013-01-01

    In this paper, the proof of concept of a smart rotor is illustrated by aeroelastic simulations on a small-scale rotor and comparison with wind tunnel experiments. The application of advanced feedback controllers using actively deformed flaps in the wind tunnel measurements is shown to alleviate d...

  5. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-01-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  6. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  7. Selective Small Molecule Activators of TREK-2 Channels Stimulate Dorsal Root Ganglion c-Fiber Nociceptor Two-Pore-Domain Potassium Channel Currents and Limit Calcium Influx.

    Science.gov (United States)

    Dadi, Prasanna K; Vierra, Nicholas C; Days, Emily; Dickerson, Matthew T; Vinson, Paige N; Weaver, C David; Jacobson, David A

    2017-03-15

    The two-pore-domain potassium (K2P) channel TREK-2 serves to modulate plasma membrane potential in dorsal root ganglia c-fiber nociceptors, which tunes electrical excitability and nociception. Thus, TREK-2 channels are considered a potential therapeutic target for treating pain; however, there are currently no selective pharmacological tools for TREK-2 channels. Here we report the identification of the first TREK-2 selective activators using a high-throughput fluorescence-based thallium (Tl + ) flux screen (HTS). An initial pilot screen with a bioactive lipid library identified 11-deoxy prostaglandin F2α as a potent activator of TREK-2 channels (EC 50 ≈ 0.294 μM), which was utilized to optimize the TREK-2 Tl + flux assay (Z' = 0.752). A HTS was then performed with 76 575 structurally diverse small molecules. Many small molecules that selectively activate TREK-2 were discovered. As these molecules were able to activate single TREK-2 channels in excised membrane patches, they are likely direct TREK-2 activators. Furthermore, TREK-2 activators reduced primary dorsal root ganglion (DRG) c-fiber Ca 2+ influx. Interestingly, some of the selective TREK-2 activators such as 11-deoxy prostaglandin F2α were found to inhibit the K2P channel TREK-1. Utilizing chimeric channels containing portions of TREK-1 and TREK-2, the region of the TREK channels that allows for either small molecule activation or inhibition was identified. This region lies within the second pore domain containing extracellular loop and is predicted to play an important role in modulating TREK channel activity. Moreover, the selective TREK-2 activators identified in this HTS provide important tools for assessing human TREK-2 channel function and investigating their therapeutic potential for treating chronic pain.

  8. First mile, first inch

    CSIR Research Space (South Africa)

    Morris, C

    2007-05-01

    Full Text Available Access to Information and Communication Technologies (ICTs) remains one of the biggest challenges to Africa in leapfrogging the development chasm. The African digital divide can be in part attributed to a restrictive regulatory policy...

  9. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    Science.gov (United States)

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  10. Refurbishment and modification of existing protective shipping packages (for 30-inch UF{sub 6} cylinders) per USDOT specification No. USA-DOT-21PF-1A

    Energy Technology Data Exchange (ETDEWEB)

    Housholder, W.R. [Nuclear Containers, Incorporated, Elizabethton, TN (United States)

    1991-12-31

    This paper addresses the refurbishment procedures for existing shipping containers for 30-inch diameter UF{sub 6} cylinders in accordance with DOT Specification 21PF-1 and the criteria used to determine rejection when such packages are unsuitable for refurbishment.

  11. Specification for modular plug-in unit and standard 19-inch rack mounting unit based on NIM standard (for electronic nuclear instruments)

    International Nuclear Information System (INIS)

    1978-01-01

    The object is to define standard dimensions of a modular system based on NIM standard and comprising the plug-in unit Type N specified in IEC Publication 482, Dimensions of Electronic Instrument Modules (for Nuclear Electronic Instruments), the corresponding 19-inch rack mounting unit Type NC (conforming to IEC Publication 297, Dimensions of Panels and Racks) and the associated connectors. (author)

  12. CONSIDERATIONS REGARDING THE USE OF MODERN MANAGEMENT METHODS IN PLANNING THE MARKETING ACTIVITY WITHIN THE SMALL AND MEDIUM-SIZED ENTERPRISES

    Directory of Open Access Journals (Sweden)

    Olteanu Valerica

    2012-07-01

    Full Text Available This paper aims to highlight, from a marketing perspective, the manner and conditions in which small and medium-sized enterprises can use modern management methods in planning the marketing activity. Using modern methods of management are particularly important for managers of these organizations and especially for marketers. Thus, the following methods play a significant role within the marketing activitiesn#8217; development for marketing specialists, namely: management by objectives, management by budgets, management by projects, and management by product. The high degree of understanding and using the above methods is, in the current economic environment, one of the determinants of the market success of small and medium-sized enterprises. In the current context, the adoption of the management by objectives is not a facultative option for the small and medium-sized enterprises, but rather a binding one in the context of adopting and practicing an efficient marketing with significant results on the development of marketing programs comprised within them. Similarly to the management by objectives, the use of the management by budgets within the small and medium-sized enterprises has a series of features required by their smaller size, features that should be considered by marketers. Regarding the use of management by projects, this method has to constitute the foundation for the elaboration of marketing programs developed within the small and medium-sized enterprises, thereby allowing shaping an action that can be accompanied by success in achieving the goals comprised within the marketing programs. Finally, the role of the management by product is extremely important in the marketing activity within the small and medium-sized enterprises, especially in the operationalization of concepts such as strategic marketing and tactical marketing. This paper thus outlines from a marketing point of view the main issues aiming at understanding and using

  13. Hyperlipidemia-induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters.

    Science.gov (United States)

    Stancu, Camelia S; Carnuta, Mihaela G; Sanda, Gabriela M; Toma, Laura; Deleanu, Mariana; Niculescu, Loredan S; Sasson, Shlomo; Simionescu, Maya; Sima, Anca V

    2015-11-01

    We aimed at investigating the mechanisms linking hyperlipidemia (HL) with dysfunctional HDL and its main antioxidant enzyme, paraoxonase1 (PON1). PON1 expression and activity was determined in the small intestine, liver, and sera of normal and HL hamsters and associated with the ER stress (ERS) and the development of aortic valve lesions. Male Golden Syrian hamsters were fed standard chow (N) or standard diet with 3% cholesterol and 15% butter for 16 weeks. All hamsters on fat diet developed HL, 50% also hyperglycemia (HLHG) and a fourfold increased homeostasis model assessment of insuline resistance. PON1 expression was reduced in the small intestine and liver (N > HL > HLHG) along with the increased extent of ERS, oxidized lipids, and decreased expression of liver X receptors beta (LXRβ) in the small intestine, peroxisome proliferator-activated receptor-γ (PPARγ) in the liver, and of the glucose transporter 4 in the myocardium. Serum PON1 levels decreased along with the increase of oxidized LDL and lesion areas of the aortic valves (N > HL > HLHG). The fat diet activates the ERS and oxidative stress, decreases LXRβ, PPARγ, and PON1 in the small intestine, liver, and sera of all HL animals, in parallel with the appearance of atherosclerotic lesions in the aortic valves. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Microsoft Access Small Business Solutions State-of-the-Art Database Models for Sales, Marketing, Customer Management, and More Key Business Activities

    CERN Document Server

    Hennig, Teresa; Linson, Larry; Purvis, Leigh; Spaulding, Brent

    2010-01-01

    Database models developed by a team of leading Microsoft Access MVPs that provide ready-to-use solutions for sales, marketing, customer management and other key business activities for most small businesses. As the most popular relational database in the world, Microsoft Access is widely used by small business owners. This book responds to the growing need for resources that help business managers and end users design and build effective Access database solutions for specific business functions. Coverage includes::; Elements of a Microsoft Access Database; Relational Data Model; Dealing with C

  15. Differences in the pattern of ventricular activation in small rodents determined by morphological organization of the cardiac ventricular conduction system

    NARCIS (Netherlands)

    van Veen, Toon A. B.; Hubens, Lisette E. G.; de Bakker, Jacques M. T.; van Rijen, Harold V. M.

    2010-01-01

    Ventricular activation of the mouse heart differs significantly compared to activation in larger mammals. Knowledge of structural and functional characteristics of laboratory animals is essential for evaluation of results obtained from experiments. The present study was performed to evaluate whether

  16. Performance analysis of active damped small DC-link capacitor based drive for unbalanced input voltage supply

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig

    2011-01-01

    A small DC-link capacitor based drive is presented in this paper. The drive shows negative impedance instability at operating points with high power load. A phase portrait is presented for input filter states which exhibit a limit cycle. When the drive is operated with unbalanced input supply...

  17. Role of Individual Positive Charges in the Membrane Orientation and Activity of Transporters of the Small Multidrug Resistance Family

    NARCIS (Netherlands)

    Kolbusz, Magdalena A.; Slotboom, Dirk Jan; Lolkema, Juke S.

    2012-01-01

    The effect of individual positively charged residues on the orientation in the membrane was analyzed in three dual-topology transporters of the small. multidrug resistance (SMR) family: AAVE4701aave of Acidovorax avenae, EMREecol of Escherichia coli, and RRUA0272rrub of Rhodospirillum rubrum. It is

  18. Inviting Argument by Analogy: Analogical-Mapping-Based Comparison Activities as a Scaffold for Small-Group Argumentation

    Science.gov (United States)

    Emig, Brandon R.; McDonald, Scott; Zembal-Saul, Carla; Strauss, Susan G.

    2014-01-01

    This study invited small groups to make several arguments by analogy about simple machines. Groups were first provided training on analogical (structure) mapping and were then invited to use analogical mapping as a scaffold to make arguments. In making these arguments, groups were asked to consider three simple machines: two machines that they had…

  19. Credit-constrained in risky activities? The determinants of the capital stocks of micro and small firms in Western Africa

    NARCIS (Netherlands)

    M. Grimm (Michael); S. Lange (Simon); J. Lay (Jann)

    2012-01-01

    textabstractMicro and small enterprises (MSEs) in developing countries are typically considered to be severely credit constrained. Additionally, high business risks may partly explain why the capital stocks of MSEs remain low. This article analyzes the determinants of the capital stocks of MSEs in

  20. The Effects of Exhaustive Military Activities in Man. The Performance of Small Isolated Military Units in Extreme Environmental Conditions

    Science.gov (United States)

    2001-03-01

    functions Regular body functions are of importance for anybody in an extreme climate. Constipation is very often a problem at the beginning of any...groups problems may arise. One of the remedies is to let everybody do his share. If the total work load is low, any workload how small it is may be a

  1. Affordable Development and Demonstration of a Small NTR Engine and Stage: How Small is Big Enough?

    Science.gov (United States)

    Borowski, Stanley K.; Sefcik, Robert J.; Fittje, James E.; McCurdy, David R.; Qualls, Arthur L.; Schnitzler, Bruce G.; Werner, James E.; Weitzberg (Abraham); Joyner, Claude R.

    2015-01-01

    The Nuclear Thermal Rocket (NTR) derives its energy from fission of uranium-235 atoms contained within fuel elements that comprise the engine's reactor core. It generates high thrust and has a specific impulse potential of approximately 900 seconds - a 100% increase over today's best chemical rockets. The Nuclear Thermal Propulsion (NTP) project, funded by NASA's AES program, includes five key task activities: (1) Recapture, demonstration, and validation of heritage graphite composite (GC) fuel (selected as the "Lead Fuel" option); (2) Engine Conceptual Design; (3) Operating Requirements Definition; (4) Identification of Affordable Options for Ground Testing; and (5) Formulation of an Affordable Development Strategy. During FY'14, a preliminary DDT&E plan and schedule for NTP development was outlined by GRC, DOE and industry that involved significant system-level demonstration projects that included GTD tests at the NNSS, followed by a FTD mission. To reduce cost for the GTD tests and FTD mission, small NTR engines, in either the 7.5 or 16.5 klbf thrust class, were considered. Both engine options used GC fuel and a "common" fuel element (FE) design. The small approximately 7.5 klbf "criticality-limited" engine produces approximately 157 megawatts of thermal power (MWt) and its core is configured with parallel rows of hexagonal-shaped FEs and tie tubes (TTs) with a FE to TT ratio of approximately 1:1. The larger approximately 16.5 klbf Small Nuclear Rocket Engine (SNRE), developed by LANL at the end of the Rover program, produces approximately 367 MWt and has a FE to TT ratio of approximately 2:1. Although both engines use a common 35 inch (approximately 89 cm) long FE, the SNRE's larger diameter core contains approximately 300 more FEs needed to produce an additional 210 MWt of power. To reduce the cost of the FTD mission, a simple "1-burn" lunar flyby mission was considered to reduce the LH2 propellant loading, the stage size and complexity. Use of existing and

  2. BnaA.bZIP1 Negatively Regulates a Novel Small Peptide Gene, BnaC.SP6, Involved in Pollen Activity

    Directory of Open Access Journals (Sweden)

    Xuanpeng Wang

    2017-12-01

    Full Text Available Small peptides secreted to the extracellular matrix control many aspects of the plant’s physiological activities which were identified in Arabidopsis thaliana, called ATSPs. Here, we isolated and characterized the small peptide gene Bna.SP6 from Brassica napus. The BnaC.SP6 promoter was cloned and identified. Promoter deletion analysis suggested that the -447 to -375 and -210 to -135 regions are crucial for the silique septum and pollen expression of BnaC.SP6, respectively. Furthermore, the minimal promoter region of p158 (-210 to -52 was sufficient for driving gene expression specifically in pollen and highly conserved in Brassica species. In addition, BnaA.bZIP1 was predominantly expressed in anthers where BnaC.SP6 was also expressed, and was localized to the nuclei. BnaA.bZIP1 possessed transcriptional activation activity in yeast and protoplast system. It could specifically bind to the C-box in p158 in vitro, and negatively regulate p158 activity in vivo. BnaA.bZIP1 functions as a transcriptional repressor of BnaC.SP6 in pollen activity. These results provide novel insight into the transcriptional regulation of BnaC.SP6 in pollen activity and the pollen/anther-specific promoter regions of BnaC.SP6 may have their potential agricultural application for new male sterility line generation.

  3. Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation.

    Science.gov (United States)

    Kim, Ki Young; Ahn, Jin Hee; Cheon, Hyae Gyeong

    2007-09-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we elucidated the apoptotic mechanism of PPARgamma activation in human lung cancers by using a novel PPARgamma agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPARgamma activation selectively inhibited cell viability of non-small-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPARgamma activation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompanied by increased expression of proline oxidase (POX), a redox enzyme expressed in mitochondria, upon incubation with the agonists. POX RNA interference treatment blocked PPARgamma-induced ROS formation and cytotoxicity, suggesting that POX plays a functional role in apoptosis through ROS formation. The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl ether, a PPARgamma antagonist, and by knockdown of PPARgamma expression, indicating the involvement of PPARgamma in these actions. The results of the present study suggest that PPARgamma activation induces apoptotic cell death in non-small-cell lung carcinoma mainly through ROS formation via POX induction.

  4. Using Cryptocurrency in the Activities of Ukrainian Small and Medium Enterprises in order to Improve their Investment Attractiveness

    OpenAIRE

    Ivashchenko Alla I.

    2016-01-01

    The aim of the article is to analyze the main features of cryptocurrency with respect to the identification of main advantages and disadvantages of using cryptocurrency as a method of effecting cashless payments by small and medium enterprises in order to increase the level of their investment attractiveness. The article describes the basic characteristics of cryptocurrencies and Bitcon as the most common among them. The Bitcoin emission mechanism has been built and the dynamics of c...

  5. The empirical relationship between the managerial conduct and internal control activities in South African small, medium and micro enterprises

    OpenAIRE

    Juan-Pierre Bruwer; Philna Coetzee; Jacolize Meiring

    2017-01-01

    Background: Although South African small, medium and micro enterprises (SMMEs) play an imperative role in the stimulation of the national economy, previous research studies show that these business entities have severe sustainability problems as approximately 75% of them fail after being in operation for only 3 years. The latter dispensation is pinned on the belief that South African SMMEs make use of inadequate and ineffective internal control systems. Aim: Since a system of internal cont...

  6. 77 FR 59374 - Certain Small Diameter Carbon and Alloy Seamless Standard, Line and Pressure Pipe (Under 41/2

    Science.gov (United States)

    2012-09-27

    ...] Certain Small Diameter Carbon and Alloy Seamless Standard, Line and Pressure Pipe (Under 4\\1/2\\ Inches... administrative review of the antidumping order on certain small diameter carbon and alloy seamless standard, line...: September 20, 2012. Christian Marsh, Deputy Assistant Secretary for Antidumping and Countervailing Duty...

  7. Effect of desamino-cholecystokinin-octapeptide (CCK-7) on the intraluminal pressure and myoelectrical activity of the gall-bladder, stomach, and small intestine in conscious dogs.

    OpenAIRE

    Milenov, E.; Nieber, K.; Niedrich, H.; Oehme, P.; Vogt, W. E.

    1983-01-01

    Desamino-cholecystokinin-octapeptide (CCK-7) increased the gall-bladder pressure and decreased the gastric pressure following i.v. infusion in conscious dogs. In small intestine and Heidenhain pouch CCK-7 exerted an initial excitatory effect followed by an inhibitory effect on intraluminal pressure and peristalsis. In all organs the effect of CCK-7 on pressure was correlated with a change of spike discharge. CCK-7 is more potent on gastrointestinal motor activity than a Boots preparation of p...

  8. Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N

    2013-01-01

    682753A, which blocks oxysterol-induced G-protein activation, β-arrestin recruitment and B-cell chemotaxis. We furthermore demonstrate that activation triggers pertussis toxin-sensitive MAP kinase phosphorylation, which is also inhibited by GSK682753A. Thus, EBI2 signalling in B cells mediates key...

  9. Identification of a Small Molecule Activator for AphB, a LysR-Type Virulence Transcriptional Regulator in Vibrio cholerae.

    Science.gov (United States)

    Privett, Britney R; Pellegrini, Maria; Kovacikova, Gabriela; Taylor, Ronald K; Skorupski, Karen; Mierke, Dale; Kull, F Jon

    2017-07-25

    AphB is a LysR-type transcriptional regulator (LTTR) that cooperates with a second transcriptional activator, AphA, at the tcpPH promoter to initiate expression of the virulence cascade in Vibrio cholerae. Because it is not yet known whether AphB responds to a natural ligand in V. cholerae that influences its ability to activate transcription, we used a computational approach to identify small molecules that influence its activity. In silico docking was used to identify potential ligands for AphB, and saturation transfer difference nuclear magnetic resonance was subsequently employed to access the validity of promising targets. We identified a small molecule, BP-15, that specifically binds the C-terminal regulatory domain of AphB and increases its activity. Interestingly, molecular docking predicts that BP-15 does not bind in the putative primary effector-binding pocket located at the interface of RD-I and RD-II as in other LTTRs, but rather at the dimerization interface. The information gained in this study helps us to further understand the mechanism by which transcriptional activation by AphB is regulated by suggesting that AphB has a secondary ligand binding site, as observed in other LTTRs. This study also lays the groundwork for the future design of inhibitory molecules to block the V. cholerae virulence cascade, thereby preventing the devastating symptoms of cholera infection.

  10. Effects of phenylated compounds of methylglyoxal bis(guanylhydrazone) on diamine oxidase activity from rat small intestine.

    Science.gov (United States)

    Balaña-Fouce, R; Pulido, T G; Escudero, D O; Sanz-Sanchez, F

    1986-01-01

    Two phenylated compounds of methylglyoxal bis(guanylhydrazone), potentially inhibitors of diamine oxidase activity, have been synthesized: phenylglyoxal bis(guanylhydrazone) and diphenylglyoxal bis(guanylhydrazone). Their inhibitory capacity was tested: while PGBG was able to reduce the enzyme activity by 50% at 1.3 microM, DPGBG was only able to reduce diamine oxidase activity by less than 2% at a concentration 1000-fold higher. The inhibition of PGBG was non-competitive and the Ki calculated by a Dixon plot was estimated as 1.7 microM.

  11. Systematic review with meta-analysis: magnetic resonance enterography vs. computed tomography enterography for evaluating disease activity in small bowel Crohn's disease.

    Science.gov (United States)

    Qiu, Y; Mao, R; Chen, B-L; Li, X-H; He, Y; Zeng, Z-R; Li, Z-P; Chen, M-H

    2014-07-01

    Magnetic resonance enterography (MRE) has been proposed as a non-ionising alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and MRE in patients with small bowel Crohn's disease (CD) with variable results. To compare the overall diagnostic accuracy in assessing the activity of small bowel and complications. MEDLINE, EMBASE and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a pre-defined reference standard. Pooled sensitivity, specificity, the weighted area under the curve (AUC), incremental yield (IY) and other diagnostic indices were evaluated. A total of 290 CD patients from six different studies were analysed. The pooled sensitivity and specificity for MRE in detecting active small bowel CD was 87.9% [95% confidence interval (CI), 81.8-92.5] and 81.2% (95% CI: 71.9-88.4) respectively. The AUC under the summary receiver-operating characteristic (sROC) of MRE was 0.905 (SEM 0.03, standard error of the mean). Likewise, the pooled sensitivity and specificity of CTE in detecting active small bowel CD was 85.8% (95% CI: 79.2-90.9) and 83.6% (95% CI: 75.3-90.1) with the AUC of 0.898. The AUC of MRE in detecting fistula, stenosis and abscess was 0.936, 0.931 and 0.996, respectively, compared to 0.963, 0.616 and 0.899 of CTE. No statistically significant IY for MRE vs. CTE was found (fixed model, P > 0.05). Magnetic resonance enterography has a diagnostic effectiveness comparable to computed tomography enterography, thus may serve as a radiation-free alternative for evaluation of patients with Crohn's disease. © 2014 John Wiley & Sons Ltd.

  12. Phospholipase A/sub 2/ activity towards vesicles of DPPC and DMPC-DSPC containing small amounts of SMPC

    DEFF Research Database (Denmark)

    Høyrup, Lise Pernille Kristine; Mouritsen, Ole G.; Jørgensen, Kent

    2001-01-01

    Phospholipase A/sub 2/ (PLA/sub 2/) is an interfacially active enzyme whose hydrolytic activity is known to be enhanced in one-component phospholipid bilayer substrates exhibiting dynamic micro-heterogeneity. In this study the activity of PLA/sub 2/ towards large unilamellar vesicles composed...... of DPPC:SMPC and DMPC:DSPC:SMPC is investigated using fluorescence and HPLC techniques. Phase diagrams of the mixtures are established by differential scanning calorimetry and the PLA/sub 2/ activity, monitored by the lag time, is correlated with the phase behavior of the mixtures. In addition, the degree...... it is demonstrated that PLA/sub 2/ preferentially hydrolyzes the short chain DMPC lipid. This discriminative effect becomes less pronounced when the asymmetric lipid SMPC is present in the lipid substrate. Inclusion of SMPC into either DPPC or DMPC:DSPC vesicles prolongs the lag time. The results clearly show...

  13. Effects of intestinal secretagogues and distension on small bowel myoelectric activity in fasted and fed conscious dogs

    Science.gov (United States)

    da Cunha Melo, J.; Summers, R. W.; Thompson, H. H.; Wingate, D. L.; Yanda, R.

    1981-01-01

    1. Defined jejunal segments were perfused with solutions of bile salts and of ricinoleic acid during fasting and after feeding in two groups of conscious dogs, one with the segment in continuity, and the other with a Thirty-Vella loop. Myoelectric activity was recorded from chronically implanted electrodes on the jejunal segment and also from the proximal and distal in situ bowel. 2. The results in both groups were identical. During fasting, migrating complexes were present in the segment, but were replaced by intermittent spike activity during chenodeoxycholate without and with ricinoleic acid perfusion. After food, when migrating complexes were replaced by intermittent spike activity, none of the solutions produced any consistent effect. 3. In fasted animals, low levels of distension (15 mmHg) interrupted the migrating complexes in the segment and induced intermittent spike activity which was similar to that seen with the secretagogues. The migrating complexes in the main bowel continued during distension. In fed animals, spike activity increased in the segment during distension at 25 mmHg and decreased in the main bowel. In both groups, distension of the segment to pressures between 37.5 and 50 mmHg abolished spike activity both in the distended segment and the main bowel in fasted and fed states, and, in fasted dogs, migrating complexes were also abolished. 4. These results demonstrate that the inhibitory intestino-intestinal reflex is mediated through extrinsic nerves and does not require an intact myenteric plexus, whereas the altered myoelectric activity induced by secretagogues is a local effect and does not spread to adjacent bowel through either intrinsic or extrinsic neural pathways. It seems likely that the local motor effect of secretagogues is a result of net secretion, producing distension to pressures below the threshold required to activate the intestino-intestinal reflex. PMID:7338821

  14. Using Cryptocurrency in the Activities of Ukrainian Small and Medium Enterprises in order to Improve their Investment Attractiveness

    Directory of Open Access Journals (Sweden)

    Ivashchenko Alla I.

    2016-08-01

    Full Text Available The aim of the article is to analyze the main features of cryptocurrency with respect to the identification of main advantages and disadvantages of using cryptocurrency as a method of effecting cashless payments by small and medium enterprises in order to increase the level of their investment attractiveness. The article describes the basic characteristics of cryptocurrencies and Bitcon as the most common among them. The Bitcoin emission mechanism has been built and the dynamics of changes in the value, difficulty of its «extracting» or «mining», the market capitalization for 2009–2016 have been analyzed. In this connection the identified main trends and the relationship between the analyzed indicators are highlighted. The attitude of the authorities of different countries to «mining» and using cryptocurrency in calculations is shown, the monitoring of leading international financial institutions in terms of the use of Bitcoinis is carried out. In addition, the leaders among the existing cryptocurrency exchanges are determined, and the level of their market capitalization is shown, a comparative analysis of the traditional currency and cryptocurrency is conducted, an assessment of financial institutions that work with Bitcoin in Ukraine is performed, the attention being focused on the main advantages and disadvantages of using cryptocurrency in small and medium business. Taking into account all the positive aspects there justified the prospects of using the presented in the article finance cryptoinstruments, in particular Bitcoin, in order to improve the investment attractiveness.

  15. On-going development on MINT's small angle neutron scattering (SANS) facility upgrading and related research activities

    International Nuclear Information System (INIS)

    Mohamed, Abdul Aziz Bin; Mohd, Shukri Bin; Muhammad, Azali Bin

    2003-01-01

    The TRIGA MARK II Research reactor at the Malaysian Institute for Nuclear Research (MINT) was commissioned in July 1982: next year will be its 20 year criticality. Since then various works have been performed to utilize the neutrons produced from this steady state reactor. Projects undertaken are the development and utilization of the Neutron Radiography (MyNR) and Small Angle Neutron Scattering (MySANS) facilities. Materials research, together with traditional scientific interest in understanding matter at the atomic scale, requires detail knowledge of the arrangement and the dynamics of the atoms or molecules. To enhance Malaysian research and development in this area in particular nanoparticle and nanostructure, MINT has made a dedicated commitment to strengthen the utilizing and maintaining the existing small angle neutron scattering facility to its optimal. This paper describes the recent progress of the MySANS facility and its proposed applications in materials science and technology research and education. Both management and technical strategies are generally explained. In addition a future work plan is also noted. (author)

  16. Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro.

    Science.gov (United States)

    Yoshino, Hironori; Iwabuchi, Miyu; Kazama, Yuka; Furukawa, Maho; Kashiwakura, Ikuo

    2018-04-01

    Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

  17. Vertical Force-deflection Characteristics of a Pair of 56-inch-diameter Aircraft Tires from Static and Drop Tests with and Without Prerotation

    Science.gov (United States)

    Smiley, Robert F; Horne, Walter B

    1957-01-01

    The vertical force-deflection characteristics were experimentally determined for a pair of 56-inch-diameter tires under static and drop-test conditions with and without prerotation. For increasing force, the tires were found to be least stiff for static tests, almost the same as for the static case for prerotation drop tests as long as the tires remain rotating, and appreciably stiffer for drop tests without prerotation.

  18. 49 CFR 231.24 - Box and other house cars with roofs, 16 feet 10 inches or more above top of rail. 1

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars with roofs, 16 feet 10... APPLIANCE STANDARDS § 231.24 Box and other house cars with roofs, 16 feet 10 inches or more above top of.... Same as specified for “Box and Other House Cars.” (2) Dimensions. Same as specified for “Box and Other...

  19. Hydrogen Sulfide Releasing 2-Mercaptoacrylic Acid-Based Derivative Possesses Cytoprotective Activity in a Small Intestine of Rats with Medication-Induced Enteropathy

    Directory of Open Access Journals (Sweden)

    Yulia Sklyarova

    2017-10-01

    Full Text Available Small intestinal injury is known to be one of the most commonly appearing pathologies, resulting in the use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs, antitumor drugs and angiotensin-converting enzyme (ACE inhibitors. The principal objective of this study is to evaluate the action of a novel mercaptoacrylic acid derivative able to release H2S on parameters of NO-synthase system and oxidative stress. Inducing enteropathy, three types of medications were used: indomethacin, an NSAID (35 mg/kg; methotrexate, an antitumor drug (10 mg/kg; and enalapril, an ACE inhibitor (2 mg/kg/day. 2-[(4-chlorophenyl-carbamoyl-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl-acrylic acid (2C3DHTA was introduced based on the background of medication-induced enteropathy (10 mg/kg/day. The survey showed that malondialdehyde (MDA concentration, myeloperoxidase (MPO activity, superoxide dismutase (SOD, catalase, and NO-synthases (NOS were determined in the small intestinal mucosa. The increase in inducible NO-synthase (iNOS activity was due to indomethacin and methotrexate administration. Constitutive NO-synthase (cNOS activity was decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by 2C3DHTA, which returned iNOS activity to its control level and increased cNOS activity. The enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested, activity of MPO was increased. MPO activity and manifestations of oxidative stress were decreased by 2C3DHTA. Effects of 2C3DHTA can be explained by the action of H2S, released from this compound in the gastrointestinal (GI system.

  20. Reduction of lateral forces between the railway vehicle and the track in small-radius curves by means of active elements

    Directory of Open Access Journals (Sweden)

    Michálek T.

    2011-12-01

    Full Text Available This paper deals with a possibility of reduction of guiding forces magnitude in small-radius curves by means of active elements. These guiding forces characterize the lateral force interaction between the rail vehicle and the track and influence the wear of wheels and rails in curves. Their magnitudes are assessed in the framework of vehicle authorization process. However, in case of new railway vehicles with axleload of approximately 20t and more it is problematic to meet the condition of maximum value of the quasistatic guiding force which acts on the outer wheel of the 1st wheelset in small-radius curves. One of the possible ways how to reduce these forces is using the system of active yaw dampers. By means of computer simulations of guiding behaviour of a new electric locomotive, comparison of reached values of the quasistatic guiding forces in case of locomotive equipped with active yaw dampers and without them was performed. Influences of magnitude of force generated by the active yaw dampers, friction coefficient in wheel/rail contact and curve radius were analysed in this work, as well.

  1. ASSESSMENT OF RELEASE RATES FOR RADIONUCLIDES IN ACTIVATED CONCRETE.

    Energy Technology Data Exchange (ETDEWEB)

    SULLIVAN,T.M.

    2003-08-23

    The Maine Yankee (MY) nuclear power plant is undergoing the process of decontamination and decommissioning (D&D). Part of the process requires analyses that demonstrate that any radioactivity that remains after D&D will not cause exposure to radioactive contaminants to exceed acceptable limits. This requires knowledge of the distribution of radionuclides in the remaining material and their potential release mechanisms from the material to the contacting groundwater. In this study the concern involves radionuclide contamination in activated concrete in the ICI Sump below the containment building. Figures 1-3 are schematic representations of the ICI Sump. Figure 2 and 3 contain the relevant dimensions needed for the analysis. The key features of Figures 2 and 3 are the 3/8-inch carbon steel liner that isolates the activated concrete from the pit and the concrete wall, which is between 7 feet and 7 feet 2 inches thick. During operations, a small neutron flux from the reactor activated the carbon steel liner and the concrete outside the liner. Current MY plans call for filling the ICI sump with compacted sand.

  2. Information in small neuronal ensemble activity in the hippocampal CA1 during delayed non-matching to sample performance in rats

    Directory of Open Access Journals (Sweden)

    Takahashi Susumu

    2009-09-01

    Full Text Available Abstract Background The matrix-like organization of the hippocampus, with its several inputs and outputs, has given rise to several theories related to hippocampal information processing. Single-cell electrophysiological studies and studies of lesions or genetically altered animals using recognition memory tasks such as delayed non-matching-to-sample (DNMS tasks support the theories. However, a complete understanding of hippocampal function necessitates knowledge of the encoding of information by multiple neurons in a single trial. The role of neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed quantitatively in this study using multi-neuronal recordings and an artificial neural network classifier as a decoder. Results The activity of small neuronal ensembles (6-18 cells over brief time intervals (2-50 ms contains accurate information specifically related to the matching/non-matching of continuously presented stimuli (stimulus comparison. The accuracy of the combination of neurons pooled over all the ensembles was markedly lower than those of the ensembles over all examined time intervals. Conclusion The results show that the spatiotemporal patterns of spiking activity among cells in the small neuronal ensemble contain much information that is specifically useful for the stimulus comparison. Small neuronal networks in the hippocampal CA1 might therefore act as a comparator during recognition memory tasks.

  3. Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

    International Nuclear Information System (INIS)

    Mi, Shanwei; Xiang, Gang; Yuwen, Daolu; Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang; Su, Yongqian; Shen, Yan; Xu, Qiang

    2016-01-01

    Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

  4. Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1.

    Science.gov (United States)

    Cockburn, Ingrid L; Pesce, Eva-Rachele; Pryzborski, Jude M; Davies-Coleman, Michael T; Clark, Peter G K; Keyzers, Robert A; Stephens, Linda L; Blatch, Gregory L

    2011-05-01

    Plasmodium falciparum heat shock protein 70 (PfHsp70-1) is thought to play an essential role in parasite survival and virulence in the human host, making it a potential antimalarial drug target. A malate dehydrogenase based aggregation suppression assay was adapted for the screening of small molecule modulators of Hsp70. A number of small molecules of natural (marine prenylated alkaloids and terrestrial plant naphthoquinones) and related synthetic origin were screened for their effects on the protein aggregation suppression activity of purified recombinant PfHsp70-1. Five compounds (malonganenone A-C, lapachol and bromo-β-lapachona) were found to inhibit the chaperone activity of PfHsp70-1 in a concentration dependent manner, with lapachol preferentially inhibiting PfHsp70-1 compared to another control Hsp70. Using growth inhibition assays on P. falciparum infected erythrocytes, all of the compounds, except for malonganenone B, were found to inhibit parasite growth with IC(50) values in the low micromolar range. Overall, this study has identified two novel classes of small molecule inhibitors of PfHsp70-1, one representing a new class of antiplasmodial compounds (malonganenones). In addition to demonstrating the validity of PfHsp70-1 as a possible drug target, the compounds reported in this study will be potentially useful as molecular probes for fundamental studies on Hsp70 chaperone function.

  5. Fundulus heteroclitus gonadotropins.5: Small scale chromatographic fractionation of pituitary extracts into components with different steroidogenic activities using homologous bioassays

    Directory of Open Access Journals (Sweden)

    Petrino Teresa R

    2004-03-01

    Full Text Available Abstract Fractionation and characterization of gonadotropins (GtH from Fundulus heteroclitus pituitary extracts were carried out using a biocompatible liquid chromatographic procedure (Pharmacia FPLC system. Chromatographic fractions were monitored for gonadotropic activities (induction of oocyte maturation and steroid production using homologous follicle bioassays in vitro. Size-exclusion chromatography eluted gonadotropic activity in one major protein peak (Mr ~ 30,000. Anion-exchange and hydrophobic-interaction chromatography (HIC yielded two distinct peaks of 17beta-estradiol (E2- and 17alpha-hydroxy,20beta-dihydroprogesterone (DHP-promoting activity with associated oocyte maturation. Two-dimensional chromatography (chromatofocusing followed by HIC resolved pituitary extracts into two active fractions; both induced E2 synthesis, but one was relatively poor in eliciting DHP and testosterone production. Thus, using homologous bioassays, at least two quantitatively different gonadotropic (steroidogenic activities: an E2-promoting gonadotropin (GtH I-like and a DHP-promoting gonadotropin (GtH II-like, which has a lower isoelectric point but greater hydrophobicity than the former, can be distinguished from F. heteroclitus pituitaries by a variety of chromatographic procedures. This study complements previous biochemical and molecular data in F. heteroclitus and substantiates the duality of GtH function in a multiple-spawning teleost.

  6. The determination of plutonium alpha activity in urine, faeces and biological materials

    International Nuclear Information System (INIS)

    Bains, M.E.D.

    1963-07-01

    Methods have been developed for the determination of plutonium alpha activity in urine, faeces and biological materials. The chemical stages involved give practically complete separation of all extraneous material from the plutonium, which is electrodeposited on to a 0.5 inch stainless steel disc to produce a thin high resolution source. The limit of detection is 0.025 μμc/sample (sixteen-hour count) when the sources are counted in a small scintillator counter, but is lowest when counted in a counter which counts particles of energy 5.05-5.25 MeV only, and which therefore discriminates against small quantities of α-active materials introduced with the reagents in the final electrodeposition stage of the process. (Any such alpha activity may readily be identified by alpha pulse height analysis). (author)

  7. A noncognate interaction with anti-receptor antibody-activated helper T cells induces small resting murine B cells to proliferate and to secrete antibody

    DEFF Research Database (Denmark)

    Owens, T

    1988-01-01

    on resting B cells (even in the presence of intact F23.1 antibody), but could induce antibody secretion by anti-Ig-preactivated B cells. Both F23.1+ clones (E9.D4 and 4.35F2) and one F23.1- clone (D2.2) could synergize with supernatants from activated E9.D4 T cells to induce B cell activation. F(ab')2......Culture of small resting allogeneic B cells (of an irrelevant haplotype) with two clones of T helper (Th) cells that were activated by the F23.1 anti-T cell receptor antibody led to the activation of B cells to proliferate and to secrete antibody. Th cell supernatants by themselves had no effect...... fragments of F23.1 induced E9.D4 to activate B cells as efficiently as intact F23.1 and B cell populations that had been incubated with F23.1 were not activated when cultured with E9.D4, although T cells recognized cell-presented F23.1 and were weakly activated. Reduction of the density of F23.1 adsorbed...

  8. 3-Amino-4-aminoximidofurazan derivatives: small molecules possessing antimicrobial and antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa.

    Science.gov (United States)

    Das, M C; Paul, S; Gupta, P; Tribedi, P; Sarkar, S; Manna, D; Bhattacharjee, S

    2016-04-01

    The therapeutic treatment of microbial infections involving biofilm becomes quite challenging because of its increasing antibiotic resistance capacities. Towards this direction, in the present study we have evaluated the antibiofilm property of synthesized 3-amino-4-aminoximidofurazan compounds having polyamine skeleton. These derivatives were synthesized by incorporating furazan and biguanide moieties. Different 3-amino-4-aminoximidofurazan derivatives (PI1-4) were synthesized via protic acid catalysis and subsequently characterized by (1) H NMR and (13) C NMR spectra, recorded at 400 and 100 MHz respectively. We have tested the antimicrobial and antibiofilm activities of these synthetic derivatives (PI1-4) against both Staphylococcus aureus and Pseudomonas aeruginosa. The compounds so tested were also compared with standard antibiotics namely Tobramycin (Ps. aeruginosa) and Azithromycin (Staph. aureus) which were used as a positive control in all experimental sets. All these compounds (PI1-4) exhibited moderate to significant antimicrobial activities against both micro-organisms wherein compound PI3 showed maximum activity. Biofilm inhibition of both micro-organisms was then evaluated by crystal violet and safranin staining, estimation of biofilm total protein and microscopy methods using sub-MIC dose of these compounds. Results showed that all compounds executed anti biofilm activity against both Staph. aureus and Ps. aeruginosa wherein compound PI3 exhibited maximum activity. In relation with microbial biofilm inhibition, we have observed reduction in bacterial motility, proteolytic activity and secreted exo-polysaccharide (EPS) from both Staph. aureus and Ps. aeruginosa when they were grown in presence of these compounds. While addressing the issue of toxicity on host, we have observed that these molecules exhibited minimum level of R.B.C degradation. These findings establish the antibacterial and anti biofilm properties of 3-amino-4-aminoximidofurazan

  9. Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

    DEFF Research Database (Denmark)

    Huelsenbeck, Stefanie C; Roggenkamp, Dennis; May, Martin

    2013-01-01

    B expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1...... without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1....

  10. Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism.

    Science.gov (United States)

    Batra, Raj K; Lin, Ying; Sharma, Sherven; Dohadwala, Mariam; Luo, Jie; Pold, Mehis; Dubinett, Steven M

    2003-02-01

    T lymphocyte survival is critical for the development and maintenance of an effective host antitumor immune response; however, the tumor environment can negatively impact T-cell survival. Lymphocytes exposed to tumor supernatants (TSNs) were evaluated for apoptosis after mitogen stimulation. TSN was observed to significantly enhance phorbol 12-myristate 13-acetate/ionomycin- and anti-CD3-stimulated lymphocyte apoptosis. Enhanced lymphocyte apoptosis was associated with an impairment of nuclear factor kappa B nuclear translocation and diminished I kappa B alpha degradation. In lymphocytes stimulated after exposure to TSNs, cytoplasmic I kappa B alpha persisted as a result of alterations in I kappa B kinase (IKK) activity. Accordingly, although there were no apparent differences in IKK component concentrations, lymphocytes preexposed to TSNs exhibited markedly reduced IKK activity. We conclude that non-small cell lung cancer-derived soluble factors promote apoptosis in activated lymphocytes by an IKK-dependent pathway.

  11. Evaluation of spatial sensitivity of a prompt gamma neutron activation analysis facility for the in vivo determination of nitrogen in small animals

    International Nuclear Information System (INIS)

    Kasviki, K.; Ioannina University; Stamatelatos, I.E.; Kalef-Ezra, J.

    2007-01-01

    We investigated the spatial dependence of the sensitivity of nitrogen measurement with a prompt gamma neutron activation analysis (PGNAA) system for small animals and developed an analysis procedure that permits the reduction of systematic errors due to that dependence. The analysis procedure is based on neutron and photon transport calculations performed using the MCNP code in order to evaluate the sensitivity of the PGNAA facility. The system can be calibrated experimentally using a small number of phantoms of known size and composition. The calculation approach can then be used to predict responses for animal body sizes and shapes relatively to those experimentally determined and to include the effect of tissue inhomogeneities. Our calculations were verified by experimental measurements performed for a set of cylindrical inhomogeneous phantoms. The calculated to experimental ratios observed were within 6%. (author)

  12. SOCIO-ECONOMIC ACTIVITY DETERMINANTS OF SMALL AND MEDIUM-SIZED BUSINESSES ON BORDER AREAS IN WARMIŃSKO-MAZURSKIE VOIVODESHIP

    Directory of Open Access Journals (Sweden)

    Zbigniew Brodziński

    2016-03-01

    Full Text Available The aim of the article was getting to know the factors, determining socio-economic activity of small and mediumsized businesses on border areas in Warmińsko-Mazurskie voivodeship. The study was conducted by telephone interviewing in 2015 amongst randomly selected group of 76 entrepreneurs. The gathered empirical data allowed to determine the areas which need taking action from local authorities to work for socio-economic development of border areas and improve the functionality conditions of the already existing companies. In entrepreneurs’ opinion, an important element in small and medium-sized businesses development is advertisement of the area and introduction of investment incentives. The study shows that endogenous possibilities of entrepreneurship development are limited. The most frequently raised issues were connected with the functioning of companies in their remote location, and also progressing depopulation of the area and low purchasing power of the local community.

  13. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle

    DEFF Research Database (Denmark)

    Bultot, Laurent; Jensen, Thomas Elbenhardt; Lai, Yu-Chiang

    2016-01-01

    AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β...

  14. α-pyrones: Small molecules with versatile structural diversity reflected in multiple pharmacological activities-an update.

    Science.gov (United States)

    Bhat, Zubair Shanib; Rather, Muzafar Ahmad; Maqbool, Mubashir; Lah, Hafiz Ul; Yousuf, Syed Khalid; Ahmad, Zahoor

    2017-07-01

    The investigations in the chemistry and biology of α-pyrone (2-pyrone) are of vital importance as they constitute an essential pharmacophore in many naturally occurring and biologically active synthetic agents. They are a promising class of biorenewable platform chemicals that provide access to an array of chemical products and intermediates. Literature survey reveals that a simple change in the substitution pattern on the 2-pyrone ring system often leads to diverse biological activities. In this review, we present a brief overview of 2-pyrone pharmacophore followed by highlighting their pharmacological properties and potential applicability till date. Particular attention is focused on the distinctive chemotherapeutic activities of 2-pyrones as anti-HIV, anti-TB and anti-cancer agents followed by their potential role against neurodegeneration, hypercholesterolemia, microbial infections, chronic obstructive lung disease, inflammation, antinociception and immunomodulation. Since 2005, when 2-pyrones came in limelight, their detailed pharmacological activities have been well documented. This review has mainly been prepared on the basis of original reports published in recent two decades with an aim to attract the attention of researchers towards this versatile scaffold for future endeavors that may lead to the development of potential drug candidates against above diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. The empirical relationship between the managerial conduct and internal control activities in South African small, medium and micro enterprises

    Directory of Open Access Journals (Sweden)

    Juan-Pierre Bruwer

    2017-07-01

    Aim: Since a system of internal control comprises five inter-related elements, while also taking into consideration that management is ultimately responsible for the internal control in their respective business entities, which is greatly influenced by their managerial conduct, this research study placed focus on determining the relationship which exist between the managerial conduct and the internal control activities evident in South African SMMEs. Setting: This study was conducted in the Cape Metropole, South Africa by obtaining responses from 240 stakeholders of SMMEs: 120 members of management and 120 employees. Methods: In order to achieve the latter, quantitative data were collected through a questionnaire and analysed accordingly through both descriptive statistics and inferential statistics. Results: From the results, a very weak negative statistically significant relationship was identified between the managerial conduct and the internal control activities evident in South African SMMEs. Conclusion: Essentially, management and employees should revisit the internal control activities evident in their respective SMMEs through placing emphasis on those internal control activities which can be built on their control environment.

  16. Optimized circuit design for flexible 8-bit RFID transponders with active layer of ink-jet printed small molecule semiconductors

    NARCIS (Netherlands)

    Kjellander, B.K.C.; Smaal, W.T.T.; Myny, K.; Genoe, J.; Dehaene, W.; Heremans, P.; Gelinck, G.H.

    2013-01-01

    We ink-jet print a blend of 6,13-bis(triisopropyl-silylethynyl)pentacene and polystyrene as the active layer for flexible circuits. The discrete ink-jet printed transistors exhibit a saturation mobility of 0.5 cm2 V -1 s-1. The relative spread in transistor characteristics can be very large. This

  17. Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling

    Science.gov (United States)

    Smith, Jessica L.; Stein, David A.; Shum, David; Fischer, Matthew A.; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A.; Früh, Klaus

    2014-01-01

    ABSTRACT Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other

  18. In vasculitis of small muscular arteries, activation of vessel-infiltrating CD8 T cells seems to be antigen-independent.

    Science.gov (United States)

    Kobayashi, Mikiko; Ogawa, Eisaku; Okuyama, Ryuhei; Kanno, Hiroyuki

    2018-02-01

    The etiology of polyarteritis nodosa (PAN) and localized PAN is still unknown, although a T cell-mediated immune mechanism has been considered. CD8 T cells participate not only in the antigen-dependent adaptive immune system, but also in the antigen-independent innate immune system. Non-antigen-activated CD8 T cells express a unique phenotype: granzyme B (GrB) positive /CD25 negative /programmed death-1 (PD-1) negative. The aims of this study were to assess the participation of T cells, especially innate CD8 T cells, in the development of vasculitis. Twenty-eight consecutive cases of skin biopsy specimens with cutaneous vasculitis of small muscular arteries (CVSMA) were retrieved. The series comprises of 21 cases of cutaneous arteritis, three cases of PAN, and four cases of rheumatoid vasculitis. Cases of antineutrophil cytoplasmic antibody-associated vasculitis were excluded. The phenotypes of infiltrating lymphocytes in vasculitis lesions were evaluated by immunohistochemistry. In most cases of CVSMA, the number of CD8 T cells infiltrating the intima was higher than that of CD4 T cells, and significant numbers of GrB-positive cells, which represent activated CD8 T cells, were observed. However, GrB/CD25-double-positive cells, which correspond to antigen-activated T cells, were very few in a small number of cases. Cells positive for PD-1, which is also expressed on antigen-activated CD8 T cells, were not detected. We conclude that a T cell-mediated immune mechanism, involving cytotoxic CD8 T cells, may play a role in the development of CVSMA. Low expression of CD25 in activated CD8 T cells suggests that activation was antigen-independent.

  19. Insights into the Activity and Deactivation of the Methanol-to-Olefins Process over Different Small-Pore Zeolites As Studied with Operando UV–vis Spectroscopy

    Science.gov (United States)

    2017-01-01

    The nature and evolution of the hydrocarbon pool (HP) species during the Methanol-to-Olefins (MTO) process for three small-pore zeolite catalysts, with a different framework consisting of large cages interconnected by small eight-ring windows (CHA, DDR, and LEV) was studied at reaction temperatures between 350 and 450 °C using a combination of operando UV–vis spectroscopy and online gas chromatography. It was found that small differences in cage size, shape, and pore structure of the zeolite frameworks result in the generation of different hydrocarbon pool species. More specifically, it was found that the large cage of CHA results in the formation of a wide variety of hydrocarbon pool species, mostly alkylated benzenes and naphthalenes. In the DDR cage, 1-methylnaphthalene is preferentially formed, while the small LEV cage generally contains fewer hydrocarbon pool species. The nature and evolution of these hydrocarbon pool species was linked with the stage of the reaction using a multivariate analysis of the operando UV–vis spectra. In the 3-D pore network of CHA, the reaction temperature has only a minor effect on the performance of the MTO catalyst. However, for the 2-D pore networks of DDR and LEV, an increase in the applied reaction temperature resulted in a dramatic increase in catalytic activity. For all zeolites in this study, the role of the hydrocarbon species changes with reaction temperature. This effect is most clear in DDR, in which diamantane and 1-methylnaphthalene are deactivating species at a reaction temperature of 350 °C, whereas at higher temperatures diamantane formation is not observed and 1-methylnaphthalene is an active species. This results in a different amount and nature of coke species in the deactivated catalyst, depending on zeolite framework and reaction temperature. PMID:28603658

  20. Insights into the Activity and Deactivation of the Methanol-to-Olefins Process over Different Small-Pore Zeolites As Studied with Operando UV-vis Spectroscopy.

    Science.gov (United States)

    Goetze, Joris; Meirer, Florian; Yarulina, Irina; Gascon, Jorge; Kapteijn, Freek; Ruiz-Martínez, Javier; Weckhuysen, Bert M

    2017-06-02

    The nature and evolution of the hydrocarbon pool (HP) species during the Methanol-to-Olefins (MTO) process for three small-pore zeolite catalysts, with a different framework consisting of large cages interconnected by small eight-ring windows (CHA, DDR, and LEV) was studied at reaction temperatures between 350 and 450 °C using a combination of operando UV-vis spectroscopy and online gas chromatography. It was found that small differences in cage size, shape, and pore structure of the zeolite frameworks result in the generation of different hydrocarbon pool species. More specifically, it was found that the large cage of CHA results in the formation of a wide variety of hydrocarbon pool species, mostly alkylated benzenes and naphthalenes. In the DDR cage, 1-methylnaphthalene is preferentially formed, while the small LEV cage generally contains fewer hydrocarbon pool species. The nature and evolution of these hydrocarbon pool species was linked with the stage of the reaction using a multivariate analysis of the operando UV-vis spectra. In the 3-D pore network of CHA, the reaction temperature has only a minor effect on the performance of the MTO catalyst. However, for the 2-D pore networks of DDR and LEV, an increase in the applied reaction temperature resulted in a dramatic increase in catalytic activity. For all zeolites in this study, the role of the hydrocarbon species changes with reaction temperature. This effect is most clear in DDR, in which diamantane and 1-methylnaphthalene are deactivating species at a reaction temperature of 350 °C, whereas at higher temperatures diamantane formation is not observed and 1-methylnaphthalene is an active species. This results in a different amount and nature of coke species in the deactivated catalyst, depending on zeolite framework and reaction temperature.

  1. High-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU.

    Science.gov (United States)

    Rani, Chitra; Mehra, Rukmankesh; Sharma, Rashmi; Chib, Reena; Wazir, Priya; Nargotra, Amit; Khan, Inshad Ali

    2015-12-01

    N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N and C terminal domains catalyzes uridyltransferase and acetyltransferase activities, respectively. Final product of GlmU catalyzed reaction, uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), acts as sugar donor providing GlcNAc residues in the synthesis of peptidoglycan and a disaccharide linker (D-N-GlcNAc-1-rhamnose), the key structural components of Mycobacterium tuberculosis (M. tuberculosis) cell wall. In the present study, we have searched new inhibitors against acetyltransferase activity of M. tuberculosis GlmU. A subset of 1607 synthetic compounds, selected through dual approach i.e., in-silico and whole cell screen against 20,000 compounds from ChemBridge library, was further screened using an in-vitro high throughput bioassay to identify inhibitors of acetyltransferase domain of M. tuberculosis GlmU. Four compounds were found to inhibit GlmU enzyme specific to acetyltransferase activity, with IC50 values ranging from 9 to 70 μM. Two compounds (6624116, 5655606) also exhibited whole cell activity against drug susceptible as well as drug resistant M. tuberculosis. These two compounds also exhibited increased anti-TB activity when tested in combination with rifampicin, isoniazid and ethambutol, however 5655606 was cytotoxic to eukaryotic cell line. These results demonstrate that identified chemical scaffolds can be used as inhibitors of M. tuberculosis cell wall enzyme after optimizations for future anti-TB drug development program. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Small Data

    NARCIS (Netherlands)

    S. Pemberton (Steven)

    2014-01-01

    htmlabstractThe term “Open Data” often goes hand in hand with the term “Big Data”, where large data sets get released allowing for analysis, but the Cinderella of the Open Data ball is Small Data, small amounts of data, nonetheless possibly essential, that are too small to be put in some database or

  3. Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells

    International Nuclear Information System (INIS)

    Mao Qiqi; Li Yubing; Zheng Xiangyi; Yang Kai; Shen Huafeng; Qin Jie; Bai Yu; Kong Debo; Jia Xiaolong; Xie Liping

    2008-01-01

    Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21 WAF1/CIP1 (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this inhibitory effect was associated with relocalization of β-catenin from the nucleus to the plasma membrane and decreased β-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer

  4. Synthesis: Small library of hybrid scaffolds of benzothiazole having hydrazone and evaluation of their β-glucuronidase activity.

    Science.gov (United States)

    Taha, Muhammad; Arbin, Mastura; Ahmat, Norizan; Imran, Syahrul; Rahim, Fazal

    2018-04-01

    Due to the great biological importance of β-glucuronidase inhibitors, here in this study, we have synthesized a library of novel benzothiazole derivatives (1-30), characterized by different spectroscopic methods and evaluated for β-glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6, 8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC 50 value ranging in between 16.50 ± 0.26 and 59.45 ± 1.12 when compared with standard d-Saccharic acid 1,4-lactone (48.4 ± 1.25 µM). Except compound 8 and 23 all active analogs showed better potential than the standard. Structure activity relationship has been established. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Neutron activation analysis of trace metals in the hair and organs of small animals treated chronically with Hg and Mn

    International Nuclear Information System (INIS)

    Ohmori, S.; Hashimoto, K.

    1985-01-01

    For the purpose of studying the secretion of exogenous toxic metals into hair, the relation between their concenrations in hair and in organs, and the metal shift Hg or Mn was orally administered to Guinea pigs for protracted periods. The distributions of metals in hair and organs were examined by means of neutron activation analysis. It was found that the administration of Hg at high dose resulted in abnormally high Hg levels in hair from the 2nd dosing week and in organs after 25 weeks of dosing, and in a reduced motor activity after 25 weeks of administration. There occurred metal shifts in hair as well. Administration of Mn at high doses, on the other hand, showed no such biological influences, although a dose-dependent increase of Mn in hair was detected with time. (author)

  6. High Source Levels and Small Active Space of High-Pitched Song in Bowhead Whales (Balaena mysticetus)

    DEFF Research Database (Denmark)

    Tervo, Outi M.; Christoffersen, Mads F.; Simon, Malene

    2012-01-01

    The low frequency, powerful vocalizations of blue and fin whales may potentially be detected by conspecifics across entire ocean basins. In contrast, humpback and bowhead whales produce equally loud, but more complex broadband vocalizations composed of higher frequencies that suffer from higher...... attenuation. Here we evaluate the active space of high-pitched song notes of bowhead whales (Balaena mysticetus) in Western Greenland using measurements of song source levels and ambient noise. Four independent GPS-synchronized hydrophones were deployed through holes in the ice to localize vocalizing bowhead...... whales, estimate source levels and measure ambient noise. The song had a mean apparent source level of 185 ± 2 dB rms re 1µPa and a high mean centroid frequency of 444 ± 48 Hz. Using measured ambient noise levels in the area and Arctic sound spreading models, the estimated active space of these song...

  7. Structure?Activity Relationship Studies of Indole-Based Compounds as Small Molecule HIV-1 Fusion Inhibitors Targeting Glycoprotein 41

    OpenAIRE

    Zhou, Guangyan; Sofiyev, Vladimir; Kaur, Hardeep; Snyder, Beth A.; Mankowski, Marie K.; Hogan, Priscilla A.; Ptak, Roger G.; Gochin, Miriam

    2014-01-01

    We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure?activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and molecular properties. Thirty new compounds were evaluated in binding, cell?cell fusion, and viral replication assays. Below a 1 ?M threshold, correlation between binding and biologi...

  8. Growth hormone activates hepatic and cerebral cholesterol metabolism in small-for-gestational age children without catch-up growth.

    Science.gov (United States)

    Hirayama, Satoshi; Nagasaka, Hironori; Nakagawa, Saori; Takuwa, Mayuko; Nakacho, Mariko; Yorifuji, Tohru; Kondou, Hiroki; Tsukahara, Hirokazu; Morioka, Ichiro; Ishida, Akihito; Yamato, Susumu; Miida, Takashi

    Growth hormone (GH) replacement therapy improves hypercholesterolemia in patients with GH deficiency, suggesting that GH modulates cholesterol metabolism. We examined GH effects on lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism in small-for-gestational age (SGA) children without catch-up growth. This study examined SGA children without catch-up growth (n = 22) and healthy children (controls, n = 11). Based on parents' choice, 11 SGA children received GH at 0.23 to 0.25 mg/kg/d for 6 months, and at 0.34 to 0.36 mg/kg/d for the subsequent 6 months (GH (+) group). The other SGA children received no GH (GH (-) group, n = 11). We ascertained baseline and posttreatment lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism. Baseline lipid profiles of SGA children and controls were similar. Serum 24S-hydroxycholesterol (marker for cerebral cholesterol metabolism) concentration was 19% lower in SGA children than in controls (P children without catch-up growth. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  9. Activators and Effectors of the Small G Protein Arf1 in Regulation of Golgi Dynamics During the Cell Division Cycle.

    Science.gov (United States)

    Jackson, Catherine L

    2018-01-01

    When eukaryotic cells divide, they must faithfully segregate not only the genetic material but also their membrane-bound organelles into each daughter cell. To assure correct partitioning of cellular contents, cells use regulatory mechanisms to verify that each stage of cell division has been correctly accomplished before proceeding to the next step. A great deal is known about mechanisms that regulate chromosome segregation during cell division, but we know much less about the mechanisms by which cellular organelles are partitioned, and how these processes are coordinated. The Golgi apparatus, the central sorting and modification station of the secretory pathway, disassembles during mitosis, a process that depends on Arf1 and its regulators and effectors. Prior to total disassembly, the Golgi ribbon in mammalian cells, composed of alternating cisternal stacks and tubular networks, undergoes fission of the tubular networks to produce individual stacks. Failure to carry out this unlinking leads to cell division arrest at late G2 prior to entering mitosis, an arrest that can be relieved by inhibition of Arf1 activation. The level of active Arf1-GTP drops during mitosis, due to inactivation of the major Arf1 guanine nucleotide exchange factor at the Golgi, GBF1. Expression of constitutively active Arf1 prevents Golgi disassembly, and leads to defects in chromosome segregation and cytokinesis. In this review, we describe recent advances in understanding the functions of Arf1 regulators and effectors in the crosstalk between Golgi structure and cell cycle regulation.

  10. Effects of dietary supplementation of Chinese medicinal herbs on polymorphonuclear neutrophil immune activity and small intestinal morphology in weanling pigs.

    Science.gov (United States)

    Huang, C W; Lee, T T; Shih, Y C; Yu, B

    2012-04-01

    The purpose of this study was to evaluate the effects of dietary Chinese medicinal herbs (CMH) supplementation composed of Panax ginseng, Dioscoreaceae opposite, Atractylodes macrocephala, Glycyrrhiza uralensis, Ziziphus jujube and Platycodon grandiflorum, on the performance, intestinal tract morphology and immune activity in weanling pigs. Two hundred and forty weaned pigs were assigned randomly to four dietary groups including the negative control (basal diet), 0.1% CMH, 0.3% CMH and 0.114% antibiotic (Chlortetracycline calcium Complex, Sulfathiazole and Procaine Penicillin G) supplementation groups for a 28-day feeding trial. Results indicated that both CMH supplementation groups had a better gain and feed/gain than control group (CT) during the first 2 weeks of the experimental period. The 0.3% CMH had a significant decrease in the diarrhoea score in first 10 days of experimental period when compared with other groups. The CMH supplementation groups had a higher villous height, increased lactobacilli counts in digesta of ileum and decreased coliform counts in colon compared with CT. The immune activities of polymorphonuclear leucocytes (PMNs), including the respiratory burst and Salmonella-killing ability, were significantly enhanced in CMH supplementation groups at day 7 of experiment period. The CMH and antibiotic supplementations increased the nutrient digestibility such as dietary dry matter, crude protein and gross energy in weanling pigs. In conclusion, the dietary CMH supplementation improved intestinal morphology and immune activities of PMNs, thus giving rise to nutrient digestibility and reduce diarrhoea frequency in weanling pigs. © 2011 Blackwell Verlag GmbH.

  11. High source levels and small active space of high-pitched song in bowhead whales (Balaena mysticetus.

    Directory of Open Access Journals (Sweden)

    Outi M Tervo

    Full Text Available The low-frequency, powerful vocalizations of blue and fin whales may potentially be detected by conspecifics across entire ocean basins. In contrast, humpback and bowhead whales produce equally powerful, but more complex broadband vocalizations composed of higher frequencies that suffer from higher attenuation. Here we evaluate the active space of high frequency song notes of bowhead whales (Balaena mysticetus in Western Greenland using measurements of song source levels and ambient noise. Four independent, GPS-synchronized hydrophones were deployed through holes in the ice to localize vocalizing bowhead whales, estimate source levels and measure ambient noise. The song had a mean apparent source level of 185±2 dB rms re 1 µPa @ 1 m and a high mean centroid frequency of 444±48 Hz. Using measured ambient noise levels in the area and Arctic sound spreading models, the estimated active space of these song notes is between 40 and 130 km, an order of magnitude smaller than the estimated active space of low frequency blue and fin whale songs produced at similar source levels and for similar noise conditions. We propose that bowhead whales spatially compensate for their smaller communication range through mating aggregations that co-evolved with broadband song to form a complex and dynamic acoustically mediated sexual display.

  12. Activators and Effectors of the Small G Protein Arf1 in Regulation of Golgi Dynamics During the Cell Division Cycle

    Directory of Open Access Journals (Sweden)

    Catherine L. Jackson

    2018-03-01

    Full Text Available When eukaryotic cells divide, they must faithfully segregate not only the genetic material but also their membrane-bound organelles into each daughter cell. To assure correct partitioning of cellular contents, cells use regulatory mechanisms to verify that each stage of cell division has been correctly accomplished before proceeding to the next step. A great deal is known about mechanisms that regulate chromosome segregation during cell division, but we know much less about the mechanisms by which cellular organelles are partitioned, and how these processes are coordinated. The Golgi apparatus, the central sorting and modification station of the secretory pathway, disassembles during mitosis, a process that depends on Arf1 and its regulators and effectors. Prior to total disassembly, the Golgi ribbon in mammalian cells, composed of alternating cisternal stacks and tubular networks, undergoes fission of the tubular networks to produce individual stacks. Failure to carry out this unlinking leads to cell division arrest at late G2 prior to entering mitosis, an arrest that can be relieved by inhibition of Arf1 activation. The level of active Arf1-GTP drops during mitosis, due to inactivation of the major Arf1 guanine nucleotide exchange factor at the Golgi, GBF1. Expression of constitutively active Arf1 prevents Golgi disassembly, and leads to defects in chromosome segregation and cytokinesis. In this review, we describe recent advances in understanding the functions of Arf1 regulators and effectors in the crosstalk between Golgi structure and cell cycle regulation.

  13. Characterization of a small molecule inhibitor of melanogenesis that inhibits tyrosinase activity and scavenges nitric oxide (NO).

    Science.gov (United States)

    Chung, Ki Wung; Jeong, Hyoung Oh; Jang, Eun Ji; Choi, Yeon Ja; Kim, Dae Hyun; Kim, So Ra; Lee, Kyung Jin; Lee, Hye Jin; Chun, Pusoon; Byun, Youngjoo; Moon, Hyung Ryong; Chung, Hae Young

    2013-10-01

    Excessive melanin production and accumulation are characteristics of a large number of skin diseases, including melasma, and post-inflammatory hyperpigmentation. During our on-going search for new agents with an inhibitory effect on tyrosinase, we synthesized a new type of tyrosinase inhibitor, 4-(thiazolidin-2-yl)benzene-1,2-diol (MHY-794), which directly inhibits mushroom tyrosinase. The inhibitory effect of MHY-794 on tyrosinase activity and nitric oxide (NO) scavenging activity was evaluated in cell free system. Additional experiments were performed using B16F10 melanoma cells to demonstrate the effects of MHY-794 in vitro. HRM2 hairless mice were used to evaluate anti-melanogenic effects of MHY-794 in vivo. MHY-794 effectively inhibited mushroom tyrosinase activity in cell free system. In silico docking simulation also supported the inhibitory effects of MHY-794 on mushroom tyrosinase. MHY-794 also proved to be effective at scavenging nitric oxide (NO), which serves as an important modulator in the melanogenesis signaling pathway. In addition, MHY-794 effectively inhibited SNP (NO donor)-induced melanogenesis by directly inhibiting tyrosinase and diminishing NO-mediated melanogenesis signaling in B16 melanoma cells. The anti-melanogenic effects of MHY-794 were further confirmed in HRM2 hairless mice. Ultraviolet light (UV) significantly up-regulated NO-mediated melanogenesis signaling in HRM2 hairless mice, but MHY-794 effectively inhibited both melanogenesis and diminished UV-induced NO-signaling. Our results indicate that MHY-794 is highly effective at inhibiting NO-mediated melanogenesis in vitro and in vivo by direct NO scavenging and directly inhibiting tyrosinase activity, and suggest that MHY-794 be considered a new developmental candidate for the treatment of hyper-pigmentation disorders. MHY-794, which showed great efficacy on NO-mediated melanogenesis by direct NO scavenging as well as direct inhibition of tyrosinase catalytic activity, might be

  14. Determination of trace elements in small water samples by total reflexion X-ray fluorescence (TXRF) and by neutron activation analysis (NAA)

    Energy Technology Data Exchange (ETDEWEB)

    Lieser, K.H. (Fachbereich Chemie, Eduard Zintl-Inst., Technische Hochschule Darmstadt (Germany)); Flakowski, M. (Fachbereich Chemie, Eduard Zintl-Inst., Technische Hochschule Darmstadt (Germany)); Hoffmann, P. (Fachbereich Chemie, Eduard Zintl-Inst., Technische Hochschule Darmstadt (Germany))

    1994-09-01

    The problems encountered in the determination of trace elements in small sample volumes of the order of 1 to 10 [mu]l (e.g. in droplets of water) are discussed. Total reflexion X-ray fluorescence (TXRF) and neutron activation analysis (NAA) are applied for the determination of Na, Mg, K, Ca, Mn, Fe, Co, and Cu in concentrations of 0.01 to 10 mg/L in 1 to 10 [mu]L of water. The applied methods are described, the results are discussed and the advantages of TXRF are brought forward. (orig.)

  15. Investigating mutation-specific biological activities of small molecules using quantitative structure-activity relationship for epidermal growth factor receptor in cancer.

    Science.gov (United States)

    Anoosha, P; Sakthivel, R; Gromiha, M Michael

    2017-12-01

    Epidermal Growth Factor Receptor (EGFR) is a potential drug target in cancer therapy. Missense mutations play major roles in influencing the protein function, leading to abnormal cell proliferation and tumorigenesis. A number of EGFR inhibitor molecules targeting ATP binding domain were developed for the past two decades. Unfortunately, they become inactive due to resistance caused by new mutations in patients, and previous studies have also reported noticeable differences in inhibitor binding to distinct known driver mutants as well. Hence, there is a high demand for identification of EGFR mutation-specific inhibitors. In our present study, we derived a set of anti-cancer compounds with biological activities against eight typical EGFR known driver mutations and developed quantitative structure-activity relationship (QSAR) models for each separately. The compounds are grouped based on their functional scaffolds, which enhanced the correlation between compound features and respective biological activities. The models for different mutants performed well with a correlation coefficient, (r) in the range of 0.72-0.91 on jack-knife test. Further, we analyzed the selected features in different models and observed that hydrogen bond and aromaticity-related features play important roles in predicting the biological activity of a compound. This analysis is complimented with docking studies, which showed the binding patterns and interactions of ligands with EGFR mutants that could influence their activities. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Anti-tumor activity of a novel HS-mimetic-vascular endothelial growth factor binding small molecule.

    Directory of Open Access Journals (Sweden)

    Kazuyuki Sugahara

    Full Text Available The angiogenic process is controlled by variety of factors of which the vascular endothelial growth factor (VEGF pathway plays a major role. A series of heparan sulfate mimetic small molecules targeting VEGF/VEGFR pathway has been synthesized. Among them, compound 8 (2-butyl-5-chloro-3-(4-nitro-benzyl-3H-imidazole-4-carbaldehyde was identified as a significant binding molecule for the heparin-binding domain of VEGF, determined by high-throughput-surface plasmon resonance assay. The data predicted strong binding of compound 8 with VEGF which may prevent the binding of VEGF to its receptor. We compared the structure of compound 8 with heparan sulfate (HS, which have in common the functional ionic groups such as sulfate, nitro and carbaldehyde that can be located in similar positions of the disaccharide structure of HS. Molecular docking studies predicted that compound 8 binds at the heparin binding domain of VEGF through strong hydrogen bonding with Lys-30 and Gln-20 amino acid residues, and consistent with the prediction, compound 8 inhibited binding of VEGF to immobilized heparin. In vitro studies showed that compound 8 inhibits the VEGF-induced proliferation migration and tube formation of mouse vascular endothelial cells, and finally the invasion of a murine osteosarcoma cell line (LM8G7 which secrets high levels of VEGF. In vivo, these effects produce significant decrease of tumor burden in an experimental model of liver metastasis. Collectively, these data indicate that compound 8 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of endothelial cell migration and angiogenesis mediated by VEGF. In conclusion, compound 8 may normalize the tumor vasculature and microenvironment in tumors probably by inhibiting the binding of VEGF to its receptor.

  17. Borreliacidal activity of Borrelia metal transporter A (BmtA binding small molecules by manganese transport inhibition

    Directory of Open Access Journals (Sweden)

    Wagh D

    2015-02-01

    Full Text Available Dhananjay Wagh,* Venkata Raveendra Pothineni,* Mohammed Inayathullah, Song Liu, Kwang-Min Kim, Jayakumar Rajadas Biomaterials and Advanced Drug Delivery Laboratory, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA, USA *These authors contributed equally to this work  Abstract: Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection. We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA, a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then, tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays. Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 µg/mL (250 µM. Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall. Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia.  Keywords: Lyme disease, BmtA, Borrelia burgdorferi, desloratadine, Bac Titer-Glo assay

  18. Protein kinase CK2 is coassembled with small conductance ca(2+)-activated k(+) channels and regulates channel gating

    DEFF Research Database (Denmark)

    Bildl, Wolfgang; Strassmaier, Tim; Thurm, Henrike

    2004-01-01

    and serves as the Ca2+ sensor. Here we show that, in addition, the cytoplasmic N and C termini of the channel protein form a polyprotein complex with the catalytic and regulatory subunits of protein kinase CK2 and protein phosphatase 2A. Within this complex, CK2 phosphorylates calmodulin at threonine 80......, reducing by 5-fold the apparent Ca2+ sensitivity and accelerating channel deactivation. The results show that native SK channels are polyprotein complexes and demonstrate that the balance between kinase and phosphatase activities within the protein complex shapes the hyperpolarizing response mediated by SK...

  19. Antidiarrheal activity of wood creosote: inhibition of muscle contraction and enterotoxin-induced fluid secretion in rabbit small intestine.

    Science.gov (United States)

    Ogata, N; Shibata, T

    2001-01-01

    Wood creosote has long been used as an antidiarrheal agent, but its mechanism of action is not well understood. To elucidate the mechanism of its antidiarrheal activity, we have addressed questions whether it inhibits fluid secretion induced by Escherichia coli heat-stable enterotoxin (STa) in rabbit jejunum in vivo, and whether it inhibits muscle contraction of isolated rabbit ileum ex vivo. Wood creosote (10-100 mg/l) instilled in a ligated loop of jejunum inhibited STa-induced fluid secretion (p creosote is attributable to its antisecretory and antimotility effects. Copyright 2001 S. Karger AG, Basel

  20. Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway.

    Science.gov (United States)

    Mi, Shanwei; Xiang, Gang; Yuwen, Daolu; Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang; Su, Yongqian; Shen, Yan; Xu, Qiang

    2016-11-01

    Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Synthesis, pharmacological characterization, and structure-activity relationship studies of small molecular agonists for the orphan GPR88 receptor.

    Science.gov (United States)

    Jin, Chunyang; Decker, Ann M; Huang, Xi-Ping; Gilmour, Brian P; Blough, Bruce E; Roth, Bryan L; Hu, Yang; Gill, Joseph B; Zhang, X Peter

    2014-07-16

    GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorders. The signal transduction pathway and receptor functions of GPR88, however, are still largely unknown due to the lack of endogenous and synthetic ligands. In this paper, we report the synthesis of a GPR88 agonist 2-PCCA and its pure diastereomers, which were functionally characterized in both transiently and stably expressing GPR88 HEK293 cells. 2-PCCA inhibited isoproterenol-stimulated cAMP accumulation in a concentration-dependent manner in cells expressing GPR88 but not in the control cells, suggesting that the observed cAMP inhibition is mediated through GPR88 and that GPR88 is coupled to Gαi. 2-PCCA did not induce calcium mobilization in GPR88 cells, indicating no Gαq-mediated response. A structure-activity relationship (SAR) study of 2-PCCA was also conducted to explore the key structural features for GPR88 agonist activity.

  2. Effect of thyme oil on small intestine integrity and antioxidant status, phagocytic activity and gastrointestinal microbiota in rabbits.

    Science.gov (United States)

    Placha, Iveta; Chrastinova, Lubica; Laukova, Andrea; Cobanova, Klaudia; Takacova, Jana; Strompfova, Viola; Chrenkova, Maria; Formelova, Zuzana; Faix, Stefan

    2013-06-01

    The effects of 0.5 g thyme oil per kg dry matter (DM) of diet on duodenal tissue integrity, antioxidant status, phagocytic activity and selected microbiota in the caecum and faeces of rabbits were studied. Twenty-four rabbits were divided into two groups and were fed a commercial granulated diet for growing rabbits (CD) with access to water ad libitum. The first group was fed the CD, while to the CD of the second group thyme oil was added. Intestinal integrity was tested by measuring the transepithelial electrical resistance (TEER). Thyme oil significantly increased the value of total antioxidant status (TAS) in the blood plasma and glutathione peroxidase (GPx) activity in the liver, and it decreased malondialdehyde (MDA) concentration in the duodenal tissue. Thyme oil resulted in strengthened intestinal integrity, as the essential oil supplementation significantly increased TEER values in the experiment. The faecal microbiota of rabbits was almost completely balanced in both groups, and only a slight decrease was found in the microbial population at day 42 of the trial. In both groups, the bacterial counts were generally lower in the caecum than in the faecal samples. In conclusion, dietary supplementation with 0.5 g/kg DM thyme oil may improve intestinal integrity, and it may have an antioxidant effect. A tendency was also found for thyme oil to stimulate the abundance of some microbes beneficial in the rabbit gut.

  3. Assessment of dynamic contrast enhancement of the small bowel in active Crohn's disease using 3D MR enterography

    Energy Technology Data Exchange (ETDEWEB)

    Knuesel, Patrick R.; Kubik, Rahel A.; Crook, David W. [Department of Radiology, Kantonsspital Baden, CH-5404 Baden (Switzerland); Eigenmann, Franz [Department of Internal Medicine, Kantonsspital Baden, CH-5404 Baden (Switzerland); Froehlich, Johannes M. [Department of Radiology, Kantonsspital Baden, CH-5404 Baden (Switzerland)], E-mail: froehlich@guerbet.ch

    2010-03-15

    Purpose: To retrospectively compare the dynamic contrast enhancement of the small bowel segments with and without active Crohn's disease at 3D MR enterography (MRE). Materials and methods: Thirteen patients (five men, eight women; mean age 41.2 years; range 29-56) were imaged on a 1.5-T MR scanner (Sonata, Siemens Medical) with standard MR sequences after having ingested 1000 ml of a 3% mannitol solution. Subsequently, high resolution 3D gradient-echo (volumetric interpolated breath-hold examination = VIBE) data sets were obtained pre-contrast and 20-40 s, 60-80 s, and 120-140 s after i.v. Gd-DOTA administration (0.2 mmol/kg). Signal enhancement was measured on single slices both in normal and histologically confirmed (12/13) inflamed small bowel wall segments as well as in the aorta, the psoas muscle, and the background to calculate signal-to-noise (SNR) and contrast-to-noise ratios (CNR). Results: Small bowel wall enhancement was significantly higher (p < 0.05) in inflamed compared to normal segments at 20-40 s (SNR inflamed: 58.7 {+-} 33.8 vs normal: 36.0 {+-} 19.8; p = 0.048; CNR inflamed: 34.8 {+-} 23.4 vs normal: 16.3 {+-} 11.2; p = 0.017) and at 60-80 s (SNR: 60.3 {+-} 25.1 vs 41.9 {+-} 20.0; p = 0.049; CNR: 34.9 {+-} 15.1 vs 19.3 {+-} 13.2; p = 0.01) after i.v. contrast administration, respectively. Even at 120-140 s CNR was still increased in inflamed segments (33.7 {+-} 16.0 vs 18.1 {+-} 13.2; p = 0.04), while differences in SNR did not attain statistical significance (63.0 {+-} 26.2 vs 45.3 {+-} 23.3; p = 0.15). Conclusion: In active Crohn's disease, histologically confirmed inflamed small bowel wall segments demonstrate a significantly increased early uptake of gadolinium on 3D VIBE sequences compared to normal small bowel segments.

  4. Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation

    Science.gov (United States)

    Yang, Hung-Chih; Xing, Sifei; Shan, Liang; O’Connell, Karen; Dinoso, Jason; Shen, Anding; Zhou, Yan; Shrum, Cynthia K.; Han, Yefei; Liu, Jun O.; Zhang, Hao; Margolick, Joseph B.; Siliciano, Robert F.

    2009-01-01

    The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ T cells were transduced with the prosurvival molecule Bcl-2, and the resulting cells were shown to recapitulate the quiescent state of resting CD4+ T cells in vivo. Using this model system, we screened small-molecule libraries and identified a compound that reactivated latent HIV-1 without inducing global T cell activation, 5-hydroxynaphthalene-1,4-dione (5HN). Unlike previously described latency-reversing agents, 5HN activated latent HIV-1 through ROS and NF-κB without affecting nuclear factor of activated T cells (NFAT) and PKC, demonstrating that TCR pathways can be dissected and utilized to purge latent virus. Our study expands the number of classes of latency-reversing therapeutics and demonstrates the utility of this in vitro model for finding strategies to eradicate HIV-1 infection. PMID:19805909

  5. The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616.

    Science.gov (United States)

    Sato, Takuya; Nonoyama, Shouta; Kimura, Akane; Nagata, Yuji; Ohtsubo, Yoshiyuki; Tsuda, Masataka

    2017-08-15

    Iron and heme play very important roles in various metabolic functions in bacteria, and their intracellular homeostasis is maintained because high concentrations of free forms of these molecules greatly facilitate the Fenton reaction-mediated production of large amounts of reactive oxygen species that severely damage various biomolecules. The ferric uptake regulator (Fur) from Burkholderia multivorans ATCC 17616 is an iron-responsive global transcriptional regulator, and its fur deletant exhibits pleiotropic phenotypes. In this study, we found that the phenotypes of the fur deletant were suppressed by an additional mutation in hemP The transcription of hemP was negatively regulated by Fur under iron-replete conditions and was constitutive in the fur deletant. Growth of a hemP deletant was severely impaired in a medium containing hemin as the sole iron source, demonstrating the important role of HemP in hemin utilization. HemP was required as a transcriptional activator that specifically binds the promoter-containing region upstream of a Fur-repressive hmuRSTUV operon, which encodes the proteins for hemin uptake. A hmuR deletant was still able to grow using hemin as the sole iron source, albeit at a rate clearly lower than that of the wild-type strain. These results strongly suggested (i) the involvement of HmuR in hemin uptake and (ii) the presence in ATCC 17616 of at least part of other unknown hemin uptake systems whose expression depends on the HemP function. Our in vitro analysis also indicated high-affinity binding of HemP to hemin, and such a property might modulate transcriptional activation of the hmu operon. IMPORTANCE Although the hmuRSTUV genes for the utilization of hemin as a sole iron source have been identified in a few Burkholderia strains, the regulatory expression of these genes has remained unknown. Our analysis in this study using B. multivorans ATCC 17616 showed that its HemP protein is required for expression of the hmuRSTUV operon, and the

  6. Comparison of Small-Scale Actively and Passively Q-Switched Eye-Safe Intracavity Optical Parametric Oscillators at 1.57 μm

    International Nuclear Information System (INIS)

    Miao Jie-Guang; Pan Yu-Zhai; Qu Shi-Liang

    2012-01-01

    The first experimental comparison between the actively and passively Q-switched intracavity optical parametric oscillators (IOPOs) at 1.57 μm driven by a small-scale diode-pumped Nd:YVO 4 laser are thoroughly presented. It is found that the performances of the two types of IOPOs are complementary. The actively Q-switched IOPO features a shorter pulse duration, a higher peak power, and a superior power and pulse stability. However, in terms of compactness, operation threshold and conversion efficiency, passively Q-switched IOPOs are more attractive. It is further indicated that the passively Q-switched IOPO at 1.57μm is a promising and cost-effective eye-safe laser source, especially at the low and moderate output levels. In addition, instructional improvement measures for the two types of IOPOs are also summarized. (fundamental areas of phenomenology(including applications))

  7. Discovery of quinoline small molecules with potent dispersal activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a scaffold hopping strategy.

    Science.gov (United States)

    Abouelhassan, Yasmeen; Garrison, Aaron T; Burch, Gena M; Wong, Wilson; Norwood, Verrill M; Huigens, Robert W

    2014-11-01

    Staphylococcus aureus and Staphylococcus epidermidis are recognized as the most frequent cause of biofilm-associated nosocomial and indwelling medical device infections. Biofilm-associated infections are known to be highly resistant to our current arsenal of clinically used antibiotics and antibacterial agents. To exacerbate this problem, no therapeutic option exists that targets biofilm-dependent machinery critical to Staphylococcal biofilm formation and maintenance. Here, we describe the discovery of a series of quinoline small molecules that demonstrate potent biofilm dispersal activity against methicillin-resistant S. aureus and S. epidermidis using a scaffold hopping strategy. This interesting class of quinolines also has select synthetic analogues that demonstrate potent antibacterial activity and biofilm inhibition against S. aureus and S. epidermidis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Identification and X-ray co-crystal structure of a small-molecule activator of LFA-1-ICAM-1 binding.

    Science.gov (United States)

    Hintersteiner, Martin; Kallen, Jörg; Schmied, Mario; Graf, Christine; Jung, Thomas; Mudd, Gemma; Shave, Steven; Gstach, Hubert; Auer, Manfred

    2014-04-22

    Stabilization of protein-protein interactions by small molecules is a concept with few examples reported to date. Herein we describe the identification and X-ray co-crystal structure determination of IBE-667, an ICAM-1 binding enhancer for LFA-1. IBE-667 was designed based on the SAR information obtained from an on-bead screen of tagged one-bead one-compound combinatorial libraries by confocal nanoscanning and bead picking (CONA). Cellular assays demonstrate the activity of IBE-667 in promoting the binding of LFA-1 on activated immune cells to ICAM-1. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  9. Effect of Boards in Small-Sided Street Soccer Games on Movement Pattern and Physiological Response in Recreationally Active Young Men

    DEFF Research Database (Denmark)

    Randers, Morten B; Brix, Jonathan; Hagman, Marie

    2018-01-01

    after WB than after WOB (7.1±1.0 vs. 5.5±1.2, p conclusion, intensity was sufficiently high in both game formats to expect short- and long-term health improvements as a result of regular participation. Boards affected movement pattern and physiological demands, producing higher......The present study investigated whether street soccer might be proposed as an alternative to recreational small-sided games on grass as a health-enhancing activity, and specifically the effects of the boards surrounding the pitch. Eleven recreationally active young males (28.4±4.2 (±SD) yrs, 19...... used to evaluate exercise intensity and physiological strain. Total number of accelerations (19%) and Player Load (18%) were higher (p whereas total distance covered (12%), high-speed running (59%) and peak speed (11%) were lower (p Moreover, HRmean...

  10. The Small Helm Project: an academic activity addressing international corruption for undergraduate civil engineering and construction management students.

    Science.gov (United States)

    Benzley, Steven E

    2006-04-01

    This paper presents an academic project that addresses the issue of international corruption in the engineering and construction industry, in a manner that effectively incorporates several learning experiences. The major objectives of the project are to provide the students a learning activity that will 1) make a meaningful contribution within the disciplines being studied; 2) teach by experience a significant principle that can be valuable in numerous situations during an individual's career, and 3) engage the minds, experiences, and enthusiasm of the participants in a real ethical challenge that is prevalent in all of their chosen professional fields. The paper describes the full details of the project, the actual implementation of it during Winter Semester 2005, the experiences gained during the initial trial, and the modifications and improvements incorporated for future implementation.

  11. The ketone body metabolite β-hydroxybutyrate induces an antidepression-associated ramification of microglia via HDACs inhibition-triggered Akt-small RhoGTPase activation.

    Science.gov (United States)

    Huang, Chao; Wang, Peng; Xu, Xing; Zhang, Yaru; Gong, Yu; Hu, Wenfeng; Gao, Minhui; Wu, Yue; Ling, Yong; Zhao, Xi; Qin, Yibin; Yang, Rongrong; Zhang, Wei

    2018-02-01

    Direct induction of macrophage ramification has been shown to promote an alternative (M2) polarization, suggesting that the ramified morphology may determine the function of immune cells. The ketone body metabolite β-hydroxybutyrate (BHB) elevated in conditions including fasting and low-carbohydrate ketogenic diet (KD) can reduce neuroinflammation. However, how exactly BHB impacts microglia remains unclear. We report that BHB as well as its producing stimuli fasting and KD induced obvious ramifications of murine microglia in basal and inflammatory conditions in a reversible manner, and these ramifications were accompanied with microglial profile toward M2 polarization and phagocytosis. The protein kinase B (Akt)-small RhoGTPase axis was found to mediate the effect of BHB on microglial shape change, as (i) BHB activated the microglial small RhoGTPase (Rac1, Cdc42) and Akt; (ii) Akt and Rac1-Cdc42 inhibition abolished the pro-ramification effect of BHB; (iii) Akt inhibition prevented the activation of Rac1-Cdc42 induced by BHB treatment. Incubation of microglia with other classical histone deacetylases (HDACs) inhibitors, but not G protein-coupled receptor 109a (GPR109a) activators, also induced microglial ramification and Akt activation, suggesting that the BHB-induced ramification of microglia may be triggered by HDACs inhibition. Functionally, Akt inhibition was found to abrogate the effects of BHB on microglial polarization and phagocytosis. In neuroinflammatory models induced by lipopolysaccharide (LPS) or chronic unpredictable stress (CUS), BHB prevented the microglial process retraction and depressive-like behaviors, and these effects were abolished by Akt inhibition. Our findings for the first time showed that BHB exerts anti-inflammatory actions via promotion of microglial ramification. © 2017 Wiley Periodicals, Inc.

  12. Small Data

    OpenAIRE

    Pemberton, Steven

    2014-01-01

    htmlabstractThe term “Open Data” often goes hand in hand with the term “Big Data”, where large data sets get released allowing for analysis, but the Cinderella of the Open Data ball is Small Data, small amounts of data, nonetheless possibly essential, that are too small to be put in some database or online dataset to be put to use. RDFa is a technology that allows Cinderella to go to the ball.

  13. Involvement of MAPKs and PLC Pathways in Modulation of Pacemaking Activity by So-Cheong-Ryong-Tang in Interstitial Cells of Cajal from Murine Small Intestine

    Directory of Open Access Journals (Sweden)

    Min Woo Hwang

    2013-01-01

    Full Text Available Purpose. Interstitial cells of Cajal (ICCs are the pacemaker cells that generate slow waves in the gastrointestinal (GI tract. We have aimed to investigate the effects of Socheongryong-Tang (SCRT in ICCs from mouse’s small intestine. Methods. The whole-cell patch-clamp configuration was used to record membrane potentials from cultured ICCs. Intracellular Ca2+ ([Ca2+]i increase was studied in cultured ICCs using fura-2 AM. Results. ICCs generated pacemaker potentials in mouse’s small intestine. SCRT produced membrane depolarization in current clamp mode. Y25130 (5-HT3 receptor antagonist and RS39604 (5-HT4 receptor antagonist blocked SCRT-induced membrane depolarizations, whereas SB269970 (5-HT7 receptor antagonist did not. When GDP-β-S (1 mM was in the pipette solution, SCRT did not induce the membrane depolarizations. [Ca2+]i analysis showed that SCRT increased [Ca2+]i. In the presence of PD98059 (p42/44 MAPK inhibitor, SCRT did not produce membrane depolarizations. In addition, SB203580 (p38 MAPK inhibitor and JNK inhibitors blocked the depolarizations by SCRT in pacemaker potentials. Furthermore, the membrane depolarizations by SCRT were not inhibited by U-73122, an active phospholipase C (PLC inhibitor, but by U-73343, an inactive PLC inhibitor. Conclusion. These results suggest that SCRT might affect GI motility by the modulation of pacemaker activity through MAPKs and PLC pathways in the ICCs.

  14. Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

    Directory of Open Access Journals (Sweden)

    Meng Cui

    2014-10-01

    Full Text Available The small- and intermediate-conductance Ca2+-activated potassium (SK/IK channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca2+-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca2+ sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators. © 2014 S. Karger AG, Basel

  15. Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain.

    Science.gov (United States)

    Moutaoufik, Mohamed Taha; Morrow, Geneviève; Maaroufi, Halim; Férard, Céline; Finet, Stéphanie; Tanguay, Robert M

    2017-07-01

    The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form. In vitro, the chaperone-like activity of wild-type DmHsp27 was comparable with that of its two isolated populations and to the single population of the R122G, R131G, and R135G using luciferase as substrate. However, using insulin, the chaperone-like activity of wild-type DmHsp27 was lower than that of R122G and R131G mutants. Altogether, the results characterize wild-type DmHsp27 and its alpha-crystallin domain (ACD) arginine mutants and may give insight into protection mechanism of sHsps.

  16. Towards the use of small amounts of activated charcoal along with well-type NaI(Tl) detector for indoor radon measurements

    International Nuclear Information System (INIS)

    Al-Azmi, D.

    2006-01-01

    The feasibility of using small quantities of activated charcoal and a 7.6 cm x 7.6 cm NaI(Tl) well-type detector was investigated for indoor radon measurements. Vials, filled with 10 g of charcoal, were exposed for different indoor radon concentration levels typical of Kuwait dwellings. After exposure, the vials were sealed and kept for 3 h to allow radon to come into radioactive equilibrium with its progenies and were then analysed by gamma-ray spectrometry using the well-type NaI(Tl) detector. The variation of radon absorption by the vials filled with charcoal with exposure time was also studied. A comparative study of the present technique with the standard technique of using 70 g charcoal canisters and flat NaI detector was also performed. After establishing the suitability of the technique, the charcoal vials were then used to investigate the effect of air-ventilation on the concentration levels of the indoor radon. Results show that there is a reduction in the radon concentration level (up to 25%) when the air-ventilation system was switched on. The paper presents the results of the study on the feasibility of combining small amounts of activated charcoal with a well-type NaI(Tl) detector in the measurement of indoor radon concentrations. (authors)

  17. Small centrifugal pumps for low-thrust rocket engines

    Science.gov (United States)

    Furst, R. B.

    1986-01-01

    Six small, low specific speed centrifugal pump configurations were designed, fabricated, and tested. The configurations included shrouded, and 25 and 100% admission open face impellers with 2 inch tip diameters; 25, 50, and 100% emission vaned diffusers; and volutes with conical exits. Impeller tip widths varied from 0.030 inch to 0.052 inch. Design specific speeds (N sub s = RPM*GPM**0.5.FT**0.75) were 430 (four configurations) and 215 (two configurations). The six configurations were tested with water as the pumped fluid. Noncavitating performance results are presented for the design speed of 24,500 rpm over a flowrate range from 1 to 6 gpm for the N sub s = 430 configurations and test speeds up to 29,000 rpm over a flowrate range from 0.3 to 1.2 gpm for the N sub s = 215 configurations. Cavitating performance results are presented over a flowrate range from 60 to 120% of design flow. Fabrication of the small pump conponents is also discussed.

  18. Actigraphic assessment of daily sleep-activity pattern abnormalities reflects self-assessed depression and anxiety in outpatients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Du-Quiton, Jovelyn; Wood, Patricia A; Burch, James B; Grutsch, James F; Gupta, Digant; Tyer, Kevin; Lis, Christopher G; Levin, Robert D; Quiton, Dinah Faith T; Reynolds, Justin L; Hrushesky, William J M

    2010-02-01

    We measured subjectively evaluated depression and anxiety, and objectively measured daily sleep-activity patterns in inpatients and outpatients with advanced non-small cell lung cancer (NSCLC) and determined whether cancer-associated depression and anxiety are accompanied by characteristic circadian rhythm abnormalities. Equal numbers of inpatients (n=42) and outpatients (n=42) with advanced NSCLC were studied. Baseline depression and anxiety, assessed by the Hospital Anxiety and Depression Scale (HADS), and actigraphy were recorded before chemotherapy initiation. The effects of the presence and severity of chronic obstructive pulmonary disease (COPD) on depression, anxiety, and actigraphy were assessed only among the 42 outpatients. Anxiety occurred in 40% and depression in 25% of these lung cancer patients, equally among inpatients and outpatients. All patients suffer extremely disturbed daily sleep-activity cycles but each patient also maintains some degree of circadian organization. Outpatients maintain more robust daily activity patterns and longer, more consolidated nighttime sleep compared with inpatients. The more disrupted the daily sleep-activity rhythm, the worse the depression and/or anxiety scores for outpatients. These relationships are obscured among inpatients. COPD has no independent measurable effects on the daily organization of sleep-activity, depression, or anxiety. Lung cancer patients whose diurnal activity is disturbed by prolonged and frequent sedentary episodes and whose sleep is disturbed by frequent and prolonged waking are most anxious and depressed. These findings and relationships are masked by hospitalization. Since diurnal exercise improves both sleep and mood, it is reasonable to test whether enhancing daytime activity and nighttime sleep can diminish cancer-associated depression.

  19. Peroxisome Proliferator-Activated Receptor-γ Inhibits Transformed Growth of Non-Small Cell Lung Cancer Cells through Selective Suppression of Snail

    Directory of Open Access Journals (Sweden)

    Rashmi Choudhary

    2010-03-01

    Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.

  20. Hangman Catalysis for Photo–and Photoelectro–Chemical Activation of Water Proton-Coupled Electron Transfer Mechanisms of Small Molecule Activation

    Energy Technology Data Exchange (ETDEWEB)

    Nocera, Daniel G. [Harvard Univ., Cambridge, MA (United States)

    2013-03-15

    The weakest link for the large-scale deployment of solar energy and for that matter, any renewable energy source, is its storage. The energy needs of future society demands are so large that storage must be in the form of fuels owing to their high energy density. Indeed, society has intuitively understood this disparity in energy density as it has developed over the last century as all large-scale energy storage in our society is in the form of fuels. But these fuels are carbon-based. The imperative for the discipline of chemistry, and more generally science, is to develop fuel storage methods that are easily scalable, carbon-neutral and sustainable. These methods demand the creation of catalysts to manage the multi-electron, multi-proton transformations of the conversion of small molecules into fuels. The splitting of water using solar light is a fuel-forming reaction that meets the imperative of large scale energy storage. As light does not directly act on water to engender its splitting into its elemental components, we have designed “hangman” catalysts to effect the energy conversion processes needed for the fuel forming reactions. The hangman construct utilizes a pendant acid/base functionality within the secondary coordination sphere that is “hung” above the redox platform onto which substrate binds. In this way, we can precisely control the delivery of a proton to the substrate, thus ensuring efficient coupling between the proton and electron. An emphasis was on the coupling of electron and proton in the hydrogen evolution reaction (HER) on Ni, Co and Fe porphyrin platforms. Electrokinetic rate laws were developed to define the proton-coupled electron transfer (PCET) mechanism. The HER of Co and Fe porphyrins was metal-centered. Surprisingly, HER this was not the case for Ni porphyrins. In this system, the PCET occurred at the porphyrin platform to give rise to a phlorin. This is one of the first examples of an HER occurring via ligand non