Sample records for processor assembly upa

  1. Development Status of the International Space Station Urine Processor Assembly

    NASA Technical Reports Server (NTRS)

    Holder, Donald W.; Hutchens, Cindy F.

    2003-01-01

    NASA, Marshall Space Flight Center (MSFC) is developing a Urine Processor Assembly (UPA) for the International Space Station (ISS). The UPA uses Vapor Compression Distillation (VCD) technology to reclaim water from pre-treated urine. This water is further processed by the Water Processor Assembly (WPA) to potable quality standards for use on the ISS. NASA has developed this technology over the last 25-30 years. Over this history, many technical issues were solved with thousands of hours of ground testing that demonstrate the ability of the UPA technology to reclaim water from urine. In recent years, NASA MSFC has been responsible for taking the UPA technology to "flight design" maturity. This paper will give a brief overview of the UPA design and a status of the major design and development efforts completed recently to mature the UPA to a flight level.

  2. Upgrades to the ISS Water Recovery System

    NASA Technical Reports Server (NTRS)

    Kayatin, Matthew J.; Carter, Donald L.; Schunk, Richard G.; Pruitt, Jennifer M.

    2016-01-01

    The International Space Station Water Recovery System (WRS) is comprised of the Water Processor Assembly (WPA) and the Urine Processor Assembly (UPA). The WRS produces potable water from a combination of crew urine (first processed through the UPA), crew latent, and Sabatier product water. Though the WRS has performed well since operations began in November 2008, several modifications have been identified to improve the overall system performance. These modifications can reduce resupply and improve overall system reliability, which is beneficial for the ongoing ISS mission as well as for future NASA manned missions. The following paper details efforts to reduce the resupply mass of the WPA Multifiltration Bed, develop improved catalyst for the WPA Catalytic Reactor, evaluate optimum operation of UPA through parametric testing, and improve reliability of the UPA fluids pump and Distillation Assembly.

  3. Upgrades to the ISS Water Recovery System

    NASA Technical Reports Server (NTRS)

    Kayatin, Matthew; Takada, Kevin; Carter, Layne

    2017-01-01

    The ISS Water Recovery System (WRS) includes the Water Processor Assembly (WPA) and the Urine Processor Assembly (UPA). The WRS produces potable water from a combination of crew urine (first processed through the UPA), crew latent, and Sabatier product water. Though the WRS has performed well since operations began in November 2008, several modifications have been identified to improve the overall system performance. These modifications can reduce resupply and improve overall system reliability, which is beneficial for the ongoing ISS mission as well as for future NASA manned missions. The following paper details efforts to improve the WPA through the use of Reverse Osmosis technology to reduce the resupply mass of the WPA Multifiltration Bed and improved catalyst for the WPA Catalytic Reactor to reduce the operational temperature and pressure. For the UPA, this paper discusses progress on various concepts for improving the reliability of the UPA, including the implementation of a more reliable drive belt, improved methods for managing condensate in the stationary bowl of the Distillation Assembly, deleting the Separator Plumbing Assembly, and evaluating upgrades to the UPA vacuum pump.

  4. WRS2 UPA DA Removal

    NASA Image and Video Library

    2009-11-23

    ISS021-E-032275 (23 Nov. 2009) --- NASA astronaut Leland Melvin, STS-129 mission specialist, holds the failed Urine Processor Assembly / Distillation Assembly (UPA DA) in the Destiny laboratory of the International Space Station while space shuttle Atlantis remains docked with the station. Melvin and European Space Agency astronaut Frank De Winne (out of frame), Expedition 21 commander, removed and packed the UPA DA, then transferred it from the Water Recovery System 2 (WRS-2) rack to Atlantis for stowage on the middeck.

  5. WRS2 UPA DA Removal

    NASA Image and Video Library

    2009-11-23

    ISS021-E-032273 (23 Nov. 2009) --- European Space Agency astronaut Frank De Winne, Expedition 21 commander, holds the failed Urine Processor Assembly / Distillation Assembly (UPA DA) in the Destiny laboratory of the International Space Station while space shuttle Atlantis remains docked with the station. De Winne and NASA astronaut Leland Melvin (out of frame), STS-129 mission specialist, removed and packed the UPA DA, then transferred it from the Water Recovery System 2 (WRS-2) rack to Atlantis for stowage on the middeck.

  6. Upgrades to the International Space Station Water Recovery System

    NASA Technical Reports Server (NTRS)

    Kayatin, Matthew J.; Pruitt, Jennifer M.; Nur, Mononita; Takada, Kevin C.; Carter, Layne

    2017-01-01

    The International Space Station (ISS) Water Recovery System (WRS) includes the Water Processor Assembly (WPA) and the Urine Processor Assembly (UPA). The WRS produces potable water from a combination of crew urine (first processed through the UPA), crew latent, and Sabatier product water. Though the WRS has performed well since operations began in November 2008, several modifications have been identified to improve the overall system performance. These modifications aim to reduce resupply and improve overall system reliability, which is beneficial for the ongoing ISS mission as well as for future NASA manned missions. The following paper details efforts to improve the WPA through the use of reverse osmosis membrane technology to reduce the resupply mass of the WPA Multi-filtration Bed and improved catalyst for the WPA Catalytic Reactor to reduce the operational temperature and pressure. For the UPA, this paper discusses progress on various concepts for improving the reliability of the system, including the implementation of a more reliable drive belt, improved methods for managing condensate in the stationary bowl of the Distillation Assembly, and evaluating upgrades to the UPA vacuum pump.

  7. Status of the International Space Station Regenerative ECLSS Water Recovery and Oxygen Generation Systems

    NASA Technical Reports Server (NTRS)

    Bagdigian, Robert M.; Cloud, Dale

    2005-01-01

    NASA is developing three racks containing regenerative water recovery and oxygen generation systems (WRS and OGS) for deployment on the International Space Station (ISS). The major assemblies included in these racks are the Water Processor Assembly (WPA), Urine Processor Assembly (UPA), Oxygen Generation Assembly (OGA), and the Power Supply Module (PSM) supporting the OGA. The WPA and OGA are provided by Hamilton Sundstrand Space Systems International (HSSSI), Inc., while the UPA and PSM are developed in- house by the Marshall Space Flight Center (MSFC). The assemblies have completed the manufacturing phase and are in various stages of testing and integration into the flight racks. This paper summarizes the status as of April 2005 and describes some of the technical challenges encountered and lessons learned over the past year.

  8. Compatibility Testing of Non-Metallic Materials for the Urine Processor Assembly (UPA) of International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    Wingard, Charles Doug; Munafo, Paul M. (Technical Monitor)

    2001-01-01

    In the International Space Station (ISS), astronauts will convert urine into potable water with the Urine Processor Assembly (UPA). The urine is distilled, with the concentrated form containing about 15% brine solids, and the dilute form as a blend of pre-treated urine/wastewater. Eighteen candidate non-metallic materials for use with the UPA were tested in 2000 for compatibility with the concentrated and dilute urine solutions for continuous times of at least 30 days, and at conditions of 0.5 psia pressure and 100 F, to simulate the working UPA environment. A primary screening test for each material (virgin and conditioned) was dynamic mechanical analysis (DMA) in the stress relaxation mode, with the test data used to predict material performance for a 10-year use in space. Data showed that most of the candidate materials passed the compatibility testing, although a few significant changes in stress relaxation modulus were observed.

  9. Status of the Regenerative ECLS Water Recovery System

    NASA Technical Reports Server (NTRS)

    Carter, Donald Layne

    2010-01-01

    The regenerative Water Recovery System (WRS) has completed its first full year of operation on the International Space Station (ISS). The major assemblies included in this system are the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of May 2010, and describes the technical challenges encountered and lessons learned over the past year.

  10. Investigation of DMSD Trend in the ISS Water Processor Assembly

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Bowman, Elizabeth; Wilson, Mark; Gentry, Greg; Rector, Tony

    2013-01-01

    The ISS Water Recovery System (WRS) is responsible for providing potable water to the crew, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. The WRS includes the Water Processor Assembly (WPA) and the Urine Processor Assembly (UPA). The WPA processes condensate from the cabin air and distillate produced by the UPA. In 2010, an increasing trend in the Total Organic Carbon (TOC) in the potable water was ultimately identified as dimethylsilanediol (DMSD). The increasing trend was ultimately reversed after replacing the WPA's two multifiltration beds. However, the reason for the TOC trend and the subsequent recovery was not understood. A subsequent trend occurred in 2012. This paper summarizes the current understanding of the fate of DMSD in the WPA, how the increasing TOC trend occurred, and the plan for modifying the WPA to prevent recurrence.

  11. Status of the Node 3 Regenerative Environmental Cpntrol& Life Support System Water Recovery & Oxygen Generation Systems

    NASA Technical Reports Server (NTRS)

    Carrasquillo, Robyn L.

    2003-01-01

    NASA s Marshall Space Flight Center is providing three racks containing regenerative water recovery and oxygen generation systems (WRS and OGS) for flight on the lnternational Space Station s (ISS) Node 3 element. The major assemblies included in these racks are the Water Processor Assembly (WPA), Urine Processor Assembly (UPA), Oxygen Generation Assembly (OGA), and the Power Supply Module (PSM) supporting the OGA. The WPA and OGA are provided by Hamilton Sundstrand Space Systems lnternational (HSSSI), while the UPA and PSM are being designed and manufactured in-house by MSFC. The assemblies are currently in the manufacturing and test phase and are to be completed and integrated into flight racks this year. This paper gives an overview of the technologies and system designs, technical challenges encountered and solved, and the current status.

  12. Installing the ARFTA (Advanced Recycle Filter Tank Assembly)

    NASA Image and Video Library

    2011-10-10

    ISS029-E-021648 (10 Oct. 2011) --- NASA astronaut Mike Fossum, Expedition 29 commander, installs the Advanced Recycle Filter Tank Assembly (ARFTA) at the Urine Processor Assembly / Water Recovery System (UPA WRS) in the Destiny laboratory of the International Space Station.

  13. Preventing Precipitation in the ISS Urine Processor

    NASA Technical Reports Server (NTRS)

    Muirhead, Dean; Carter, Layne; Williamson, Jill; Chambers, Antja

    2017-01-01

    The ISS Urine Processor Assembly (UPA) was initially designed to achieve 85% recovery of water from pretreated urine on ISS. Pretreated urine is comprised of crew urine treated with flush water, an oxidant (chromium trioxide), and an inorganic acid (sulfuric acid) to control microbial growth and inhibit precipitation. Unfortunately, initial operation of the UPA on ISS resulted in the precipitation of calcium sulfate at 85% recovery. This occurred because the calcium concentration in the crew urine was elevated in microgravity due to bone loss. The higher calcium concentration precipitated with sulfate from the pretreatment acid, resulting in a failure of the UPA due to the accumulation of solids in the Distillation Assembly. Since this failure, the UPA has been limited to a reduced recovery of water from urine to prevent calcium sulfate from reaching the solubility limit. NASA personnel have worked to identify a solution that would allow the UPA to return to a nominal recovery rate of 85%. This effort has culminated with the development of a pretreatment based on phosphoric acid instead of sulfuric acid. By eliminating the sulfate associated with the pretreatment, the brine can be concentrated to a much higher concentration before calcium sulfate reach the solubility limit. This paper summarizes the development of this pretreatment and the testing performed to verify its implementation on ISS.

  14. Upgrades to the ISS Water Recovery System

    NASA Technical Reports Server (NTRS)

    Pruitt, Jennifer M.; Carter, Layne; Bagdigian, Robert M.; Kayatin, Mattthew J.

    2015-01-01

    The ISS Water Recovery System (WRS) includes the Water Processor Assembly (WPA) and the Urine Processor Assembly (UPA). The WRS produces potable water from a combination of crew urine (first processed through the UPA), crew latent, and Sabatier product water. The WRS has been operational on ISS since November 2008, producing over 21,000 L of potable water during that time. Though the WRS has performed well during this time, several modifications have been identified to improve the overall system performance. These modifications can reduce resupply and improve overall system reliability, which is beneficial for the ongoing ISS mission as well as for future NASA manned missions. The following paper lists these modifications, how they improve WRS performance, and a status on the ongoing development effort.

  15. Status of the Regenerative ECLSS Water Recovery System

    NASA Technical Reports Server (NTRS)

    Carter, Donald Layne

    2009-01-01

    NASA has completed the delivery of the regenerative Water Recovery System (WRS) for the International Space Station (ISS). The major assemblies included in this system are the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the final effort to deliver the hardware to the Kennedy Space Center for launch on STS-126, the on-orbit status as of April 2009, and describes some of the technical challenges encountered and lessons learned over the past year.

  16. Environmental Control and Life Support Systems Testing Facility at MSFC

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. Scientists and engineers at the MSFC are working together to provide the ISS with systems that are safe, efficient, and cost-effective. These compact and powerful systems are collectively called the Environmental Control and Life Support Systems, or simply, ECLSS. This photograph shows the Urine Processor Assembly (UPA) which utilizes the Vapor Compression Distillation (VCD) technology. The VCD is used for integrated testing of the entire Water Recovery System (WRS) and development testing of the Urine Processor Assembly. The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the Water Processor Assembly (WPA). The WPA removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. Product water quality is monitored primarily through conductivity measurements. Unacceptable water is sent back through the WPA for reprocessing. Clean water is sent to a storage tank.

  17. Evaluation of Technologies to Prevent Precipitation During Water Recovery from Urine

    NASA Technical Reports Server (NTRS)

    Broyan, James L., Jr.; Pickering, Karen D.; Adam, Niklas M.; Mitchell, Julie L.; Anderson, Molly S.; Carter, Layne; Muirhead, Dean; Gazda, Daniel B.

    2011-01-01

    The International Space Station (ISS) Urine Processor Assembly (UPA) experienced a hardware failure in the Distillation Assembly (DA) in October 2010. Initially the UPA was operated to recover 85% of the water from urine through distillation, concentrating the contaminants in the remaining urine. The DA failed due to precipitation of calcium sulfate (gypsum) which caused a loss of UPA function. The ISS UPA operations have been modified to only recover 70% of the water minimizing gypsum precipitation risk but substantially increasing water resupply needs. This paper describes the feasibility assessment of several technologies (ion exchange, chelating agents, threshold inhibitors, and Lorentz devices) to prevent gypsum precipitation. The feasibility assessment includes the development of assessment methods, chemical modeling, bench top testing, and validation testing in a flight-like ground UPA unit. Ion exchange technology has been successfully demonstrated and has been recommended for further development. The incorporation of the selected technology will enable water recovery to be increased from 70% back to the original 85% and improve the ISS water balance.

  18. Williams in US Lab

    NASA Image and Video Library

    2010-02-10

    S130-E-006844 (10 Feb. 2010) --- NASA astronaut Jeffrey Williams, Expedition 22 commander, installs a Urine Processor Assembly / Distillation Assembly (UPA DA) in the Water Recovery System (WRS) rack in the Destiny laboratory of the International Space Station while space shuttle Endeavour (STS-130) remains docked with the station.

  19. Compatibility Testing of Polymeric Materials for the Urine Processor Assembly (UPA) of International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    Wingard, Charles D.

    2003-01-01

    In the International Space Station (ISS), astronauts will convert urine into potable water with the Urine Processor Assembly (UPA) by a distillation process. The urine is pre-treated, containing flush water and stabilizers. About 2.5% solids in the urine are concentrated up to 16% brine through distillation. Dynamic mechanical analysis (DMA) in the stress relaxation mode was primarily used to test 15 polymeric UPA materials for compatibility with the pre-treated and brine solutions. There were concerns that chromium trioxide (CrO3), a stabilizer not in the original pre-treat formulation for similar compatibility testing in 2000, could have an adverse effect on these polymers. DMA testing is partially complete for polymeric material samples immersed in the two solutions at room temperature for as long as 200 days. By comparing each material (conditioned and virgin), the stress relaxation modulus (E) was determined for short-term use and predicted for as long as a 10-year use in space. Such a delta E showed a decrease of as much as 79% for a Nylon material, but an increase as much as 454% for a polysulfone material, with increasing immersion time.

  20. ECLSS Sustaining Compatibility Testing on Urine Processor Assembly Nonmetallic Materials for Reformulation of Pretreated Urine Solution

    NASA Technical Reports Server (NTRS)

    Wingard, C. D.

    2015-01-01

    On International Space Station (ISS), the Urine Processor Assembly (UPA) converts human urine and flush water into potable water. The urine is acid-pretreated primarily to control microbial growth. In recent years, the sulfuric acid (H2SO4) pretreatment was believed to be largely responsible for producing salt crystals capable of plugging filters in UPA components and significantly reducing the percentage of water recovery from urine. In 2012, ISS management decided to change the acid pretreatment for urine from sulfuric to phosphoric with the goal of eliminating or minimizing formation of salt crystals. In 2013-2014, as part of the qualification of the phosphoric acid (H3PO4) formulation, samples of 12 nonmetallic materials used in UPA components were immersed for up to one year in pretreated urine and brine solutions made with the new H3PO4 formulation. Dynamic mechanical analysis (DMA) was used to measure modulus (stiffness) of the immersed samples compared to virgin control samples. Such compatibility data obtained by DMA for the H3PO4-based solutions were compared to DMA data obtained for the H2SO4-based solutions in 2002-2003.

  1. International Space Station (ISS)

    NASA Image and Video Library

    2001-02-01

    The Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. Scientists and engineers at the MSFC are working together to provide the ISS with systems that are safe, efficient, and cost-effective. These compact and powerful systems are collectively called the Environmental Control and Life Support Systems, or simply, ECLSS. This photograph shows the fifth generation Urine Processor Development Hardware. The Urine Processor Assembly (UPA) is a part of the Water Recovery System (WRS) on the ISS. It uses a chase change process called vapor compression distillation technology to remove contaminants from urine. The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the Water Processor Assembly (WPA). The WPA removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. Product water quality is monitored primarily through conductivity measurements. Unacceptable water is sent back through the WPA for reprocessing. Clean water is sent to a storage tank.

  2. Marshburn updates software on the WHC UPA in the Node 3

    NASA Image and Video Library

    2013-01-17

    ISS034-E-031133 (17 Jan. 2013) --- NASA astronaut Tom Marshburn, Expedition 34 flight engineer, updates software on the Waste and Hygiene Compartment?s Urine Processor Assembly in the Tranquility node of the International Space Station.

  3. Marshburn updates software on the WHC UPA in the Node 3

    NASA Image and Video Library

    2013-01-17

    ISS034-E-031130 (17 Jan. 2013) --- NASA astronaut Tom Marshburn, Expedition 34 flight engineer, updates software on the Waste and Hygiene Compartment?s Urine Processor Assembly in the Tranquility node of the International Space Station.

  4. Environmental Control and Life Support Systems Testing Facility at MSFC

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. Scientists and engineers at the MSFC are working together to provide the ISS with systems that are safe, efficient, and cost-effective. These compact and powerful systems are collectively called the Environmental Control and Life Support Systems, or simply, ECLSS. This photograph shows the fifth generation Urine Processor Development Hardware. The Urine Processor Assembly (UPA) is a part of the Water Recovery System (WRS) on the ISS. It uses a chase change process called vapor compression distillation technology to remove contaminants from urine. The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the Water Processor Assembly (WPA). The WPA removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. Product water quality is monitored primarily through conductivity measurements. Unacceptable water is sent back through the WPA for reprocessing. Clean water is sent to a storage tank.

  5. Life Testing of the Vapor Compression Distillation/Urine Processing Assembly (VCD/UPA) at the Marshall Space Flight Center (1993 to 1997)

    NASA Technical Reports Server (NTRS)

    Wieland, P.; Hutchens, C.; Long, D.; Salyer, B.

    1998-01-01

    Wastewater and urine generated on the International Space Station will be processed to recover pure water using vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processor Assembly (UPA), life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPA'S, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have operating lives of approximately 4,800 hours, equivalent to 3.9 years of operation on ISS for a crew of three at an average processing rate of 1.76 kg/h (3.97 lb/h). Precise alignment of the flex-splines of the fluids and purge pump motor drives is essential to avoid premature failure after about 400 hours of operation. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA.

  6. Status of ISS Water Management and Recovery

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Wilson, Laura Labuda; Orozco, Nicole

    2012-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment, and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of May 2011, and describes the technical challenges encountered and lessons learned over the past year.

  7. Status of ISS Water Management and Recovery

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Pruitt, Jennifer; Brown, Christopher A.; Bazley, Jesse; Gazda, Daniel; Schaezler, Ryan; Bankers, Lyndsey

    2016-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of May 2016 and describes the technical challenges encountered and lessons learned over the past year.

  8. Status of ISS Water Management and Recovery

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Brown, Christopher; Orozco, Nicole

    2014-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment, and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of June 2013, and describes the technical challenges encountered and lessons learned over the past year.

  9. Status of ISS Water Management and Recovery

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Tobias, Barry; Orozco, Nicole

    2012-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment, and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of June 2012, and describes the technical challenges encountered and lessons learned over the past year.

  10. Status of ISS Water Management and Recovery

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Takada, Kevin; Gazda, Daniel; Brown, Christopher; Bazley, Jesse; Schaezler, Ryan; Bankers, Lyndsey

    2017-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of June 2017 and describes the technical challenges encountered and lessons learned over the past year.

  11. Status of ISS Water Management and Recovery

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Pruitt, Jennifer; Brown, Christopher A.; Schaezler, Ryan; Bankers, Lyndsey

    2015-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment, and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of May 2015 and describes the technical challenges encountered and lessons learned over the past two years.

  12. Challenges with Operating a Water Recovery System (WRS) in the Microgravity Environment of the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    Carter, Donald Layne

    2017-01-01

    The ISS WRS produces potable water from crew urine, crew latent, and Sabatier product water. This system has been operational on ISS since November 2008, producing over 30,000 L of water during that time. The WRS includes a Urine Processor Assembly (UPA) to produce a distillate from the crew urine. This distillate is combined with the crew latent and Sabatier product water and further processed by the Water Processor Assembly (WPA) to the potable water. The UPA and WPA use technologies commonly used on ISS for water purification, including filtration, distillation, adsorption, ion exchange, and catalytic oxidation. The primary challenge with the design and operation of the WRS has been with implementing these technologies in microgravity. The absence of gravity has created unique issues that impact the constituency of the waste streams, alter two-phase fluid dynamics, and increases the impact of particulates on system performance. NASA personnel continue to pursue upgrades to the existing design to improve reliability while also addressing their viability for missions beyond ISS.

  13. Environmental Control and Life Support System, Water Recovery System

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The Environmental Control and Life Support System (ECLSS) Group of the Flight Projects Directorate at the Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. This is a close-up view of ECLSS Water Recovery System (WRS) racks. The MSFC's ECLSS Group overseas much of the development of the hardware that will allow a constant supply of clean water for four to six crewmembers aboard the ISS. The WRS provides clean water through the reclamation of wastewaters, including water obtained from the Space Shuttle's fuel cells, crewmember urine, used shower, handwash and oral hygiene water cabin humidity condensate, and Extravehicular Activity (EVA) wastes. The WRS is comprised of a Urine Processor Assembly (UPA), and a Water Processor Assembly (WPA). The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the WPA, which removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. Product water quality is monitored primarily through conductivity measurements. Unacceptable water is sent back through the WPA for reprocessing. Clean water is sent to a storage tank. The water must meet stringent purity standards before consumption by the crew. The UPA provided by the MSFC and the WRA is provided by the prime contractor, Hamilton Sundstrand Space Systems, International (HSSSI) from Cornecticut.

  14. Use of DSC and DMA Techniques to Help Investigate a Material Anomaly for PTFE Used in Processing a Piston Cup for the Urine Processor Assembly (UPA) on International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    Wingard, Doug

    2010-01-01

    Human urine and flush water are eventually converted into drinking water with the Urine Processor Assembly (UPA) aboard the International Space Station (ISS). This conversion is made possible through the Distillation Assembly (DA) of the UPA. One component of the DA is a molded circular piston cup made of virgin polytetrafluoroethylene (PTFE). The piston cup is assembled to a titanium component using eight fasteners and washers. Molded PTFE produced for spare piston cups in the first quarter of 2010 was different in appearance and texture, and softer than material molded for previous cups. For the suspect newer PTFE material, cup fasteners were tightened to only one-half the required torque value, yet the washers embedded almost halfway into the material. The molded PTFE used in the DA piston cup should be Type II, based on AMS 3667D and ASTM D4894 specifications. The properties of molded PTFE are considerably different between Type I and II materials. Engineers working with the DA thought that if Type I PTFE was molded by mistake instead of Type II material, that could have resulted in the anomalous material properties. Typically, the vendor molds flat sheet PTFE from the same material lot used to mold the piston cups, and tensile testing as part of quality control should verify that the PTFE is Type II material. However, for this discrepant lot of material, such tensile data was not available. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were two of the testing techniques used at the NASA/Marshall Space Flight Center (MSFC) to investigate the anomaly for the PTFE material. Other techniques used on PTFE specimens were: Shore D hardness testing, tensile testing on dog bone specimens and a qualitative estimation of porosity by optical and scanning electron microscopy.

  15. Ion Exchange Technology Development in Support of the Urine Processor Assembly Precipitation Prevention Project for the International Space Station

    NASA Technical Reports Server (NTRS)

    Mitchell, Julie L.; Broyan, James L.; Pickering, Karen D.; Adam, Niklas; Casteel, Michael; Callahan, Michael; Carrier, Chris

    2012-01-01

    In support of the Urine Processor Assembly Precipitation Prevention Project (UPA PPP), multiple technologies were explored to prevent CaSO4 2H2O (gypsum) precipitation during the on-orbit distillation process. Gypsum precipitation currently limits the water recovery rate onboard the International Space Station (ISS) to 70% versus the planned 85% target water recovery rate. Due to its ability to remove calcium cations in pretreated augmented urine (PTAU), ion exchange was selected as one of the technologies for further development by the PPP team. A total of 13 ion exchange resins were evaluated in various equilibrium and dynamic column tests with solutions of dissolved gypsum, urine ersatz, PTAU, and PTAU brine at 85% water recovery. While initial evaluations indicated that the Purolite SST60 resin had the highest calcium capacity in PTAU (0.30 meq/mL average), later tests showed that the Dowex G26 and Amberlite FPC12H resins had the highest capacity (0.5 meq/mL average). Testing at the Marshall Spaceflight Center (MSFC) integrates the ion exchange technology with a UPA ground article under flight-like pulsed flow conditions with PTAU. To date, no gypsum precipitation has taken place in any of the initial evaluations.

  16. International Space Station (ISS)

    NASA Image and Video Library

    2001-03-01

    The Environmental Control and Life Support System (ECLSS) Group of the Flight Projects Directorate at the Marshall Space Flight Center in Huntsville, Alabama, is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. This photograph shows the mockup of the the ECLSS to be installed in the Node 3 module of the ISS. From left to right, shower rack, waste management rack, Water Recovery System (WRS) Rack #2, WRS Rack #1, and Oxygen Generation System (OGS) rack are shown. The WRS provides clean water through the reclamation of wastewaters and is comprised of a Urine Processor Assembly (UPA) and a Water Processor Assembly (WPA). The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the WPA. The WPA removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. The OGS produces oxygen for breathing air for the crew and laboratory animals, as well as for replacing oxygen loss. The OGS is comprised of a cell stack, which electrolyzes (breaks apart the hydrogen and oxygen molecules) some of the clean water provided by the WRS, and the separators that remove the gases from the water after electrolysis.

  17. Biological Water Processor and Forward Osmosis Secondary Treatment

    NASA Technical Reports Server (NTRS)

    Shull, Sarah; Meyer, Caitlin

    2014-01-01

    The goal of the Biological Water Processor (BWP) is to remove 90% organic carbon and 75% ammonium from an exploration-based wastewater stream for four crew members. The innovative design saves on space, power and consumables as compared to the ISS Urine Processor Assembly (UPA) by utilizing microbes in a biofilm. The attached-growth system utilizes simultaneous nitrification and denitrification to mineralize organic carbon and ammonium to carbon dioxide and nitrogen gas, which can be scrubbed in a cabin air revitalization system. The BWP uses a four-crew wastewater comprised of urine and humidity condensate, as on the ISS, but also includes hygiene (shower, shave, hand washing and oral hygiene) and laundry. The BWP team donates 58L per day of this wastewater processed in Building 7.

  18. Environmental Control and Life Support System Mockup

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Environmental Control and Life Support System (ECLSS) Group of the Flight Projects Directorate at the Marshall Space Flight Center in Huntsville, Alabama, is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. This photograph shows the mockup of the the ECLSS to be installed in the Node 3 module of the ISS. From left to right, shower rack, waste management rack, Water Recovery System (WRS) Rack #2, WRS Rack #1, and Oxygen Generation System (OGS) rack are shown. The WRS provides clean water through the reclamation of wastewaters and is comprised of a Urine Processor Assembly (UPA) and a Water Processor Assembly (WPA). The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the WPA. The WPA removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. The OGS produces oxygen for breathing air for the crew and laboratory animals, as well as for replacing oxygen loss. The OGS is comprised of a cell stack, which electrolyzes (breaks apart the hydrogen and oxygen molecules) some of the clean water provided by the WRS, and the separators that remove the gases from the water after electrolysis.

  19. Ion Exchange Technology Development in Support of the Urine Processor Assembly Precipitation Prevention Project for the International Space Station

    NASA Technical Reports Server (NTRS)

    Mitchell, Julie L.; Broyan, James L.; Pickering, Karen D.; Adam, Niklas; Casteel, Michael; Callaham, Michael; Carrier, Chris

    2011-01-01

    In support of the Urine Processor Assembly Precipitation Prevention Project (UPA PPP), multiple technologies were explored to prevent CaSO4 dot 2H2O (gypsum) precipitation during the on-orbit distillation process. Gypsum precipitation currently limits the water recovery rate onboard the International Space Station (ISS) to 70% versus the planned 85% target water recovery rate. Due to its advanced performance in removing calcium cations in pretreated augmented urine (PTAU), ion exchange was selected as one of the technologies for further development by the PPP team. A total of 12 ion exchange resins were evaluated in various equilibrium and dynamic column tests with solutions of dissolved gypsum, urine ersatz, PTAU, and PTAU brine at 85% water recovery. While initial evaluations indicated that the Purolite SST60 resin had the highest calcium capacity in PTAU (0.30 meq/mL average), later tests showed that the Dowex G26 and Amberlite FPC12H resins had the highest capacity (0.5 meq/mL average). Further dynamic column testing proved that G26 performance is +/- 10% of that value at flow rates of 0.45 and 0.79 Lph under continuous flow, and 10.45 Lph under pulsed flow. Testing at the Marshall Spaceflight Center (MSFC) integrates the ion exchange technology with a UPA ground article under flight-like pulsed flow conditions with PTAU. To date, no gypsum precipitation has taken place in any of the initial evaluations.

  20. Clean Water for Remote Locations

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Marshall Space Flight Center engineers are working on creating the Regenerative Environmental Control and Life Support System, a complex system of devices intended to sustain the astronauts living on the ISS and, in the future, sustain those who are blasting off to the Moon or Mars. The devices make use of the available resources, by turning wastewater from respiration, sweat, and urine into drinkable water. One of the devices that Marshall has been working on is the Water Recovery System (WRS). Marshall has teamed with long-time NASA contractor, Hamilton Sundstrand Space Systems International, Inc., of Windsor Locks, Connecticut. Hamilton Sundstrand, the original designer of the life support devices for the space suits, developed the Water Processor Assembly (WPA). It, along with the Urine Processor Assembly (UPA) developed by Marshall, combines to make up the total system, which is about the size of two refrigerators, and will support up to a six-member crew. The system is currently undergoing final testing and verification. "The Water Processor Assembly can produce up to about 28 gallons of potable recycled water each day," said Bob Bagdigian, Marshall Regenerative Environmental Control and Life Support System project manager. After the new systems are installed, annual delivered water to the ISS should decrease by approximately 15,960 pounds, or about 1,600 gallons.

  1. Ion Exchange Technology Development in Support of the Urine Processor Assembly

    NASA Technical Reports Server (NTRS)

    Mitchell, Julie; Broyan, James; Pickering, Karen

    2013-01-01

    The urine processor assembly (UPA) on the International Space Station (ISS) recovers water from urine via a vacuum distillation process. The distillation occurs in a rotating distillation assembly (DA) where the urine is heated and subjected to sub-ambient pressure. As water is removed, the original organics, salts, and minerals in the urine become more concentrated and result in urine brine. Eventually, water removal will concentrate the urine brine to super saturation of individual constituents, and precipitation occurs. Under typical UPA DA operating conditions, calcium sulfate or gypsum is the first chemical to precipitate in substantial quantity. During preflight testing with ground urine, the UPA achieved 85% water recovery without precipitation. However, on ISS, it is possible that crewmember urine can be significantly more concentrated relative to urine from ground donors. As a result, gypsum precipitated in the DA when operating at water recovery rates at or near 85%, causing the failure and subsequent re14 NASA Tech Briefs, September 2013 placement of the DA. Later investigations have demonstrated that an excess of calcium and sulfate will cause precipitation at water recovery rates greater than 70%. The source of the excess calcium is likely physiological in nature, via crewmembers' bone loss, while the excess sulfate is primarily due to the sulfuric acid component of the urine pretreatment. To prevent gypsum precipitation in the UPA, the Precipitation Prevention Project (PPP) team has focused on removing the calcium ion from pretreated urine, using ion exchange resins as calcium removal agents. The selectivity and effectiveness of ion exchange resins are determined by such factors as the mobility of the liquid phase through the polymer matrix, the density of functional groups, type of functional groups bound to the matrix, and the chemical characteristics of the liquid phase (pH, oxidation potential, and ionic strength). Previous experience with ion exchange resins has demonstrated that the most effective implementation for an ion exchange resin is a cartridge, or column, in which the resin is contained. Based on the results of equilibrium and sub-scale dynamic column testing, a possible solution for mitigating the calcium precipitation issue on the ISS has been identified. From an original pool of 13 ion exchange resins, two candidates have been identified that demonstrate substantial calcium removal on the sub-scale. The dramatic reduction in resin performance from published calcium uptake demonstrates the need for thorough evaluation of resins at the low pH and strong oxidizing environment present in the UPA. Chemical variations in the influent (calcium concentrations and pretreatment dosing) appear to have a noticeable impact on the calcium capacity of the resin. Low calcium concentrations and high pretreatment dosing will likely result in a decrease in calcium capacity. Conversely, low pre trea t - ment dosing will likely result in an increase in calcium capacity. In contrast, investigations at a variety of flow rates, length-to-diameter ratios, resin volumes, and flow regimes (continuous versus pulsed) show that changes in physical parameters do not have substantial impacts on resin performance in the very low specific velocity ranges of interest. This result is particularly useful because most commercial applications at higher specific velocities do show a relatively strong relationship between flow and capacity. The lack of a strong relationship will allow more flexibility in the implementation of an ion exchange bed for flight. Verification of subscale tests with flight-scale resin beds is recommended prior to implementation in the on-orbit UPA.

  2. Selection of a Brine Processor Technology for NASA Manned Missions

    NASA Technical Reports Server (NTRS)

    Carter, Donald L.; Gleich, Andrew F.

    2016-01-01

    The current ISS Water Recovery System (WRS) reclaims water from crew urine, humidity condensate, and Sabatier product water. Urine is initially processed by the Urine Processor Assembly (UPA) which recovers 75% of the urine as distillate. The remainder of the water is present in the waste brine which is currently disposed of as trash on ISS. For future missions this additional water must be reclaimed due to the significant resupply penalty for missions beyond Low Earth Orbit (LEO). NASA has pursued various technology development programs for a brine processor in the past several years. This effort has culminated in a technology down-select to identify the optimum technology for future manned missions. The technology selection is based on various criteria, including mass, power, reliability, maintainability, and safety. Beginning in 2016 the selected technology will be transitioned to a flight hardware program for demonstration on ISS. This paper summarizes the technology selection process, the competing technologies, and the rationale for the technology selected for future manned missions.

  3. Status of the International Space Station Waste and Hygiene Compartment

    NASA Technical Reports Server (NTRS)

    Walker, Stephanie; Zahner, Christopher

    2010-01-01

    The Waste and Hygiene Compartment (WHC) serves as the primary system for removal and containment of metabolic waste and hygiene activities on board the United States segment of the International Space Station (ISS). The WHC was launched on ULF 2 and is currently in the U.S. Laboratory and is integrated into the Water Recovery System (WRS) where pretreated urine is processed by the Urine Processor Assembly (UPA). The waste collection part of the WHC system is derived from the Service Module system and was provided by RSC-Energia along with additional hardware to allow for urine delivery to the UPA. The System has been integrated in an ISS standard equipment rack structure for use on the U.S. segment of the ISS. The system has experienced several events of interest during the deployment, checkout, and operation of the system during its first year of use and these will be covered in this paper. Design and on-orbit performance will also be discussed.

  4. International Space Station (ISS) Advanced Recycle Filter Tank Assembly (ARFTA)

    NASA Technical Reports Server (NTRS)

    Nasrullah, Mohammed K.

    2013-01-01

    The International Space Station (ISS) Recycle Filter Tank Assembly (RFTA) provides the following three primary functions for the Urine Processor Assembly (UPA): volume for concentrating/filtering pretreated urine, filtration of product distillate, and filtration of the Pressure Control and Pump Assembly (PCPA) effluent. The RFTAs, under nominal operations, are to be replaced every 30 days. This poses a significant logistical resupply problem, as well as cost in upmass and new tanks purchase. In addition, it requires significant amount of crew time. To address and resolve these challenges, NASA required Boeing to develop a design which eliminated the logistics and upmass issues and minimize recurring costs. Boeing developed the Advanced Recycle Filter Tank Assembly (ARFTA) that allowed the tanks to be emptied on-orbit into disposable tanks that eliminated the need for bringing the fully loaded tanks to earth for refurbishment and relaunch, thereby eliminating several hundred pounds of upmass and its associated costs. The ARFTA will replace the RFTA by providing the same functionality, but with reduced resupply requirements

  5. UPA Fill Drain Valve Modification kit installation

    NASA Image and Video Library

    2016-01-25

    ISS046e023885 (01/25/2016) --- NASA astronaut Tim Kopra performs regular maintenance on the Urine Processing Assembly (UPA) aboard the International Space Station. The UPA is used by the crew to recycle water for use on the station. The image shows Tim replacing the brine filter from the UPA Fill Drain Valve enclosure.

  6. Post-Flight Microbial Analysis of Samples from the International Space Station Water Recovery System and Oxygen Generation System

    NASA Technical Reports Server (NTRS)

    Birmele, Michele N.

    2011-01-01

    The Regenerative, Environmental Control and Life Support System (ECLSS) on the International Space Station (ISS) includes the the Water Recovery System (WRS) and the Oxygen Generation System (OGS). The WRS consists of a Urine Processor Assembly (UPA) and Water Processor Assembly (WPA). This report describes microbial characterization of wastewater and surface samples collected from the WRS and OGS subsystems, returned to KSC, JSC, and MSFC on consecutive shuttle flights (STS-129 and STS-130) in 2009-10. STS-129 returned two filters that contained fluid samples from the WPA Waste Tank Orbital Recovery Unit (ORU), one from the waste tank and the other from the ISS humidity condensate. Direct count by microscopic enumeration revealed 8.38 x 104 cells per mL in the humidity condensate sample, but none of those cells were recoverable on solid agar media. In contrast, 3.32 x lOs cells per mL were measured from a surface swab of the WRS waste tank, including viable bacteria and fungi recovered after S12 days of incubation on solid agar media. Based on rDNA sequencing and phenotypic characterization, a fungus recovered from the filter was determined to be Lecythophora mutabilis. The bacterial isolate was identified by rDNA sequence data to be Methylobacterium radiotolerans. Additional UPA subsystem samples were returned on STS-130 for analysis. Both liquid and solid samples were collected from the Russian urine container (EDV), Distillation Assembly (DA) and Recycle Filter Tank Assembly (RFTA) for post-flight analysis. The bacterium Pseudomonas aeruginosa and fungus Chaetomium brasiliense were isolated from the EDV samples. No viable bacteria or fungi were recovered from RFTA brine samples (N= 6), but multiple samples (N = 11) from the DA and RFTA were found to contain fungal and bacterial cells. Many recovered cells have been identified to genus by rDNA sequencing and carbon source utilization profiling (BiOLOG Gen III). The presence of viable bacteria and fungi from WRS and OGS subsystems demonstrates the need for continued monitoring of ECLSS during future ISS operations and investigation of advanced antimicrobial controls.

  7. Coiled Brine Recovery Assembly (CoBRA): A New Approach to Recovering Water from Wastewater Brines

    NASA Technical Reports Server (NTRS)

    Pensinger, Stuart J.

    2015-01-01

    Brine water recovery represents a current technology gap in water recycling for human spaceflight. The role of a brine processor is to take the concentrated discharge from a primary wastewater processor, called brine, and recover most of the remaining water from it. The current state-of-the-art primary processor is the ISS Urine Processor Assembly (UPA) that currently achieves 70% water recovery. Recent advancements in chemical pretreatments are expected to increase this to 85% in the near future. This is a welcome improvement, yet is still not high enough for deep space transit. Mission architecture studies indicate that at least 95% is necessary for a Mars mission, as an example. Brine water recovery is the technology that bridges the gap between 85% and 95%, and moves life support systems one step closer to full closure of the water loop. Several brine water recovery systems have been proposed for human spaceflight, most of them focused on solving two major problems: operation in a weightless environment, and management and containment of brine residual. Brine residual is the leftover byproduct of the brine recovery process, and is often a viscous, sticky paste, laden with crystallized solid particles. Due to the chemical pretreatments added to wastewater prior to distillation in a primary processor, these residuals are typically toxic, which further complicates matters. Isolation of crewmembers from these hazardous materials is paramount. The Coiled Brine Recovery Assembly (CoBRA) is a recently developed concept from the Johnson Space Center that offers solutions to these challenges. CoBRA is centered on a softgoods evaporator that enables a passive fill with brine, and regeneration by discharging liquid brine residual to a collection bag. This evaporator is meant to be lightweight, which allows it to be discarded along with the accumulated brine solids contained within it. This paper discusses design and development of a first CoBRA prototype, and reports initial test results.

  8. Cascade Distiller System Performance Testing Interim Results

    NASA Technical Reports Server (NTRS)

    Callahan, Michael R.; Pensinger, Stuart; Sargusingh, Miriam J.

    2014-01-01

    The Cascade Distillation System (CDS) is a rotary distillation system with potential for greater reliability and lower energy costs than existing distillation systems. Based upon the results of the 2009 distillation comparison test (DCT) and recommendations of the expert panel, the Advanced Exploration Systems (AES) Water Recovery Project (WRP) project advanced the technology by increasing reliability of the system through redesign of bearing assemblies and improved rotor dynamics. In addition, the project improved the CDS power efficiency by optimizing the thermoelectric heat pump (TeHP) and heat exchanger design. Testing at the NASA-JSC Advanced Exploration System Water Laboratory (AES Water Lab) using a prototype Cascade Distillation Subsystem (CDS) wastewater processor (Honeywell d International, Torrance, Calif.) with test support equipment and control system developed by Johnson Space Center was performed to evaluate performance of the system with the upgrades as compared to previous system performance. The system was challenged with Solution 1 from the NASA Exploration Life Support (ELS) distillation comparison testing performed in 2009. Solution 1 consisted of a mixed stream containing human-generated urine and humidity condensate. A secondary objective of this testing is to evaluate the performance of the CDS as compared to the state of the art Distillation Assembly (DA) used in the ISS Urine Processor Assembly (UPA). This was done by challenging the system with ISS analog waste streams. This paper details the results of the AES WRP CDS performance testing.

  9. Environmental Control and Life Support Integration Strategy for 6-Crew Operations Stephanie Duchesne

    NASA Technical Reports Server (NTRS)

    Duchesne, Stephanie M.

    2009-01-01

    The International Space Station (ISS) crew compliment has increased in size from 3 to 6 crew members . In order to support this increase in crew on ISS, the United States on-orbit Segment (USOS) has been outfitted with a suite of regenerative Environmental Control and Life Support (ECLS) hardware including an Oxygen Generation System(OGS), Waste and Hygiene Compartment (WHC), and a Water Recovery System (WRS). The WRS includes the Urine Processor Assembly (UPA) and the Water Processor Assembly (WPA). With this additional life support hardware, the ISS has achieved full redundancy in its on-orbit life support system between the USOS and Russian Segment (RS). The additional redundancy created by the Regenerative ECLS hardware creates the opportunity for independent support capabilities between segments, and for the first time since the start of ISS, the necessity to revise Life Support strategy agreements. Independent operating strategies coupled with the loss of the Space Shuttle supply and return capabilities in 2010 offer new and unique challenges. This paper will discuss the evolution of the ISS Life Support hardware strategy in support of 6-Crew on ISS, as well as the continued work that is necessary to ensure the support of crew and ISS Program objectives through the life of station.

  10. Environmental Control and Life Support Integration Strategy for 6-Crew Operations

    NASA Technical Reports Server (NTRS)

    Duchesne, Stephanie M.; Tressler, Chad H.

    2010-01-01

    The International Space Station (ISS) crew complement has increased in size from 3 to 6 crew members. In order to support this increase in crew on ISS, the United States on-orbit Segment (USOS) has been outfitted with a suite of regenerative Environmental Control and Life Support (ECLS) hardware including an Oxygen Generation System (OGS), Waste and Hygiene Compartment (WHC), and a Water Recovery System (WRS). The WRS includes the Urine Processor Assembly (UPA) and the Water Processor Assembly (WPA). With this additional life support hardware, the ISS has achieved full redundancy in its on-orbit life support system between the t OS and Russian Segment (RS). The additional redundancy created by the Regenerative ECLS hardware creates the opportunity for independent support capabilities between segments, and for the first time since the start of ISS, the necessity to revise Life Support strategy agreements. Independent operating strategies coupled with the loss of the Space Shuttle supply and return capabilities in 2010 offer new and unique challenges. This paper will discuss the evolution of the ISS Life Support hardware strategy in support of 6-Crew on ISS, as well as the continued work that is necessary to ensure the support of crew and ISS Program objectives through the life of station

  11. Regenerative (Regen) ECLSS Operations Water Balance

    NASA Technical Reports Server (NTRS)

    Tobias, Barry

    2010-01-01

    In November 2008, the Water Regenerative System racks were launched aboard Space Shuttle flight, STS-126 (ULF2) and installed and activated on the International Space Station (ISS). These racks, consisting of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA), completed the installation of the Regenerative (Regen) ECLSS systems which includes the Oxygen Generator Assembly (OGA) that was launched 2 years prior. With the onset of active water management on the US segment of the ISS, a new operational concept was required, that of "water balance." Even more recently, in 2010 the Sabatier system came online which converts H2 and CO2 into water and methane. The Regen ECLSS systems accept condensation from the atmosphere, urine from crew, and processes that fluid via various means into potable water which is used for crew drinking, building up skip-cycle water inventory, and water for electrolysis to produce oxygen. Specification rates of crew urine output, condensate output, O2 requirements, toilet flush water and drinking needs are well documented and used as a general plan when Regen ECLSS came online. Spec rates are useful in long term planning, however, daily or weekly rates are dependent on a number of variables. The constantly changing rates created a new challenge for the ECLSS flight controllers, who are responsible for operating the ECLSS systems onboard ISS. This paper will review the various inputs to rate changes and inputs to planning events, including but not limited to; crew personnel makeup, Regen ECLSS system operability, vehicle traffic, water containment availability, and Carbon Dioxide Removal Assembly (CDRA) capability. Along with the inputs that change the various rates, the paper will review the different systems, their constraints and finally the operational means by which flight controllers manage this new challenge of "water balance."

  12. Results of the Vapor Compression Distillation Flight Experiment (VCD-FE)

    NASA Technical Reports Server (NTRS)

    Hutchens, Cindy; Graves, Rex

    2004-01-01

    Vapor Compression Distillation (VCD) is the chosen technology for urine processing aboard the International Space Station (ISS). Key aspects of the VCD design have been verified and significant improvements made throughout the ground;based development history. However, an important element lacking from previous subsystem development efforts was flight-testing. Consequently, the demonstration and validation of the VCD technology and the investigation of subsystem performance in micro-gravity were the primary goals of the VCD-FE. The Vapor Compression Distillation Flight Experiment (VCD-E) was a flight experiment aboard the Space Shuttle Columbia during the STS-107 mission. The VCD-FE was a full-scale developmental version of the Space Station Urine Processor Assembly (UPA) and was designed to test some of the potential micro-gravity issues with the design. This paper summarizes the experiment results.

  13. Life Testing of the Vapor Compression Distillation Urine Processing Assembly (VCD/UPA) at the Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Wieland, Paul O.

    1998-01-01

    Wastewater and urine generated on the International Space Station will be processed to recover pure water. The method selected is vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processing Assembly (UPA), accelerated life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPAS, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have an operating life of approximately 4800 hours. Precise alignment of the flex-spline of the fluids pump is essential to avoid failure of the pump after about 400 hours of operation. Also, leakage around the seals of the drive shaft of the fluids pump and purge pump must be eliminated for continued good performance. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA.

  14. Evaluation of Brine Processing Technologies for Spacecraft Wastewater

    NASA Technical Reports Server (NTRS)

    Shaw, Hali L.; Flynn, Michael; Wisniewski, Richard; Lee, Jeffery; Jones, Harry; Delzeit, Lance; Shull, Sarah; Sargusingh, Miriam; Beeler, David; Howard, Jeanie; hide

    2015-01-01

    Brine drying systems may be used in spaceflight. There are several advantages to using brine processing technologies for long-duration human missions including a reduction in resupply requirements and achieving high water recovery ratios. The objective of this project was to evaluate four technologies for the drying of spacecraft water recycling system brine byproducts. The technologies tested were NASA's Forward Osmosis Brine Drying (FOBD), Paragon's Ionomer Water Processor (IWP), NASA's Brine Evaporation Bag (BEB) System, and UMPQUA's Ultrasonic Brine Dewatering System (UBDS). The purpose of this work was to evaluate the hardware using feed streams composed of brines similar to those generated on board the International Space Station (ISS) and future exploration missions. The brine formulations used for testing were the ISS Alternate Pretreatment and Solution 2 (Alt Pretreat). The brines were generated using the Wiped-film Rotating-disk (WFRD) evaporator, which is a vapor compression distillation system that is used to simulate the function of the ISS Urine Processor Assembly (UPA). Each system was evaluated based on the results from testing and Equivalent System Mass (ESM) calculations. A Quality Function Deployment (QFD) matrix was also developed as a method to compare the different technologies based on customer and engineering requirements.

  15. International Space Station Water Balance Operations

    NASA Technical Reports Server (NTRS)

    Tobias, Barry; Garr, John D., II; Erne, Meghan

    2011-01-01

    In November 2008, the Water Regenerative System racks were launched aboard Space Shuttle flight, STS-126 (ULF2) and installed and activated on the International Space Station (ISS). These racks, consisting of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA), completed the installation of the Regenerative (Regen) Environmental Control and Life Support Systems (ECLSS), which includes the Oxygen Generation Assembly (OGA) that was launched 2 years prior. With the onset of active water management on the US segment of the ISS, a new operational concept was required, that of water balance . In November of 2010, the Sabatier system, which converts H2 and CO2 into water and methane, was brought on line. The Regen ECLSS systems accept condensation from the atmosphere, urine from crew, and processes that fluid via various means into potable water, which is used for crew drinking, building up skip-cycle water inventory, and water for electrolysis to produce oxygen. Specification (spec) rates of crew urine output, condensate output, O2 requirements, toilet flush water, and drinking needs are well documented and used as the best guess planning rates when Regen ECLSS came online. Spec rates are useful in long term planning, however, daily or weekly rates are dependent upon a number of variables. The constantly changing rates created a new challenge for the ECLSS flight controllers, who are responsible for operating the ECLSS systems onboard ISS from Mission Control in Houston. This paper reviews the various inputs to water planning, rate changes, and dynamic events, including but not limited to: crew personnel makeup, Regen ECLSS system operability, vehicle traffic, water storage availability, and Carbon Dioxide Removal Assembly (CDRA), Sabatier, and OGA capability. Along with the inputs that change the various rates, the paper will review the different systems, their constraints, and finally the operational challenges and means by which flight controllers manage this new concept of "water balance."

  16. Environmental Control and Life Support Integration Strategy for 6-Crew Operations

    NASA Technical Reports Server (NTRS)

    2009-01-01

    The International Space Station (ISS) crew compliment will be increasing in size from 3 to 6 crew members in the summer of 2009. In order to support this increase in crew on ISS, the United States on-orbit Segment (USOS) has been outfitted with a suite of regenerative Environmental Control and Life Support (ECLS) hardware including an Oxygen Generation System(OGS), Waste and Hygiene Compartment (WHC), and a Water Recovery System (WRS). The WRS includes the Urine Processor Assembly (UPA) and the Water Processor Assembly (WPA). A critical step in advancing to a 6Crew support capability on ISS is a full checkedout and verification of the Regenerative ECLS hardware. With a successful checkout, the ISS will achieve full redundancy in its onorbit life support system between the USOS and Russian Segment (RS). The additional redundancy created by the Regenerative ECLS hardware creates the opportunity for independent support capabilities between segments, and for the first time since the start of ISS, the necessity to revise Life Support strategy agreements. Independent operating strategies coupled with the loss of the Space Shuttle supply and return capabilities in 2010 offers additional challenges. These challenges create the need for a higher level of onorbit consumables reserve to ensure crewmember life support during a system failure. This paper will discuss the evolution of the ISS Life Support hardware strategy in support of 6Crew on ISS, as well as the continued work which will be necessary to ensure the support of crew and ISS Program objectives through the life of station.

  17. Getting Out of Orbit: Water Recycling Requirements and Technology Needs for Long Duration Missions Away from Earth

    NASA Technical Reports Server (NTRS)

    Barta, Daniel J.

    2017-01-01

    Deep-space crewed missions will not have regular access to the Earth's resources or the ability to rapidly return to Earth if a system fails. As crewed missions extend farther from Earth for longer periods, habitation systems must become more self-sufficient and reliable for safe, healthy, and sustainable human exploration. For human missions to Mars, Environmental Control and Life Support Systems (ECLSS) must be able operate for up to 1,100 days with minimal spares and consumables. These missions will require capabilities to more fully recycle atmospheric gases and wastewater to substantially reduce mission costs. Even with relatively austere requirements for use, water represents one of the largest consumables by mass. Systems must be available to extract and recycle water from all sources of waste. And given that there will be no opportunity to send samples back to Earth for analysis, analytical measurements will be limited to monitoring hardware brought on board the spacecraft. The Earth Reliant phase of NASA's exploration strategy includes leveraging the International Space Station (ISS) to demonstrate advanced capabilities for a robust and reliable ECLSS. The ISS Water Recovery System (WRS) includes a Urine Processor Assembly (UPA) for distillation and recovery of water from urine and a Water Processor Assembly (WPA) to process humidity condensate and urine distillate into potable water. Possible enhancements to more fully "close the water loop" include recovery of water from waste brines and solid wastes. A possible game changer is the recovery of water from local planetary resources through use of In Situ Resource Utilization (ISRU) technologies. As part of the development and demonstration sequence, NASA intends to utilize cis-Lunar space as a Proving Ground to verify systems for deep space habitation by conducting extended duration missions to validate our readiness for Mars.

  18. International Space Station USOS Waste and Hygiene Compartment Development

    NASA Technical Reports Server (NTRS)

    Link, Dwight E., Jr.; Broyan, James Lee, Jr.; Gelmis, Karen; Philistine, Cynthia; Balistreri, Steven

    2007-01-01

    The International Space Station (ISS) currently provides human waste collection and hygiene facilities in the Russian Segment Service Module (SM) which supports a three person crew. Additional hardware is planned for the United States Operational Segment (USOS) to support expansion of the crew to six person capability. The additional hardware will be integrated in an ISS standard equipment rack structure that was planned to be installed in the Node 3 element; however, the ISS Program Office recently directed implementation of the rack, or Waste and Hygiene Compartment (WHC), into the U.S. Laboratory element to provide early operational capability. In this configuration, preserved urine from the WHC waste collection system can be processed by the Urine Processor Assembly (UPA) in either the U.S. Lab or Node 3 to recover water for crew consumption or oxygen production. The human waste collection hardware is derived from the Service Module system and is provided by RSC-Energia. This paper describes the concepts, design, and integration of the WHC waste collection hardware into the USOS including integration with U.S. Lab and Node 3 systems.

  19. The operational cloud retrieval algorithms from TROPOMI on board Sentinel-5 Precursor

    NASA Astrophysics Data System (ADS)

    Loyola, Diego G.; Gimeno García, Sebastián; Lutz, Ronny; Argyrouli, Athina; Romahn, Fabian; Spurr, Robert J. D.; Pedergnana, Mattia; Doicu, Adrian; Molina García, Víctor; Schüssler, Olena

    2018-01-01

    This paper presents the operational cloud retrieval algorithms for the TROPOspheric Monitoring Instrument (TROPOMI) on board the European Space Agency Sentinel-5 Precursor (S5P) mission scheduled for launch in 2017. Two algorithms working in tandem are used for retrieving cloud properties: OCRA (Optical Cloud Recognition Algorithm) and ROCINN (Retrieval of Cloud Information using Neural Networks). OCRA retrieves the cloud fraction using TROPOMI measurements in the ultraviolet (UV) and visible (VIS) spectral regions, and ROCINN retrieves the cloud top height (pressure) and optical thickness (albedo) using TROPOMI measurements in and around the oxygen A-band in the near infrared (NIR). Cloud parameters from TROPOMI/S5P will be used not only for enhancing the accuracy of trace gas retrievals but also for extending the satellite data record of cloud information derived from oxygen A-band measurements, a record initiated with the Global Ozone Monitoring Experiment (GOME) on board the second European Remote-Sensing Satellite (ERS-2) over 20 years ago. The OCRA and ROCINN algorithms are integrated in the S5P operational processor UPAS (Universal Processor for UV/VIS/NIR Atmospheric Spectrometers), and we present here UPAS cloud results using the Ozone Monitoring Instrument (OMI) and GOME-2 measurements. In addition, we examine anticipated challenges for the TROPOMI/S5P cloud retrieval algorithms, and we discuss the future validation needs for OCRA and ROCINN.

  20. A debugger-interpreter with setup facilities for assembly programs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dolinskii, I.S.; Zisel`man, I.M.; Belotskii, S.L.

    1995-11-01

    In this paper a software program allowing one to introduce and debug the descriptions of the von Nuemann architecture processors and their assemblers, efficiently debug assembly programs, and investigate the instruction sets of the described processors is considered. For a description of the processor sematics and assembler syntax, a metassembly language is suggested.

  1. A data base processor semantics specification package

    NASA Technical Reports Server (NTRS)

    Fishwick, P. A.

    1983-01-01

    A Semantics Specification Package (DBPSSP) for the Intel Data Base Processor (DBP) is defined. DBPSSP serves as a collection of cross assembly tools that allow the analyst to assemble request blocks on the host computer for passage to the DBP. The assembly tools discussed in this report may be effectively used in conjunction with a DBP compatible data communications protocol to form a query processor, precompiler, or file management system for the database processor. The source modules representing the components of DBPSSP are fully commented and included.

  2. Unaligned instruction relocation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bertolli, Carlo; O'Brien, John K.; Sallenave, Olivier H.

    In one embodiment, a computer-implemented method includes receiving source code to be compiled into an executable file for an unaligned instruction set architecture (ISA). Aligned assembled code is generated, by a computer processor. The aligned assembled code complies with an aligned ISA and includes aligned processor code for a processor and aligned accelerator code for an accelerator. A first linking pass is performed on the aligned assembled code, including relocating a first relocation target in the aligned accelerator code that refers to a first object outside the aligned accelerator code. Unaligned assembled code is generated in accordance with the unalignedmore » ISA and includes unaligned accelerator code for the accelerator and unaligned processor code for the processor. A second linking pass is performed on the unaligned assembled code, including relocating a second relocation target outside the unaligned accelerator code that refers to an object in the unaligned accelerator code.« less

  3. Unaligned instruction relocation

    DOEpatents

    Bertolli, Carlo; O'Brien, John K.; Sallenave, Olivier H.; Sura, Zehra N.

    2018-01-23

    In one embodiment, a computer-implemented method includes receiving source code to be compiled into an executable file for an unaligned instruction set architecture (ISA). Aligned assembled code is generated, by a computer processor. The aligned assembled code complies with an aligned ISA and includes aligned processor code for a processor and aligned accelerator code for an accelerator. A first linking pass is performed on the aligned assembled code, including relocating a first relocation target in the aligned accelerator code that refers to a first object outside the aligned accelerator code. Unaligned assembled code is generated in accordance with the unaligned ISA and includes unaligned accelerator code for the accelerator and unaligned processor code for the processor. A second linking pass is performed on the unaligned assembled code, including relocating a second relocation target outside the unaligned accelerator code that refers to an object in the unaligned accelerator code.

  4. In situ Observation of Direct Electron Transfer Reaction of Cytochrome c Immobilized on ITO Electrode Modified with 11-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}undecylphosphonic Acid Self-assembled Monolayer Film by Electrochemical Slab Optical Waveguide Spectroscopy.

    PubMed

    Matsuda, Naoki; Okabe, Hirotaka; Omura, Ayako; Nakano, Miki; Miyake, Koji

    2017-01-01

    To immobilize cytochrome c (cyt.c) on an ITO electrode while keeping its direct electron transfer (DET) functionality, the ITO electrode surface was modified with 11-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}undecylphosphonic acid (CH 3 O (CH 2 CH 2 O) 3 C 11 H 22 PO(OH) 2 , M-EG 3 -UPA) self-assembled monolayer (SAM) film. After a 100-times washing process to exchange a phosphate buffer saline solution surrounding cyt.c and ITO electrode to a fresh one, an in situ observation of visible absorption spectral change with slab optical waveguide (SOWG) spectroscopy showed that 87.7% of the cyt.c adsorbed on the M-EG 3 -UPA modified ITO electrode remained on the ITO electrode. The SOWG absorption spectra corresponding to oxidized and reduced cyt.c were observed with setting the ITO electrode potential at 0.3 and -0.3 V vs. Ag/AgCl, respectively, while probing the DET reaction between cyt.c and ITO electrode occurred. The amount of cyt.c was evaluated to be about 19.4% of a monolayer coverage based on the coulomb amount in oxidation and reduction peaks on cyclic voltammetry (CV) data. The CV peak current maintained to be 83.4% compared with the initial value for a M-EG 3 -UPA modified ITO electrode after 60 min continuous scan with 0.1 V/s between 0.3 and -0.3 V vs. Ag/AgCl.

  5. Integrated Advanced Microwave Sounding Unit-A(AMSU-A). Engineering Test Report: METSAT A1 Signal Processor, (P/N 1331670-2, S /N F05)

    NASA Technical Reports Server (NTRS)

    Lund, D.

    1998-01-01

    This report presents a description of the tests performed, and the test data, for the AI METSAT Signal Processor Assembly P/N 1331670-2, S/N F05. The assembly was tested in accordance with AE-26754, "METSAT Signal Processor Scan Drive and Integration Procedure." The objective is to demonstrate functionality of the signal processor prior to instrument integration.

  6. Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Engineering Test Report: METSAT A1 Signal Processor (P/N 1331670-2, S/N F03)

    NASA Technical Reports Server (NTRS)

    Lund, D.

    1998-01-01

    This report presents a description of tests performed, and the test data, for the A1 METSAT Signal Processor Assembly PN: 1331679-2, S/N F03. This assembly was tested in accordance with AE-26754, "METSAT Signal Processor Scan Drive Test and Integration Procedure." The objective is to demonstrate functionality of the signal processor prior to instrument integration.

  7. Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Engineering Test Report: METSAT A1 Signal Processor (P/N: 1331670-2, S/N: F04)

    NASA Technical Reports Server (NTRS)

    Lund, D.

    1998-01-01

    This report presents a description of the tests performed, and the test data, for the A1 METSAT Signal Processor Assembly PN: 1331679-2, S/N F04. The assembly was tested in accordance with AE-26754, "METSAT Signal Processor Scan Drive Test and Integration Procedure." The objective is to demonstrate functionality of the signal processor prior to instrument integration.

  8. Space Station Environmental Control and Life Support System Purge Control Pump Assembly Modeling and Analysis

    NASA Technical Reports Server (NTRS)

    Schunk, R. Gregory; Hunt, Patrick L. (Technical Monitor)

    2001-01-01

    Preliminary results from a thermal/flow analysis of the Purge Control Pump Assembly (PCPA) indicate that pump performance (mass flow rate) is enhanced via cooling of the housing and lowering of the inlet vapor quality. Under a nominal operational profile (25% duty cycle or less), at the maximum motor dissipation, it appears that the peristaltic tubing temperature will still remain significantly below the expected UPA condenser temperature (78 F max versus approximately 105 F in the condenser) permitting condensation in the pump head.

  9. Integrated Advanced Microwave Sounding Unit-A (AMSU-A): Engineering Test Report: METSAT A2 Signal Processor (P/N 1331120-2, S/N F03) S/N 107

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This report presents a description of the tests performed, and the test data, for the A2 METSAT Signal Processor Assembly PN: 1331120-2, S/N F03. The assembly was tested in accordance with AE-26754, "METSAT Signal Processor Scan Drive Test and Integration Procedure."

  10. Integrated Advanced Microwave Sounding Unit-A (AMSU-A): Engineering Test Report, METSAT A2 Signal Processor (P/N 1331120-2, S/N F04) S/N 108

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This report presents a description of the tests performed, and the test data, for the A2 METSAT Signal Processor Assembly PN: 1331120-2, S/N F04. The assembly was tested in accordance with AE-26754, "METSAT Signal Processor Scan Drive Test and Integration Procedure."

  11. System and method for controlling a combustor assembly

    DOEpatents

    York, William David; Ziminsky, Willy Steve; Johnson, Thomas Edward; Stevenson, Christian Xavier

    2013-03-05

    A system and method for controlling a combustor assembly are disclosed. The system includes a combustor assembly. The combustor assembly includes a combustor and a fuel nozzle assembly. The combustor includes a casing. The fuel nozzle assembly is positioned at least partially within the casing and includes a fuel nozzle. The fuel nozzle assembly further defines a head end. The system further includes a viewing device configured for capturing an image of at least a portion of the head end, and a processor communicatively coupled to the viewing device, the processor configured to compare the image to a standard image for the head end.

  12. A parallel algorithm for generation and assembly of finite element stiffness and mass matrices

    NASA Technical Reports Server (NTRS)

    Storaasli, O. O.; Carmona, E. A.; Nguyen, D. T.; Baddourah, M. A.

    1991-01-01

    A new algorithm is proposed for parallel generation and assembly of the finite element stiffness and mass matrices. The proposed assembly algorithm is based on a node-by-node approach rather than the more conventional element-by-element approach. The new algorithm's generality and computation speed-up when using multiple processors are demonstrated for several practical applications on multi-processor Cray Y-MP and Cray 2 supercomputers.

  13. Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation

    PubMed Central

    Veljkovic, D. Kika; Rivard, Georges E.; Diamandis, Maria; Blavignac, Jessica; Cramer-Bordé, Elisabeth M.

    2009-01-01

    Quebec platelet disorder (QPD) is an inherited bleeding disorder associated with increased urokinase plasminogen activator (uPA) in platelets but not in plasma, intraplatelet plasmin generation, and α-granule protein degradation. These abnormalities led us to investigate uPA expression by QPD CD34+ progenitors, cultured megakaryocytes, and platelets, and whether uPA was stored in QPD α-granules. Although QPD CD34+ progenitors expressed normal amounts of uPA, their differentiation into megakaryocytes abnormally increased expression of the uPA gene but not the flanking genes for vinculin or calcium/calmodulin-dependent protein kinase IIγ on chromosome 10. The increased uPA production by cultured QPD megakaryocytes mirrored their production of α-granule proteins, which was normal. uPA was localized to QPD α-granules and it showed extensive colocalization with α-granule proteins in both cultured QPD megakaryocytes and platelets, and with plasminogen in QPD platelets. In QPD megakaryocytes, cultured without or with plasma as a source of plasminogen, α-granule proteins were stored undegraded and this was associated with much less uPA-plasminogen colocalization than in QPD platelets. Our studies indicate that the overexpression of uPA in QPD emerges with megakaryocyte differentiation, without altering the expression of flanking genes, and that uPA is costored with α-granule proteins prior to their proteolysis in QPD. PMID:19029443

  14. Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation.

    PubMed

    Veljkovic, D Kika; Rivard, Georges E; Diamandis, Maria; Blavignac, Jessica; Cramer-Bordé, Elisabeth M; Hayward, Catherine P M

    2009-02-12

    Quebec platelet disorder (QPD) is an inherited bleeding disorder associated with increased urokinase plasminogen activator (uPA) in platelets but not in plasma, intraplatelet plasmin generation, and alpha-granule protein degradation. These abnormalities led us to investigate uPA expression by QPD CD34(+) progenitors, cultured megakaryocytes, and platelets, and whether uPA was stored in QPD alpha-granules. Although QPD CD34(+) progenitors expressed normal amounts of uPA, their differentiation into megakaryocytes abnormally increased expression of the uPA gene but not the flanking genes for vinculin or calcium/calmodulin-dependent protein kinase IIgamma on chromosome 10. The increased uPA production by cultured QPD megakaryocytes mirrored their production of alpha-granule proteins, which was normal. uPA was localized to QPD alpha-granules and it showed extensive colocalization with alpha-granule proteins in both cultured QPD megakaryocytes and platelets, and with plasminogen in QPD platelets. In QPD megakaryocytes, cultured without or with plasma as a source of plasminogen, alpha-granule proteins were stored undegraded and this was associated with much less uPA-plasminogen colocalization than in QPD platelets. Our studies indicate that the overexpression of uPA in QPD emerges with megakaryocyte differentiation, without altering the expression of flanking genes, and that uPA is costored with alpha-granule proteins prior to their proteolysis in QPD.

  15. Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques

    PubMed Central

    Brenner, Robert M.; Slayden, Ov D.; Nath, Anita; Tsong, YY; Sitruk-Ware, Regine

    2010-01-01

    Background Ulipristal (CDB-2914; UPA) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. Study Design Short lengths of Silastic tubing either empty (n=3), or containing UPA (n=5), were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. Results During treatment, animals with an empty IUS menstruated for a mean total of 11.66 ± 0.88 days while UPA-IUS treated animals bled for only 1 ± 0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. Conclusions In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal. PMID:20227552

  16. The effects of upaB deletion and the double/triple deletion of upaB, aatA, and aatB genes on pathogenicity of avian pathogenic Escherichia coli.

    PubMed

    Zhu-Ge, Xiang-Kai; Pan, Zi-Hao; Tang, Fang; Mao, Xiang; Hu, Lin; Wang, Shao-Hui; Xu, Bin; Lu, Cheng-Ping; Fan, Hong-Jie; Dai, Jian-Jun

    2015-12-01

    Autotransporters (ATs) are associated with pathogenesis of Avian Pathogenic Escherichia coli (APEC). The molecular characterization of APEC ATs can provide insights about their relevance to APEC pathogenesis. Here, we characterized a conventional autotransporter UpaB in APEC DE205B genome. The upaB existed in 41.9 % of 236 APEC isolates and was predominantly associated with ECOR B2 and D. Our studies showed that UpaB mediates the DE205B adhesion in DF-1 cells, and enhances autoaggregation and biofilm formation of fimbria-negative E. coli AAEC189 (MG1655Δfim) in vitro. Deletion of upaB of DE205B attenuates the virulence in duck model and early colonization in the duck lungs during APEC systemic infection. Furthermore, double and triple deletion of upaB, aatA, and aatB genes cumulatively attenuated DE205B adhesion in DF-1 cells, accompanying with decreased 50 % lethal dose (LD50) in duck model and the early colonization in the duck lungs. However, DE205BΔupaB/ΔaatA/ΔaatB might "compensate" the influence of gene deletion by upregulating the expression of fimbrial adhesin genes yqiL, yadN, and vacuolating autotransporter vat during early colonization of APEC. Finally, we demonstrated that vaccination with recombinant UpaB, AatA, and AatB proteins conferred protection against colisepticemia caused by DE205B infection in duck model.

  17. The ISS Water Processor Catalytic Reactor as a Post Processor for Advanced Water Reclamation Systems

    NASA Technical Reports Server (NTRS)

    Nalette, Tim; Snowdon, Doug; Pickering, Karen D.; Callahan, Michael

    2007-01-01

    Advanced water processors being developed for NASA s Exploration Initiative rely on phase change technologies and/or biological processes as the primary means of water reclamation. As a result of the phase change, volatile compounds will also be transported into the distillate product stream. The catalytic reactor assembly used in the International Space Station (ISS) water processor assembly, referred to as Volatile Removal Assembly (VRA), has demonstrated high efficiency oxidation of many of these volatile contaminants, such as low molecular weight alcohols and acetic acid, and is considered a viable post treatment system for all advanced water processors. To support this investigation, two ersatz solutions were defined to be used for further evaluation of the VRA. The first solution was developed as part of an internal research and development project at Hamilton Sundstrand (HS) and is based primarily on ISS experience related to the development of the VRA. The second ersatz solution was defined by NASA in support of a study contract to Hamilton Sundstrand to evaluate the VRA as a potential post processor for the Cascade Distillation system being developed by Honeywell. This second ersatz solution contains several low molecular weight alcohols, organic acids, and several inorganic species. A range of residence times, oxygen concentrations and operating temperatures have been studied with both ersatz solutions to provide addition performance capability of the VRA catalyst.

  18. In vitro and in vivo effects of ulipristal acetate on fertilization and early embryo development in mice.

    PubMed

    Gómez-Elías, Matías D; Munuce, María J; Bahamondes, Luis; Cuasnicú, Patricia S; Cohen, Débora J

    2016-01-01

    Does ulipristal acetate (UPA), a selective progesterone receptor modulator used for emergency contraception (EC), interfere with fertilization or early embryo development in vitro and in vivo? At doses similar to those used for EC, UPA does not affect mouse gamete transport, fertilization or embryo development. UPA acts as an emergency contraceptive mainly by inhibiting or delaying ovulation. However, there is little information regarding its effects on post-ovulatory events preceding implantation. This was an in vitro and in vivo experimental study involving the use of mouse gametes and embryos from at least three animals in each set of experiments. For in vitro fertilization experiments, mouse epididymal spermatozoa capacitated in the presence of different concentrations of UPA (0-1000 ng/ml) were used to inseminate cumulus-intact or cumulus-free eggs in the presence or absence of UPA during gamete co-incubation, and the percentage of fertilized eggs was determined. For in vivo fertilization experiments, superovulated females caged with proven fertile males were injected with UPA (40 mg/kg) or vehicle just before or just after mating and the percentage of fertilized eggs recovered from the ampulla was determined. To investigate the effect of UPA on embryo development, zygotes were recovered from mated females, cultured in the presence of UPA (1000 ng/ml) for 4 days and the progression of embryo development was monitored daily. In vitro studies revealed that the presence of UPA during capacitation and/or gamete co-incubation does not affect fertilization. Whereas the in vivo administration of UPA at the same time as hCG injection produced a decrease in the number of eggs ovulated compared with controls (vehicle injected animals, P < 0.05), no effects on fertilization were observed when UPA was administered shortly before or after mating. No differences were observed in either the percentage of cleaved embryos or the cleavage speed when UPA was present during in vitro embryo culture. Considering the ethical and technical limitations inherent to the use of human gametes for fertilization studies, the mouse model was used as an approach for exploring the potential effects of UPA on in vivo sperm transport and fertilization. Nevertheless, the extrapolation of these results to humans requires further investigation. This study presents new evidence on the lack of effect of UPA on gamete interaction and embryo development, providing new insights into the mechanism of action of UPA as an emergency contraceptive method with potential clinical implications. These new findings could contribute to increase the acceptability and proper use of UPA as an emergency contraceptive method. This study was partially supported by a National Agency of Scientific and Technological Promotion (ANPCyT), Argentina grants PICT 2011-061 to D.J.C. and PICT 2011-2023 to P.S.C. None of the authors has any competing interests to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. San Francisco urban partnership agreement : national evaluation report.

    DOT National Transportation Integrated Search

    2014-11-01

    This document presents the final report on the national evaluation of the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The UPA program targeted congestion reduction throu...

  20. Pharmacy access to ulipristal acetate in Hawaii: is a prescription enough?

    PubMed

    Bullock, Holly; Steele, Sarah; Kurata, Nicole; Tschann, Mary; Elia, Jennifer; Kaneshiro, Bliss; Salcedo, Jennifer

    2016-05-01

    To determine pharmacy availability of ulipristal acetate (UPA) and compare to availability of levonorgestrel-containing emergency contraceptive pills (LNG-ECPs). We conducted an observational population-based study utilizing a telephone-based secret shopper methodology. Researchers called all 198 unique retail pharmacies in Hawaii on December 2013-June 2014, representing themselves as patients and physicians. Only 2.6% of pharmacies had UPA immediately available, though 22.8% reported ability to order UPA. In contrast, 82.4% reported immediate availability of LNG-ECPs. No significant difference in availability was reported to patients and physicians. Availability of UPA is limited and significantly lower compared to LNG-ECPs. The study period did overlap with a change in distributor for UPA, likely capturing some disruption of the supply chain. Systems-based interventions are needed to address barriers to obtaining UPA. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Urokinase plasminogen activator mRNA is induced by IL-1alpha and TNF-alpha in in vitro acantholysis.

    PubMed

    Feliciani, Claudio; Toto, Paola; Wang, Binghe; Sauder, Daniel N; Amerio, Pierluigi; Tulli, Antonio

    2003-08-01

    The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1alpha and TNF-alpha are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1alpha and TNF-alpha are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1alpha, TNF-alpha and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1alpha, TNF-alpha and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1alpha/TNF-alpha mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-1alpha, anti-TNF-alpha and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1alpha and anti-TNF-alpha antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1alpha/TNF-alpha mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction.

  2. EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

    PubMed Central

    2012-01-01

    Backgrounds An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Methods Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. Results OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Conclusions Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion. PMID:22443116

  3. EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression.

    PubMed

    Lescaille, Géraldine; Menashi, Suzanne; Cavelier-Balloy, Bénédicte; Khayati, Farah; Quemener, Cathy; Podgorniak, Marie Pierre; Naïmi, Benyoussef; Calvo, Fabien; Lebbe, Céleste; Mourah, Samia

    2012-03-23

    An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

  4. Carbon Dioxide Reduction Post-Processing Sub-System Development

    NASA Technical Reports Server (NTRS)

    Abney, Morgan B.; Miller, Lee A.; Greenwood, Zachary; Barton, Katherine

    2012-01-01

    The state-of-the-art Carbon Dioxide (CO2) Reduction Assembly (CRA) on the International Space Station (ISS) facilitates the recovery of oxygen from metabolic CO2. The CRA utilizes the Sabatier process to produce water with methane as a byproduct. The methane is currently vented overboard as a waste product. Because the CRA relies on hydrogen for oxygen recovery, the loss of methane ultimately results in a loss of oxygen. For missions beyond low earth orbit, it will prove essential to maximize oxygen recovery. For this purpose, NASA is exploring an integrated post-processor system to recover hydrogen from CRA methane. The post-processor, called a Plasma Pyrolysis Assembly (PPA) partially pyrolyzes methane to recover hydrogen with acetylene as a byproduct. In-flight operation of post-processor will require a Methane Purification Assembly (MePA) and an Acetylene Separation Assembly (ASepA). Recent efforts have focused on the design, fabrication, and testing of these components. The results and conclusions of these efforts will be discussed as well as future plans.

  5. Minnesota urban partnership agreement national evaluation : content analysis test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the content analysis test plan for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing congestion by employing ...

  6. Minnesota urban partnership agreement national evaluation : telecommuting test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the telecommuting test plan for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing congestion by employing str...

  7. San Francisco urban partnership agreement : national evaluation plan.

    DOT National Transportation Integrated Search

    2009-12-22

    This report provides an analytic framework for evaluating the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects to be evaluated focus on those r...

  8. Minnesota urban partnership agreement national evaluation : cost benefit analysis test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the cost benefit analysis test plan for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing congestion by emplo...

  9. Minnesota urban partnership agreement national evaluation : safety data test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report provides the safety data test plan for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing congestion by employing strat...

  10. Minnesota urban partnership agreement national evaluation : traffic system data test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the traffic system data test plan for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing congestion by employi...

  11. Minnesota urban partnership agreement national evaluation : exogenous factors test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the exogenous factors test plan for the national evaluation of the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reduc...

  12. San Francisco urban partnership agreement, national evaluation : exogenous factors test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing exogenous factors data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects...

  13. Minnesota urban partnership agreement national evaluation : tolling test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the test plan for collecting and analyzing toll data for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing co...

  14. San Francisco urban partnership agreement, national evaluation : environmental data test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing environmental data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects foc...

  15. Minnesota urban partnership agreement national evaluation : transit system data test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the test plan for collecting and analyzing transit system data for the Minnesota Urban Partnership Agreement (UPA) National Evaluation under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA...

  16. Seattle/Lake Washington corridor urban partnership agreement : national evaluation report.

    DOT National Transportation Integrated Search

    2014-12-01

    This document presents the final report on the national evaluation of the Seattle/Lake Washington Corridor (LWC) Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Seattle UPA projects f...

  17. MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells.

    PubMed

    Salvi, Alessandro; Sabelli, Cristiano; Moncini, Silvia; Venturin, Marco; Arici, Bruna; Riva, Paola; Portolani, Nazario; Giulini, Stefano M; De Petro, Giuseppina; Barlati, Sergio

    2009-06-01

    Urokinase-type plasminogen activator (uPA) and c-met play a major role in cancer invasion and metastasis. Evidence has suggested that uPA and c-met overexpression may be coordinated in human hepatocellular carcinoma (HCC). In the present study, to understand whether the expression of these genes might be coregulated by specific microRNAs (miRs) in human cells, we predicted that Homo sapiens microRNA-23b could recognize two sites in the 3'-UTR of uPA and four sites in the c-met 3'-UTR by the algorithm pictar. The miR-23b expression analysis in human tumor and normal cells revealed an inverse trend with uPA and c-met expression, indicating that uPA and c-met negative regulation might depend on miR-23b expression. Transfection of miR-23b molecules in HCC cells (SKHep1C3) led to inhibition of protein expression of the target genes and caused a decrease in cell migration and proliferation capabilities. Furthermore, anti-miR-23b transfection in human normal AB2 dermal fibroblasts upregulated the expression of endogenous uPA and c-met. Cotransfection experiments in HCC cells of the miR-23b with pGL4.71 Renilla luciferase reporter gene constructs, containing the putative uPA and c-met 3'-UTR target sites, and with the pGL3 firefly luciferase-expressing vector showed a decrease in the relative luciferase activity. This would indicate that miR-23b can recognize target sites in the 3'-UTR of uPA and of c-met mRNAs and translationally repress the expression of uPA and c-met in HCC cells. The evidence obtained shows that overexpression of miR-23b leads to uPA and c-met downregulation and to decreased migration and proliferation abilities of HCC cells.

  18. San Francisco urban partnership agreement, national evaluation : cost benefit analysis test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing cost and benefit data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects ...

  19. San Francisco urban partnership agreement, national evaluation : traveler information data test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing traveler information data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA proje...

  20. San Francisco urban partnership agreement, national evaluation : traffic system data test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing traffic system data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects fo...

  1. San Francisco urban partnership agreement, national evaluation : transit system data test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing the transit system data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA project...

  2. In vitro regulation of pericellular proteolysis in prostatic tumor cells treated with bombesin.

    PubMed

    Festuccia, C; Guerra, F; D'Ascenzo, S; Giunciuglio, D; Albini, A; Bologna, M

    1998-01-30

    Bombesin is a potent inducer of signal trasduction pathways involved in the proliferation and invasion of androgen-insensitive prostatic tumor cells. This study examines the bombesin-mediated modulation of pericellular proteolysis, monitoring cell capability to migrate and invade basement membranes, using a chemo-invasion assay and analyzing protease production. The results suggest that bombesin could modulate the invasive potential of prostatic cell lines regulating secretion and cell-surface uptake of uPA and MMP-9 activation. In fact, in PC3 and DU145 cells but not in LNCaP cells, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) are induced by bombesin treatment. Bombesin also stimulates cell proliferation and this effect can be inhibited blocking uPA by antibodies and/or uPA inhibitor p-aminobenzamidine. Moreover, HMW-uPA induces cell proliferation in LNCaP cells, which do not produce uPA in the basal conditions, while PC3 and DU145 cell growth is supported by autocrine production of uPA. The increment of uPA activity on the external plasma membrane causes an increased pericellular plasmin activation. This effect is inhibited by antibodies against uPA and by p-aminobenzamidine. Similarly to EGF, bombesin stimulates secretion and activation of MMP-9 and TIMP-1 production. MMP-9 activation can be also obtained by HMW-uPA treatment, suggesting that plasma-membrane-bound uPA can start a proteolytic cascade involving MMP-9. Therefore, in in vitro assays, bombesin is able to modulate pericellular proteolysis and cell proliferation, differently distributing and activating proteolytic activities. This effect can be related to the "non-random" degradation of the extracellular matrix in which membrane uPA-uPAreceptor complexes could start bombesin-induced directional protein degradation during metastatic spread.

  3. 1999 status of the nation's highways, bridges and transit : conditions and performance : report to Congress : executive summary

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing telecommuting/TDM data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects...

  4. Urokinase-type plasminogen activator: a new target for male contraception?

    PubMed

    Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

    2015-01-01

    Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P < 0.05) when compared with control groups. However, the mating capacity and reproductive organ weights had no obvious change, and histological analysis of the testes and epididymides also showed normal morphology for immunized male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P < 0.05). Together, these observations indicated that subcutaneous injection human uPA to the male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development.

  5. [Emergency contraception: efficacy difference between levonorgestrel and ulipristal acetate depending on the follicular size at the time of an unprotected sexual intercourse].

    PubMed

    Jamin, C

    2015-03-01

    The most used treatment in the world for emergency contraception is the levonorgestrel (LNG) pill. However, its efficacy decreases if it is administered 3 days after unprotected sexual intercourse, whereas the ulipristal acetate (UPA) pill is effective up until 5 days afterwards. Pooled clinical data show that UPA is more effective than LNG when taken very shortly after intercourse (within 24h) or, conversely, between 72 and 120 h after intercourse. UPA is also more effective than LNG in inhibiting follicular rupture when administered near the time of ovulation. We show here why overall UPA is more effective than LNG in reducing the rate of unwanted pregnancies by demonstrating the effect of each product depending on the follicular size at the time of an unprotected sexual intercourse We also explain the difference between UPA and LNG in the maximum time to administration simply by the shift in ovulation and the fact that UPA has an effect on larger follicles than LNG does (18 mm vs. 14 mm), without postulating a hypothetical endometrial effect. We also explain why UPA and LNG remain emergency contraceptives and should not be used for daily contraception. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Stimulation of cell-surface urokinase-type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin.

    PubMed

    Ushiro, S; Mizoguchi, K; Yoshida, S; Jimi, S; Fujiwara, T; Yoshida, M; Wei, E T; Kitabgi, P; Amagaya, S; Ono, M; Kuwano, M

    1997-12-01

    To investigate if neurotensin (NT) could induce activation of urokinase-type plasminogen activator (uPA) in vascular endothelial cells, we utilized the acetyl-NT (8-13) analogue, TJN-950, in which the C-terminal leucine is reduced to leucinol. TJN-950 inhibited the binding of 125I-NT to membranes of newborn rat brains and of COS-7 cells transfected with rat NT receptor cDNA, but at 10(4) higher doses than NT (8-13). However, TJN-950 was as effective as NT in inducing the fibrinolytic activity in bovine vascular aortic and human umbilical vein endothelial cells, and enhanced the migration of vascular endothelial cells. Moreover, administration of TJN-950 induced neovascularization in the rat cornea in vivo. TJN-950 had no effect on expression of uPA, plasminogen activator inhibitor-1 or uPA receptor mRNA. The binding of 125I-TJN-950 to cell membranes was blocked by unlabeled uPA and TJN-950, but not the amino-terminal or 12-32 fragment of uPA. TJN-950 may enhance uPA activity in vascular endothelial cells by interacting with the uPA receptor, resulting in induction of angiogenesis.

  7. Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.

    PubMed

    Chen, Xiao-Xin; Leung, George Pak-Heng; Zhang, Zhang-Jin; Xiao, Jian-Bo; Lao, Li-Xing; Feng, Feng; Mak, Judith Choi-Wo; Wang, Ying; Sze, Stephen Cho-Wing; Zhang, Kalin Yan-Bo

    2017-09-01

    Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells. The results showed that UPAs significantly inhibited cell viability and migration ability in a dose-dependent manner. Moreover, UPAs induced apoptosis in a dose-dependent manner which was associated with increased cellular reactive oxygen species production, loss of mitochondrial membrane potential, increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential therapeutic agents for breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. WATERLOPP V2/64: A highly parallel machine for numerical computation

    NASA Astrophysics Data System (ADS)

    Ostlund, Neil S.

    1985-07-01

    Current technological trends suggest that the high performance scientific machines of the future are very likely to consist of a large number (greater than 1024) of processors connected and communicating with each other in some as yet undetermined manner. Such an assembly of processors should behave as a single machine in obtaining numerical solutions to scientific problems. However, the appropriate way of organizing both the hardware and software of such an assembly of processors is an unsolved and active area of research. It is particularly important to minimize the organizational overhead of interprocessor comunication, global synchronization, and contention for shared resources if the performance of a large number ( n) of processors is to be anything like the desirable n times the performance of a single processor. In many situations, adding a processor actually decreases the performance of the overall system since the extra organizational overhead is larger than the extra processing power added. The systolic loop architecture is a new multiple processor architecture which attemps at a solution to the problem of how to organize a large number of asynchronous processors into an effective computational system while minimizing the organizational overhead. This paper gives a brief overview of the basic systolic loop architecture, systolic loop algorithms for numerical computation, and a 64-processor implementation of the architecture, WATERLOOP V2/64, that is being used as a testbed for exploring the hardware, software, and algorithmic aspects of the architecture.

  9. Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF-κB, uPA activator and MMP9.

    PubMed

    Tong, Weihua; Wang, Quan; Sun, Donghui; Suo, Jian

    2016-11-01

    Curcumin, an active nontoxic ingredient of turmeric, possesses potent anti-inflammatory, antioxidant and anti-cancer properties; however, the molecular mechanisms of curcumin are not fully understood. The transcription factor nuclear factor-κB (NF-κB) is key in cellular processes, and the expression/activation of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9) are crucial for cell invasion. The present study investigated the hypothesis that curcumin inhibits colon cancer cell invasion by modulating NF-κB-mediated expression and activation of uPA and MMP9. Human colon cancer SW480 and LoVo cells were treated with various concentrations of curcumin. Curcumin was demonstrated to dose-dependently inhibit the adhesion and proliferation ability of LoVo and SW480 cells using Transwell and MTT assays, respectively. In addition, curcumin activated 5' AMP-activated protein kinase (AMPK) and suppressed p65 NF-κB phosphorylation, as shown by western blot analysis. Compound C, a potent AMPK inhibitor, abolished curcumin-induced inhibition of NF-κB, uPA and MMP9, suggesting that AMPK activation is responsible for curcumin-mediated NF-κB, uPA and MMP9 inhibition. The binding activity of NF-κB to DNA was examined and western blotting and quantitative polymerase reaction was performed to detect the effect of curcumin on the expression of uPA and MMP9. The present results revealed that curcumin significantly decreased the expression of uPA and MMP9 and NF-κB DNA binding activity. Furthermore, curcumin decreased the level of the p65 subunit of NF-κB binding to the promoter of the gene encoding uPA and MMP9, which suppressed transcriptional activation of uPA and MMP9. Overall, the present data suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and subsequent inhibition of p65 NF-κB, uPA and MMP9. The therapeutic potential of curcumin for colon cancer metastasis required additional study.

  10. Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs).

    PubMed

    Wang, Li; Zhang, Yi; Wang, Weiguo; Zhu, Yunjie; Chen, Yang; Tian, Bole

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3'-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53-R273H. Upregulation of uPA abolished CP-31398-mediated restoration of mutant p53 transcriptional activity in panc-1 CSCs. Gemcitabine treatment induced ER stress and promoted mutant p53-R273H stabilization via transcriptionally activated uPA which may contribute to chemoresistance to gemcitabine. Notably, upregulation of uPA by gemcitabine treatment may lead to the failure of CP-31398; thus, a novel strategy for modulating mutant p53 function needs to be developed.

  11. Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs)

    PubMed Central

    Wang, Weiguo; Zhu, Yunjie; Chen, Yang

    2017-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. Methods We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3’-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Results Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53-R273H. Upregulation of uPA abolished CP-31398-mediated restoration of mutant p53 transcriptional activity in panc-1 CSCs. Conclusion Gemcitabine treatment induced ER stress and promoted mutant p53-R273H stabilization via transcriptionally activated uPA which may contribute to chemoresistance to gemcitabine. Notably, upregulation of uPA by gemcitabine treatment may lead to the failure of CP-31398; thus, a novel strategy for modulating mutant p53 function needs to be developed. PMID:28854261

  12. Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

    PubMed

    Kahr, W H; Zheng, S; Sheth, P M; Pai, M; Cowie, A; Bouchard, M; Podor, T J; Rivard, G E; Hayward, C P

    2001-07-15

    The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

  13. Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.

    PubMed

    Schmitt, Manfred; Mengele, Karin; Napieralski, Rudolf; Magdolen, Viktor; Reuning, Ute; Gkazepis, Apostolos; Sweep, Fred; Brünner, Nils; Foekens, John; Harbeck, Nadia

    2010-11-01

    The prognostic and/or predictive value of the cancer biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for several cancer types in numerous clinically relevant retrospective or prospective studies, including a multicenter breast cancer therapy trial (Chemo-N0). Consequently, for the first time ever for any cancer biomarker for breast cancer, uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At present, two other breast cancer therapy trials, NNBC-3 and Plan B, also incorporating uPA and PAI-1 as treatment-assignment tools are in effect. Furthermore, small synthetic molecules targeting uPA are currently in Phase II clinical trials in patients afflicted with advanced cancer of the ovary, breast or pancreas.

  14. Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

    PubMed

    De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

    2016-07-01

    Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.

  15. Methane Post-Processor Development to Increase Oxygen Recovery beyond State-of-the-Art Carbon Dioxide Reduction Technology

    NASA Technical Reports Server (NTRS)

    Abney, Morgan; Miller, Lee; Greenwood, Zach; Iannantuono, Michelle; Jones, Kenny

    2013-01-01

    State-of-the-art life support carbon dioxide (CO2) reduction technology, based on the Sabatier reaction, is theoretically capable of 50% recovery of oxygen from metabolic CO2. This recovery is constrained by the limited availability of reactant hydrogen. Post-processing of the methane byproduct from the Sabatier reactor results in hydrogen recycle and a subsequent increase in oxygen recovery. For this purpose, a Methane Post-Processor Assembly containing three sub-systems has been developed and tested. The assembly includes a Methane Purification Assembly (MePA) to remove residual CO2 and water vapor from the Sabatier product stream, a Plasma Pyrolysis Assembly (PPA) to partially pyrolyze methane into hydrogen and acetylene, and an Acetylene Separation Assembly (ASepA) to purify the hydrogen product for recycle. The results of partially integrated testing of the sub-systems are reported.

  16. Methane Post-Processor Development to Increase Oxygen Recovery beyond State-of-the-Art Carbon Dioxide Reduction Technology

    NASA Technical Reports Server (NTRS)

    Abney, Morgan B.; Greenwood, Zachary; Miller, Lee A.; Alvarez, Giraldo; Iannantuono, Michelle; Jones, Kenny

    2013-01-01

    State-of-the-art life support carbon dioxide (CO2) reduction technology, based on the Sabatier reaction, is theoretically capable of 50% recovery of oxygen from metabolic CO2. This recovery is constrained by the limited availability of reactant hydrogen. Post-processing of the methane byproduct from the Sabatier reactor results in hydrogen recycle and a subsequent increase in oxygen recovery. For this purpose, a Methane Post-Processor Assembly containing three sub-systems has been developed and tested. The assembly includes a Methane Purification Assembly (MePA) to remove residual CO2 and water vapor from the Sabatier product stream, a Plasma Pyrolysis Assembly (PPA) to partially pyrolyze methane into hydrogen and acetylene, and an Acetylene Separation Assembly (ASepA) to purify the hydrogen product for recycle. The results of partially integrated testing of the sub-systems are reported

  17. Data processing with microcode designed with source coding

    DOEpatents

    McCoy, James A; Morrison, Steven E

    2013-05-07

    Programming for a data processor to execute a data processing application is provided using microcode source code. The microcode source code is assembled to produce microcode that includes digital microcode instructions with which to signal the data processor to execute the data processing application.

  18. Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy.

    PubMed

    Qin, Wenyi; Gui, Gerald; Zhang, Ke; Twelves, Dominique; Kliethermes, Beth; Sauter, Edward R

    2012-02-01

    Herein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND) of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1) predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF) which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery. In the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11) ND samples collected from different participants requiring breast surgery, all of whom also had TF results. uPA expression was higher in pre- and PAI-1 in postmenopausal women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively), or benign pathology (p = .017 and .033, respectively); and 2) abnormal (atypia or cancer) versus benign pathology (p = .018 and .052, respectively). High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC) of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time. uPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these markers may prove useful in early breast cancer detection.

  19. Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy

    PubMed Central

    2012-01-01

    Background Herein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND) of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1) predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF) which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery. Methods In the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11) ND samples collected from different participants requiring breast surgery, all of whom also had TF results. Results uPA expression was higher in pre- and PAI-1 in postmenopausal women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively), or benign pathology (p = .017 and .033, respectively); and 2) abnormal (atypia or cancer) versus benign pathology (p = .018 and .052, respectively). High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC) of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time. Conclusions uPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these markers may prove useful in early breast cancer detection. PMID:22296682

  20. Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment.

    PubMed

    Blavignac, Jessica; Bunimov, Natalia; Rivard, Georges E; Hayward, Catherine P M

    2011-09-01

    Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with reduced platelet counts and a unique gain-of-function defect in fibrinolysis due to increased expression and storage of urokinase plasminogen activator (uPA) by megakaryocytes. QPD increases risks for bleeding and its key clinical feature is delayed-onset bleeding, following surgery, dental procedures or trauma, which responds only to treatment with fibrinolytic inhibitors. The genetic cause of the disorder is a tandem duplication mutation of the uPA gene, PLAU, which upregulates uPA expression in megakaryocytes by an unknown mechanism. The increased platelet stores of uPA trigger plasmin-mediated degradation of QPD α-granule proteins. The gain-of-function defect in fibrinolysis is thought to be central to the pathogenesis of QPD bleeding as the activation of QPD platelets leads to release of uPA from α-granules and accelerated clot lysis. The purpose of this review is to summarize current knowledge on QPD pathogenesis and the recommended approaches to QPD diagnosis and treatment. Thieme Medical Publishers.

  1. Up-Regulation of PAI-1 and Down-Regulation of uPA Are Involved in Suppression of Invasiveness and Motility of Hepatocellular Carcinoma Cells by a Natural Compound Berberine.

    PubMed

    Wang, Xuanbin; Wang, Ning; Li, Hongliang; Liu, Ming; Cao, Fengjun; Yu, Xianjun; Zhang, Jingxuan; Tan, Yan; Xiang, Longchao; Feng, Yibin

    2016-04-16

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death and its prognosis remains poor due to the high risk of tumor recurrence and metastasis. Berberine (BBR) is a natural compound derived from some medicinal plants, and accumulating evidence has shown its potent anti-tumor activity with diverse action on tumor cells, including inducing cancer cell death and blocking cell cycle and migration. Molecular targets of berberine involved in its inhibitory effect on the invasiveness remains not yet clear. In this study, we identified that berberine exhibits a potent inhibition on the invasion and migration of HCC cells. This was accompanied by a dose-dependent down-regulation of expression of Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 in berberine-treated HCC cells. Furthermore, berberine inactivated p38 and Erk1/2 signaling pathway in HCC cells. Primarily, this may be attributed to the up-regulation of plasminogen activator inhibitor-1 (PAI-1), a tumor suppressor that can antagonize uPA receptor and down-regulation of uPA. Blockade of uPA receptor-associated pathways leads to reduced invasiveness and motility of berberine-treated HCC cells. In conclusion, our findings identified for the first time that inactivation of uPA receptor by up-regulation of PAI-1 and down-regulation of uPA is involved in the inhibitory effect of berberine on HCC cell invasion and migration.

  2. RhoA/ROCK pathway mediates leptin-induced uPA expression to promote cell invasion in ovarian cancer cells.

    PubMed

    Ghasemi, Ahmad; Hashemy, Seyed Isaac; Aghaei, Mahmoud; Panjehpour, Mojtaba

    2017-04-01

    Previous studies have shown that leptin, an adipocyte-secreted hormone, stimulates ovarian cancer invasion. Here, we investigated the contribution of uPA in leptin-induced ovarian cancer cell invasion. The cell invasion and migration experiments were carried out using matrigel invasion and wound healing assays in ovarian cancer cell lines (OVCAR3, SKOV3and CaoV-3). The mechanism underlying the invasive effect of leptin was examined using cell transfection with Ob-Rb siRNA, pre-treatment with a specific inhibitor of RhoA and ROCK, RhoA activation assay, OB-Rb, Rock and upA protein expression. Our results show that leptin induced ovarian cancer cell invasion via up-regulating upA in a time and dose-dependent manner, which was attenuated using knockdown of OB-Rb by siRNA. Moreover, pre-incubation with C3 (inhibitor of RhoA) and Y-27632 (inhibitor of ROCK) effectively attenuated leptin-induced upA expression and inhibited invasive ability of ovarian cancer cells. We also found that pretreatment with inhibitors of PI3K/AKT (LY294002), JAK/STAT (AG490) and NF-kB (BAY 11-7082) significantly reduced leptin-induced upA expression. Collectively, our findings demonstrate that OB-Rb, RhoA/ROCK, PI3K/AKT, JAK/STAT pathways and NF-kB activation are involved in leptin-induced upA expression. These results may provide a new mechanism that facilitates leptin-induced ovarian cancer invasion. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The urokinase plasminogen activator system components are regulated by vascular endothelial growth factor D in bovine oviduct.

    PubMed

    García, Daniela C; Russo-Maenza, Agostina; Miceli, Dora C; Valdecantos, Pablo A; Roldán-Olarte, Mariela

    2018-06-08

    SummaryThe mammalian oviduct plays a pivotal role in the success of early reproductive events. The urokinase plasminogen activator system (uPAS) is present in the bovine oviduct and is involved in extracellular matrix remodelling through plasmin generation. This system can be regulated by several members of the vascular endothelial growth factors (VEGF) and their receptors. In this study, the VEGF-D effect on the regulation of uPAS was evaluated. First, RT-polymerase chain reaction (PCR) analyses were used to evidence the expression of VEGF-D and its receptors in oviductal epithelial cells (BOEC). VEGF-D, VEGFR2 and VEGFR3 transcripts were found in ex vivo and in vitro BOEC, while only VEGFR2 mRNA was present after in vitro conditions. VEGF-D showed a regulatory effect on uPAS gene expression in a dose-dependent manner, inducing an increase in the expression of both uPA and its receptor (uPAR) at 24 h post-induction and decreases in the expression of its inhibitor (PAI-1). In addition, the regulation of cell migration induced by VEGF-D and uPA in BOEC monolayer cultures was analyzed. The wound areas of monolayer cultures incubated with VEGF-D 10 ng/ml or uPA 10 nM were modified and significant differences were found at 24 h for both stimulations. These results indicated that uPAS and VEGF-D systems can modify the arrangement of the bovine oviductal epithelium and contribute to the correct maintenance of the oviductal microenvironment.

  4. Mechanisms regulating plasminogen activators in transformed retinal ganglion cells

    PubMed Central

    Rock, Nathan; Chintala, Shravan K.

    2008-01-01

    Irreversible loss of retinal ganglion cells (RGCs) is a major clinical issue in glaucoma, but the mechanisms that lead to RGC death are currently unclear. We have previously reported that elevated levels of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) cause the death of RGCs in vivo and transformed retinal ganglion cells (RGC-5) in vitro. Yet, it is unclear how secreted proteases such as tPA and uPA directly cause RGCs' death. In this study, by employing RGC-5 cells, we report that tPA and uPA elicit their direct effect through the low-density lipoprotein-related receptor-1 (LRP-1). We also show that blockade of protease-LRP-1 interaction leads to a compete reduction in autocrine synthesis of tPA and uPA, and prevents protease-mediated death of RGC-5 cells. RGC-5 cells were cultured in serum-free medium and treated with 2.0 uM Staurosporine to induce their differentiation. Neurite outgrowth was observed by a phase contrast microscope and quantified by NeuroJ imaging software. Proteolytic activities of tPA and uPA were determined by zymography assays. Cell viability was determined by MTT assays. Compared to untreated RGC-5 cells, cells treated with Staurosporine differentiated, synthesized and secreted elevated levels of tPA and uPA, and underwent cell death. In contrast, when RGC-5 cells were treated with Staurosporine along with the receptor associated protein (RAP), proteolytic activities of both tPA and uPA were significantly reduced. Under these conditions, a significant number of RGC-5 cells survived and showed increased neurite outgrowth. These results indicate that LRP-1 regulates autocrine synthesis of tPA and uPA in RGC-5 cells and suggest that the use of RAP to antagonize the effect of proteases may be a way to prevent RGC death in glaucoma. PMID:18243176

  5. "I don't know what I would have done." Women's experiences acquiring ulipristal acetate emergency contraception online from 2011 to 2015.

    PubMed

    Smith, Nicole K; Cleland, Kelly; Wagner, Brandon; Trussell, James

    2017-04-01

    This study describes women's reasons for seeking ulipristal acetate (UPA) for emergency contraception (EC) through the only authorized online retailer for UPA EC in the US. Women aged 14 to 59 years, living in states that allow prescription medications to be shipped from out-of-state, accessed the KwikMed online pharmacy between January 2011 and December 2015. After completing a medical eligibility screener, women answered optional multiple-choice questions. To obtain UPA through KwikMed, individuals must be female, 50 years of age or younger, not currently pregnant or breastfeeding and not attempting to order UPA more than once within 30 days or more than four times per year. Over the 5-year period, KwikMed provided 8019 prescriptions for UPA, and the number of women using this service more than tripled over time. Among women who responded to the survey questions (n=7133; response rate = 89%), most sought EC because of a condom failure (45.3%) or because they did not use regular contraception (41.2%). More than half (53.5%) of women reported that they chose UPA because of its effectiveness compared to levonorgestrel EC pills, and 58.9% preferred ordering UPA online because they found it easier than getting it from a doctor, clinic or pharmacy. This study documents the importance of providing confidential services for acquiring EC online. Benefits of online access include convenience, less embarrassment, avoiding situations in which a provider might refuse to provide EC because of their own ideological belief and more reliable availability for this time-sensitive contraceptive. Though physical, logistical and societal barriers can restrict women's access to EC, this study demonstrates that providing access to UPA online empowers women to obtain EC when they need it. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Gyro and Accelerometer Based Navigation System for a Mobile Autonomous Robot.

    DTIC Science & Technology

    1985-12-02

    special thanks goes to our thesis advisor Dr. Matthew Kabrisky for having the confidence to turn us loose on this project. Additionally, we would...Wordmaster Word Processor 1 Wordstar Word Processor 1 Virtual Devices Robo A 6802 Cross Assembler 1 Modem 720 Communication Program 1 CP/M Operating

  7. Virtualization for Cost-Effective Teaching of Assembly Language Programming

    ERIC Educational Resources Information Center

    Cadenas, José O.; Sherratt, R. Simon; Howlett, Des; Guy, Chris G.; Lundqvist, Karsten O.

    2015-01-01

    This paper describes a virtual system that emulates an ARM-based processor machine, created to replace a traditional hardware-based system for teaching assembly language. The virtual system proposed here integrates, in a single environment, all the development tools necessary to deliver introductory or advanced courses on modern assembly language…

  8. Electromagnetic compatibility test report for the tethered satellite data acquisition and control assembly

    NASA Astrophysics Data System (ADS)

    Hoskins, Douglas; Snead, Robert

    1988-05-01

    This report details the results of an electromagnetic compatibility test on the SCI Systems Data Acquisition and Control Assembly (DACA). This assembly is an electronic processor which controls the central communication link from the Tethered Satellite System (TSS) to the Space Transportation System Orbiter Space Shuttle.

  9. Advanced On-Board Processor (AOP). [for future spacecraft applications

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Advanced On-board Processor the (AOP) uses large scale integration throughout and is the most advanced space qualified computer of its class in existence today. It was designed to satisfy most spacecraft requirements which are anticipated over the next several years. The AOP design utilizes custom metallized multigate arrays (CMMA) which have been designed specifically for this computer. This approach provides the most efficient use of circuits, reduces volume, weight, assembly costs and provides for a significant increase in reliability by the significant reduction in conventional circuit interconnections. The required 69 CMMA packages are assembled on a single multilayer printed circuit board which together with associated connectors constitutes the complete AOP. This approach also reduces conventional interconnections thus further reducing weight, volume and assembly costs.

  10. Dual Fan Separator within the Universal Waste Management System

    NASA Technical Reports Server (NTRS)

    Stapleton, Tom; Converse, Dave; Broyan, James Lee, Jr.

    2014-01-01

    Since NASA's new spacecraft in development for both LEO and Deep Space capability have considerable crew volume reduction in comparison to the Space Shuttle, it is clear that NASA requires a smaller and less expensive commode. The UTAS Universal Waste Management System (UWMS) was designed to address these new constraints, resulting in an 80% volume reduction in the cabin while enhancing performance. Whereas all of the current space commodes use air flow to capture both urine and feces and separate air from the captured air/urine mixture, the UWMS commode and urine fans and the urine separator were combined into a single unit. This unit enables use of a single motor and motor controller, which provides considerable packaging and weight efficiency. In some of the intended platform applications for the UWMS, the urine is pumped to a water reclamation system. The ISS Urine Processor Assembly (UPA) system requires delivered urine to include less than 0.25% air inclusion. Air inclusion in centrifugal urine separators is greatly dependent on its rotational speed. To satisfy this requirement, a gear reducer was included, allowing the fans to rotate at a much higher speed than the separator. This new design, the Dual Fan Separator (DFS) has been designed, prototyped and tested. This paper will outline the studies and analysis performed to develop the design configuration for testing. The studies included a configuration trade study, dynamic stability analysis of the rotating bodies and a performance analysis of included labyrinth seals. NASA is considereing a program to fly the UWMS aboard the ISS as a flight experiment. The goal of the design activity is to elevate the Technical Readiness Level (TRL) of the Dual Fan Separator and determine if the concept is ready to be included in flight experiment deliverable.

  11. Development of an Advanced Recycle Filter Tank Assembly for the ISS Urine Processor Assembly

    NASA Technical Reports Server (NTRS)

    Link, Dwight E., Jr.; Carter, Donald Layne; Higbie, Scott

    2010-01-01

    Recovering water from urine is a process that is critical to supporting larger crews for extended missions aboard the International Space Station. Urine is collected, preserved, and stored for processing into water and a concentrated brine solution that is highly toxic and must be contained to avoid exposure to the crew. The brine solution is collected in an accumulator tank, called a Recycle Filter Tank Assembly (RFTA) that must be replaced monthly and disposed in order to continue urine processing operations. In order to reduce resupply requirements, a new accumulator tank is being developed that can be emptied on orbit into existing ISS waste tanks. The new tank, called the Advanced Recycle Filter Tank Assembly (ARFTA) is a metal bellows tank that is designed to collect concentrated brine solution and empty by applying pressure to the bellows. This paper discusses the requirements and design of the ARFTA as well as integration into the urine processor assembly.

  12. Cell surface antigens in renal tumour cells: detection by immunoluminescence and enzymatic analysis

    PubMed Central

    Laube, F; Göhring, B; Sann, H; Willhardt, I

    2001-01-01

    Two renal cell carcinoma cell lines (49RC 43STR and 75RC 2STR) were characterized by detection of the cell surface proteins: CD44(var), intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator (uPA) and its receptor and aminopeptidase N (APN). To detect their localization the immunoluminescent technique was used. In addition, the enzyme activity of uPA and APN was investigated in cell suspensions as well as in monolayers. The latter procedure was more advantageous since the additional use of HPLC permits a single registration of the fluorescent hydrolysis-product AMC (7-amino-4-methylcoumarin) without interference by cellular autofluorescence or non-reacted fluorescent substrate. Unlike 75RC 2STR, the cell line 49RC 43STR expressed high levels of uPA and APN. Contrary to that the cell line 75RC 2STR expressed high levels of ICAM-1 and CD44(v6), whereas 49RC 43STR showed a low level of ICAM-1 and no distinct light signal with anti-CD44(v6). The uPA activity was measured directly as well as indirectly (via plasmin) with the substrate Z-Gly-Gly-Arg-AMC. Both activator and plasmin activity were inhibited by D-Val-Phe-Lys-CMK and phenylmethylsulfonyl fluoride. The anti-catalytic antibody to uPA and that to uPA receptor were found to be inhibiting the uPA activity in a concentration-dependent manner. APN activity was assayed using alanine-p-nitroanilide. Peptidase activity was effectively inhibited by 1,10-phenanthroline and partly inhibited by ethylenediamine-tetraacetic acid. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556847

  13. “I don't know what I would have done.” Women's experiences acquiring ulipristal acetate emergency contraception online from 2011 to 2015

    PubMed Central

    Smith, Nicole K.; Cleland, Kelly; Wagner, Brandon; Trussell, James

    2016-01-01

    Objectives This study describes women's reasons for seeking ulipristal acetate (UPA) for emergency contraception (EC) through the only authorized online retailer for UPA EC in the US. Study design Women aged 14 to 59 years, living in states that allow prescription medications to be shipped from out-of-state, accessed the KwikMed online pharmacy between January 2011 and December 2015. After completing a medical eligibility screener, women answered optional multiple-choice questions. To obtain UPA through KwikMed, individuals must be female, 50 years of age or younger, not currently pregnant or breastfeeding and not attempting to order UPA more than once within 30 days or more than four times per year. Results Over the five-year period, KwikMed provided 8,019 prescriptions for UPA, and the number of women using this service more than tripled over time. Among women who responded to the survey questions (n=7,133; response rate = 89%), most sought EC because of a condom failure (45.3%) or because they did not use regular contraception (41.2%). More than half (53.5%) of women reported that they chose UPA because of its effectiveness compared to levonorgestrel EC pills, and 58.9% preferred ordering UPA online because they found it easier than getting it from a doctor, clinic, or pharmacy. Conclusions This study documents the importance of providing confidential services for acquiring EC online. Benefits of online access include convenience, less embarrassment, avoiding situations in which a provider might refuse to provide EC because of their own ideological belief, and more reliable availability for this time-sensitive contraceptive. PMID:27769767

  14. Gene expression changes in uterine myomas in response to ulipristal acetate treatment.

    PubMed

    Courtoy, Guillaume E; Donnez, Jacques; Ambroise, Jérôme; Arriagada, Pablo; Luyckx, Mathieu; Marbaix, Etienne; Dolmans, Marie-Madeleine

    2018-05-07

    Does ulipristal acetate (UPA) modify the expression of genes related to apoptosis or the extracellular matrix in uterine myomas and are any modifications associated with a clinical response? Targeted analysis of 176 apoptosis- or extracellular-matrix-related genes was conducted using polymerase chain reaction (PCR) arrays. Relevant results were validated by quantitative PCR. Four groups were established: responsive short-term (one course, n = 9), responsive long-term (two to four courses, n = 9), non-responsive (n = 9), and the control group who was not given any hormone therapy (n = 9). The clinical response was monitored by medical imagery and considered significant when volume reduction was greater than 25%. Compared with untreated myomas, significant changes in expression of four genes were found in UPA-treated myomas. Gene expression of integrin subunit beta 4 was repressed by UPA treatment (fold change [FC] = -12.50, P < 0.001, q < 0.001), tenascin-C expression was downregulated in UPA-responsive patients (FC = -2.50, P = 0.010, q = 0.090), survivin was repressed in short-term UPA-responsive tumours (FC = -7.69, P < 0.001, q = 0.010), and catenin delta 2 gene expression was upregulated in non-responsive myomas (FC = +7.36, P < 0.001, q = 0.010). This characterization provides the first molecular distinction between myomas responsive or non-responsive to UPA treatment. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  15. Inhibitory effect of amiloride on the urokinase plasminogen activators in prostatic cancer.

    PubMed

    Ray, P; Bhatti, R; Gadarowski, J; Bell, N; Nasruddin, S

    1998-01-01

    The diuretic drug amiloride (AMLD), which competitively inhibits the catalytic activity of urokinase plasminogen activators (UPA), was used to study its effects on the proteolytic enzymes implicated in the invasiveness and metastases in a prostatic tumor model carrying two different sublines of adenocarcinoma of the prostate. Our data showed that UPA activity was significantly higher, both in the cytosol and pellet of R3327-AT3, a fast-growing highly metastatic and androgen-insensitive tumor, as compared to the G3327-G subline, a slow-growing nonmetastatic tumor of the prostate. The UPA activity in AT3 tumor dropped when the rats were treated with AMLD for 3 weeks. The UPA activity in the sera and tumor effusions from rats with AT3 tumor was significantly higher as compared to those with G subline tumor. The number of pulmonary metastatic foci was the same in untreated rats as compared to those treated with AMLD. The lymph node inspection after 3 weeks revealed no secondary tumor in the AMLD-treated group. The role of UPA in the metastases of prostate cancer is discussed.

  16. Integral Fast Reactor fuel pin processor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levinskas, D.

    1993-01-01

    This report discusses the pin processor which receives metal alloy pins cast from recycled Integral Fast Reactor (IFR) fuel and prepares them for assembly into new IFR fuel elements. Either full length as-cast or precut pins are fed to the machine from a magazine, cut if necessary, and measured for length, weight, diameter and deviation from straightness. Accepted pins are loaded into cladding jackets located in a magazine, while rejects and cutting scraps are separated into trays. The magazines, trays, and the individual modules that perform the different machine functions are assembled and removed using remote manipulators and master-slaves.

  17. Integral Fast Reactor fuel pin processor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levinskas, D.

    1993-03-01

    This report discusses the pin processor which receives metal alloy pins cast from recycled Integral Fast Reactor (IFR) fuel and prepares them for assembly into new IFR fuel elements. Either full length as-cast or precut pins are fed to the machine from a magazine, cut if necessary, and measured for length, weight, diameter and deviation from straightness. Accepted pins are loaded into cladding jackets located in a magazine, while rejects and cutting scraps are separated into trays. The magazines, trays, and the individual modules that perform the different machine functions are assembled and removed using remote manipulators and master-slaves.

  18. Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

    NASA Astrophysics Data System (ADS)

    Hankins, Patrick Leon

    While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT-CT imaging studies showed the preferential accumulation of these nanobins in an orthotopic model of breast cancer. Due to their biocompatibility, robustness, and extensive history in the clinic, liposomes are an ideal drug delivery vehicle for the development of targeted therapies. The data presented in this thesis demonstrates the potential for active targeting to increase the therapeutic index of nanoscale drug delivery systems by increasing antitumor effect while simultaneously preventing drug uptake in peripheral tissue. In particular, targeting nanoparticles to the uPA system is a promising strategy for the treatment of many advanced, metastatic cancers.

  19. a Real-Time Computer Music Synthesis System

    NASA Astrophysics Data System (ADS)

    Lent, Keith Henry

    A real time sound synthesis system has been developed at the Computer Music Center of The University of Texas at Austin. This system consists of several stand alone processors that were constructed jointly with White Instruments in Austin. These processors can be programmed as general purpose computers, but are provided with a number of specialized interfaces including: MIDI, 8 bit parallel, high speed serial, 2 channels analog input (18 bit A/Ds, 48kHz sample rate), and 4 channels analog output (18 bit D/As). In addition, a basic music synthesis language (Music56000) has been written in assembly code. On top of this, a symbolic compiler (PatchWork) has been developed to enable algorithms which run in these processors to be created graphically. And finally, a number of efficient time domain numerical models have been developed to enable the construction, simulation, control, and synthesis of many musical acoustics systems in real time on these processors. Specifically, assembly language models for cylindrical and conical horn sections, dissipative losses, tone holes, bells, and a number of linear and nonlinear boundary conditions have been developed.

  20. A VME-based software trigger system using UNIX processors

    NASA Astrophysics Data System (ADS)

    Atmur, Robert; Connor, David F.; Molzon, William

    1997-02-01

    We have constructed a distributed computing platform with eight processors to assemble and filter data from digitization crates. The filtered data were transported to a tape-writing UNIX computer via ethernet. Each processor ran a UNIX operating system and was installed in its own VME crate. Each VME crate contained dual-port memories which interfaced with the digitizers. Using standard hardware and software (VME and UNIX) allows us to select from a wide variety of non-proprietary products and makes upgrades simpler, if they are necessary.

  1. System support software for the Space Ultrareliable Modular Computer (SUMC)

    NASA Technical Reports Server (NTRS)

    Hill, T. E.; Hintze, G. C.; Hodges, B. C.; Austin, F. A.; Buckles, B. P.; Curran, R. T.; Lackey, J. D.; Payne, R. E.

    1974-01-01

    The highly transportable programming system designed and implemented to support the development of software for the Space Ultrareliable Modular Computer (SUMC) is described. The SUMC system support software consists of program modules called processors. The initial set of processors consists of the supervisor, the general purpose assembler for SUMC instruction and microcode input, linkage editors, an instruction level simulator, a microcode grid print processor, and user oriented utility programs. A FORTRAN 4 compiler is undergoing development. The design facilitates the addition of new processors with a minimum effort and provides the user quasi host independence on the ground based operational software development computer. Additional capability is provided to accommodate variations in the SUMC architecture without consequent major modifications in the initial processors.

  2. Electrical Prototype Power Processor for the 30-cm Mercury electric propulsion engine

    NASA Technical Reports Server (NTRS)

    Biess, J. J.; Frye, R. J.

    1978-01-01

    An Electrical Prototpye Power Processor has been designed to the latest electrical and performance requirements for a flight-type 30-cm ion engine and includes all the necessary power, command, telemetry and control interfaces for a typical electric propulsion subsystem. The power processor was configured into seven separate mechanical modules that would allow subassembly fabrication, test and integration into a complete power processor unit assembly. The conceptual mechanical packaging of the electrical prototype power processor unit demonstrated the relative location of power, high voltage and control electronic components to minimize electrical interactions and to provide adequate thermal control in a vacuum environment. Thermal control was accomplished with a heat pipe simulator attached to the base of the modules.

  3. Evaluating local indirect addressing in SIMD proc essors

    NASA Technical Reports Server (NTRS)

    Middleton, David; Tomboulian, Sherryl

    1989-01-01

    In the design of parallel computers, there exists a tradeoff between the number and power of individual processors. The single instruction stream, multiple data stream (SIMD) model of parallel computers lies at one extreme of the resulting spectrum. The available hardware resources are devoted to creating the largest possible number of processors, and consequently each individual processor must use the fewest possible resources. Disagreement exists as to whether SIMD processors should be able to generate addresses individually into their local data memory, or all processors should access the same address. The tradeoff is examined between the increased capability and the reduced number of processors that occurs in this single instruction stream, multiple, locally addressed, data (SIMLAD) model. Factors are assembled that affect this design choice, and the SIMLAD model is compared with the bare SIMD and the MIMD models.

  4. The duplication mutation of Quebec platelet disorder dysregulates PLAU, but not C10orf55, selectively increasing production of normal PLAU transcripts by megakaryocytes but not granulocytes.

    PubMed

    Hayward, Catherine P M; Liang, Minggao; Tasneem, Subia; Soomro, Asim; Waye, John S; Paterson, Andrew D; Rivard, Georges E; Wilson, Michael D

    2017-01-01

    Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 78 kb region of chromosome 10 containing PLAU (the uPA gene) and C10orf55, a gene of unknown function. QPD increases uPA in platelets and megakaryocytes >100 fold, far more than expected for a gene duplication. To investigate the tissue-specific effect that PLAU duplication has on gene expression and transcript structure in QPD, we tested if QPD leads to: 1) overexpression of normal or unique PLAU transcripts; 2) increased uPA in leukocytes; 3) altered levels of C10orf55 mRNA and/or protein in megakaryocytes and leukocytes; and 4) global changes in megakaryocyte gene expression. Primary cells and cultured megakaryocytes from donors were prepared for quantitative reverse polymerase chain reaction analyses, RNA-seq and protein expression analyses. Rapidly isolated blood leukocytes from QPD subjects showed only a 3.9 fold increase in PLAU transcript levels, in keeping with the normal to minimally increased uPA in affinity purified, QPD leukocytes. All subjects had more uPA in granulocytes than monocytes and minimal uPA in lymphocytes. QPD leukocytes expressed PLAU alleles in proportions consistent with an extra copy of PLAU on the disease chromosome, unlike QPD megakaryocytes. QPD PLAU transcripts were consistent with reference gene models, with a much higher proportion of reads originating from the disease chromosome in megakaryocytes than granulocytes. QPD and control megakaryocytes contained minimal reads for C10orf55, and C10orf55 protein was not increased in QPD megakaryocytes or platelets. Finally, our QPD megakaryocyte transcriptome analysis revealed a global down regulation of the interferon type 1 pathway. We suggest that the low endogenous levels of uPA in blood are actively regulated, and that the regulatory mechanisms are disrupted in QPD in a megakaryocyte-specific manner.

  5. The duplication mutation of Quebec platelet disorder dysregulates PLAU, but not C10orf55, selectively increasing production of normal PLAU transcripts by megakaryocytes but not granulocytes

    PubMed Central

    Soomro, Asim; Waye, John S.; Paterson, Andrew D.; Rivard, Georges E.; Wilson, Michael D.

    2017-01-01

    Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 78 kb region of chromosome 10 containing PLAU (the uPA gene) and C10orf55, a gene of unknown function. QPD increases uPA in platelets and megakaryocytes >100 fold, far more than expected for a gene duplication. To investigate the tissue-specific effect that PLAU duplication has on gene expression and transcript structure in QPD, we tested if QPD leads to: 1) overexpression of normal or unique PLAU transcripts; 2) increased uPA in leukocytes; 3) altered levels of C10orf55 mRNA and/or protein in megakaryocytes and leukocytes; and 4) global changes in megakaryocyte gene expression. Primary cells and cultured megakaryocytes from donors were prepared for quantitative reverse polymerase chain reaction analyses, RNA-seq and protein expression analyses. Rapidly isolated blood leukocytes from QPD subjects showed only a 3.9 fold increase in PLAU transcript levels, in keeping with the normal to minimally increased uPA in affinity purified, QPD leukocytes. All subjects had more uPA in granulocytes than monocytes and minimal uPA in lymphocytes. QPD leukocytes expressed PLAU alleles in proportions consistent with an extra copy of PLAU on the disease chromosome, unlike QPD megakaryocytes. QPD PLAU transcripts were consistent with reference gene models, with a much higher proportion of reads originating from the disease chromosome in megakaryocytes than granulocytes. QPD and control megakaryocytes contained minimal reads for C10orf55, and C10orf55 protein was not increased in QPD megakaryocytes or platelets. Finally, our QPD megakaryocyte transcriptome analysis revealed a global down regulation of the interferon type 1 pathway. We suggest that the low endogenous levels of uPA in blood are actively regulated, and that the regulatory mechanisms are disrupted in QPD in a megakaryocyte-specific manner. PMID:28301587

  6. Qualifications of drivers - vision and diabetes

    DOT National Transportation Integrated Search

    2011-01-01

    San Francisco UPA projects focus on reducing traffic congestion related to parking in downtown San Francisco. Intelligent transportation systems (ITS) technologies underlie many of the San Francisco UPA projects, including parking and roadway sensors...

  7. Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type I plasminogen activator inhibitor.

    PubMed

    Sordat, B; Reiter, L; Cajot, J F

    1990-12-02

    Gene transfer techniques were utilized to evaluate the role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in enhancing or preventing the expression of the invasive malignant phenotype, respectively. Mouse L-cell transfectants expressing human uPA or human PAI-1 as well as mouse B16 transfectants expressing mouse uPA or human PAI-1 were generated. These transfectants were tested using a variety of experimental methods including smooth muscle cell matrix solubilization in vitro, lung colony formation in vivo and co-cultures of antagonist-expressing cells in vitro. Results from these studies provide direct evidence for an enhancing role of uPA in malignant invasion and experimental metastasis and for a modulatory role of PAI-1 in tumor cell-mediated breakdown of extracellular matrices.

  8. Current management of myomas: the place of medical therapy with the advent of selective progesterone receptor modulators.

    PubMed

    Donnez, Jacques; Arriagada, Pablo; Donnez, Olivier; Dolmans, Marie-Madeleine

    2015-12-01

    To review the current management of myomas with the advent of selective progesterone receptor modulators. Selective progesterone receptor modulators have proved effective and recent publications on the use of ulipristal acetate (UPA) have analyzed the performance of long-term intermittent utilization of 10 mg UPA given in repeated courses of 3 months. This long-term intermittent therapy maximizes the efficacy of UPA. Indeed, control of bleeding is achieved sooner after each course. With each subsequent course, a statistically greater number of patients show a fibroid volume reduction of more than 50%. The choice of therapy is influenced by different factors, such as the severity of symptoms, tumor characteristics, age, and wish to preserve the uterus (and fertility). Use of UPA will undoubtedly modify the surgical approach.

  9. Downregulation of Extracellular Matrix Metalloproteinase Inducer by scFv-M6-1B9 Intrabody Suppresses Cervical Cancer Invasion Through Inhibition of Urokinase-Type Plasminogen Activator.

    PubMed

    Panich, Tipattaraporn; Tragoolpua, Khajornsak; Pata, Supansa; Tayapiwatana, Chatchai; Intasai, Nutjeera

    2017-02-01

    Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) accelerates tumor invasion and metastasis via activation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) expression. The authors were interested in whether the scFv-M6-1B9 intrabody against EMMPRIN that retains EMMPRIN in endoplasmic reticulum could be a potential tool to suppress cervical cancer invasion through inhibition of uPA. The chimeric adenoviral vector Ad5/F35-scFv-M6-1B9 was transferred into human cervical carcinoma HeLa cells to produce the scFv-M6-1B9 intrabody against EMMPRIN. Cell surface expression of EMMPRIN, the membrane-bound uPA, the enzymatic activity of secreted uPA, and the invasion ability were analyzed. The scFv-M6-1B9 intrabody successfully diminished the cell surface expression of EMMPRIN and the membrane-bound uPA on HeLa cells. uPA activity from tissue culture media of EMMPRIN-downregulated HeLa cells was decreased. The invasion ability of HeLa cells harboring scFv-M6-1B9 intrabody was also suppressed. These results suggested that the scFv-M6-1B9 intrabody might represent a potential approach for invasive cervical cancer treatment. The application of scFv-M6-1B9 intrabody in animal experiments and preclinical studies would be investigated further.

  10. Urban Partnership Agreement and Congestion Reduction Demonstration : National Evaluation Framework

    DOT National Transportation Integrated Search

    2008-11-21

    This report provides an analytical framework for evaluating six deployments under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) and Congestion Reduction Demonstration (CRD) Programs. The six UPA/CRD sites...

  11. Minnesota : innovative choices for congestion relief.

    DOT National Transportation Integrated Search

    2011-01-01

    Minnesota UPA projects focus on reducing traffic congestion in the I-35W corridor and in downtown Minneapolis. ITS technologies underlie many of the Minnesota UPA projects, including those centered on tolling, real-time traffic and transit informatio...

  12. Effects of ulipristal acetate on human embryo attachment and endometrial cell gene expression in an in vitro co-culture system.

    PubMed

    Berger, C; Boggavarapu, N R; Menezes, J; Lalitkumar, P G L; Gemzell-Danielsson, K

    2015-04-01

    Does ulipristal acetate (UPA) used for emergency contraception (EC) interfere with the human embryo implantation process? UPA, at the dosage used for EC, does not affect human embryo implantation process, in vitro. A single pre-ovulatory dose of UPA (30 mg) acts by delaying or inhibiting ovulation and is recommended as first choice among emergency contraceptive pills due to its efficacy. The compound has also been demonstrated to have a dose-dependent effect on the endometrium, which theoretically could impair endometrial receptivity but its direct action on human embryo implantation has not yet been studied. Effect of UPA on embryo implantation process was studied in an in vitro endometrial construct. Human embryos were randomly added to the cultures and cultured for 5 more days with UPA (n = 10) or with vehicle alone (n = 10) to record the attachment of embryos. Endometrial biopsies were obtained from healthy, fertile women on cycle day LH+4 and stromal and epithelial cells were isolated. A three-dimensional in vitro endometrial co-culture system was constructed by mixing stromal cells with collagen covered with a layer of epithelial cells and cultured in progesterone containing medium until confluence. The treatment group received 200 ng/ml of UPA. Healthy, viable human embryos were placed on both control and treatment cultures. Five days later the cultures were tested for the attachment of embryos and the 3D endometrial constructs were analysed for endometrial receptivity markers by real-time PCR. There was no significant difference in the embryo attachment rate between the UPA treated group and the control group as 5 out of 10 human embryos exposed to UPA and 7 out of 10 embryos in the control group attached to the endometrial cell surface (P = 0.650). Out of 17 known receptivity genes studied here, only 2 genes, HBEGF (P = 0.009) and IL6 (P = 0.025) had a significant up-regulation and 4 genes, namely HAND2 (P = 0.003), OPN (P = 0.003), CALCR (P = 0.016) and FGF2 (P = 0.023) were down-regulated with the exposure of UPA, compared with control group. This proof of concept study was conducted with a few human embryos, as their availability was limited. Although the 3D model used for this study is well established and the artificial endometrial luminal epithelium shown to express progesterone regulated markers of endometrial receptivity it is still an in vitro model, lacking all cell types that constitute the receptive endometrium in vivo. This study provides new insights on the mechanism of action of UPA on human embryo implantation, demonstrating that UPA in a dosage used for EC does not affect embryo viability and the implantation process of embryo. Progesterone receptor modulators (PRMs) hold the potential to be attractive estrogen- and gestagen-free contraceptives and thus may be made available to a larger proportion of women globally due to these findings. Swedish Research Council (K2010-54X-14212-09-3) and support provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska University Hospital. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Environmental Control and Life Support Systems Test Facility at MSFC

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. Scientists and engineers at the MSFC are working together to provide the ISS with systems that are safe, efficient, and cost-effective. These compact and powerful systems are collectively called the Environmental Control and Life Support Systems, or simply, ECLSS. In this photograph, the life test area on the left of the MSFC ECLSS test facility is where various subsystems and components are tested to determine how long they can operate without failing and to identify components needing improvement. Equipment tested here includes the Carbon Dioxide Removal Assembly (CDRA), the Urine Processing Assembly (UPA), the mass spectrometer filament assemblies and sample pumps for the Major Constituent Analyzer (MCA). The Internal Thermal Control System (ITCS) simulator facility (in the module in the right) duplicates the function and operation of the ITCS in the ISS U.S. Laboratory Module, Destiny. This facility provides support for Destiny, including troubleshooting problems related to the ITCS.

  14. International Space Station (ISS)

    NASA Image and Video Library

    2001-02-01

    The Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. Scientists and engineers at the MSFC are working together to provide the ISS with systems that are safe, efficient, and cost-effective. These compact and powerful systems are collectively called the Environmental Control and Life Support Systems, or simply, ECLSS. In this photograph, the life test area on the left of the MSFC ECLSS test facility is where various subsystems and components are tested to determine how long they can operate without failing and to identify components needing improvement. Equipment tested here includes the Carbon Dioxide Removal Assembly (CDRA), the Urine Processing Assembly (UPA), the mass spectrometer filament assemblies and sample pumps for the Major Constituent Analyzer (MCA). The Internal Thermal Control System (ITCS) simulator facility (in the module in the right) duplicates the function and operation of the ITCS in the ISS U.S. Laboratory Module, Destiny. This facility provides support for Destiny, including troubleshooting problems related to the ITCS.

  15. Use of ulipristal acetate and levonorgestrel for emergency contraception: a follow-up study.

    PubMed

    Baird, Aisling Susan; Trussell, James; Webb, Anne

    2015-04-01

    Previously we showed that increasing the choice of emergency contraception (EC) guided by medical eligibility did not result in wholesale large-scale usage of ulipristal acetate (UPA). This further 12-month study aimed to answer three questions. (1) Does offering choice of EC lead to change in methods used? (2) Are women who choose UPA more likely than those who choose levonorgestrel (LNG) to continue using condoms for subsequent contraception or to decline any ongoing contraception? (3) Do more women choosing LNG 'quick start' hormonal contraception? A retrospective study of EC episodes (1 April 2012 to 31 March 2013) by quarters. Among women offered all three methods of EC (49.1%) we noted the method chosen, and decisions on ongoing contraception among those choosing either LNG or UPA. Differences were tested for statistical significance. In 6110 episodes of EC, LNG was issued in 69.2%, UPA in 26.0%, and a copper intrauterine device (Cu-IUD) was fitted in 4.8%. Quarter by quarter, the data show a small decline in LNG use, suggesting plateauing by the last quarter, and a significant increase in UPA use between the first and the other three quarters (p<0.001). Use of the Cu-IUD remained static. The percentage of women offered three methods rose to 54.2%. In women offered full choice (3000; 49.1%) we saw a significant increase in choice of UPA, from 39.3% to 48.6% (p<0.001). Women who chose LNG were more likely to quick start (p=0.02) or be continuing contraception already used (p<0.001). Overall, those choosing UPA were more likely to use condoms (p<0.001) but were no more likely to decline ongoing contraception (p=0.13). There was a significant increase in women using UPA for EC compared with our previous study, particularly among those wishing to use condoms for continuing contraception. Women choosing LNG were more likely to quick start pills or to continue current hormonal contraception. Detailed attention to continuing contraception following EC may be an important factor in the prevention of unwanted pregnancy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Expression and activity analysis of a new fusion protein targeting ovarian cancer cells.

    PubMed

    Su, Manman; Chang, Weiqin; Wang, Dingding; Cui, Manhua; Lin, Yang; Wu, Shuying; Xu, Tianmin

    2015-09-01

    The aim of the present study was to develop a new therapeutic drug to improve the prognosis of ovarian cancer patients. Human urokinase-type plasminogen activator (uPA)17-34-kunitz-type protease inhibitor (KPI) eukaryotic expression vector was constructed and recombinant human uPA17-34-KPI (rhuPA17-34-KPI) in P. pastoris was expressed. In the present study, the DNA sequences that encode uPA 17-34 amino acids were created according to the native amino acids sequence and inserted into the KPI-pPICZαC vector, which was constructed. Then, uPA17‑34-KPI-pPICZαC was transformed into P. pastoris X-33, and rhuPA17-34-KPI was expressed by induction of methanol. The bioactivities of a recombinant fusion protein were detected with trypsin inhibition analysis, and the inhibitory effects on the growth of ovarian cancer cells were identified using the TUNEL assay, in vitro wound‑healing assay and Matrigel model analysis. The results of the DNA sequence analysis of the recombinant vector uPA17-34-KPI‑pPICZα demonstrated that the DNA‑encoding human uPA 17-34 amino acids, 285-288 amino acids of amyloid precursor protein (APP) and 1-57 amino acids of KPI were correctly inserted into the pPICZαC vector. Following induction by methonal, the fusion protein with a molecular weight of 8.8 kDa was observed using SDS-PAGE and western blot analysis. RhuPA17-34-KPI was expressed in P. pastoris with a yield of 50 mg/l in a 50-ml tube. The recombinant fusion protein was able to inhibit the activity of trypsin, inhibit growth and induce apoptosis of SKOV3 cells, and inhibit the invasion and metastasis of ovarian cancer cells. By considering uPA17-34 amino acid specific binding uPAR as the targeted part of fusion protein and utilizing the serine protease inhibitor activity of KPI, it was found that the recombinant fusion protein uPA17-34-KPI inhibited the invasion and metastasis of ovarian tumors, and may therefore be regarded as effective in targeted treatment.

  17. Minnesota urban partnership agreement national evaluation : surveys, interviews, and focus groups test plan.

    DOT National Transportation Integrated Search

    2009-11-17

    This report presents the test plan for developing, conducting, and analyzing surveys, interviews, and focus groups for evaluating the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Prog...

  18. Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9.

    PubMed

    Ho, Yung-Tsuan; Yang, Jai-Sing; Li, Tsai-Chung; Lin, Jen-Jyh; Lin, Jaung-Geng; Lai, Kuang-Chi; Ma, Chia-Yu; Wood, W Gibson; Chung, Jing-Gung

    2009-07-08

    There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IkappaK and NF-kappaB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-kappaB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells.

  19. Performance Qualification Test of the ISS Water Processor Assembly (WPA) Expendables

    NASA Technical Reports Server (NTRS)

    Carter, Layne; Tabb, David; Tatara, James D.; Mason, Richard K.

    2005-01-01

    The Water Processor Assembly (WPA) for use on the International Space Station (ISS) includes various technologies for the treatment of waste water. These technologies include filtration, ion exchange, adsorption, catalytic oxidation, and iodination. The WPA hardware implementing portions of these technologies, including the Particulate Filter, Multifiltration Bed, Ion Exchange Bed, and Microbial Check Valve, was recently qualified for chemical performance at the Marshall Space Flight Center. Waste water representing the quality of that produced on the ISS was generated by test subjects and processed by the WPA. Water quality analysis and instrumentation data was acquired throughout the test to monitor hardware performance. This paper documents operation of the test and the assessment of the hardware performance.

  20. Meeting the Customer's Needs for Mobility and Safety During Construction and Maintenance Operations

    DOT National Transportation Integrated Search

    2011-01-01

    This report presents the Survey, Interviews, and Workshops Test Plan for the national evaluation of the Seattle/Lake Washington Corridor (LWC) Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Progr...

  1. Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by endogenous plasminogen activator inhibitor-1.

    PubMed

    Deshet, Naamit; Lupu-Meiri, Monica; Espinoza, Ingrid; Fili, Oded; Shapira, Yuval; Lupu, Ruth; Gershengorn, Marvin C; Oron, Yoram

    2008-09-01

    PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-induced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor 1-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by endogenous uPA is limited by PN's degradation and negatively controlled by endogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists.

  2. Extracellular Collagen Promotes Interleukin-1β-Induced Urokinase-Type Plasminogen Activator Production by Human Corneal Fibroblasts.

    PubMed

    Sugioka, Koji; Kodama-Takahashi, Aya; Yoshida, Koji; Aomatsu, Keiichi; Okada, Kiyotaka; Nishida, Teruo; Shimomura, Yoshikazu

    2017-03-01

    Keratocytes maintain homeostasis of the corneal stroma through synthesis, secretion, and degradation of collagen fibrils of the extracellular matrix. Given that these cells are essentially embedded in a collagen matrix, keratocyte-collagen interactions may play a key role in regulation of the expression or activation of enzymes responsible for matrix degradation including urokinase-type plasminogen activator (uPA), plasmin, and matrix metalloproteinases (MMPs). We examined the effect of extracellular collagen on the production of uPA by corneal fibroblasts (activated keratocytes) stimulated with the proinflammatory cytokine interleukin-1β (IL-1β). Human corneal fibroblasts were cultured either on plastic or in a three-dimensional gel of type I collagen. Plasminogen activators were detected by fibrin zymography, whereas the IL-1 receptor (IL-1R) and MMPs were detected by immunoblot analysis. Collagen degradation by corneal fibroblasts was assessed by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Collagen and IL-1β synergistically increased the synthesis and secretion of uPA in corneal fibroblasts. Collagen also upregulated IL-1R expression in the cells in a concentration-dependent manner. The conversion of extracellular plasminogen to plasmin, as well as the plasminogen-dependent activation of MMP-1 and MMP-3 and degradation of collagen apparent in three-dimensional cultures of corneal fibroblasts exposed to IL-1β, were all abolished by a selective uPA inhibitor. Collagen and IL-1β cooperate to upregulate uPA production by corneal fibroblasts. Furthermore, IL-1β-induced collagen degradation by these cells appears to be strictly dependent on uPA expression and mediated by a uPA-plasmin-MMP pathway.

  3. Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

    PubMed Central

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion. PMID:23940799

  4. Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement.

    PubMed

    Zhan, Jing; Gu, Zhi-yuan; Wu, Li-qun; Zhang, Yin-kai; Hu, Ji-an

    2005-06-20

    The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling. Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques. The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks. The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

  5. Krüppel-like factor 17 inhibits urokinase plasminogen activator gene expression to suppress cell invasion through the Src/p38/MAPK signaling pathway in human lung adenocarcinoma

    PubMed Central

    Huang, Shuai; Li, Jiong; Liu, Xiao-Yan; Pan, Xing-Fei; Wang, Qin-Qin; Chen, Li; Lin, Ming-Juan; Huang, Zhi-Hong; Ma, Hong-Ming; Wu, Yi; Liu, Sheng-Ming; Zhou, Yan-Bin

    2017-01-01

    Krüppel-like factor 17 (KLF17) has been reported to be involved in invasion and metastasis suppression in lung cancer, but the molecular mechanisms underlying the anti-invasion and anti-metastasis roles of KLF17 in lung cancer are not fully illustrated. Here, we showed that KLF17 inhibited the invasion of A549 and H322 cells; the anti-invasion effect of KLF17 was associated with the suppression of urokinase plasminogen activator (uPA/PLAU) expression. KLF17 can bind with the promoter of uPA and inhibit its expression. Enforced expression of uPA abrogated the anti-invasion effect of KLF17 in A549 and H322 cells. In addition, immunohistochemistry staining showed that the protein expression of KLF17 was negatively correlated with that of uPA in archived samples from patients with lymph node metastasis of lung adenocarcinoma (rho = −0.62, P = 0.01). The mutually exclusive expression of KLF17 with uPA could predict lymph node metastasis for lung adenocarcinoma (AUC = 0.758, P = 0.005). Enforced expression of KLF17 inhibited the expression of phosphorylated Src and phosphorylated p38/MAPK in A549 and H322 cells. The invasiveness of the cells were suppressed by treating with sb203580 (p38/MAPK inhibitor) or HY-13805 (PP2, Src inhibitor). furthermore, p38/MAPK inhibition could block the KLF17-induced reduction of p-p38/MAPK and uPA, and Src inhibition enhanced the KLF17-induced suppression of p-Src and uPA in A549 and H322 cells. In conclusion, our study indicated that KLF17 suppressed the uPA-mediated invasion of lung adenocarcinoma. The Src and p38/MAPK signaling pathways were suggested as mediators of KLF17-induced uPA inhibition, thus providing evidence that KLF17 might be a potential anti-invasion candidate for lung adenocarcinoma. PMID:28454121

  6. A New Class of Orthosteric uPAR•uPA Small-Molecule Antagonists Are Allosteric Inhibitors of the uPAR•Vitronectin Interaction

    PubMed Central

    Liu, Degang; Zhou, Donghui; Wang, Bo; Knabe, William Eric; Meroueh, Samy O.

    2015-01-01

    The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that is at the center of an intricate network of protein-protein interactions. Its immediate binding partners are the serine proteinase urokinase (uPA), and vitronectin (VTN), a component of the extracellular matrix. uPA and VTN bind at distinct sites on uPAR to promote extracellular matrix degradation and integrin signaling, respectively. Here, we report the discovery of a new class of pyrrolone small-molecule inhibitors of the tight ∼1 nM uPAR•uPA protein-protein interaction. These compounds were designed to bind to the uPA pocket on uPAR. The highest affinity compound, namely 7, displaced a fluorescently-labeled α-helical peptide (AE147-FAM) with an inhibition constant Ki of 0.7 µM and inhibited the tight uPAR•uPAATF interaction with an IC50 of 18 µM. Biophysical studies with surface plasmon resonance showed that VTN binding is highly dependent on uPA. This cooperative binding was confirmed as 7, which binds at the uPAR•uPA interface, also inhibited the distal VTN•uPAR interaction. In cell culture, 7 blocked the uPAR•uPA interaction in uPAR-expressing human embryonic kidney (HEK-293) cells, and impaired cell adhesion to VTN, a process that is mediated by integrins. As a result, 7 inhibited integrin signaling in MDA-MB-231 cancer cells as evidenced by a decrease in focal adhesion kinase (FAK) phosphorylation and Rac1 GTPase activation. Consistent with these results, 7 blocked breast MDA-MB-231 cancer cell invasion with IC50 values similar to those observed in ELISA and surface plasmon resonance competition studies. Explicit-solvent molecular dynamics simulations show that the cooperativity between uPA and VTN is attributed to stabilization of uPAR motion by uPA. In addition, free energy calculations revealed that uPA stabilizes the VTN•uPARSMB interaction through more favorable electrostatics and entropy. Disruption of the uPAR•VTNSMB interaction by 7 is consistent with the cooperative binding to uPAR by uPA and VTN. Interestingly, the VTNSMB•uPAR interaction was less favorable in the VTNSMB•uPAR•7 complex suggesting potential cooperativity between 7 and VTN. Compound 7 provides an excellent starting point for the development of more potent derivatives to explore uPAR biology. PMID:25671694

  7. A new class of orthosteric uPAR·uPA small-molecule antagonists are allosteric inhibitors of the uPAR·vitronectin interaction.

    PubMed

    Liu, Degang; Zhou, Donghui; Wang, Bo; Knabe, William Eric; Meroueh, Samy O

    2015-06-19

    The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that is at the center of an intricate network of protein-protein interactions. Its immediate binding partners are the serine proteinase urokinase (uPA), and vitronectin (VTN), a component of the extracellular matrix. uPA and VTN bind at distinct sites on uPAR to promote extracellular matrix degradation and integrin signaling, respectively. Here, we report the discovery of a new class of pyrrolone small-molecule inhibitors of the tight ∼1 nM uPAR·uPA protein-protein interaction. These compounds were designed to bind to the uPA pocket on uPAR. The highest affinity compound, namely 7, displaced a fluorescently labeled α-helical peptide (AE147-FAM) with an inhibition constant Ki of 0.7 μM and inhibited the tight uPAR·uPAATF interaction with an IC50 of 18 μM. Biophysical studies with surface plasmon resonance showed that VTN binding is highly dependent on uPA. This cooperative binding was confirmed as 7, which binds at the uPAR·uPA interface, also inhibited the distal VTN·uPAR interaction. In cell culture, 7 blocked the uPAR·uPA interaction in uPAR-expressing human embryonic kidney (HEK-293) cells and impaired cell adhesion to VTN, a process that is mediated by integrins. As a result, 7 inhibited integrin signaling in MDA-MB-231 cancer cells as evidenced by a decrease in focal adhesion kinase (FAK) phosphorylation and Rac1 GTPase activation. Consistent with these results, 7 blocked breast MDA-MB-231 cancer cell invasion with IC50 values similar to those observed in ELISA and surface plasmon resonance competition studies. Explicit-solvent molecular dynamics simulations show that the cooperativity between uPA and VTN is attributed to stabilization of uPAR motion by uPA. In addition, free energy calculations revealed that uPA stabilizes the VTNSMB·uPAR interaction through more favorable electrostatics and entropy. Disruption of the uPAR·VTNSMB interaction by 7 is consistent with the cooperative binding to uPAR by uPA and VTN. Interestingly, the VTNSMB·uPAR interaction was less favorable in the VTNSMB·uPAR·7 complex suggesting potential cooperativity between 7 and VTN. Compound 7 provides an excellent starting point for the development of more potent derivatives to explore uPAR biology.

  8. Urokinase-type Plasminogen Activator Resulting from Endometrial Carcinogenesis Enhances Tumor Invasion and Correlates with Poor Outcome of Endometrial Carcinoma Patients

    PubMed Central

    Huang, Chia-Yen; Chang, Ming-Cheng; Huang, Wei-Yun; Huang, Ching-Ting; Tang, Yu-Chien; Huang, Hsien-Da; Kuo, Kuan-Ting; Chen, Chi-An; Cheng, Wen-Fang

    2015-01-01

    The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC), and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia, and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis, and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC. PMID:26033187

  9. Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase.

    PubMed

    Shetty, Praveenkumar; Velusamy, Thirunavukkarasu; Bhandary, Yashodhar P; Liu, Ming C; Shetty, Sreerama

    2010-02-01

    The interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, plays a central role in several pathophysiological processes, including cancer. uPA induces its own cell surface receptor expression through stabilization of uPAR mRNA. The mechanism involves binding of a 51 nt uPAR mRNA coding sequence with phosphoglycerate kinase (PGK) to down regulate cell surface uPAR expression. Tyrosine phosphorylation of PGK mediated by uPA treatment enhances uPAR mRNA stabilization. In contrast, inhibition of tyrosine phosphorylation augments PGK binding to uPAR mRNA and attenuates uPA-induced uPAR expression. Mapping the specific peptide region of PGK indicated that its first quarter (amino acids 1-100) interacts with uPAR mRNA. To determine if uPAR expression by uPA is regulated through activation of tyrosine residues of PGK, we mutated the specific tyrosine residue and tested mutant PGK for its ability to interfere with uPAR expression. Inhibition of tyrosine phosphorylation by mutating Y76 residue abolished uPAR expression induced by uPA treatment. These findings collectively demonstrate that Y76 residue present in the first quarter of the PGK molecule is involved in lung epithelial cell surface uPAR expression. This region can effectively mimic the function of a whole PGK molecule in inhibiting tumor cell growth.

  10. AutA and AutR, Two Novel Global Transcriptional Regulators, Facilitate Avian Pathogenic Escherichia coli Infection.

    PubMed

    Zhuge, Xiangkai; Tang, Fang; Zhu, Hongfei; Mao, Xiang; Wang, Shaohui; Wu, Zongfu; Lu, Chengping; Dai, Jianjun; Fan, Hongjie

    2016-04-26

    Bacteria can change its lifestyle during inhabiting in host niches where they survive and replicate by rapidly altering gene expression pattern to accommodate the new environment. In this study, two novel regulators in avian pathogenic Escherichia coli (APEC) were identified and designated as AutA and AutR. RT-PCR and β-galactosidase assay results showed that AutA and AutR co-regulated the expression of adhesin UpaB in APEC strain DE205B. Electrophoretic mobility shift assay showed that AutA and AutR could directly bind the upaB promoter DNA. In vitro transcription assay indicated that AutA could activate the upaB transcription, while AutR inhibited the upaB transcription due to directly suppressing the activating effect of AutA on UpaB expression. Transcriptome analysis showed that AutA and AutR coherently affected the expression of hundreds of genes. Our study confirmed that AutA and AutR co-regulated the expression of DE205B K1 capsule and acid resistance systems in E. coli acid fitness island (AFI). Moreover, phenotypic heterogeneity in expression of K1 capsule and acid resistance systems in AFI during host-pathogen interaction was associated with the regulation of AutA and AutR. Collectively speaking, our studies presented that AutA and AutR are involved in APEC adaptive lifestyle change to facilitate its infection.

  11. Selective progesterone receptor modulator (SPRM) ulipristal acetate (UPA) and its effects on the human endometrium.

    PubMed

    Whitaker, L H R; Murray, A A; Matthews, R; Shaw, G; Williams, A R W; Saunders, P T K; Critchley, H O D

    2017-03-01

    What is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids? UPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation. Administration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes). Data on the impact of the SPRM UPA administration on endometrial sex-steroid receptor expression, progesterone (P)-regulated genes and cell proliferation are currently lacking. Observational study with histological and molecular analyses to delineate impact of treatment with UPA on endometrium. Endometrial samples (n = 9) were collected at hysterectomy from women aged 39 to 49 with uterine fibroids treated with UPA (oral 5 mg daily) for 9-12 weeks. Control proliferative (n = 9) and secretory (n = 9) endometrium from women aged 38-52 with fibroids were derived from institutional tissue archives. Study setting was a University Research Institute. Endometrial biopsies were collected with institutional ethical approval and written informed consent. Concentrations of mRNAs encoded by steroid receptors, P-regulated genes and factors in decidualised endometrium were quantified with qRT-PCR. Immunohistochemistry was employed for localization of progesterone (PR, PRB), androgen (AR), estrogen (ERα) receptors and expression of FOXO1, HAND2, HOXA10, PTEN homologue. Endometrial glandular and stromal cell proliferation was objectively quantified using Ki67. UPA induced morphological changes in endometrial tissue consistent with PAEC. A striking change in expression patterns of PR and AR was detected compared with either proliferative or secretory phase samples. There were significant changes in pattern of expression of mRNAs encoded by IGFBP-1, FOXO1, IL-15, HAND2, IHH and HOXA10 compared with secretory phase samples consistent with low agonist activity in endometrium. Expression of mRNA encoded by FOXM1, a transcription factor implicated in cell cycle progression, was low in UPA-treated samples. Cell proliferation (Ki67 positive nuclei) was lower in samples from women treated with UPA compared with those in the proliferative phase. N/A. A small number of well-characterized patients were studied in-depth. The impacts on morphology, molecular and cellular changes with SPRM, UPA administration on symptom control remains to be determined. P plays a pivotal role in endometrial function. P-action is mediated through interaction with the PR. These data provide support for onward development of the SPRM class of compounds as effective long-term medical therapy for heavy menstrual bleeding. H.O.D.C. received has clinical research support for laboratory consumables and staff from Bayer Pharma Ag and provides consultancy advice (no personal remuneration) for Bayer Pharma Ag, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc.; A.R.W.W. has received consultancy payments from Bayer, Gedeon Richter, Preglem SA, HRA Pharma; L.H.R.W., A.A.M., R.M., G.S. and P.T.K.S. have no conflicts of interest. Study funded in part from each of: Medical Research Council (G1002033; G1100356/1; MR/N022556/1); National Health Institute for Health Research (12/206/520) and TENOVUS Scotland. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

  12. Selective progesterone receptor modulator (SPRM) ulipristal acetate (UPA) and its effects on the human endometrium

    PubMed Central

    Whitaker, L.H.R.; Murray, A.A.; Matthews, R.; Shaw, G.; Williams, A.R.W.; Saunders, P.T.K.

    2017-01-01

    Abstract STUDY QUESTION What is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids? SUMMARY ANSWER UPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation. WHAT IS KNOWN ALREADY Administration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes). Data on the impact of the SPRM UPA administration on endometrial sex-steroid receptor expression, progesterone (P)-regulated genes and cell proliferation are currently lacking. STUDY DESIGN SIZE, DURATION Observational study with histological and molecular analyses to delineate impact of treatment with UPA on endometrium. Endometrial samples (n = 9) were collected at hysterectomy from women aged 39 to 49 with uterine fibroids treated with UPA (oral 5 mg daily) for 9–12 weeks. Control proliferative (n = 9) and secretory (n = 9) endometrium from women aged 38–52 with fibroids were derived from institutional tissue archives. PARTICIPANTS/MATERIALS, SETTING, METHODS Study setting was a University Research Institute. Endometrial biopsies were collected with institutional ethical approval and written informed consent. Concentrations of mRNAs encoded by steroid receptors, P-regulated genes and factors in decidualised endometrium were quantified with qRT-PCR. Immunohistochemistry was employed for localization of progesterone (PR, PRB), androgen (AR), estrogen (ERα) receptors and expression of FOXO1, HAND2, HOXA10, PTEN homologue. Endometrial glandular and stromal cell proliferation was objectively quantified using Ki67. MAIN RESULTS AND THE ROLE OF CHANCE UPA induced morphological changes in endometrial tissue consistent with PAEC. A striking change in expression patterns of PR and AR was detected compared with either proliferative or secretory phase samples. There were significant changes in pattern of expression of mRNAs encoded by IGFBP-1, FOXO1, IL-15, HAND2, IHH and HOXA10 compared with secretory phase samples consistent with low agonist activity in endometrium. Expression of mRNA encoded by FOXM1, a transcription factor implicated in cell cycle progression, was low in UPA-treated samples. Cell proliferation (Ki67 positive nuclei) was lower in samples from women treated with UPA compared with those in the proliferative phase. LARGE SCALE DATA N/A. LIMITATIONS REASONS FOR CAUTION A small number of well-characterized patients were studied in-depth. The impacts on morphology, molecular and cellular changes with SPRM, UPA administration on symptom control remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS P plays a pivotal role in endometrial function. P-action is mediated through interaction with the PR. These data provide support for onward development of the SPRM class of compounds as effective long-term medical therapy for heavy menstrual bleeding. STUDY FUNDING/COMPETING INTEREST(S) H.O.D.C. received has clinical research support for laboratory consumables and staff from Bayer Pharma Ag and provides consultancy advice (no personal remuneration) for Bayer Pharma Ag, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc.; A.R.W.W. has received consultancy payments from Bayer, Gedeon Richter, Preglem SA, HRA Pharma; L.H.R.W., A.A.M., R.M., G.S. and P.T.K.S. have no conflicts of interest. Study funded in part from each of: Medical Research Council (G1002033; G1100356/1; MR/N022556/1); National Health Institute for Health Research (12/206/520) and TENOVUS Scotland. PMID:28130434

  13. Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women.

    PubMed

    Brache, Vivian; Sitruk-Ware, Regine; Williams, Alistair; Blithe, Diana; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Tsong, Yun-Yen; Sivin, Irving; Nath, Anita; Sussman, Heather; Cochon, Leila; Miranda, Maria Jose; Reyes, Verónica; Faundes, Anibal; Mishell, Daniel

    2012-05-01

    Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation. This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21-40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated. Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 "4-week treatment cycles." A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%). In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Long-term treatment of uterine fibroids with ulipristal acetate ☆.

    PubMed

    Donnez, Jacques; Vázquez, Francisco; Tomaszewski, Janusz; Nouri, Kazem; Bouchard, Philippe; Fauser, Bart C J M; Barlow, David H; Palacios, Santiago; Donnez, Olivier; Bestel, Elke; Osterloh, Ian; Loumaye, Ernest

    2014-06-01

    To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids. Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo. European clinical gynecology centers. Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding. Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo. Amenorrhea, fibroid volume, endometrial histology. After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2-6 days). Median fibroid volume change was -45% (interquartile range, -66%; -25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were -63%, -67%, and -72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology. Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids. ClinicalTrials.gov (www.clinicaltrials.gov) registration numbers NCT01156857 (PEARL III) and NCT01252069 (PEARL III extension). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women

    PubMed Central

    Brache, Vivian; Sitruk-Ware, Regine; Williams, Alistair; Blithe, Diana; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Tsong, Yun-Yen; Sivin, Irving; Nath, Anita; Sussman, Heather; Cochon, Leila; Miranda, Maria Jose; Reyes, Verónica; Faundes, Anibal; Mishell, Daniel

    2012-01-01

    Background Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600–800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation. Study Design This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21–40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated. Results Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 “4-week treatment cycles.” A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%). Conclusion In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects. PMID:22176795

  16. A self-sustained, complete and miniaturized methanol fuel processor for proton exchange membrane fuel cell

    NASA Astrophysics Data System (ADS)

    Yang, Mei; Jiao, Fengjun; Li, Shulian; Li, Hengqiang; Chen, Guangwen

    2015-08-01

    A self-sustained, complete and miniaturized methanol fuel processor has been developed based on modular integration and microreactor technology. The fuel processor is comprised of one methanol oxidative reformer, one methanol combustor and one two-stage CO preferential oxidation unit. Microchannel heat exchanger is employed to recover heat from hot stream, miniaturize system size and thus achieve high energy utilization efficiency. By optimized thermal management and proper operation parameter control, the fuel processor can start up in 10 min at room temperature without external heating. A self-sustained state is achieved with H2 production rate of 0.99 Nm3 h-1 and extremely low CO content below 25 ppm. This amount of H2 is sufficient to supply a 1 kWe proton exchange membrane fuel cell. The corresponding thermal efficiency of whole processor is higher than 86%. The size and weight of the assembled reactors integrated with microchannel heat exchangers are 1.4 L and 5.3 kg, respectively, demonstrating a very compact construction of the fuel processor.

  17. Rationale for the new GP deprivation payment scheme in England: effects of moving from electoral ward to enumeration district underprivileged area scores.

    PubMed Central

    Bajekal, M; Alves, B; Jarman, B; Hurwitz, B

    2001-01-01

    BACKGROUND: The Department of Health introduced a new deprivation payments system for general practitioners (GPs) on 1 April 1999. Following a three-year phasing-in process, registered patients will attract deprivation payments based on the underprivileged area (UPA) score of their enumeration district (ED) of residence, rather than their electoral ward, changing the pattern and distribution of payments throughout England. AIM: To assess the rationale behind the changed deprivation payments system for GPs in England and to examine its impact on GP and practice payments. DESIGN OF STUDY: A quantitative study modelling practice-based deprivation payments. SETTING: A total of 25,450 unrestricted principal GPs in 8919 practices in England. METHOD: The effect of three new components in the system were examined: changes in the ED score ranges attracting payment, the percentage increase in the size of successive payment bands, and the total budget. The relationship between consultation rates (used as a proxy for workload) and UPA score was examined, together with changes in GP payments calculated nationally and by geographical area. RESULTS: A total of 11.6% of the population of England live in wards with a UPA score of 30 or more, qualifying for deprivation payments, and a similar proportion (11.4%) live in EDs with a UPA score of 20 or more. The larger percentage increases in the size of payments in successive ED UPA bands is supported by the modelled relationship between consultation rate and UPA score. Financially, under the new deprivations payment system, entitlement widens with 88% of practices receiving a payment. Overall, 74% of GPs gain and 13% lose (3% losing more than 1500 Pounds), with 13% receiving no payment. CONCLUSION: The new ED system maps onto the previous system well. Moreover, it more finely discriminates between smaller areas of different relative deprivation and, thereby, targets payments more accurately. PMID:11407049

  18. Rationale for the new GP deprivation payment scheme in England: effects of moving from electoral ward to enumeration district underprivileged area scores.

    PubMed

    Bajekal, M; Alves, B; Jarman, B; Hurwitz, B

    2001-06-01

    The Department of Health introduced a new deprivation payments system for general practitioners (GPs) on 1 April 1999. Following a three-year phasing-in process, registered patients will attract deprivation payments based on the underprivileged area (UPA) score of their enumeration district (ED) of residence, rather than their electoral ward, changing the pattern and distribution of payments throughout England. To assess the rationale behind the changed deprivation payments system for GPs in England and to examine its impact on GP and practice payments. A quantitative study modelling practice-based deprivation payments. A total of 25,450 unrestricted principal GPs in 8919 practices in England. The effect of three new components in the system were examined: changes in the ED score ranges attracting payment, the percentage increase in the size of successive payment bands, and the total budget. The relationship between consultation rates (used as a proxy for workload) and UPA score was examined, together with changes in GP payments calculated nationally and by geographical area. A total of 11.6% of the population of England live in wards with a UPA score of 30 or more, qualifying for deprivation payments, and a similar proportion (11.4%) live in EDs with a UPA score of 20 or more. The larger percentage increases in the size of payments in successive ED UPA bands is supported by the modelled relationship between consultation rate and UPA score. Financially, under the new deprivations payment system, entitlement widens with 88% of practices receiving a payment. Overall, 74% of GPs gain and 13% lose (3% losing more than 1500 Pounds), with 13% receiving no payment. The new ED system maps onto the previous system well. Moreover, it more finely discriminates between smaller areas of different relative deprivation and, thereby, targets payments more accurately.

  19. Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.

    PubMed

    Wakita, Toshiaki; Hayashi, Tatsuya; Nishioka, Junji; Tamaru, Hiroshi; Akita, Nobuyuki; Asanuma, Kunihiro; Kamada, Haruhiko; Gabazza, Esteban C; Ido, Masaru; Kawamura, Juichi; Suzuki, Koji

    2004-02-10

    Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki-1 cells). No differences were detected between the nucleotide sequence of the major cis-elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki-1 cells, an RPTEC-derived RCC cell line. The in vitro invasiveness of Caki-1 cells transfected with a PCI expression vector was significantly decreased compared to mock-transfected Caki-1 cells, and it was blocked in the presence of anti-PCI antibody. Since PCI itself did not affect the proliferation rate of Caki-1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat-inactivated PCI and plasminogen activator inhibitor (PAI)-1 on the invasive potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki-1 cells, which express uPA, was significantly enhanced by the addition of uPA, and it was inhibited by anti-uPA antibody, PCI and PAI-1, but not by heat-inactivated PCI. In addition, uPA activity was significantly decreased and uPA-PCI complex level was significantly increased in the culture medium of PCI expression vector-transfected Caki-1 cells as compared to mock-transfected Caki-1 cells. These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells. The results of our study suggest that PCI might be a potential therapeutic agent for inhibiting renal tumor invasion. Copyright 2003 Wiley-Liss, Inc.

  20. A microcomputer based frequency-domain processor for laser Doppler anemometry

    NASA Technical Reports Server (NTRS)

    Horne, W. Clifton; Adair, Desmond

    1988-01-01

    A prototype multi-channel laser Doppler anemometry (LDA) processor was assembled using a wideband transient recorder and a microcomputer with an array processor for fast Fourier transform (FFT) computations. The prototype instrument was used to acquire, process, and record signals from a three-component wind tunnel LDA system subject to various conditions of noise and flow turbulence. The recorded data was used to evaluate the effectiveness of burst acceptance criteria, processing algorithms, and selection of processing parameters such as record length. The recorded signals were also used to obtain comparative estimates of signal-to-noise ratio between time-domain and frequency-domain signal detection schemes. These comparisons show that the FFT processing scheme allows accurate processing of signals for which the signal-to-noise ratio is 10 to 15 dB less than is practical using counter processors.

  1. Dual Fan Separator within the Universal Waste Management System

    NASA Technical Reports Server (NTRS)

    Stapleton, Tom; Converse, Dave; Broyan, James Lee, Jr.

    2014-01-01

    Since NASA's new spacecraft in development for both LEO and Deep Space capability have considerable crew volume reduction in comparison to the Space Shuttle, the need became apparent for a smaller commode. In response the Universal Waste Management System (UWMS) was designed, resulting in an 80% volume reduction from the last US commode, while enhancing performance. The ISS WMS and previous shuttle commodes have a fan supplying air flow to capture feces and a separator to capture urine and separate air from the captured air/urine mixture. The UWMS combined both rotating equipment components into a single unit, referred to at the Dual Fan Separator (DFS). The combination of these components resulted in considerable packaging efficiency and weight reduction, removing inter-component plumbing, individual mounting configurations and required only a single motor and motor controller, in some of the intended UWMS platform applications the urine is pumped to the ISS Urine Processor Assembly (UPA) system. It requires the DFS to include less than 2.00% air inclusion, by volume, in the delivered urine. The rotational speed needs to be kept as low as possible in centrifugal urine separators to reduce air inclusion in the pumped fluid, while fans depend on rotational speed to develop delivered head. To satisfy these conflicting requirements, a gear reducer was included, allowing the fans to rotate at a much higher speed than the separator. This paper outlines the studies and analysis performed to develop the DFS configuration. The studies included a configuration trade study, dynamic stability analysis of the rotating bodies and a performance analysis of included labyrinth seals. NASA is considering a program to fly the UWMS aboard the ISS as a flight experiment. The goal of this activity is to advance the Technical Readiness Level (TRL) of the DFS and determine if the concept is ready to be included as part of the flight experiment deliverable.

  2. Water Processor and Oxygen Generation Assembly

    NASA Technical Reports Server (NTRS)

    Bedard, John

    1997-01-01

    This report documents the results of the tasks which initiated efforts on design issues relating to the Water Processor (WP) and the Oxygen Generation Assembly (OGA) Flight Hardware for the International Space Station. This report fulfills the Statement of Work deliverables requirement for contract H-29387D. The following lists the tasks required by contract H-29387D: (1) HSSSI shall coordinate a detailed review of WP/OGA Flight Hardware program requirements with personnel from MSFC to identify requirements that can be eliminated without affecting the technical integrity of the WP/OGA Hardware; (2) HSSSI shall conduct the technical interchanges with personnel from MSFC to resolve design issues related to WP/OGA Flight Hardware; (3) HSSSI will initiate discussions with Zellwegger Analytics, Inc. to address design issues related to WP and PCWQM interfaces.

  3. C-MOS array design techniques: SUMC multiprocessor system study

    NASA Technical Reports Server (NTRS)

    Clapp, W. A.; Helbig, W. A.; Merriam, A. S.

    1972-01-01

    The current capabilities of LSI techniques for speed and reliability, plus the possibilities of assembling large configurations of LSI logic and storage elements, have demanded the study of multiprocessors and multiprocessing techniques, problems, and potentialities. Evaluated are three previous systems studies for a space ultrareliable modular computer multiprocessing system, and a new multiprocessing system is proposed that is flexibly configured with up to four central processors, four 1/0 processors, and 16 main memory units, plus auxiliary memory and peripheral devices. This multiprocessor system features a multilevel interrupt, qualified S/360 compatibility for ground-based generation of programs, virtual memory management of a storage hierarchy through 1/0 processors, and multiport access to multiple and shared memory units.

  4. [Sexist attitudes and recognition of abuse in young couples].

    PubMed

    García-Díaz, Vanesa; Lana-Pérez, Alberto; Fernández-Feito, Ana; Bringas-Molleda, Carolina; Rodríguez-Franco, Luis; Rodríguez-Díaz, F Javier

    2017-09-18

    To explore the association between gender-role attitudes and the recognition of abuse among adolescents and young adults during dating relationships. Cross-correlation study. 57 schools of secondary education, vocational education and university in five provinces of Spain (Huelva, Seville, A Coruña, Pontevedra and Asturias). 4,337 students aged between 15 and 26 years (40.6% males and 59.4% female) who had a dating relationship that lasted more than a month. The Gender Role Attitudes Scale was used, which consists of 20 indicators of egalitarian or sexism attitudes at the family, social and occupational level. The students also reported whether they suffered from recognized abuse (RA), unperceived abuse (UPA), or not abused (NA). In the whole sample, 68.6% declared themselves NA, 26.4% were under a situation of UPA, and 5.0% were RA. The RA group was more frequent among the females (6.3%), ≥18 years (6.4%) and university students (6.9%). UPA was more common in males (30.2%). The most sexist attitudes were found in the occupational dimension and especially in men and adolescents (15-17 years). Less sexist attitudes were associated with a lower probability of experiencing UPA (odds ratio=.71; P-trend<.001). Sexism seems to hinder the recognition of abuse. Achieving gender equity in adolescence and youth is imperative. Public health efforts should focus on men, as they constitute the group with more sexist attitudes and with higher prevalence of UPA. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  5. Measuring the metastatic potential of cancer cells

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.; Gratzner, Howard; Atassi, M. Z.

    1993-01-01

    Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

  6. ETIOLOGY, TRIGGERS AND NEUROCHEMICAL CIRCUITS ASSOCIATED WITH UNEXPECTED, EXPECTED, AND LABORATORY-INDUCED PANIC ATTACKS

    PubMed Central

    Johnson, Philip L.; Federici, Lauren M.; Shekhar, Anantha

    2014-01-01

    Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene x environment and gene x hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states. PMID:25130976

  7. [Tumor-associated prognostic factors of the plasminogen activator family: determination and clinical value of u-PA, t-PA, PAI-1, and PAI-2].

    PubMed

    Mengele, K; Harbeck, N; Reuning, U; Magdolen, V; Schmitt, M

    2005-08-01

    Proteolytic factors belonging t the plasminogen activator family (plasmin, u-PA, t-PA, u-PAR, PAI-1, and PAI-2), which usually are involved in blood clotting and degradation of blood clots, are also present in healthy and diseased tissue of the kidney, lung, liver, gastro-intestinal tract, breast, prostate, ovary, and brain. These factors are engaged in brain development, angiogenesis and vascular invasion, wound healing as well as in placenta development and embryogenesis. Plasminogen activators u-PA and t-PA, their inhibitors PAI-1 and PAI-2, and the u-PA-receptor (u-PAR, CD87) are often elevated in solid malignant tumour tissues compared to their normal counterparts. In breast cancer patients, an elevated tumour tissue extract antigen content of u-PA, PAI-1, and u-PAR is associated with increased tumour aggressiveness and poor prognosis; in contrary, an elevated content of t-PA and PAI-2 indicates a favourable prognosis. For clinical relevant determination of these proteolytic factors in tumour tissue extracts, only enzymo-immunometric tests (ELISA) are recommended. Enzymometric and enzymographic tests are actually conducted only in an experimental, preclinical context.

  8. Integrated High-Speed Torque Control System for a Robotic Joint

    NASA Technical Reports Server (NTRS)

    Davis, Donald R. (Inventor); Radford, Nicolaus A. (Inventor); Permenter, Frank Noble (Inventor); Valvo, Michael C. (Inventor); Askew, R. Scott (Inventor)

    2013-01-01

    A control system for achieving high-speed torque for a joint of a robot includes a printed circuit board assembly (PCBA) having a collocated joint processor and high-speed communication bus. The PCBA may also include a power inverter module (PIM) and local sensor conditioning electronics (SCE) for processing sensor data from one or more motor position sensors. Torque control of a motor of the joint is provided via the PCBA as a high-speed torque loop. Each joint processor may be embedded within or collocated with the robotic joint being controlled. Collocation of the joint processor, PIM, and high-speed bus may increase noise immunity of the control system, and the localized processing of sensor data from the joint motor at the joint level may minimize bus cabling to and from each control node. The joint processor may include a field programmable gate array (FPGA).

  9. Quebec platelet disorder.

    PubMed

    Hayward, Catherine P M; Rivard, Georges E

    2011-04-01

    Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with a unique gain-of-function defect in fibrinolysis. In the past 5 years, there have been important advances in the understanding of the pathogenesis of QPD, including its genetic cause, which is a copy number variation mutation of PLAU, the gene for urokinase plasminogen activator (uPA). QPD is the first bleeding disorder identified to be caused by a PLAU mutation and it is also the first bleeding disorder recognized to result from a gene copy number mutation. The molecular defect of QPD leads to marked overexpression of uPA during megakaryopoiesis, producing profibrinolytic platelets that contain active forms of uPA in their α-granules. This article summarizes expert opinions on the features of QPD and recent advances in the understanding of its pathogenesis and genetic cause.

  10. Urokinase and its Receptors in Chronic Kidney Disease

    PubMed Central

    Zhang, Guoqiang; Eddy, Allison A.

    2011-01-01

    Since the recognition that plasminogen activator inhibitor-1 (PAI-1) is a powerful profibrotic molecule, there has been considerable interest in deciphering the extent to which this effect is mediated by its ability to inhibit serine proteases with downstream effects on fibrogenesis. This review will summarize current knowledge about the serine protease urokinase-type plasminogen activator and its high affinity receptor uPAR/CD87 as it pertains to chronic kidney disease (CKD) progression. An emerging theme is that the effects of PAI-1 and uPAR appear to be organ- and site-specific. Normal kidney tubules produce a large quantity of uPA that is secreted into the urinary space. Activity levels increase during CKD presumably due to new sources of production by macrophages and fibroblasts. By activating hepatocyte growth factor and degrading fibrinogen uPA may have anti-fibrotic effects. However CKD severity after experimental ureteral obstruction is not altered by endogenous uPA deficiency. Beneficial effects of exogenous uPA have been reported in experimental models of fibrosis in the lung and liver but CKD awaits exploration. Absent in normal kidneys uPAR is expressed by both renal parenchymal cells and inflammatory cells in a variety of pathological states. Such expression appears beneficial based on studies performed in uPAR-deficient mice. The uPAR promotes bacterial clearance in infectious diseases. In CKD uPAR expression is associated with high uPA activity but its most important effect appears to be due to scavenging activities and effects on cell recruitment and migration. Although uPAR itself is a non-signaling receptor, it interacts with a variety of co-receptors to modify cellular behavior. Best known are interactions with the low-density lipoprotein receptor-related protein (LRP-1) that lead to PAI-1 endocytosis and degradation, and interactions with several integrins to regulate matrix-dependent cell migration. Contacts with the receptor for the complement C5a component and the interleukin −6 receptor gp130 are examples of other recently recognized interactions. In addition to uPA, vitronectin and high molecular weight kininogen are alternate uPAR ligands that could be implicated in CKD progression. uPAR may also be shed from cell membranes. This soluble form (suPAR) has been detected in plasma and urine and is known to be a chemoattractant for leukocytes that express the formyl-peptide-receptor-like receptor 1/lipoxin A4 receptor. In addition to uPAR several other receptors, including some of the uPAR co-receptors, may also bind directly to uPA and activate cell signaling pathways. The roles of these newer uPAR ligands and uPA receptors are just beginning to be investigated. Since many of them are expressed in the kidney, their potential participation in CKD pathogenesis will be of interest. PMID:18508599

  11. Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index.

    PubMed

    Praditpan, Piyapa; Hamouie, Angie; Basaraba, Cale N; Nandakumar, Renu; Cremers, Serge; Davis, Anne R; Westhoff, Carolyn L

    2017-05-01

    This study compares the pharmacokinetics (PK) of levonorgestrel (LNG) emergency contraceptive (EC) and ulipristal acetate (UPA)-EC between normal-body mass index (BMI) and obese-BMI women. This prospective, randomized crossover study evaluates the PK of women after single doses of LNG-EC (1.5mg) and UPA-EC (30mg). Study procedures took place during clinical research unit admissions, where participants received a standardized meal and each study drug, in random order, during two separate 24-h admissions. Study staff collected 14 blood specimens (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 48h). We evaluated serum concentrations of LNG and UPA using liquid chromatography-tandem mass spectroscopy and estimated the PK parameters of both drugs using noncompartmental analysis. The main outcome of this study was a comparison of between-group differences in AUC 0-24 . Thirty-two women completed the study (16 in each group). Among normal-BMI and obese-BMI participants, the mean BMIs were 22.0 (range 18.8-24.6) and 34.3 (range 30.6-39.9), respectively. After LNG-EC, mean AUC 0-24 and maximum concentration (C max ) were 50% lower among obese-BMI women than among normal-BMI women (AUC 0-24 100.8 vs. 208.5ng*h/mL, IQR obese-BMI 35.8, IQR normal-BMI 74.2, p≤.01; C max 10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC 0-24 and C max were similar between obese-BMI and normal-BMI women (AUC 0-24 362.5 vs. 293.5ng*h/mL, IQR obese-BMI 263.2, IQR normal-BMI 112.5, p=.15; C max 95.6 vs. 89.3ng/mL, p=.70). After a single dose of EC, obese-BMI women are exposed to lower concentrations of LNG and similar concentrations of UPA, when compared to normal-BMI women. Differences in LNG-EC PK by BMI group may underlie and account for the lower LNG-EC efficacy reported among obese-BMI women, but modest differences in UPA-EC PK by BMI group provide less support for variable efficacy. A pharmacodynamic study may be able to clarify whether these PK differences account for observed differences in LNG-EC and UPA-EC efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

    PubMed

    Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

    2017-07-01

    Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, P<0.007). There was significant up-regulation of cardiac mac Arg1 and YM1 with MI in both WT and uPA null mice (n=4-9 per genotype and condition). Treatment with plasmin increased expression of Arg1 and YM1 in cultured cardiac macs. Histologic analysis revealed increased density of activated fibroblasts and M2 macs in SR-uPA hearts post-infarction with associated increases in fibrosis. Cardiac macs isolated from human hearts with ischemic heart disease expressed increased levels of the M2 marker CD206 in comparison to blood-derived macs (4.9±1.3). Cardiac macs in mouse and human hearts adopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids

    PubMed Central

    Florova, Galina; Azghani, Ali; Karandashova, Sophia; Kurdowska, Anna K.; Idell, Steven

    2013-01-01

    Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0–80 min and 24 h after IPFT with scuPA (0–0.5 mg/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with α-macroglobulin (αM) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. The peak of uPA activity (5–40 min) reciprocally correlated with the dose of intrapleural scuPA. Endogenous active PAI-1 (10–20 nM) decreased the rate of intrapleural scuPA activation. The slow step of intrapleural inactivation of free uPA (t1/2β = 40 ± 10 min) was dose independent and 6.7-fold slower than in blood. Up to 260 ± 70 nM of αM/uPA formed in vivo [second order association rate (kass) = 580 ± 60 M−1·s−1]. αM/uPA and products of its degradation contributed to durable intrapleural plasminogen activation up to 24 h after IPFT. Active PAI-1, active α2M, and α2M/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of αM/uPA; and 3) slow intrapleural degradation of αM/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications. PMID:23997178

  14. A Biologically-Based Alternative Water Processor for Long Duration Space Missions

    NASA Technical Reports Server (NTRS)

    Barta, Daniel J.; Pickering, Karen D.; Meyer, Caitlin; Pensinger, Stuart; Vega, Leticia; Flynn, Michael; Jackson, Andrew; Wheeler, Raymond

    2015-01-01

    A wastewater recovery system has been developed that combines novel biological and physicochemical components for recycling wastewater on long duration space missions. Functionally, this Alternative Water Processor (AWP) would replace the Urine Processing Assembly on the International Space Station and reduce or eliminate the need for the multifiltration beds of the Water Processing Assembly (WPA). At its center are two unique game changing technologies: 1) a biological water processor (BWP) to mineralize organic forms of carbon and nitrogen and 2) an advanced membrane processor (Forward Osmosis Secondary Treatment) for removal of solids and inorganic ions. The AWP is designed for recycling larger quantities of wastewater from multiple sources expected during future exploration missions, including urine, hygiene (hand wash, shower, oral and shave) and laundry. The BWP utilizes a single-stage membrane-aerated biological reactor for simultaneous nitrification and denitrification. The Forward Osmosis Secondary Treatment (FOST) system uses a combination of forward osmosis (FO) and reverse osmosis (RO), is resistant to biofouling and can easily tolerate wastewaters high in non-volatile organics and solids associated with shower and/or hand washing. The BWP was operated continuously for over 300 days. After startup, the mature biological system averaged 85% organic carbon removal and 44% nitrogen removal, close to maximum based on available carbon. The FOST has averaged 93% water recovery, with a maximum of 98%. If the wastewater is slighty acidified, ammonia rejection is optimal. This paper will provide a description of the technology and summarize results from ground-based testing using real wastewater.

  15. Repeated intermittent ulipristal acetate in the treatment of uterine fibroids: a cost-effectiveness analysis.

    PubMed

    Geale, Kirk; Saridogan, Ertan; Lehmann, Matthieu; Arriagada, Pablo; Hultberg, Marcus; Henriksson, Martin

    2017-01-01

    There are limited treatment options available for women with moderate to severe symptoms of uterine fibroids (UFs) who wish to avoid surgery. For these women, treatment with standard pharmaceuticals such as contraceptives is often insufficient to relieve symptoms, and patients may require surgery despite their wish to avoid it. Clinical trials demonstrate that ulipristal acetate 5 mg (UPA) is an effective treatment for this patient group, but its cost-effectiveness has not been assessed in this population. A decision-analytic model was developed to simulate a cohort of patients in this population under treatment with UPA followed by surgery as needed compared to treatment with iron and non-steroidal anti-inflammatory drug (NSAID) followed by surgery as needed (best supportive care, BSC). The analysis took the perspective of the National Health Service (NHS) in England, UK, and was based on the published UPA clinical trials. Results were calculated for the long-term costs and quality-adjusted life years (QALYs) for each treatment arm and combined into an incremental cost-effectiveness ratio (ICER) as the primary outcome. The impact of parameter uncertainty on the results was assessed using scenario, deterministic, and probabilistic sensitivity analyses. The results show that treating patients with the UPA strategy, instead of the BSC strategy, results in an additional cost of £1,115 and a gain of 0.087 QALYs, resulting in an ICER of £12,850. Given commonly accepted cost-effectiveness thresholds in England, the use of UPA as a repeated, intermittent treatment for women with moderate to severe symptoms of UF wishing to avoid surgery is likely to be a cost-effective intervention when compared to BSC.

  16. Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells.

    PubMed Central

    Kondoh, N.; Yamada, T.; Kihara-Negishi, F.; Yamamoto, M.; Oikawa, T.

    1998-01-01

    To investigate the cell biological function of PU.1, a member of the Ets family of transcription factors, a vector capable of expressing the protein was transfected into HT1080 human fibrosarcoma cells. Exogenous expression of PU.1 in HT1080 cells reduced colony-forming efficiency but stimulated cell migration in soft agar, although it did not affect cell growth in adherent culture. Expression of the urokinase-type plasminogen activator (uPA) mRNA, which is known to be correlated with cell migration and invasion, was enhanced in PU.1 transfectants compared with mock transfectants. Run-on analysis demonstrated that uPA transcription was unaffected by PU.1, suggesting that this enhancement mainly occurs at a post-transcriptional level. On the other hand, treatment of HT1080 cells with the synthetic glucocorticoid dexamethasone (DEX; 10(-7) M) significantly reduced uPA gene expression at a transcriptional level. Furthermore, DEX inhibited cell migration in soft agar without affecting cell growth. These negative effects of DEX on uPA expression and cell migration were alleviated by the expression of PU.1 in HT1080 cells, whereas expression of the N-ras oncogene, which is responsible for maintenance of the transformed phenotypes in HT1080 cells, was unaffected by PU.1 expression or DEX treatment in the cells. Our results suggest that expression of PU.1 can stimulate uPA gene expression at the post-transcriptional level, which may subsequently lead to activation of cell motility and/or reduced cell-cell adhesion, but reduces anchorage-independent growth of HT1080 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9743289

  17. Enhanced Venous Thrombus Resolution in Plasminogen Activator Inhibitor Type-2 Deficient Mice

    PubMed Central

    Siefert, Suzanne A; Chabasse, Christine; Mukhopadhyay, Subhradip; Hoofnagle, Mark H; Strickland, Dudley K; Sarkar, Rajabrata; Antalis, Toni M

    2014-01-01

    Background The resolution of deep vein thrombosis (DVT) requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. PAI-2 is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. Objective To investigate the role of PAI-2 in venous thrombus formation and resolution. Methods Venous thrombus resolution was compared in wild type C57BL/6, PAI-2 -/- and PAI-1 -/- mice using the stasis model of DVT. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA, and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. Results We found that absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2 -/- mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2 deficient thrombi had increased levels of the neutrophil chemoattractant, CXCL2, which was associated with early enhanced neutrophil recruitment. Conclusions These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. PMID:25041188

  18. Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

    PubMed

    Siefert, S A; Chabasse, C; Mukhopadhyay, S; Hoofnagle, M H; Strickland, D K; Sarkar, R; Antalis, T M

    2014-10-01

    The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. To investigate the role of PAI-2 in venous thrombus formation and resolution. Venous thrombus resolution was compared in wild-type C57BL/6, PAI-2(-/-) , and PAI-1(-/-) mice using the stasis model of deep vein thrombosis. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. We found that the absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2(-/-) mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2-deficient thrombi had increased levels of the neutrophil chemoattractant CXCL2, which was associated with early enhanced neutrophil recruitment. These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. © 2014 International Society on Thrombosis and Haemostasis.

  19. The Plasminogen Activation System Modulates Differently Adipogenesis and Myogenesis of Embryonic Stem Cells

    PubMed Central

    Hadadeh, Ola; Barruet, Emilie; Peiretti, Franck; Verdier, Monique; Bernot, Denis; Hadjal, Yasmine; Yazidi, Claire El; Robaglia-Schlupp, Andrée; De Paula, Andre Maues; Nègre, Didier; Iacovino, Michelina; Kyba, Michael; Alessi, Marie-Christine; Binétruy, Bernard

    2012-01-01

    Regulation of the extracellular matrix (ECM) plays an important functional role either in physiological or pathological conditions. The plasminogen activation (PA) system, comprising the uPA and tPA proteases and their inhibitor PAI-1, is one of the main suppliers of extracellular proteolytic activity contributing to tissue remodeling. Although its function in development is well documented, its precise role in mouse embryonic stem cell (ESC) differentiation in vitro is unknown. We found that the PA system components are expressed at very low levels in undifferentiated ESCs and that upon differentiation uPA activity is detected mainly transiently, whereas tPA activity and PAI-1 protein are maximum in well differentiated cells. Adipocyte formation by ESCs is inhibited by amiloride treatment, a specific uPA inhibitor. Likewise, ESCs expressing ectopic PAI-1 under the control of an inducible expression system display reduced adipogenic capacities after induction of the gene. Furthermore, the adipogenic differentiation capacities of PAI-1−/− induced pluripotent stem cells (iPSCs) are augmented as compared to wt iPSCs. Our results demonstrate that the control of ESC adipogenesis by the PA system correspond to different successive steps from undifferentiated to well differentiated ESCs. Similarly, skeletal myogenesis is decreased by uPA inhibition or PAI-1 overexpression during the terminal step of differentiation. However, interfering with uPA during days 0 to 3 of the differentiation process augments ESC myotube formation. Neither neurogenesis, cardiomyogenesis, endothelial cell nor smooth muscle formation are affected by amiloride or PAI-1 induction. Our results show that the PA system is capable to specifically modulate adipogenesis and skeletal myogenesis of ESCs by successive different molecular mechanisms. PMID:23145071

  20. Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

    PubMed Central

    Bhandary, Yashodhar P.; Velusamy, Thirunavukkarasu; Shetty, Praveenkumar; Shetty, Rashmi S.; Idell, Steven; Cines, Douglas B.; Jain, Deepika; Bdeir, Khalil; Abraham, Edward; Tsuruta, Yuko; Shetty, Sreerama

    2009-01-01

    Rationale: Urokinase-type plasminogen activator (uPA) receptor (uPAR) is required for the recruitment of neutrophils in response to infection. uPA induces its own expression in lung epithelial cells, which involves its interaction with cell surface uPAR. Regulation of uPAR expression is therefore crucial for uPA-mediated signaling in infectious acute lung injury (ALI). Objectives: To determine the role of uPA in uPAR expression during ALI caused by sepsis. Methods: We used Western blot, Northern blot, Northwestern assay, and immunohistochemistry. Phosphate-buffered saline– and lipopolysaccharide (LPS)-treated wild-type and uPA−/− mice were used. Measurements and Main Results: Biological activities of uPA, including proteolysis, cell adhesion, migration, proliferation, and differentiation, are dependent on its association with uPAR. Bacterial endotoxin (LPS) is a major cause of pulmonary dysfunction and infection-associated mortality. The present study shows that LPS induces uPAR expression both in vitro and in vivo, and that the mechanism involves post-transcriptional stabilization of uPAR mRNA by reciprocal interaction of phosphoglycerate kinase (PGK) and heterogeneous nuclear ribonucleoprotein C (hnRNPC) with uPAR mRNA coding region and 3′ untranslated region determinants, respectively. The process involves tyrosine phosphorylation of PGK and hnRNPC. uPA−/− mice failed to induce uPAR expression after LPS treatment. In these mice, LPS treatment failed to alter the binding of PGK and hnRNPC protein with uPAR mRNA due to lack of tyrosine phosphorylation. Conclusions: Our study shows that induction of LPS-mediated uPAR expression is mediated through tyrosine phosphorylation of PGK and hnRNPC. This involves expression of uPA as an obligate intermediary. PMID:19029002

  1. A label-free photoelectrochemical biosensor for urokinase-type plasminogen activator detection based on a g-C3N4/CdS nanocomposite.

    PubMed

    Liu, Xing-Pei; Chen, Jing-Shuai; Mao, Chang-Jie; Niu, He-Lin; Song, Ji-Ming; Jin, Bao-Kang

    2018-09-26

    Herein, we established a novel ultrasensitive photoelectrochemical biosensor for detecting urokinase-type plasminogen activator (u-PA), based on a g-C 3 N 4 /CdS nanocomposite. The prepared nanocomposite was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, ultraviolet-visible absorption spectroscopy, and Fourier transform infrared spectroscopy, thus indicating that the nanocomposite was prepared successfully. In the typical process, the prepared nanocomposite was deposited on the surface of a bare FTO electrode. After being air-dried, the g-C 3 N 4 /CdS nanocomposite modified electrode was successively incubated with antibody against urokinase-type plasminogen activator and the blocking agent BSA to produce a photoelectrochemical biosensor for u-PA. In the presence of target u-PA antigen, the photocurrent response of the prepared biosensor electrode decreased significantly. The proposed novel photoelectrochemical biosensor exhibited good sensitivity, specificity, and reproducibility for u-PA detection, and a low detection limit of 33 fg mL -1 , ranging from 1 μg mL -1 -0.1 pg mL -1 . The proposed strategy should provide a promising method for detection of other biomarkers. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Mitogenic signaling of urokinase receptor-deficient kidney fibroblasts: actions of an alternative urokinase receptor and LDL receptor-related protein.

    PubMed

    Zhang, Guoqiang; Cai, Xiaohe; López-Guisa, Jesús M; Collins, Sarah J; Eddy, Allison A

    2004-08-01

    The urokinase receptor (uPAR) attenuates myofibroblast recruitment and fibrosis in the kidney. This study examined the role of uPAR and its co-receptor LDL receptor-related protein (LRP) in the regulation of kidney fibroblast proliferation and extracellular signal-regulated kinase (ERK) signaling. Compared with uPAR+/+ cells, uPAR-/- kidney fibroblasts were hyperproliferative. UPAR-/- fibroblast proliferation was 60% inhibited by an ERK kinase inhibitor. LRP protein was reduced and extracellular accumulation of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) proteins were greater in uPAR-/- cultures. Addition of functional uPA protein or LRP antisense RNA significantly increased ERK signaling and cell mitosis in both genotypes. Enhanced uPAR-/- fibroblast proliferation was reversed by a recombinant nonfunctional uPA peptide. The density of cell-bound fluor-uPA was similar between uPAR-/- and uPAR+/+ fibroblasts (78 +/- 6 versus 92 +/- 16 units). These data suggest that uPAR-deficient kidney fibroblasts express lower levels of its scavenger co-receptor LRP, resulting in greater extracellular accumulation of uPA and PAI-1. Enhanced proliferation of uPAR-/- fibroblasts seems to be mediated by uPA-dependent ERK signaling via an alternative urokinase receptor.

  3. FPGA wavelet processor design using language for instruction-set architectures (LISA)

    NASA Astrophysics Data System (ADS)

    Meyer-Bäse, Uwe; Vera, Alonzo; Rao, Suhasini; Lenk, Karl; Pattichis, Marios

    2007-04-01

    The design of an microprocessor is a long, tedious, and error-prone task consisting of typically three design phases: architecture exploration, software design (assembler, linker, loader, profiler), architecture implementation (RTL generation for FPGA or cell-based ASIC) and verification. The Language for instruction-set architectures (LISA) allows to model a microprocessor not only from instruction-set but also from architecture description including pipelining behavior that allows a design and development tool consistency over all levels of the design. To explore the capability of the LISA processor design platform a.k.a. CoWare Processor Designer we present in this paper three microprocessor designs that implement a 8/8 wavelet transform processor that is typically used in today's FBI fingerprint compression scheme. We have designed a 3 stage pipelined 16 bit RISC processor (NanoBlaze). Although RISC μPs are usually considered "fast" processors due to design concept like constant instruction word size, deep pipelines and many general purpose registers, it turns out that DSP operations consume essential processing time in a RISC processor. In a second step we have used design principles from programmable digital signal processor (PDSP) to improve the throughput of the DWT processor. A multiply-accumulate operation along with indirect addressing operation were the key to achieve higher throughput. A further improvement is possible with today's FPGA technology. Today's FPGAs offer a large number of embedded array multipliers and it is now feasible to design a "true" vector processor (TVP). A multiplication of two vectors can be done in just one clock cycle with our TVP, a complete scalar product in two clock cycles. Code profiling and Xilinx FPGA ISE synthesis results are provided that demonstrate the essential improvement that a TVP has compared with traditional RISC or PDSP designs.

  4. Microbiological Characterization of the International Space Station Water Processor Assembly External Filter Assembly S/N 01

    NASA Technical Reports Server (NTRS)

    Weir, Natalee; Wilson, Mark; Yoets, Airan; Yoets, Airan; Molina, Thomas; Bruce, Rebekah; Sitler, Glenn; Carter, Layne

    2012-01-01

    The External Filter Assembly (EFA) S/N 01 is a mesh screen filter with a pore size of approximately 300 micron that was installed in the International Space Station (ISS) Water Processor Assembly (WPA) between the Waste Tank and the Mostly Liquid Separator (MLS) on February 11, 2010 to protect clearances in the MLS solenoid valve SV_1121_3. A removal & replacement of the EFA Filter was performed on March 22, 2011 in response to increasing pressure across the Waste Tank solenoid valve SV_1121_1 and the EFA Filter. The EFA Filter was returned on ULF6 and received in the Boeing Huntsville Laboratory on June 13, 2011. The filter was aseptically removed from the housing, and the residual water was collected for enumeration and identification of bacteria and fungi. Swab samples of the filter surface were also collected for microbiological enumeration and identification. Sample analyses were performed by Boeing Huntsville Laboratory and NASA Johnson Space Center Microbiology for comparison. Photographic documentation of the EFA filter was performed using a stereo microscope and environmental scanning electron microscope. This paper characterizes the amount and types of microorganisms on the filter surface and in the residual water from the filter housing following 1 year of utilization in the ISS WPA.

  5. Ray Meta: scalable de novo metagenome assembly and profiling

    PubMed Central

    2012-01-01

    Voluminous parallel sequencing datasets, especially metagenomic experiments, require distributed computing for de novo assembly and taxonomic profiling. Ray Meta is a massively distributed metagenome assembler that is coupled with Ray Communities, which profiles microbiomes based on uniquely-colored k-mers. It can accurately assemble and profile a three billion read metagenomic experiment representing 1,000 bacterial genomes of uneven proportions in 15 hours with 1,024 processor cores, using only 1.5 GB per core. The software will facilitate the processing of large and complex datasets, and will help in generating biological insights for specific environments. Ray Meta is open source and available at http://denovoassembler.sf.net. PMID:23259615

  6. Urokinase-Type Plasminogen Activator in a Human Sarcoma Cellular Model for Metastasis in Athymic Mice

    DTIC Science & Technology

    1990-05-01

    essential medium, used for tissue culture DMSO- Dimemthyl sulfoxide, an inhibitor of uPA production E-ACA- Epsilon aminocaproic acid , an inhibitor of uPA...inhibitors, such as E- aminocaproic acid (E-ACA), phenylmethanesulfonyl fluoride, diisopropyl-fluorophosphate, alpha tocopherol, metal ions (especially Zn...plasma was demonstrated approximately 25 years later (Astedt et al., 1978). The complete amino acid sequence of uPA was reported in 1982 (Gunzler et

  7. An Alternative Water Processor for Long Duration Space Missions

    NASA Technical Reports Server (NTRS)

    Barta, Daniel J.; Pickering, Karen D.; Meyer, Caitlin; Pennsinger, Stuart; Vega, Leticia; Flynn, Michael; Jackson, Andrew; Wheeler, Raymond

    2014-01-01

    A new wastewater recovery system has been developed that combines novel biological and physicochemical components for recycling wastewater on long duration human space missions. Functionally, this Alternative Water Processor (AWP) would replace the Urine Processing Assembly on the International Space Station and reduce or eliminate the need for the multi-filtration beds of the Water Processing Assembly (WPA). At its center are two unique game changing technologies: 1) a biological water processor (BWP) to mineralize organic forms of carbon and nitrogen and 2) an advanced membrane processor (Forward Osmosis Secondary Treatment) for removal of solids and inorganic ions. The AWP is designed for recycling larger quantities of wastewater from multiple sources expected during future exploration missions, including urine, hygiene (hand wash, shower, oral and shave) and laundry. The BWP utilizes a single-stage membrane-aerated biological reactor for simultaneous nitrification and denitrification. The Forward Osmosis Secondary Treatment (FOST) system uses a combination of forward osmosis (FO) and reverse osmosis (RO), is resistant to biofouling and can easily tolerate wastewaters high in non-volatile organics and solids associated with shower and/or hand washing. The BWP has been operated continuously for over 300 days. After startup, the mature biological system averaged 85% organic carbon removal and 44% nitrogen removal, close to stoichiometric maximum based on available carbon. To date, the FOST has averaged 93% water recovery, with a maximum of 98%. If the wastewater is slighty acidified, ammonia rejection is optimal. This paper will provide a description of the technology and summarize results from ground-based testing using real wastewater

  8. The UPA score and teenage pregnancy.

    PubMed

    Garlick, R; Ineichen, B; Hudson, F

    1993-03-01

    Teenage motherhood is often said to be the result of deficient contraceptive and abortion services. Using data from the Public Health Common Data Set (PH CDS) we demonstrate two important effects in a Regional Health Authority: higher rates of conception are related to a live birth rather than an abortion pregnancy outcome; District Health Authorities (DHAs) with high underprivileged area scores (UPA) are more likely to have high rates of conception in the teenage years than those districts with low scores.

  9. Discovery of novel urokinase plasminogen activator (uPA) inhibitors using ligand-based modeling and virtual screening followed by in vitro analysis.

    PubMed

    Al-Sha'er, Mahmoud A; Khanfar, Mohammad A; Taha, Mutasem O

    2014-01-01

    Urokinase plasminogen activator (uPA)-a serine protease-is thought to play a central role in tumor metastasis and angiogenesis and, therefore, inhibition of this enzyme could be beneficial in treating cancer. Toward this end, we explored the pharmacophoric space of 202 uPA inhibitors using seven diverse sets of inhibitors to identify high-quality pharmacophores. Subsequently, we employed genetic algorithm-based quantitative structure-activity relationship (QSAR) analysis as a competition arena to select the best possible combination of pharmacophoric models and physicochemical descriptors that can explain bioactivity variation within the training inhibitors (r (2) 162 = 0.74, F-statistic = 64.30, r (2) LOO = 0.71, r (2) PRESS against 40 test inhibitors = 0.79). Three orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least three binding modes accessible to ligands within the uPA binding pocket. This conclusion was supported by receiver operating characteristic (ROC) curve analyses of the QSAR-selected pharmacophores. Moreover, the three pharmacophores were comparable with binding interactions seen in crystallographic structures of bound ligands within the uPA binding pocket. We employed the resulting pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds. The captured hits were tested in vitro. Overall, our modeling workflow identified new low micromolar anti-uPA hits.

  10. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice

    PubMed Central

    Lund, Leif R; Green, Kirsty A; Stoop, Allart A; Ploug, Michael; Almholt, Kasper; Lilla, Jennifer; Nielsen, Boye S; Christensen, Ib J; Craik, Charles S; Werb, Zena; Danø, Keld; Rømer, John

    2006-01-01

    Simultaneous ablation of the two known activators of plasminogen (Plg), urokinase-type (uPA) and the tissue-type (tPA), results in a substantial delay in skin wound healing. However, wound closure and epidermal re-epithelialization are significantly less impaired in uPA;tPA double-deficient mice than in Plg-deficient mice. Skin wounds in uPA;tPA-deficient mice treated with the broad-spectrum matrix metalloproteinase (MMP) inhibitor galardin (N-[(2R)-2-(hydroxamido-carbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide) eventually heal, whereas skin wounds in galardin-treated Plg-deficient mice do not heal. Furthermore, plasmin is biochemically detectable in wound extracts from uPA;tPA double-deficient mice. In vivo administration of a plasma kallikrein (pKal)-selective form of the serine protease inhibitor ecotin exacerbates the healing impairment of uPA;tPA double-deficient wounds to a degree indistinguishable from that observed in Plg-deficient mice, and completely blocks the activity of pKal, but not uPA and tPA in wound extracts. These findings demonstrate that an additional plasminogen activator provides sufficient plasmin activity to sustain the healing process albeit at decreased speed in the absence of uPA, tPA and galardin-sensitive MMPs and suggest that pKal plays a role in plasmin generation. PMID:16763560

  11. Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

    PubMed Central

    Barajas-Castañeda, Luis Miguel; Cortés-Gutiérrez, Evelin; García-Rodríguez, Francisco Mario; Campos-Rodríguez, Rafael; Lara-Padilla, Eleazar; Enríquez-Rincón, Fernando; Figueroa-Arredondo, Paula

    2016-01-01

    Extracellular matrix metalloproteases and the fibrinolytic system are important protease systems interacting with each other in charge of remodeling and recycling of tissues. Their role in tumor invasion and metastasis is often discussed. In this study several metalloproteases such as MMP-1, MMP-3, MMP-9, and TIMP-1 together with molecules from the fibrinolytic system like uPA, its receptor uPAR, and its inhibitor, PAI-1, were studied by immune-histochemistry to establish a comparison with and without metastasis. From the (118) primary tumors of Mexican patients with ductal breast cancer studied, 56% were grade II and 69% were size T2; the group with metastatic ganglia included 64 samples (54.3%). In patients with metastasis the estimated expression of MMP-3 and uPA (resp., 28% and 45%) was higher than that from no metastatic tumors; it means there is higher expression of both markers in metastatic tumors (p < 0.05). At the same time, metastatic tumors showed statistically significant lower signal of PAI-1 (24%) than tumors without metastasis (p < 0.05). We concluded that overexpression of MMP-3 and uPA, altogether with diminished expression of PAI-1 from metastatic tumors, might be a crucial step towards metastasis in ductal breast cancer. Nevertheless, additional studies in different populations are necessary to establish a pattern. PMID:27975070

  12. Development and evaluation of an ultrasonic personal aerosol sampler.

    PubMed

    Volckens, J; Quinn, C; Leith, D; Mehaffy, J; Henry, C S; Miller-Lionberg, D

    2017-03-01

    Assessing personal exposure to air pollution has long proven challenging due to technological limitations posed by the samplers themselves. Historically, wearable aerosol monitors have proven to be expensive, noisy, and burdensome. The objective of this work was to develop a new type of wearable monitor, an ultrasonic personal aerosol sampler (UPAS), to overcome many of the technological limitations in personal exposure assessment. The UPAS is a time-integrated monitor that features a novel micropump that is virtually silent during operation. A suite of onboard environmental sensors integrated with this pump measure and record mass airflow (0.5-3.0 L/min, accurate within 5%), temperature, pressure, relative humidity, light intensity, and acceleration. Rapid development of the UPAS was made possible through recent advances in low-cost electronics, open-source programming platforms, and additive manufacturing for rapid prototyping. Interchangeable cyclone inlets provided a close match to the EPA PM 2.5 mass criterion (within 5%) for device flows at either 1.0 or 2.0 L/min. Battery life varied from 23 to 45 hours depending on sample flow rate and selected filter media. Laboratory tests of the UPAS prototype demonstrate excellent agreement with equivalent federal reference method samplers for gravimetric analysis of PM 2.5 across a broad range of concentrations. © 2016 The Authors. Indoor Air published by John Wiley & Sons Ltd.

  13. Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City.

    PubMed

    Barajas-Castañeda, Luis Miguel; Cortés-Gutiérrez, Evelin; García-Rodríguez, Francisco Mario; Campos-Rodríguez, Rafael; Lara-Padilla, Eleazar; Enríquez-Rincón, Fernando; Castro-Mussot, María Eugenia; Figueroa-Arredondo, Paula

    2016-01-01

    Extracellular matrix metalloproteases and the fibrinolytic system are important protease systems interacting with each other in charge of remodeling and recycling of tissues. Their role in tumor invasion and metastasis is often discussed. In this study several metalloproteases such as MMP-1, MMP-3, MMP-9, and TIMP-1 together with molecules from the fibrinolytic system like uPA, its receptor uPAR, and its inhibitor, PAI-1, were studied by immune-histochemistry to establish a comparison with and without metastasis. From the (118) primary tumors of Mexican patients with ductal breast cancer studied, 56% were grade II and 69% were size T2; the group with metastatic ganglia included 64 samples (54.3%). In patients with metastasis the estimated expression of MMP-3 and uPA (resp., 28% and 45%) was higher than that from no metastatic tumors; it means there is higher expression of both markers in metastatic tumors ( p < 0.05). At the same time, metastatic tumors showed statistically significant lower signal of PAI-1 (24%) than tumors without metastasis ( p < 0.05). We concluded that overexpression of MMP-3 and uPA, altogether with diminished expression of PAI-1 from metastatic tumors, might be a crucial step towards metastasis in ductal breast cancer. Nevertheless, additional studies in different populations are necessary to establish a pattern.

  14. Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo

    PubMed Central

    Lund, Ida K.; Rasch, Morten G.; Ingvarsen, Signe; Pass, Jesper; Madsen, Daniel H.; Engelholm, Lars H.; Behrendt, Niels; Høyer-Hansen, Gunilla

    2012-01-01

    Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target protein function(s). This approach has the advantage of being a model for therapeutic targeting. mAbs for use in mouse models can be obtained through immunization of gene-deficient mice with the autologous protein. Such mAbs react with both species-specific epitopes and epitopes conserved between species. mAbs against proteins involved in extracellular proteolysis, including plasminogen activators urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA), their inhibitor PAI-1, the uPA receptor (uPAR), two matrix metalloproteinases (MMP9 and MMP14), as well as the collagen internalization receptor uPARAP, have been developed. The inhibitory mAbs against uPA and uPAR block plasminogen activation and thereby hepatic fibrinolysis in vivo. Wound healing, another plasmin-dependent process, is delayed by an inhibitory mAb against uPA in the adult mouse. Thromboembolism can be inhibited by anti-PAI-1 mAbs in vivo. In conclusion, function-blocking mAbs are well-suited for targeted therapy in mouse models of different diseases, including cancer. PMID:22754528

  15. Peake works on the WPA

    NASA Image and Video Library

    2016-03-22

    ISS047e013845 (03/22/2016) --- ESA (European Space Agency) astronaut Tim Peake works on the Water Processor Assembly (WPA) aboard the International Space Station. The WPA is is responsible for treating waste water aboard the station for recycling back into potable water.

  16. Emergency contraception: A multispecialty survey of clinician knowledge and practices.

    PubMed

    Batur, Pelin; Cleland, Kelly; McNamara, Megan; Wu, Justine; Pickle, Sarah

    2016-02-01

    To assess knowledge and provision of emergency contraception (EC), particularly the most effective methods. A web-based survey was distributed to a cross-sectional convenience sample of healthcare providers across specialties treating reproductive-aged women. The survey was sent to 3260 practicing physicians and advanced practice clinicians in 14 academic centers between February 2013 and April 2014. We analyzed responses by provider specialty using multivariable logistic regression. The final sample included 1684 providers (response rate=51.7%). Ninety-five percent of the respondents had heard of levonorgestrel (LNG) EC. Among reproductive health specialists, 81% provide LNG EC in their practice, although only half (52%) had heard of ulipristal acetate (UPA) and very few provide it (14%). The majority in family medicine (69%) and emergency medicine (74%) provide LNG, in contrast to 42% of internists and 55% of pediatricians. However, the more effective methods [UPA and copper intrauterine device (IUD)] were little known and rarely provided outside of reproductive health specialties; 18% of internists and 14% of emergency medicine providers had heard of UPA and 4% provide it. Only 22% of emergency providers and 32% of pediatricians had heard of the copper IUD used as EC. Among reproductive health specialists, only 36% provide copper IUD as EC in their practice. Specialty, provider type and proportion of women of reproductive age in the practice were related to knowledge and provision of some forms of EC. Awareness and provision of the most effective EC methods, UPA and the copper IUD (which are provider dependent), are substantially lower than for LNG EC, especially among providers who do not focus on reproductive health. In our sample of 1684 healthcare providers from diverse specialties who treat reproductive-aged women, knowledge and provision of the most effective forms of EC (UPA and the copper IUD) are far lower than for LNG EC. Women should be offered the full range of EC methods. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Emergency contraception supply in Australian pharmacies after the introduction of ulipristal acetate: a mystery shopping mixed-methods study.

    PubMed

    Collins, Jack Charles; Schneider, Carl Richard; Moles, Rebekah Jane

    2018-05-09

    To explore the supply of emergency contraception (EC) from Australian community pharmacies after the introduction of ulipristal acetate (UPA) and to explore pharmacists' knowledge, decision-making, attitudes and beliefs surrounding supplying EC. A mixed-methods approach of mystery shopping with structured interview was employed. From August to November 2017, 20 pharmacy students mystery-shopped 10 community pharmacies in metropolitan Sydney, Australia, requesting "the morning after pill." Each pharmacy was visited five times with varying scenarios. Structured interviews were conducted immediately postvisit. Visit data were analyzed descriptively and comparatively. Interviews were transcribed verbatim and categorically analyzed. Of 50 planned visits, 43 were analyzed. EC was supplied in 38 requests by pharmacists (54% male). Levonorgestrel (LNG) was more frequently supplied than UPA (74% vs. 26%). UPA was only supplied when intercourse occurred >72 h prior. Directions for use were provided in 35 supplies. No difference in questioning or counseling was found based on sex of requester. Female pharmacists provided more counseling points (MED=4 [IQR=4-5] vs. MED=3 [IQR=0-4]; p<.01). Two pharmacists asked all guideline questions, and no pharmacist provided all guideline counseling points. Interviews elicited supply guidelines, regulatory and clinical knowledge, financial considerations, privacy and stock availability as factors influencing EC supply. EC was supplied in accordance with local legislation in all instances, with the majority supplied within the licensed timeframe for each EC formulation. LNG was supplied more frequently than UPA. UPA was only supplied in the 72-120-h timeframe. Clinical and regulatory knowledge, availability and cost to consumer were identified as factors influencing supply. This study found that despite the introduction of ulipristal acetate to the Australian market, it is not frequently supplied. Interviews identified the need for continuing professional development regarding pharmacist clinical and regulatory knowledge. Future guideline development should consider utility and user needs to optimize the implementation of guidelines. Copyright © 2018. Published by Elsevier Inc.

  18. Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand.

    PubMed

    De Souza, Melissa; Matthews, Hayden; Lee, Jodi A; Ranson, Marie; Kelso, Michael J

    2011-04-15

    Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA:uPAR interaction represent promising anti-tumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC(50)1=0.8 nM, IC(50)2=33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before proceeding to such studies, confirmation was sought that 1 and 2 retained their potencies in physiologically relevant cell-based competition assays employing uPAR's native binding partner high molecular weight uPA (HMW-uPA). This study describes a new solution phase synthesis of 1, a mixed solid/solution phase synthesis of 2 and reports the activities of 1 and 2 in semi-quantitative competition flow cytometry assays and quantitative cell-based uPA activity assays that employed HMW-uPA as the competing ligand. The flow cytometry experiments revealed that high concentrations of 2 (10-100 μM) are required to compete with HMW-uPA for uPAR binding and that 1 shows no antagonist effects at 100 μM. The cell-based enzyme activity assays similarly revealed that 1 and 2 are poor inhibitors of cell surface-bound HMW-uPA activity (IC(50) >100 μM for 1 and 2). The report highlights the dangers of identifying false-positive lead uPAR antagonists from competition assays employing labelled competing ligands other than the native HMW-uPA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. A Micro-Computer Computational Unit for an IR-CCD Intrusion Detection System.

    DTIC Science & Technology

    1980-10-01

    signal processor. In the laboratory this processor has met or exceeded all its design goals. LYN H. SKOLNIK Project Engineer i, viii AMONO I...4 +* * SEPIKY LANL ITINE’-10. - 4. 1 4* This section of :ode containrs all assembly lasosiae rotinec ft - used in the IRCCD tntruton 4eector rm r s...In arra -B47- -I- here o, ’t , ’ retore A0I o.- .tmp2,r! rotetre r5t jr t o I 00 to r.9ioter restore ro-tine THRESH - routix, for set.ing J thres

  20. Plasma Methane Pyrolysis for Spacecraft Oxygen Loop Closure

    NASA Technical Reports Server (NTRS)

    Greenwood, Z. W.

    2018-01-01

    Life support is a critical function of any crewed space vehicle or habitat. Human life support systems on the International Space Station (ISS) include a number of atmosphere revitalization (AR) technologies to provide breathable air and a comfortable living environment to the crew. The Trace Contaminant Control System removes harmful volatile organic compounds and other trace contaminants from the circulating air. The Carbon Dioxide Removal Assembly (CDRA) removes metabolic carbon dioxide (CO2) and returns air to the cabin. Humidity is kept at comfortable levels by a number of condensing heat exchangers. The Oxygen Generation Assembly (OGA) electrolyzes water to produce oxygen for the crew and hydrogen (H2) as a byproduct. A Sabatier reaction-based CO2 Reduction Assembly (CRA) was launched to the ISS in 2009 and became fully operational in June 2011.The CRA interfaces with both the OGA and CDRA. Carbon dioxide from the CDRA is compressed and stored in tanks until hydrogen is available from OGA water electrolysis. When the OGA is operational and there is CO2 available, the CRA is activated and produces methane and water via the Sabatier reaction shown in Equation 1... One approach to achieve these higher recovery rates builds upon the ISS AR architecture and includes adding a methane post-processor to recover H2 from CRA methane. NASA has been developing the Plasma Pyrolysis Assembly (PPA) to fill the role of a methane post-processor.

  1. JPRS Report, Soviet Union, Political Affairs, On Stalin and Stalinism: Historical Essays by Roy Medvedev

    DTIC Science & Technology

    1989-07-05

    commander, if the previous one is seriously wounded, as the Church needs a new high priest if the former has gone to his Maker, so a political party...JPRS-UPA-89-042 5 JULY 1989 JPRS »I» —-.I::::1: ’^ m Tariff x Soviet Union Political Affairs ON STALIN AND STALINISM: HISTORICAL ESSAYS By...Soviet Union Political Affairs ON STALIN AND STALINISM: HISTORICAL ESSAYS By Roy Medvedev JPRS-UPA-89-042 CONTENTS 5 JULY 1989 18300508 Moscow

  2. An air-bearing weight offload system for ground test of heavy LSS structures

    NASA Technical Reports Server (NTRS)

    Rice, R. B.

    1989-01-01

    The capability and use of the Gravity Offload Facility (GOF) are discussed. Briefly explained are the: truss and base casting; carriage assembly; carriage weldment; vertical lift axis control; lifting cylinder; payload gimbal; motion base layout; and control processor.

  3. Life Cycle Analysis of a SpaceCube Printed Circuit Board Assembly Using Physics of Failure Methodologies

    NASA Technical Reports Server (NTRS)

    Sood, Bhanu; Evans, John; Daniluk, Kelly; Sturgis, Jason; Davis, Milton; Petrick, David

    2017-01-01

    In this reliability life cycle evaluation of the SpaceCube 2.0 processor card, a partially populated version of the card is being evaluated to determine its durability with respect to typical GSFC mission loads.

  4. Repositioning the substrate activity screening (SAS) approach as a fragment-based method for identification of weak binders.

    PubMed

    Gladysz, Rafaela; Cleenewerck, Matthias; Joossens, Jurgen; Lambeir, Anne-Marie; Augustyns, Koen; Van der Veken, Pieter

    2014-10-13

    Fragment-based drug discovery (FBDD) has evolved into an established approach for "hit" identification. Typically, most applications of FBDD depend on specialised cost- and time-intensive biophysical techniques. The substrate activity screening (SAS) approach has been proposed as a relatively cheap and straightforward alternative for identification of fragments for enzyme inhibitors. We have investigated SAS for the discovery of inhibitors of oncology target urokinase (uPA). Although our results support the key hypotheses of SAS, we also encountered a number of unreported limitations. In response, we propose an efficient modified methodology: "MSAS" (modified substrate activity screening). MSAS circumvents the limitations of SAS and broadens its scope by providing additional fragments and more coherent SAR data. As well as presenting and validating MSAS, this study expands existing SAR knowledge for the S1 pocket of uPA and reports new reversible and irreversible uPA inhibitor scaffolds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

    PubMed Central

    Caiolfa, Valeria R.; Zamai, Moreno; Malengo, Gabriele; Andolfo, Annapaola; Madsen, Chris D.; Sutin, Jason; Digman, Michelle A.; Gratton, Enrico; Blasi, Francesco; Sidenius, Nicolai

    2007-01-01

    To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer–oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein–uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA–plasminogen activator inhibitor type 1–mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents. PMID:18056417

  6. Digital Circuit Analysis Using an 8080 Processor.

    ERIC Educational Resources Information Center

    Greco, John; Stern, Kenneth

    1983-01-01

    Presents the essentials of a program written in Intel 8080 assembly language for the steady state analysis of a combinatorial logic gate circuit. Program features and potential modifications are considered. For example, the program could also be extended to include clocked/unclocked sequential circuits. (JN)

  7. Short communication: identification of the conformational requirement for the specificities of coreceptors for human and simian immunodeficiency viruses.

    PubMed

    Shimizu, Nobuaki; Tanaka, Atsushi; Jinno-Oue, Atsushi; Mori, Takahisa; Ohtsuki, Takahiro; Hoshino, Hiroo

    2010-03-01

    More than 10 G protein-coupled receptors (GPCRs) work as coreceptors for human and simian immunodeficiency viruses (HIVs/SIVs); however, structural features critical for coreceptor activity have not been identified. Our objective was to elucidate the structural requirement of coreceptor activities. Amino-terminal regions (NTRs), extracellular loops (ECLs), and the undecapeptidyl arch (UPA) in the second ECL have been shown to be important for coreceptor function. We made chimeric coreceptors for these regions between CCR5 and GPR1, which is genetically distant from CCR5, and analyzed their activities. The coreceptor activity and specificity of CCR5 were maintained when its NTR or UPA was replaced with GPR1. In contrast, the GPR1 chimera with CCR5 NTR was used by HIV-1 strains that can use only CCR5, but not both CCR5 and CXCR4, or GPR1. GPR1 chimera with CCR5 UPA almost lost activity. All ECL chimeras could hardly maintain activity. Thus, CCR5 is more flexibly acceptable to heterologous NTR and UPA than GPR1, suggesting the existence of conformational differences made by the integration of multiple extracellular regions. This conformation may specifically interact with HIV-1 in a strain-dependent manner. Identification of a factor that is critical to make this conformation will contribute to understanding the mechanism of coreceptor function of GPCRs. For this, the coreceptor activity of GPR1, which is genetically distant from CCR5, will be a useful tool.

  8. Protein-Binding RNA Aptamers Affect Molecular Interactions Distantly from Their Binding Sites

    PubMed Central

    Dupont, Daniel M.; Thuesen, Cathrine K.; Bøtkjær, Kenneth A.; Behrens, Manja A.; Dam, Karen; Sørensen, Hans P.; Pedersen, Jan S.; Ploug, Michael; Jensen, Jan K.; Andreasen, Peter A.

    2015-01-01

    Nucleic acid aptamer selection is a powerful strategy for the development of regulatory agents for molecular intervention. Accordingly, aptamers have proven their diligence in the intervention with serine protease activities, which play important roles in physiology and pathophysiology. Nonetheless, there are only a few studies on the molecular basis underlying aptamer-protease interactions and the associated mechanisms of inhibition. In the present study, we use site-directed mutagenesis to delineate the binding sites of two 2´-fluoropyrimidine RNA aptamers (upanap-12 and upanap-126) with therapeutic potential, both binding to the serine protease urokinase-type plasminogen activator (uPA). We determine the subsequent impact of aptamer binding on the well-established molecular interactions (plasmin, PAI-1, uPAR, and LRP-1A) controlling uPA activities. One of the aptamers (upanap-126) binds to the area around the C-terminal α-helix in pro-uPA, while the other aptamer (upanap-12) binds to both the β-hairpin of the growth factor domain and the kringle domain of uPA. Based on the mapping studies, combined with data from small-angle X-ray scattering analysis, we construct a model for the upanap-12:pro-uPA complex. The results suggest and highlight that the size and shape of an aptamer as well as the domain organization of a multi-domain protein such as uPA, may provide the basis for extensive sterical interference with protein ligand interactions considered distant from the aptamer binding site. PMID:25793507

  9. The advanced receiver 2: Telemetry test results in CTA 21

    NASA Technical Reports Server (NTRS)

    Hinedi, S.; Bevan, R.; Marina, M.

    1991-01-01

    Telemetry tests with the Advanced Receiver II (ARX II) in Compatibility Test Area 21 are described. The ARX II was operated in parallel with a Block-III Receiver/baseband processor assembly combination (BLK-III/BPA) and a Block III Receiver/subcarrier demodulation assembly/symbol synchronization assembly combination (BLK-III/SDA/SSA). The telemetry simulator assembly provided the test signal for all three configurations, and the symbol signal to noise ratio as well as the symbol error rates were measured and compared. Furthermore, bit error rates were also measured by the system performance test computer for all three systems. Results indicate that the ARX-II telemetry performance is comparable and sometimes superior to the BLK-III/BPA and BLK-III/SDA/SSA combinations.

  10. iLIDS Simulations and Videos for Docking TIM

    NASA Technical Reports Server (NTRS)

    Lewis, James L.

    2010-01-01

    The video shows various aspects of the International Low Impact Docking System, including team members, some production, configuration, mated androgynous iLIDS, SCS Lockdown system, thermal analysis, electrical engineering aspects, the iLIDS control box and emulator, radiation testing at BNL, component environmental testing, component vibration testing, 3G processor board delivery system, GTA vibe test, EMA testbed, hook and hook disassembly, flex shaftdrive assembly, GSE cradle MISSE-6 Columbus, MISSE 6 and 7 seal experiments, actuated full scale seal test rig, LIDS on Hubble, dynamics test prep, EDU 54 mass emulation and SCS, load ring characterization, 6DOF proof test, SCS at 6DOF, machining EEMS and inner ring assembly, APAS assembly, inner ring fitting, rotation stand assembly, EEMS mating, and EEMS proof of concept demonstration.

  11. A new parallel-vector finite element analysis software on distributed-memory computers

    NASA Technical Reports Server (NTRS)

    Qin, Jiangning; Nguyen, Duc T.

    1993-01-01

    A new parallel-vector finite element analysis software package MPFEA (Massively Parallel-vector Finite Element Analysis) is developed for large-scale structural analysis on massively parallel computers with distributed-memory. MPFEA is designed for parallel generation and assembly of the global finite element stiffness matrices as well as parallel solution of the simultaneous linear equations, since these are often the major time-consuming parts of a finite element analysis. Block-skyline storage scheme along with vector-unrolling techniques are used to enhance the vector performance. Communications among processors are carried out concurrently with arithmetic operations to reduce the total execution time. Numerical results on the Intel iPSC/860 computers (such as the Intel Gamma with 128 processors and the Intel Touchstone Delta with 512 processors) are presented, including an aircraft structure and some very large truss structures, to demonstrate the efficiency and accuracy of MPFEA.

  12. CTF Preprocessor User's Manual

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Avramova, Maria; Salko, Robert K.

    2016-05-26

    This document describes how a user should go about using the CTF pre- processor tool to create an input deck for modeling rod-bundle geometry in CTF. The tool was designed to generate input decks in a quick and less error-prone manner for CTF. The pre-processor is a completely independent utility, written in Fortran, that takes a reduced amount of input from the user. The information that the user must supply is basic information on bundle geometry, such as rod pitch, clad thickness, and axial location of spacer grids--the pre-processor takes this basic information and determines channel placement and connection informationmore » to be written to the input deck, which is the most time-consuming and error-prone segment of creating a deck. Creation of the model is also more intuitive, as the user can specify assembly and water-tube placement using visual maps instead of having to place them by determining channel/channel and rod/channel connections. As an example of the benefit of the pre-processor, a quarter-core model that contains 500,000 scalar-mesh cells was read into CTF from an input deck containing 200,000 lines of data. This 200,000 line input deck was produced automatically from a set of pre-processor decks that contained only 300 lines of data.« less

  13. Fluorescent-Antibody Measurement Of Cancer-Cell Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    1993-01-01

    Combination of laboratory techniques provides measurements of amounts of urokinase in and between normal and cancer cells. Includes use of fluorescent antibodies specific against different forms of urokinase-type plasminogen activator, (uPA), fluorescence microscopy, quantitative analysis of images of sections of tumor tissue, and flow cytometry of different uPA's and deoxyribonucleic acid (DNA) found in suspended-tumor-cell preparations. Measurements provide statistical method for indicating or predicting metastatic potentials of some invasive tumors. Assessments of metastatic potentials based on such measurements used in determining appropriate follow-up procedures after surgical removal of tumors.

  14. A high capacity data recording device based on a digital audio processor and a video cassette recorder.

    PubMed

    Bezanilla, F

    1985-03-01

    A modified digital audio processor, a video cassette recorder, and some simple added circuitry are assembled into a recording device of high capacity. The unit converts two analog channels into digital form at 44-kHz sampling rate and stores the information in digital form in a common video cassette. Bandwidth of each channel is from direct current to approximately 20 kHz and the dynamic range is close to 90 dB. The total storage capacity in a 3-h video cassette is 2 Gbytes. The information can be retrieved in analog or digital form.

  15. A high capacity data recording device based on a digital audio processor and a video cassette recorder.

    PubMed Central

    Bezanilla, F

    1985-01-01

    A modified digital audio processor, a video cassette recorder, and some simple added circuitry are assembled into a recording device of high capacity. The unit converts two analog channels into digital form at 44-kHz sampling rate and stores the information in digital form in a common video cassette. Bandwidth of each channel is from direct current to approximately 20 kHz and the dynamic range is close to 90 dB. The total storage capacity in a 3-h video cassette is 2 Gbytes. The information can be retrieved in analog or digital form. PMID:3978213

  16. Compact propane fuel processor for auxiliary power unit application

    NASA Astrophysics Data System (ADS)

    Dokupil, M.; Spitta, C.; Mathiak, J.; Beckhaus, P.; Heinzel, A.

    With focus on mobile applications a fuel cell auxiliary power unit (APU) using liquefied petroleum gas (LPG) is currently being developed at the Centre for Fuel Cell Technology (Zentrum für BrennstoffzellenTechnik, ZBT gGmbH). The system is consisting of an integrated compact and lightweight fuel processor and a low temperature PEM fuel cell for an electric power output of 300 W. This article is presenting the current status of development of the fuel processor which is designed for a nominal hydrogen output of 1 k Wth,H2 within a load range from 50 to 120%. A modular setup was chosen defining a reformer/burner module and a CO-purification module. Based on the performance specifications, thermodynamic simulations, benchmarking and selection of catalysts the modules have been developed and characterised simultaneously and then assembled to the complete fuel processor. Automated operation results in a cold startup time of about 25 min for nominal load and carbon monoxide output concentrations below 50 ppm for steady state and dynamic operation. Also fast transient response of the fuel processor at load changes with low fluctuations of the reformate gas composition have been achieved. Beside the development of the main reactors the transfer of the fuel processor to an autonomous system is of major concern. Hence, concepts for packaging have been developed resulting in a volume of 7 l and a weight of 3 kg. Further a selection of peripheral components has been tested and evaluated regarding to the substitution of the laboratory equipment.

  17. Toward three-dimensional microelectronic systems: directed self-assembly of silicon microcubes via DNA surface functionalization.

    PubMed

    Lämmerhardt, Nico; Merzsch, Stephan; Ledig, Johannes; Bora, Achyut; Waag, Andreas; Tornow, Marc; Mischnick, Petra

    2013-07-02

    The huge and intelligent processing power of three-dimensional (3D) biological "processors" like the human brain with clock speeds of only 0.1 kHz is an extremely fascinating property, which is based on a massively parallel interconnect strategy. Artificial silicon microprocessors are 7 orders of magnitude faster. Nevertheless, they do not show any indication of intelligent processing power, mostly due to their very limited interconnectivity. Massively parallel interconnectivity can only be realized in three dimensions. Three-dimensional artificial processors would therefore be at the root of fabricating artificially intelligent systems. A first step in this direction would be the self-assembly of silicon based building blocks into 3D structures. We report on the self-assembly of such building blocks by molecular recognition, and on the electrical characterization of the formed assemblies. First, planar silicon substrates were functionalized with self-assembling monolayers of 3-aminopropyltrimethoxysilane for coupling of oligonucleotides (single stranded DNA) with glutaric aldehyde. The oligonucleotide immobilization was confirmed and quantified by hybridization with fluorescence-labeled complementary oligonucleotides. After the individual processing steps, the samples were analyzed by contact angle measurements, ellipsometry, atomic force microscopy, and fluorescence microscopy. Patterned DNA-functionalized layers were fabricated by microcontact printing (μCP) and photolithography. Silicon microcubes of 3 μm edge length as model objects for first 3D self-assembly experiments were fabricated out of silicon-on-insulator (SOI) wafers by a combination of reactive ion etching (RIE) and selective wet etching. The microcubes were then surface-functionalized using the same protocol as on planar substrates, and their self-assembly was demonstrated both on patterned silicon surfaces (88% correctly placed cubes), and to cube aggregates by complementary DNA functionalization and hybridization. The yield of formed aggregates was found to be about 44%, with a relative fraction of dimers of some 30%. Finally, the electrical properties of the formed dimers were characterized using probe tips inside a scanning electron microscope.

  18. People Considerations in Word Processing.

    ERIC Educational Resources Information Center

    Diamond, Marion L.

    1984-01-01

    Business educators preparing students for jobs in business and industry should become aware of the problems faced by workers in a typical large office environment. Word processor operators face many of the same problems as factory assembly line workers--lack of personalization, lack of incentive, and removal from the mainstream. (JOW)

  19. Effects of TGF-β1 on plasminogen activation in human dental pulp cells: Role of ALK5/Smad2, TAK1 and MEK/ERK signalling.

    PubMed

    Chang, Mei-Chi; Chang, Hsiao-Hua; Lin, Po-Shuan; Huang, Yu-An; Chan, Chiu-Po; Tsai, Yi-Ling; Lee, Shen-Yang; Jeng, Po-Yuan; Kuo, Han-Yueh; Yeung, Sin-Yuet; Jeng, Jiiang-Huei

    2018-04-01

    Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signalling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion. The phosphorylation of Smad2 and TAK1 was analysed by Pathscan ELISA or Western blotting. Cells were pretreated with SB431542 (ALK5/Smad2/3 inhibitor), 5z-7-oxozeaenol (TAK1 inhibitor) and U0126 (MEK/ERK inhibitor) for examining the related signalling. TGF-β1 slightly inhibited cell growth that was reversed by SB431542. TGF-β1 upregulated both RNA and protein expression of PAI-1 and uPAR, whereas it downregulated uPA expression. Accordingly, TGF-β1 stimulated PAI-1 and soluble uPAR (suPAR) secretion of pulp cells, whereas uPA secretion was inhibited. TGF-β1 induced the phosphorylation of Smad2 and TAK1. In addition, SB431542, 5z-7-oxozeaenol and U0126 attenuated the TGF-β1-induced secretion of PAI-1 and suPAR. These results indicate that TGF-β1 is possibly involved in the repair/regeneration and inflammatory processes of dental pulp via regulation of PAI-1, uPA and uPAR. These effects of TGF-β1 are related to activation of ALK5/Smad2, TAK1 and MEK/ERK signalling pathways. Clarifying the signal transduction for the effects of TGF-β1 is helpful for pulpo-dentin regeneration and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Real-world data of 197 patients treated with ulipristal acetate for uterine fibroids: PREMYA study French population main outcomes.

    PubMed

    Fernandez, H; Descamps, P; Koskas, M; Lopès, P; Brun, J L; Darai, E; Agostini, A

    2017-09-01

    To characterize and describe treatment with ulipristal acetate (UPA) in a preoperative setting and to evaluate the safety, effectiveness, and Health Related Quality of Life (HRQoL) outcomes in a French population treated according to standard clinical practice. Multicentre, prospective, non-interventional study (PREMYA) of patients diagnosed with moderate to severe symptoms of uterine fibroids and undergoing a preoperative treatment with UPA 5mg (Esmya ® ). Patients were followed for a total of 15months (3months UPA treatment and 12months after). Data were collected approximatively every 3months according to centre usual visit schedule. A total of 206 women were enrolled in France, of whom 197 were found to be eligible for data analysis. Physicians' assessments of patients' overall symptomatic changes, as measured on the Clinical Global Impression-Improvement (CGI-I) scale, indicated that 83.7% of patients were improved at end of treatment (month 3). On the patients' treatment benefit scale (PTBS), 94.7% of patients reported an improvement. These 2 measurements, pain and quality of life, remained improved after treatment cessation and during the entire period of follow-up. Only 58.4% of patients underwent surgery within the timeframe of the study follow-up of which the majority were of a conservative/minimal invasive nature. Many patients did not undergo surgery during the planned 12months follow-up period after treatment whereas all patients had an indication of surgery. All measurements of treatment outcome were markedly improved by 3 months of UPA 5mg treatment. NCT01635452. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol.

    PubMed

    Weng, Chia-Jui; Chou, Chai-Ping; Ho, Chi-Tang; Yen, Gow-Chin

    2012-08-01

    We previously demonstrated that 6-shogaol and 6-gingerol, two active compounds in ginger (Zingiber officinale), possess antiinvasive activity against highly metastatic hepatoma cells. The aims of this study were to evaluate the inhibitory effect and molecular mechanism underlying the transcription and translation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) in Hep3B cells as well as the antiangiogenic activity of 6-gingerol and 6-shogaol. By gelatin zymography and luciferase reporter gene assays, we found that 6-gingerol and 6-shogaol regulate MMP-2/-9 transcription. Moreover, 6-gingerol directly decreased expression of uPA, but the 6-shogaol-mediated decrease in uPA was accompanied by up-regulation of plasminogen activator inhibitor (PAI)-1. 6-Gingerol and 6-shogaol concentrations of ≥ 10 μM and ≥ 2.5 μM, respectively, significantly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling, the activation of NF-κB, and the translocation of NF-κB and STAT3. Incubation of 6-gingerol or 6-shogaol with human umbilical vein endothelial cells or rat aortas significantly attenuated tube formation. 6-Shogaol and 6-gingerol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Inhibition of urokinase-type plasminogen activator expression by dihydroartemisinin in breast cancer cells

    PubMed Central

    ZHANG, SHUQUN; MA, YINAN; JIANG, JIANTAO; DAI, ZHIJUN; GAO, XIAOYAN; YIN, XIAORAN; XI, WENTAO; MIN, WEILI

    2014-01-01

    The aim of the present study was to investigate the inhibitory effects of dihydroartemisinin (DHA) on the primary tumor growth and metastasis of the human breast cancer cell line, MDA-MB-231, in vitro. The expression levels of urokinase-type plasminogen activator (uPA) were detected by immunocytochemistry in two cell lines (MCF-7 and MDA-MB-231). The MDA-MB-231 cell activity was inhibited by various concentration gradients of DHA. The inhibitory rate, cell growth curve and apoptotic morphological observations were obtained using the MTT assay at 0, 24, 48 and 72 h. Cell scratch migration was performed at various time-points to test the cell proliferation and migration capacity. Reverse transcription-polymerase chain reaction was used to analyze the effect of DHA on uPA mRNA expression in breast cancer cells. The human breast cancer cell line, MDA-MB-231, possesses higher metastatic potential and relatively higher expression of uPA when compared with the MCF-7 cell line. DHA was found to inhibit the proliferation and migration capacity of the cell line, MDA-MB-231, in vitro. The growth inhibition occurred in a time- and dose-dependent manner, with IC50 values of 117.76±0.04, 60.26±0.12 and 52.96±0.07 μmol/l following 24, 48 and 72 h, respectively. The inhibition of uPA was observed to decrease breast cancer cell growth and migration. Thus, results of the present study indicate that DHA may be used for further studies with regard to breast cancer therapy. PMID:24765140

  3. A single preovulatory administration of ulipristal acetate affects the decidualization process of the human endometrium during the receptive period of the menstrual cycle.

    PubMed

    Lira-Albarrán, Saúl; Durand, Marta; Barrera, David; Vega, Claudia; Becerra, Rocio García; Díaz, Lorenza; García-Quiroz, Janice; Rangel, Claudia; Larrea, Fernando

    2018-04-27

    In order to get further information on the effects of ulipristal acetate (UPA) upon the process of decidualization of endometrium, a functional analysis of the differentially expressed genes in endometrium (DEG) from UPA treated-versus control-cycles of normal ovulatory women was performed. A list of 1183 endometrial DEG, from a previously published study by our group, was submitted to gene ontology, gene enrichment and ingenuity pathway analyses (IPA). This functional analysis showed that decidualization was a biological process overrepresented. Gene set enrichment analysis identified LIF, PRL, IL15 and STAT3 among the most down-regulated genes within the JAK STAT canonical pathway. IPA showed that decidualization of uterus was a bio-function predicted as inhibited by UPA. The results demonstrated that this selective progesterone receptor modulator, when administered during the periovulatory phase of the menstrual cycle, may affect the molecular mechanisms leading to endometrial decidualization in response to progesterone during the period of maximum embryo receptivity. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. C-Terminal Truncation of α-COP Affects Functioning of Secretory Organelles and Calcium Homeostasis in Hansenula polymorpha

    PubMed Central

    Chechenova, Maria B.; Romanova, Nina V.; Deev, Alexander V.; Packeiser, Anna N.; Smirnov, Vladimir N.; Agaphonov, Michael O.; Ter-Avanesyan, Michael D.

    2004-01-01

    In eukaryotic cells, COPI vesicles retrieve resident proteins to the endoplasmic reticulum and mediate intra-Golgi transport. Here, we studied the Hansenula polymorpha homologue of the Saccharomyces cerevisiae RET1 gene, encoding α-COP, a subunit of the COPI protein complex. H. polymorpha ret1 mutants, which expressed truncated α-COP lacking more than 300 C-terminal amino acids, manifested an enhanced ability to secrete human urokinase-type plasminogen activator (uPA) and an inability to grow with a shortage of Ca2+ ions, whereas a lack of α-COP expression was lethal. The α-COP defect also caused alteration of intracellular transport of the glycosylphosphatidylinositol-anchored protein Gas1p, secretion of abnormal uPA forms, and reductions in the levels of Pmr1p, a Golgi Ca2+-ATPase. Overexpression of Pmr1p suppressed some ret1 mutant phenotypes, namely, Ca2+ dependence and enhanced uPA secretion. The role of COPI-dependent vesicular transport in cellular Ca2+ homeostasis is discussed. PMID:14871936

  5. Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes

    PubMed Central

    Diamandis, Maria; Paterson, Andrew D.; Rommens, Johanna M.; Veljkovic, D. Kika; Blavignac, Jessica; Bulman, Dennis E.; Waye, John S.; Derome, Francine; Rivard, Georges E.

    2009-01-01

    Quebec platelet disorder (QPD) is an autosomal dominant disorder with high penetrance that is associated with increased risks for bleeding. The hallmark of QPD is a gain-of-function defect in fibrinolysis due to increased platelet content of urokinase plasminogen activator (uPA) without systemic fibrinolysis. We hypothesized that increased expression of uPA by differentiating QPD megakaryocytes is linked to PLAU. Genetic marker analyses indicated that QPD was significantly linked to a 2-Mb region on chromosome 10q containing PLAU with a maximum multipoint logarithm of the odds (LOD) score of +11 between markers D10S1432 and D10S1136. Analysis of PLAU by sequencing and Southern blotting excluded mutations within PLAU and its known regulatory elements as the cause of QPD. Analyses of uPA mRNA indicated that QPD distinctly increased transcript levels of the linked PLAU allele with megakaryocyte differentiation. These findings implicate a mutation in an uncharacterized cis element near PLAU as the cause of QPD. PMID:18988861

  6. Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes.

    PubMed

    Diamandis, Maria; Paterson, Andrew D; Rommens, Johanna M; Veljkovic, D Kika; Blavignac, Jessica; Bulman, Dennis E; Waye, John S; Derome, Francine; Rivard, Georges E; Hayward, Catherine P M

    2009-02-12

    Quebec platelet disorder (QPD) is an autosomal dominant disorder with high penetrance that is associated with increased risks for bleeding. The hallmark of QPD is a gain-of-function defect in fibrinolysis due to increased platelet content of urokinase plasminogen activator (uPA) without systemic fibrinolysis. We hypothesized that increased expression of uPA by differentiating QPD megakaryocytes is linked to PLAU. Genetic marker analyses indicated that QPD was significantly linked to a 2-Mb region on chromosome 10q containing PLAU with a maximum multipoint logarithm of the odds (LOD) score of +11 between markers D10S1432 and D10S1136. Analysis of PLAU by sequencing and Southern blotting excluded mutations within PLAU and its known regulatory elements as the cause of QPD. Analyses of uPA mRNA indicated that QPD distinctly increased transcript levels of the linked PLAU allele with megakaryocyte differentiation. These findings implicate a mutation in an uncharacterized cis element near PLAU as the cause of QPD.

  7. SIMNET Unit Performance Assessment System (UPAS) User’s Guide

    DTIC Science & Technology

    1992-04-01

    Final Time: 1038 Date: 91-5-10 Exercise ID: 001 Cornpany: A Platoon: 1 A : A31 B: A13 C: A10 8.K D: A43 S BRUCE 81.5K - 60.5K 2 795 -WC) 17.0K 8WOK 89.0K...Approed for public release; distbution Is unlimited. _ _oil 25 19 084 U.S. ARMY RESEARCH INSTITUTE FOR THE BEHAVIORAL AND SOCIAL SCIENCES A Field...Assessment System (UPAS) N61339-90-C-0084 User’s Guide 63007A 6. AUTHOR( S ) 795 Meliza, Larry L. (ARI); Tan, Seng C. (Univ. of Central 3204 Florida

  8. Proton exchange membrane fuel cell technology for transportation applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swathirajan, S.

    1996-04-01

    Proton Exchange Membrane (PEM) fuel cells are extremely promising as future power plants in the transportation sector to achieve an increase in energy efficiency and eliminate environmental pollution due to vehicles. GM is currently involved in a multiphase program with the US Department of Energy for developing a proof-of-concept hybrid vehicle based on a PEM fuel cell power plant and a methanol fuel processor. Other participants in the program are Los Alamos National Labs, Dow Chemical Co., Ballard Power Systems and DuPont Co., In the just completed phase 1 of the program, a 10 kW PEM fuel cell power plantmore » was built and tested to demonstrate the feasibility of integrating a methanol fuel processor with a PEM fuel cell stack. However, the fuel cell power plant must overcome stiff technical and economic challenges before it can be commercialized for light duty vehicle applications. Progress achieved in phase I on the use of monolithic catalyst reactors in the fuel processor, managing CO impurity in the fuel cell stack, low-cost electrode-membrane assembles, and on the integration of the fuel processor with a Ballard PEM fuel cell stack will be presented.« less

  9. PAI-1 (Plasminogen Activator Inhibitor-1) Expression Renders Alternatively Activated Human Macrophages Proteolytically Quiescent

    PubMed Central

    Hohensinner, Philipp J.; Baumgartner, Johanna; Kral-Pointner, Julia B.; Uhrin, Pavel; Ebenbauer, Benjamin; Thaler, Barbara; Doberer, Konstantin; Stojkovic, Stefan; Demyanets, Svitlana; Fischer, Michael B.; Huber, Kurt; Schabbauer, Gernot; Speidl, Walter S.

    2017-01-01

    Objective— Macrophages are versatile immune cells capable of polarizing into functional subsets depending on environmental stimulation. In atherosclerotic lesions, proinflammatory polarized macrophages are associated with symptomatic plaques, whereas Th2 (T-helper cell type 2) cytokine–polarized macrophages are inversely related with disease progression. To establish a functional cause for these observations, we analyzed extracellular matrix degradation phenotypes in polarized macrophages. Approach and Results— We provide evidence that proinflammatory polarized macrophages rely on membrane-bound proteases including MMP-14 (matrix metalloproteinase-14) and the serine protease uPA (urokinase plasminogen activator) together with its receptor uPAR for extracellular matrix degradation. In contrast, Th2 cytokine alternatively primed macrophages do not show different proteolytic activity in comparison to unpolarized macrophages and lack increased localization of MMP-14 and uPA receptor to the cell membrane. Nonetheless, they express the highest amount of the serine protease uPA. However, uPA activity is blocked by similarly increased expression of its inhibitor PAI-1 (plasminogen activator inhibitor 1). When inhibiting PAI-1 or when analyzing macrophages deficient in PAI-1, Th2 cytokine–polarized macrophages display the same matrix degradation capability as proinflammatory-primed macrophages. Within atherosclerotic lesions, macrophages positive for the alternative activation marker CD206 express high levels of PAI-1. In addition, to test changed tissue remodeling capacities of alternatively activated macrophages, we used a bleomycin lung injury model in mice reconstituted with PAI-1−/− bone marrow. These results supported an enhanced remodeling phenotype displayed by increased fibrosis and elevated MMP activity in the lung after PAI-1 loss. Conclusions— We were able to demonstrate matrix degradation dependent on membrane-bound proteases in proinflammatory stimulated macrophages and a forced proteolytical quiescence in alternatively polarized macrophages by the expression of PAI-1. PMID:28818858

  10. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel, E-mail: dsliva@iuhealth.org

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence ofmore » triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.« less

  11. Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.

    PubMed

    Liu, Degang; Xu, David; Liu, Min; Knabe, William Eric; Yuan, Cai; Zhou, Donghui; Huang, Mingdong; Meroueh, Samy O

    2017-03-28

    Protein-protein interactions drive every aspect of cell signaling, yet only a few small-molecule inhibitors of these interactions exist. Despite our ability to identify critical residues known as hot spots, little is known about how to effectively engage them to disrupt protein-protein interactions. Here, we take advantage of the ease of preparation and stability of pyrrolinone 1, a small-molecule inhibitor of the tight interaction between the urokinase receptor (uPAR) and its binding partner, the urokinase-type plasminogen activator uPA, to synthesize more than 40 derivatives and explore their effect on the protein-protein interaction. We report the crystal structure of uPAR bound to previously discovered pyrazole 3 and to pyrrolinone 12. While both 3 and 12 bind to uPAR and compete with a fluorescently labeled peptide probe, only 12 and its derivatives inhibit the full uPAR·uPA interaction. Compounds 3 and 12 mimic and engage different hot-spot residues on uPA and uPAR, respectively. Interestingly, 12 is involved in a π-cation interaction with Arg-53, which is not considered a hot spot. Explicit-solvent molecular dynamics simulations reveal that 3 and 12 exhibit dramatically different correlations of motion with residues on uPAR. Free energy calculations for the wild-type and mutant uPAR bound to uPA or 12 show that Arg-53 interacts with uPA or with 12 in a highly cooperative manner, thereby altering the contributions of hot spots to uPAR binding. The direct engagement of peripheral residues not considered hot spots through π-cation or salt-bridge interactions could provide new opportunities for enhanced small-molecule engagement of hot spots to disrupt challenging protein-protein interactions.

  12. Floating-Point Modules Targeted for Use with RC Compilation Tools

    NASA Technical Reports Server (NTRS)

    Sahin, Ibrahin; Gloster, Clay S.

    2000-01-01

    Reconfigurable Computing (RC) has emerged as a viable computing solution for computationally intensive applications. Several applications have been mapped to RC system and in most cases, they provided the smallest published execution time. Although RC systems offer significant performance advantages over general-purpose processors, they require more application development time than general-purpose processors. This increased development time of RC systems provides the motivation to develop an optimized module library with an assembly language instruction format interface for use with future RC system that will reduce development time significantly. In this paper, we present area/performance metrics for several different types of floating point (FP) modules that can be utilized to develop complex FP applications. These modules are highly pipelined and optimized for both speed and area. Using these modules, and example application, FP matrix multiplication, is also presented. Our results and experiences show, that with these modules, 8-10X speedup over general-purpose processors can be achieved.

  13. Does Council Tax Valuation Band (CTVB) correlate with Under-Privileged Area 8 (UPA8) score and could it be a better 'Jarman Index'?

    PubMed Central

    Beale, Norman; Taylor, Gordon; Straker-Cook, Dawn

    2001-01-01

    Background Widespread scepticism persists on the use of the Under-Privileged Area (UPA8) score of Jarman in distributing supplementary resources to so-attributed 'deprived' UK general practices. The search for better 'needs' markers continues. Having already shown that Council Tax Valuation Band (CTVB) is a predictor of UK GP workload, we compare, here, CTVB of residence of a random sample of patients with their respective 'Jarman' scores. Methods Correlation coefficient is calculated between (i) the CTVB of residence of a randomised sample of patients from an English general practice and (ii) the UPA8 scores of the relevant enumeration districts in which they live. Results There is a highly significant correlation between the two measures despite modest study size of 478 patients (85% response). Conclusions The proposal that CTVB is a marker of deprivation and of clinical demand should be examined in more detail: it correlates with 'Jarman', which is already used in NHS resource allocation. But unlike 'Jarman', CTVB is simple, objective, and free of the problems of Census data. CTVB, being household-based, can be aggregated at will. PMID:11716793

  14. Does Council Tax Valuation Band (CTVB) correlate with Under-Privileged Area 8 (UPA8) score and could it be a better 'Jarman Index'?

    PubMed

    Beale, N; Taylor, G; Straker-Cook, D

    2001-01-01

    Widespread scepticism persists on the use of the Under-Privileged Area (UPA8) score of Jarman in distributing supplementary resources to so-attributed 'deprived' UK general practices. The search for better 'needs' markers continues. Having already shown that Council Tax Valuation Band (CTVB) is a predictor of UK GP workload, we compare, here, CTVB of residence of a random sample of patients with their respective 'Jarman' scores. Correlation coefficient is calculated between (i) the CTVB of residence of a randomised sample of patients from an English general practice and (ii) the UPA8 scores of the relevant enumeration districts in which they live. There is a highly significant correlation between the two measures despite modest study size of 478 patients (85% response). The proposal that CTVB is a marker of deprivation and of clinical demand should be examined in more detail: it correlates with 'Jarman', which is already used in NHS resource allocation. But unlike 'Jarman', CTVB is simple, objective, and free of the problems of Census data. CTVB, being household-based, can be aggregated at will.

  15. Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder.

    PubMed

    Sheth, Prameet M; Kahr, Walter H A; Haq, M Anwar; Veljkovic, Dragoslava Kika; Rivard, Georges E; Hayward, Catherine P M

    2003-08-01

    The Quebec Platelet Disorder (QPD) is an unusual bleeding disorder associated with increased platelet stores of urokinase-type plasminogen activator (u-PA) and proteolysis of platelet alpha-granule proteins. The increased u-PA and proteolyzed plasminogen in QPD platelets led us to investigate possible contributions of intracellular plasmin generation to QPD alpha-granule proteolysis. ELISA indicated there were normal amounts of plasminogen and plasmin-alpha(2)-antiplasmin (PAP) complexes in QPD plasmas. Like normal platelets, QPD platelets contained only a small proportion of the blood plasminogen, however, they contained an increased amount of PAP complexes compared to normal platelets (P < 0.005). The quantities of plasminogen stored in platelets were important to induce QPD-like proteolysis of normal alpha-granule proteins by two chain u-PA (tcu-PA) in vitro. Moreover, adding supplemental plasminogen to QPD, but not to control, platelet lysates, triggered further alpha-granule protein proteolysis to forms that comigrated with plasmin degraded proteins. These data suggest the generation of increased but limiting amounts of plasmin within platelets is involved in producing the unique phenotypic changes to alpha-granule proteins in QPD platelets. The QPD is the only known bleeding disorder associated with chronic, intracellular activation of the fibrinolytic cascade.

  16. Partial Automated Alignment and Integration System

    NASA Technical Reports Server (NTRS)

    Kelley, Gary Wayne (Inventor)

    2014-01-01

    The present invention is a Partial Automated Alignment and Integration System (PAAIS) used to automate the alignment and integration of space vehicle components. A PAAIS includes ground support apparatuses, a track assembly with a plurality of energy-emitting components and an energy-receiving component containing a plurality of energy-receiving surfaces. Communication components and processors allow communication and feedback through PAAIS.

  17. A site oriented supercomputer for theoretical physics: The Fermilab Advanced Computer Program Multi Array Processor System (ACMAPS)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nash, T.; Atac, R.; Cook, A.

    1989-03-06

    The ACPMAPS multipocessor is a highly cost effective, local memory parallel computer with a hypercube or compound hypercube architecture. Communication requires the attention of only the two communicating nodes. The design is aimed at floating point intensive, grid like problems, particularly those with extreme computing requirements. The processing nodes of the system are single board array processors, each with a peak power of 20 Mflops, supported by 8 Mbytes of data and 2 Mbytes of instruction memory. The system currently being assembled has a peak power of 5 Gflops. The nodes are based on the Weitek XL Chip set. Themore » system delivers performance at approximately $300/Mflop. 8 refs., 4 figs.« less

  18. Method and apparatus for measurement of orientation in an anisotropic medium

    DOEpatents

    Gilmore, Robert Snee; Kline, Ronald Alan; Deaton, Jr., John Broddus

    1999-01-01

    A method and apparatus are provided for simultaneously measuring the anisotropic orientation and the thickness of an article. The apparatus comprises a transducer assembly which propagates longitudinal and transverse waves through the article and which receives reflections of the waves. A processor is provided to measure respective transit times of the longitudinal and shear waves propagated through the article and to calculate respective predicted transit times of the longitudinal and shear waves based on an estimated thickness, an estimated anisotropic orientation, and an elasticity of the article. The processor adjusts the estimated thickness and the estimated anisotropic orientation to reduce the difference between the measured transit times and the respective predicted transit times of the longitudinal and shear waves.

  19. Implementing the PM Programming Language using MPI and OpenMP - a New Tool for Programming Geophysical Models on Parallel Systems

    NASA Astrophysics Data System (ADS)

    Bellerby, Tim

    2015-04-01

    PM (Parallel Models) is a new parallel programming language specifically designed for writing environmental and geophysical models. The language is intended to enable implementers to concentrate on the science behind the model rather than the details of running on parallel hardware. At the same time PM leaves the programmer in control - all parallelisation is explicit and the parallel structure of any given program may be deduced directly from the code. This paper describes a PM implementation based on the Message Passing Interface (MPI) and Open Multi-Processing (OpenMP) standards, looking at issues involved with translating the PM parallelisation model to MPI/OpenMP protocols and considering performance in terms of the competing factors of finer-grained parallelisation and increased communication overhead. In order to maximise portability, the implementation stays within the MPI 1.3 standard as much as possible, with MPI-2 MPI-IO file handling the only significant exception. Moreover, it does not assume a thread-safe implementation of MPI. PM adopts a two-tier abstract representation of parallel hardware. A PM processor is a conceptual unit capable of efficiently executing a set of language tasks, with a complete parallel system consisting of an abstract N-dimensional array of such processors. PM processors may map to single cores executing tasks using cooperative multi-tasking, to multiple cores or even to separate processing nodes, efficiently sharing tasks using algorithms such as work stealing. While tasks may move between hardware elements within a PM processor, they may not move between processors without specific programmer intervention. Tasks are assigned to processors using a nested parallelism approach, building on ideas from Reyes et al. (2009). The main program owns all available processors. When the program enters a parallel statement then either processors are divided out among the newly generated tasks (number of new tasks < number of processors) or tasks are divided out among the available processors (number of tasks > number of processors). Nested parallel statements may further subdivide the processor set owned by a given task. Tasks or processors are distributed evenly by default, but uneven distributions are possible under programmer control. It is also possible to explicitly enable child tasks to migrate within the processor set owned by their parent task, reducing load unbalancing at the potential cost of increased inter-processor message traffic. PM incorporates some programming structures from the earlier MIST language presented at a previous EGU General Assembly, while adopting a significantly different underlying parallelisation model and type system. PM code is available at www.pm-lang.org under an unrestrictive MIT license. Reference Ruymán Reyes, Antonio J. Dorta, Francisco Almeida, Francisco de Sande, 2009. Automatic Hybrid MPI+OpenMP Code Generation with llc, Recent Advances in Parallel Virtual Machine and Message Passing Interface, Lecture Notes in Computer Science Volume 5759, 185-195

  20. Optical links in handheld multimedia devices

    NASA Astrophysics Data System (ADS)

    van Geffen, S.; Duis, J.; Miller, R.

    2008-04-01

    Ever emerging applications in handheld multimedia devices such as mobile phones, laptop computers, portable video games and digital cameras requiring increased screen resolutions are driving higher aggregate bitrates between host processor and display(s) enabling services such as mobile video conferencing, video on demand and TV broadcasting. Larger displays and smaller phones require complex mechanical 3D hinge configurations striving to combine maximum functionality with compact building volumes. Conventional galvanic interconnections such as Micro-Coax and FPC carrying parallel digital data between host processor and display module may produce Electromagnetic Interference (EMI) and bandwidth limitations caused by small cable size and tight cable bends. To reduce the number of signals through a hinge, the mobile phone industry, organized in the MIPI (Mobile Industry Processor Interface) alliance, is currently defining an electrical interface transmitting serialized digital data at speeds >1Gbps. This interface allows for electrical or optical interconnects. Above 1Gbps optical links may offer a cost effective alternative because of their flexibility, increased bandwidth and immunity to EMI. This paper describes the development of optical links for handheld communication devices. A cable assembly based on a special Plastic Optical Fiber (POF) selected for its mechanical durability is terminated with a small form factor molded lens assembly which interfaces between an 850nm VCSEL transmitter and a receiving device on the printed circuit board of the display module. A statistical approach based on a Lean Design For Six Sigma (LDFSS) roadmap for new product development tries to find an optimum link definition which will be robust and low cost meeting the power consumption requirements appropriate for battery operated systems.

  1. Development of new UV-I. I. Cerenkov Viewing Device

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kuribara, Masayuki; Nemoto, Koshichi

    1994-02-01

    The Cerenkov glow images from boiling-water reactors (BWR) and pressurized-water reactors (PWR) irradiated fuel assemblies are generally used for inspections. However, sometimes it is difficult or impossible to identify the image by the conventional Cerenkov Viewing Device (CVD), because of the long cooling time and/or low burnup. Now a new UV-I.I. (Ultra-Violet light Image Intensifier) CVD has been developed, which can detect the very weak Cerenkov glow from spent fuel assemblies. As this new device uses the newly developed proximity focused type UV-I.I., Cerenkov photons are used efficiently, producing better quality Cerenkov glow images. Moreover, since the image is convertedmore » to a video signal, it is easy to improve the signal to noise ratio (S/N) by an image processor. The new CVD was tested at BWR and PWR power plants in Japan, with fuel burnups ranging from 6,200--33,000 MWD/MTU (megawatt days per metric ton of uranium) and cooling times ranging from 370 to 6,200 d. The tests showed that the new CVD is superior to the conventional STA/CRIEPI CVD, and could detect very feeble Cerenkov glow images using an image processor.« less

  2. Applications Performance on NAS Intel Paragon XP/S - 15#

    NASA Technical Reports Server (NTRS)

    Saini, Subhash; Simon, Horst D.; Copper, D. M. (Technical Monitor)

    1994-01-01

    The Numerical Aerodynamic Simulation (NAS) Systems Division received an Intel Touchstone Sigma prototype model Paragon XP/S- 15 in February, 1993. The i860 XP microprocessor with an integrated floating point unit and operating in dual -instruction mode gives peak performance of 75 million floating point operations (NIFLOPS) per second for 64 bit floating point arithmetic. It is used in the Paragon XP/S-15 which has been installed at NAS, NASA Ames Research Center. The NAS Paragon has 208 nodes and its peak performance is 15.6 GFLOPS. Here, we will report on early experience using the Paragon XP/S- 15. We have tested its performance using both kernels and applications of interest to NAS. We have measured the performance of BLAS 1, 2 and 3 both assembly-coded and Fortran coded on NAS Paragon XP/S- 15. Furthermore, we have investigated the performance of a single node one-dimensional FFT, a distributed two-dimensional FFT and a distributed three-dimensional FFT Finally, we measured the performance of NAS Parallel Benchmarks (NPB) on the Paragon and compare it with the performance obtained on other highly parallel machines, such as CM-5, CRAY T3D, IBM SP I, etc. In particular, we investigated the following issues, which can strongly affect the performance of the Paragon: a. Impact of the operating system: Intel currently uses as a default an operating system OSF/1 AD from the Open Software Foundation. The paging of Open Software Foundation (OSF) server at 22 MB to make more memory available for the application degrades the performance. We found that when the limit of 26 NIB per node out of 32 MB available is reached, the application is paged out of main memory using virtual memory. When the application starts paging, the performance is considerably reduced. We found that dynamic memory allocation can help applications performance under certain circumstances. b. Impact of data cache on the i860/XP: We measured the performance of the BLAS both assembly coded and Fortran coded. We found that the measured performance of assembly-coded BLAS is much less than what memory bandwidth limitation would predict. The influence of data cache on different sizes of vectors is also investigated using one-dimensional FFTs. c. Impact of processor layout: There are several different ways processors can be laid out within the two-dimensional grid of processors on the Paragon. We have used the FFT example to investigate performance differences based on processors layout.

  3. Update on emergency contraception.

    PubMed

    Fok, Wing Kay; Blumenthal, Paul D

    2016-12-01

    Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years. Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers. Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception.

  4. Emergency Contraception: A multi-specialty survey of clinician knowledge and practices

    PubMed Central

    Batur, Pelin; Cleland, Kelly; McNamara, Megan; Wu, Justine; Pickle, Sarah

    2015-01-01

    Objectives To assess knowledge and provision of emergency contraception (EC), particularly the most effective methods. Study Design A web-based survey was distributed to a cross-sectional convenience sample of healthcare providers across specialties treating reproductive-aged women. The survey was sent to 3,260 practicing physicians and advanced practice clinicians in 14 academic centers between February 2013 and April 2014. We analyzed responses by provider specialty using multivariable logistic regression. Results The final sample included 1,684 providers (response rate = 51.7%). Ninety-five percent of the respondents had heard of levonorgestrel (LNG) EC. Among reproductive health specialists, 81% provide levonorgestrel EC in their practice, although only half (52%) had heard of ulipristal acetate (UPA) and very few provide it (14%). The majority in family medicine (69%) and emergency medicine (74%) provide levonorgestrel, in contrast to 42% of internists and 55% of pediatricians. However, the more effective methods (UPA and copper IUD) were little known and rarely provided outside of reproductive health specialties; 18% of internists and 14% of emergency medicine providers had heard of UPA and 4% provide it. Only 22% of emergency providers and 32% of pediatricians had heard of the copper IUD used as EC. Among reproductive health specialists, only 36% provide copper IUD as EC in their practice. Specialty, provider type and proportion of women of reproductive age in the practice were related to knowledge and provision of some forms of EC. Conclusions Awareness and provision of the most effective EC methods, UPA and the copper IUD (which are provider-dependent), are substantially lower than for LNG EC, especially among providers who do not focus on reproductive health. Implications In our sample of 1,684 healthcare providers from diverse specialties who treat reproductive-aged women, knowledge and provision of the most effective forms of emergency contraception (ulipristal acetate and the copper IUD) are far lower than for levonorgestrel EC. Women should be offered the full range of EC methods. PMID:26363429

  5. Simultaneous interaction with base and phosphate moieties modulates the phosphodiester cleavage of dinucleoside 3',5'-monophosphates by dinuclear Zn2+ complexes of di(azacrown) ligands.

    PubMed

    Wang, Qi; Lönnberg, Harri

    2006-08-23

    Five dinucleating ligands (1-5) and one trinucleating ligand (6) incorporating 1,5,9-triazacyclododecan-3-yloxy groups attached to an aromatic scaffold have been synthesized. The ability of the Zn(2+) complexes of these ligands to promote the transesterification of dinucleoside 3',5'-monophosphates to a 2',3'-cyclic phosphate derived from the 3'-linked nucleoside by release of the 5'-linked nucleoside has been studied over a narrow pH range, from pH 5.8 to 7.2, at 90 degrees C. The dinuclear complexes show marked base moiety selectivity. Among the four dinucleotide 3',5'-phosphates studied, viz. adenylyl-3',5'-adenosine (ApA), adenylyl-3',5'-uridine (ApU), uridylyl-3',5'-adenosine (UpA), and uridylyl-3',5'-uridine (UpU), the dimers containing one uracil base (ApU and UpA) are cleaved up to 2 orders of magnitude more readily than those containing either two uracil bases (UpU) or two adenine bases (ApA). The trinuclear complex (6), however, cleaves UpU as readily as ApU and UpA, while the cleavage of ApA remains slow. UV spectrophotometric and (1)H NMR spectroscopic studies with one of the dinucleating ligands (3) verify binding to the bases of UpU and ApU at less than millimolar concentrations, while no interaction with the base moieties of ApA is observed. With ApU and UpA, one of the Zn(2+)-azacrown moieties in all likelihood anchors the cleaving agent to the uracil base of the substrate, while the other azacrown moiety serves as a catalyst for the phosphodiester transesterification. With UpU, two azacrown moieties are engaged in the base moiety binding. The catalytic activity is, hence, lost, but it can be restored by addition of a third azacrown group on the cleaving agent.

  6. A novel embryo culture media supplement that improves pregnancy rates in mice.

    PubMed

    Highet, A R; Bianco-Miotto, T; Pringle, K G; Peura, A; Bent, S; Zhang, J; Nottle, M B; Thompson, J G; Roberts, C T

    2017-03-01

    The preimplantation embryo in vivo is exposed to numerous growth factors in the female reproductive tract, which are not recapitulated in embryo culture media in vitro The IGF2 and plasminogen activator systems facilitate blastocyst development. We hypothesized that the addition of IGF2 in combination with urokinase plasminogen activator (uPA) and plasminogen could improve rates of blastocyst hatching and implantation in mice. B6BcF1 and CBAB6F2 mouse embryos were divided into one of four supplemented culture media treatment groups: (1) control (media only); (2) 12.5 nM IGF2; (3) 10 µg/mL uPA and 5 µg/mL plasminogen; or (4) a combination of IGF2, uPA and plasminogen treatments. Embryo development to blastocyst stage and hatching were assessed before transfer to pseudopregnant recipient females and implantation, pregnancy rates and postnatal growth were assessed. After 90.5 h of culture, IGF2 + U + P treatment increased the percentage of B6BcF1 embryos that were hatching/hatched and percentage developing to blastocyst stage compared with controls (P < 0.02). Following B6BcF1 embryo transfer, IGF2 + U + P treatment increased implantation sites at day 8 of pregnancy compared with controls (P < 0.05). Replication in the CBAB6F2 mouse strain showed significant improvements in pregnancy rates at days 8 and 18 but not in blastocyst development. No adverse effects were seen on gestational age, litter size or birthweight, or the reproductive capacity of offspring of IGF2 + U + P treated embryos. For embryos susceptible to detrimental effects of in vitro culture, IGF2, uPA and plasminogen supplementation of culture media can improve pregnancy success, but the effect of treatment is dependent on the mouse strain. © 2017 Society for Reproduction and Fertility.

  7. Structure-based manual screening and automatic networking for systematically exploring sansanmycin analogues using high performance liquid chromatography tandem mass spectroscopy.

    PubMed

    Jiang, Zhi-Bo; Ren, Wei-Cong; Shi, Yuan-Yuan; Li, Xing-Xing; Lei, Xuan; Fan, Jia-Hui; Zhang, Cong; Gu, Ren-Jie; Wang, Li-Fei; Xie, Yun-Ying; Hong, Bin

    2018-05-18

    Sansanmycins (SS), one of several known uridyl peptide antibiotics (UPAs) possessing a unique chemical scaffold, showed a good inhibitory effect on the highly refractory pathogens Pseudomonas aeruginosa and Mycobacterium tuberculosis, especially on the multi-drug resistant M. tuberculosis. This study employed high performance liquid chromatography-mass spectrometry detector (HPLC-MSD) ion trap and LTQ orbitrap tandem mass spectrometry (MS/MS) to explore sansanmycin analogues manually and automatically by re-analysis of the Streptomyces sp. SS fermentation broth. The structure-based manual screening method, based on analysis of the fragmentation pathway of known UPAs and on comparisons of the MS/MS spectra with that of sansanmycin A (SS-A), resulted in identifying twenty sansanmycin analogues, including twelve new structures (1-12). Furthermore, to deeply explore sansanmycin analogues, we utilized a GNPS based molecular networking workflow to re-analyze the HPLC-MS/MS data automatically. As a result, eight more new sansanmycins (13-20) were discovered. Compound 1 was discovered to lose two amino acids of residue 1 (AA 1 ) and (2S, 3S)-N 3 -methyl-2,3-diamino butyric acid (DABA) from the N-terminus, and compounds 6, 11 and 12 were found to contain a 2',3'-dehydrated 4',5'-enamine-3'-deoxyuridyl moiety, which have not been reported before. Interestingly, three trace components with novel 5,6-dihydro-5'-aminouridyl group (16-18) were detected for the first time in the sansanmycin-producing strain. Their structures were primarily determined by detail analysis of the data from MS/MS. Compounds 8 and 10 were further confirmed by nuclear magnetic resonance (NMR) data, which proved the efficiency and accuracy of the method of HPLC-MS/MS for exploration of novel UPAs. Comparing to manual screening, the networking method can provide systematic visualization results. Manual screening and networking method may complement with each other to facilitate the mining of novel UPAs. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Quercetin Has Antimetastatic Effects on Gastric Cancer Cells via the Interruption of uPA/uPAR Function by Modulating NF-κb, PKC-δ, ERK1/2, and AMPKα.

    PubMed

    Li, Hai; Chen, Chen

    2018-06-01

    Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines. GC BGC823 and AGS cells were subjected to treatment with 10 μM Qu for 72 hours and uPAR knockdown, alone or in combination, before evaluating cell metastasis. The results showed that uPA activity and uPAR expression were higher in GC tissues than in pericarcinous tissues. Migratory and invasive activities of GC cell lines positively correlated with uPAR expression. Qu treatment decreased BGC823 and AGS cell migration and invasion, accompanied by reduced uPA and uPAR protein expression. Both Qu treatment and uPAR knockdown decreased matrix metalloproteinase-2 and -9 activity and blocked Pak1-Limk1-cofilin signaling. Qu treatment was associated with inhibition of NF-κb, PKC-δ, and ERK1/2, and with AMPKα activation. Specific inhibitors of NF-κb, PKC, and ERK1/2, and an AMPKα activator suppressed uPA and uPAR expression in GC cells. Collectively, Qu showed an antimetastatic effect on GC cells via the interruption of uPA/uPAR function and modulation of NF-κb, PKC-δ, ERK1/2, and AMPKα. This suggests that Qu is a promising agent against GC metastasis.

  9. The design of infrared information collection circuit based on embedded technology

    NASA Astrophysics Data System (ADS)

    Liu, Haoting; Zhang, Yicong

    2013-07-01

    S3C2410 processor is a 16/32 bit RISC embedded processor which based on ARM920T core and AMNA bus, and mainly for handheld devices, and high cost, low-power applications. This design introduces a design plan of the PIR sensor system, circuit and its assembling, debugging. The Application Circuit of the passive PIR alarm uses the invisibility of the infrared radiation well into the alarm system, and in order to achieve the anti-theft alarm and security purposes. When the body goes into the range of PIR sensor detection, sensors will detect heat sources and then the sensor will output a weak signal. The Signal should be amplified, compared and delayed; finally light emitting diodes emit light, playing the role of a police alarm.

  10. Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion.

    PubMed

    Magnussen, Synnove Norvoll; Hadler-Olsen, Elin; Costea, Daniela Elena; Berg, Eli; Jacobsen, Cristiane Cavalcanti; Mortensen, Bente; Salo, Tuula; Martinez-Zubiaurre, Inigo; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjorg

    2017-05-19

    Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β1 (TGF-β1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-β1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. These results show that soluble factors in the tumour microenvironment, such as TGF-β1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.

  11. The fibrinolytic system: A new target for treatment of depression with psychedelics.

    PubMed

    Idell, R D; Florova, G; Komissarov, A A; Shetty, S; Girard, R B S; Idell, S

    2017-03-01

    Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF. ProBDNF activation could potentially be supressed by competition with fibrin for plasmin and tPA. High affinity binding of plasmin and tPA to fibrin could result in a decrease of proBDNF activation during brain inflammation leading to fibrosis further perpetuating depressed mood. There is a paucity of data explaining the possible role of the fibrinolytic system or aberrant extravascular fibrin deposition in depression. We propose that within the brain, an imbalance between tPA and urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) and neuroserpin favors the inhibitors, resulting in changes in neurogenesis, synaptic plasticity, and neuroinflammation that result in depressive behavior. Our hypothesis is that peripheral inflammation mediates neuroinflammation, and that cytokines such as tumor necrosis factor alpha (TNF-α) can inhibit the fibrinolytic system by up- regulating PAI-1 and potentially neuroserpin. We propose that the decrement of the activity of tPA and uPA occurs with downregulation of uPA in part involving the binding and clearance from the surface of neural cells of uPA/PAI-1 complexes by the urokinase receptor uPAR. We infer that current antidepressants and ketamine mitigate depressive symptoms by restoring the balance of the fibrinolytic system with increased activity of tPA and uPA with down-regulated intracerebral expression of their inhibitors. We lastly hypothesize that psychedelic 5-ht2a receptor agonists, such as psilocybin, can improve mood through anti- inflammatory and pro-fibrinolytic effects that include blockade of TNF-α activity leading to decreased PAI-1 activity and increased clearance. The process involves disinhibition of tPA and uPA with subsequent increased cleavage of proBDNF which promotes neurogenesis, decreased neuroinflammation, decreased fibrin deposition, normalized glial-neuronal cross-talk, and optimally functioning neuro-circuits involved in mood. We propose that psilocybin can alleviate deleterious changes in the brain caused by chronic stress leading to restoration of homeostatic brain fibrinolytic capacity leading to euthymia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1.

    PubMed

    Peng, Wen-Huang; Tien, Yun-Chen; Huang, Chih-Yang; Huang, Tai-Hung; Liao, Jung-Chun; Kuo, Chao-Lin; Lin, Ying-Chih

    2010-02-17

    To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats. Rat hepatic fibrosis was induced by oral administration of CCl(4). Sixty SD rats were divided randomly into 6 groups: control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except for the rats in control group, all rats were administered orally with CCl(4) (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected. The results showed that FR(EtOH) (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in rats. In our study it was showed that CCl(4)-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract. Oral administration of FR(EtOH) significantly reduces CCl(4)-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver fibrosis in rats. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  13. Parallel processing for nonlinear dynamics simulations of structures including rotating bladed-disk assemblies

    NASA Technical Reports Server (NTRS)

    Hsieh, Shang-Hsien

    1993-01-01

    The principal objective of this research is to develop, test, and implement coarse-grained, parallel-processing strategies for nonlinear dynamic simulations of practical structural problems. There are contributions to four main areas: finite element modeling and analysis of rotational dynamics, numerical algorithms for parallel nonlinear solutions, automatic partitioning techniques to effect load-balancing among processors, and an integrated parallel analysis system.

  14. Osmium (VI) complexes of the 3', 5'-dinucleoside monophosphates, ApU and UpA.

    PubMed

    Daniel, F B; Behrman, E J

    1976-02-10

    The dinucleoside monophosphates, ApU and UpA, react with potassium osmate (VI) and 2,2'-bipyridyl to form the corresponding oxo-osmium (VI) bipyridyl sugar ester in which the osmate group is bonded to the terminal 2',3'-glycol. Osmium (VIII) tetroxide and 2,2'-bipyridyl react with the dinucleosides to form the corresponding oxo-osmium (VI) bipyridyl heterocyclic esters which result from addition of the tetroxide to the 5,6-double bond of the uracil residue. Although capable of transesterification reactions, these heterocyclic esters are exceptionally stable toward exchange reactions in solution. No apparent exchange was observed after 1 month. This reaction thus seems promising for single-site osmium labeling in polynucleotides.

  15. Development of a soldier-portable fuel cell power system. Part I: A bread-board methanol fuel processor

    NASA Astrophysics Data System (ADS)

    Palo, Daniel R.; Holladay, Jamie D.; Rozmiarek, Robert T.; Guzman-Leong, Consuelo E.; Wang, Yong; Hu, Jianli; Chin, Ya-Huei; Dagle, Robert A.; Baker, Eddie G.

    A 15-W e portable power system is being developed for the US Army that consists of a hydrogen-generating fuel reformer coupled to a proton-exchange membrane fuel cell. In the first phase of this project, a methanol steam reformer system was developed and demonstrated. The reformer system included a combustor, two vaporizers, and a steam reforming reactor. The device was demonstrated as a thermally independent unit over the range of 14-80 W t output. Assuming a 14-day mission life and an ultimate 1-kg fuel processor/fuel cell assembly, a base case was chosen to illustrate the expected system performance. Operating at 13 W e, the system yielded a fuel processor efficiency of 45% (LHV of H 2 out/LHV of fuel in) and an estimated net efficiency of 22% (assuming a fuel cell efficiency of 48%). The resulting energy density of 720 Wh/kg is several times the energy density of the best lithium-ion batteries. Some immediate areas of improvement in thermal management also have been identified, and an integrated fuel processor is under development. The final system will be a hybrid, containing a fuel reformer, a fuel cell, and a rechargeable battery. The battery will provide power for start-up and added capacity for times of peak power demand.

  16. Development of a Soldier-Portable Fuel Cell Power System, Part I: A Bread-Board Methanol Fuel Processor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Palo, Daniel R.; Holladay, Jamelyn D.; Rozmiarek, Robert T.

    A 15-We portable power system is being developed for the US Army, comprised of a hydrogen-generating fuel reformer coupled to a hydrogen-converting fuel cell. As a first phase of this project, a methanol steam reformer system was developed and demonstrated. The reformer system included a combustor, two vaporizers, and a steam-reforming reactor. The device was demonstrated as a thermally independent unit over the range of 14 to 80 Wt output. Assuming a 14-day mission life and an ultimate 1-kg fuel processor/fuel cell assembly, a base case was chosen to illustrate the expected system performance. Operating at 13 We, the systemmore » yielded a fuel processor efficiency of 45% (LHV of H2 out/LHV of fuel in) and an estimated net efficiency of 22% (assuming a fuel cell efficiency of 48%). The resulting energy density of 720 W-hr/kg is several times the energy density of the best lithium-ion batteries. Some immediate areas of improvement in thermal management also have been identified and an integrated fuel processor is under development. The final system will be a hybrid, containing a fuel reformer, fuel cell, and rechargeable battery. The battery will provide power for startup and added capacity for times of peak power demand.« less

  17. Effects of gestational hypertension and pre-eclampsia in mRNA expression of fibrinolysis genes in primary cultured human umbilical vein endothelial cells.

    PubMed

    Poblete-Naredo, Irais; Rodríguez-Yáñez, Yury; Corona-Núñez, Rogelio O; González-Monroy, Stuart; Salinas, Juan E; Albores, Arnulfo

    2018-05-17

    Hypertension disorders (HD) and pre-eclampsia (PRE) are leading causes of maternal deaths worldwide. PRE is associated with vascular endothelial dysfunction and with deregulation of the fibrinolysis pathway genes. Fibrinolysis is the fibrin clot hydrolysis process catalyzed by plasmin, a proteolytic enzyme formed from plasminogen. Plasminogen is cleaved by tissue-type (tPA) and urokinase-type (uPA) activators and inhibited by the plasminogen activator inhibitors type-1 (PAI-1) and type-2 (PAI-2). The whole process maintains blood hemostasis. This study aims to assess PAI-1, PAI-2, tPA and uPA mRNA expression in primary cultured human umbilical vein endothelial cells (HUVEC) isolated and cultured from healthy, HD and PRE women. Results show that PAI-1 and PAI-2 mRNA decreased in HD-HUVEC, whereas PAI-1 and uPA decreased in PRE-HUVEC cultures compared to control ones. Notably, the expression ratio between pro- and anti-fibrinolytic actors remained unchanged among the studied groups. It seems that newborn's hemostasis is maintained balanced probably by a compensatory mechanism that involves changes in the fibrinolysis gene expression profile. The real impact of these changes in mRNA expression is unknown, however, it is suggested that these changes could be associated with an increased predisposition to vascular disease development in the progeny. Copyright © 2018. Published by Elsevier Ltd.

  18. RNA Initiation with Dinucleoside Monophosphates during Transcription of Bacteriophage T4 DNA with RNA Polymerase of Escherichia coli

    PubMed Central

    Hoffman, David J.; Niyogi, Salil K.

    1973-01-01

    The effects of dinucleoside monophosphates on the transcription of phage T4 DNA by E. coli RNA polymerase have been examined at various concentrations of the sigma subunit and extremely low concentration of ribonucleoside triphosphate. The following conclusions were reached: (i) Labeled specific dinucleoside monophosphates are incorporated as chain initiators. (ii) When the ratio of sigma factor to core enzyme is small, there is a general stimulation by most 5′-guanosyl dinucleoside monophosphates. (iii) When the ratio is increased or holoenzyme is present, ApU, CpA, UpA, and GpU are the most effective stimulators. (iv) At high concentrations of sigma factor, only certain adenosine-containing dinucleoside monophosphates (ApU, CpA, UpA, and ApA) stimulate the reaction. (v) Competition hybridization studies indicate that the RNAs stimulated by dinucleoside monophosphates (ApU, CpA, UpA, and GpU) are of the T4 “early” type. (vi) Studies involving both combinations of stimulatory dinucleoside monophosphates and competitive effects of these compounds on chain initiation by ATP and GTP suggest that the stimulatory dinucleoside monophosphates act as chain initiators and may recognize part of a continuous sequence in a promoter region. Studies based on the incorporation of 3H-labeled stimulatory dinucleoside monophosphates support the above conclusions. PMID:4568732

  19. Progesterone receptor antagonism inhibits progestogen-related carcinogenesis and suppresses tumor cell proliferation.

    PubMed

    Lee, Oukseub; Choi, Mi-Ran; Christov, Konstantin; Ivancic, David; Khan, Seema A

    2016-07-01

    Blockade of the progestogen-progesterone receptor (PR) axis is a novel but untested strategy for breast cancer prevention. We report preclinical data evaluating telapristone acetate (TPA), ulipristal acetate (UPA), and mifepristone. Tumors were induced with medroxyprogesterone acetate (MPA) plus 7,12-dimethylbenz[a]anthracene (DMBA) in mice, and MPA or progesterone plus N-methyl-N-nitrosourea (MNU) in rats. Mammary gland histology, tumor incidence, latency, multiplicity, burden and histology were evaluated, along with immunohistochemical labeling of pHH3 (proliferation), CD34 (angiogenesis), and estrogen and progesterone receptors (ER and PR). A concentration gradient of TPA, UPA, and mifepristone was tested for growth inhibition of T47D spheroids. In mouse mammary glands, no tumors formed, but TPA opposed the pro-hyperplastic effects of MPA (p = 0.002). In rats, TPA decreased tumor incidence (p = 0.037 for MPA + TPA vs. MPA, and p = 0.032 for progesterone + TPA vs. progesterone) and tumor burden (p = 0.042 for progesterone + TPA vs. progesterone), with significant decreases in pHH3 and CD34 positive cells. TPA and UPA were superior to mifepristone in growth inhibition of T47D spheroids. TPA has consistent anti-tumorigenic effects in several models, which are accompanied by decreases in cell proliferation, angiogenesis, and hormone receptor expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. RASSP signal processing architectures

    NASA Astrophysics Data System (ADS)

    Shirley, Fred; Bassett, Bob; Letellier, J. P.

    1995-06-01

    The rapid prototyping of application specific signal processors (RASSP) program is an ARPA/tri-service effort to dramatically improve the process by which complex digital systems, particularly embedded signal processors, are specified, designed, documented, manufactured, and supported. The domain of embedded signal processing was chosen because it is important to a variety of military and commercial applications as well as for the challenge it presents in terms of complexity and performance demands. The principal effort is being performed by two major contractors, Lockheed Sanders (Nashua, NH) and Martin Marietta (Camden, NJ). For both, improvements in methodology are to be exercised and refined through the performance of individual 'Demonstration' efforts. The Lockheed Sanders' Demonstration effort is to develop an infrared search and track (IRST) processor. In addition, both contractors' results are being measured by a series of externally administered (by Lincoln Labs) six-month Benchmark programs that measure process improvement as a function of time. The first two Benchmark programs are designing and implementing a synthetic aperture radar (SAR) processor. Our demonstration team is using commercially available VME modules from Mercury Computer to assemble a multiprocessor system scalable from one to hundreds of Intel i860 microprocessors. Custom modules for the sensor interface and display driver are also being developed. This system implements either proprietary or Navy owned algorithms to perform the compute-intensive IRST function in real time in an avionics environment. Our Benchmark team is designing custom modules using commercially available processor ship sets, communication submodules, and reconfigurable logic devices. One of the modules contains multiple vector processors optimized for fast Fourier transform processing. Another module is a fiberoptic interface that accepts high-rate input data from the sensors and provides video-rate output data to a display. This paper discusses the impact of simulation on choosing signal processing algorithms and architectures, drawing from the experiences of the Demonstration and Benchmark inter-company teams at Lockhhed Sanders, Motorola, Hughes, and ISX.

  1. Using R in Taverna: RShell v1.2

    PubMed Central

    Wassink, Ingo; Rauwerda, Han; Neerincx, Pieter BT; Vet, Paul E van der; Breit, Timo M; Leunissen, Jack AM; Nijholt, Anton

    2009-01-01

    Background R is the statistical language commonly used by many life scientists in (omics) data analysis. At the same time, these complex analyses benefit from a workflow approach, such as used by the open source workflow management system Taverna. However, Taverna had limited support for R, because it supported just a few data types and only a single output. Also, there was no support for graphical output and persistent sessions. Altogether this made using R in Taverna impractical. Findings We have developed an R plugin for Taverna: RShell, which provides R functionality within workflows designed in Taverna. In order to fully support the R language, our RShell plugin directly uses the R interpreter. The RShell plugin consists of a Taverna processor for R scripts and an RShell Session Manager that communicates with the R server. We made the RShell processor highly configurable allowing the user to define multiple inputs and outputs. Also, various data types are supported, such as strings, numeric data and images. To limit data transport between multiple RShell processors, the RShell plugin also supports persistent sessions. Here, we will describe the architecture of RShell and the new features that are introduced in version 1.2, i.e.: i) Support for R up to and including R version 2.9; ii) Support for persistent sessions to limit data transfer; iii) Support for vector graphics output through PDF; iv)Syntax highlighting of the R code; v) Improved usability through fewer port types. Our new RShell processor is backwards compatible with workflows that use older versions of the RShell processor. We demonstrate the value of the RShell processor by a use-case workflow that maps oligonucleotide probes designed with DNA sequence information from Vega onto the Ensembl genome assembly. Conclusion Our RShell plugin enables Taverna users to employ R scripts within their workflows in a highly configurable way. PMID:19607662

  2. Parallel architecture for rapid image generation and analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nerheim, R.J.

    1987-01-01

    A multiprocessor architecture inspired by the Disney multiplane camera is proposed. For many applications, this approach produces a natural mapping of processors to objects in a scene. Such a mapping promotes parallelism and reduces the hidden-surface work with minimal interprocessor communication and low-overhead cost. Existing graphics architectures store the final picture as a monolithic entity. The architecture here stores each object's image separately. It assembles the final composite picture from component images only when the video display needs to be refreshed. This organization simplifies the work required to animate moving objects that occlude other objects. In addition, the architecture hasmore » multiple processors that generate the component images in parallel. This further shortens the time needed to create a composite picture. In addition to generating images for animation, the architecture has the ability to decompose images.« less

  3. FTMP (Fault Tolerant Multiprocessor) programmer's manual

    NASA Technical Reports Server (NTRS)

    Feather, F. E.; Liceaga, C. A.; Padilla, P. A.

    1986-01-01

    The Fault Tolerant Multiprocessor (FTMP) computer system was constructed using the Rockwell/Collins CAPS-6 processor. It is installed in the Avionics Integration Research Laboratory (AIRLAB) of NASA Langley Research Center. It is hosted by AIRLAB's System 10, a VAX 11/750, for the loading of programs and experimentation. The FTMP support software includes a cross compiler for a high level language called Automated Engineering Design (AED) System, an assembler for the CAPS-6 processor assembly language, and a linker. Access to this support software is through an automated remote access facility on the VAX which relieves the user of the burden of learning how to use the IBM 4381. This manual is a compilation of information about the FTMP support environment. It explains the FTMP software and support environment along many of the finer points of running programs on FTMP. This will be helpful to the researcher trying to run an experiment on FTMP and even to the person probing FTMP with fault injections. Much of the information in this manual can be found in other sources; we are only attempting to bring together the basic points in a single source. If the reader should need points clarified, there is a list of support documentation in the back of this manual.

  4. The Spanish Version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) Adapted as a School-Based Anxiety and Depression Prevention Program: Study Protocol for a Cluster Randomized Controlled Trial.

    PubMed

    García-Escalera, Julia; Valiente, Rosa M; Chorot, Paloma; Ehrenreich-May, Jill; Kennedy, Sarah M; Sandín, Bonifacio

    2017-08-21

    Anxiety and depression are common, impairing conditions that evidence high comorbidity rates in adolescence. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) is one of the few existing resources aimed at applying transdiagnostic treatment principles to target core dysfunctions associated with both anxiety and depression within a single protocol. To our knowledge, this is the first study examining the efficacy of the UP-A adapted as a universal preventive intervention program. The primary aim of this study is to examine whether the Spanish version of the UP-A is more effective than a waitlist (WL) control group in reducing and preventing symptoms of anxiety and depression when employed as a universal, classroom-based preventive intervention. The secondary aim is to investigate changes in a broad range of secondary outcome measures, including negative and positive affect, anxiety sensitivity, emotional avoidance, top problems ratings, school grades, depression and anxiety-related interference, self-esteem, life satisfaction, quality of life, conduct problems, hyperactivity/inattention symptoms, peer problems, prosocial behavior, school adjustment, and discipline problems. Other aims are to assess a range of possible predictors of intervention effects and to examine the feasibility and the acceptability of implementing UP-A in a prevention group format and in a school setting. A cluster, randomized, WL, controlled trial design with classroom as the unit of randomization was used in this study. Five classes including a total of 152 adolescents were randomized to the experimental or WL control groups. Participants in the experimental group received 9 55-minute sessions delivered by advanced doctoral and masters students in clinical psychology. The WL control group will receive the intervention once the 3-month follow-up assessment is completed. We have recruited participants to the cluster randomized controlled trial (RCT) and have conducted the intervention with the experimental group. We expect the WL control group to complete the intervention in July 2017. Data analysis will take place during the second semester of 2017. We expect the experimental group to outperform the WL control group at post-intervention and 3-month follow-up. We also expect the WL control group to show improvements in primary and secondary outcome measures after receiving the intervention. Results will have implications for researchers, families, and education providers. Clinicaltrials.gov NCT03123991; https://clinicaltrials.gov/ct2/show/NCT03123991 (Archived by WebCite at http://www.webcitation.org/6qp7GIzcR). ©Julia García-Escalera, Rosa M Valiente, Paloma Chorot, Jill Ehrenreich-May, Sarah M Kennedy, Bonifacio Sandín. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.08.2017.

  5. The Spanish Version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) Adapted as a School-Based Anxiety and Depression Prevention Program: Study Protocol for a Cluster Randomized Controlled Trial

    PubMed Central

    García-Escalera, Julia; Valiente, Rosa M; Ehrenreich-May, Jill; Kennedy, Sarah M; Sandín, Bonifacio

    2017-01-01

    Background Anxiety and depression are common, impairing conditions that evidence high comorbidity rates in adolescence. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) is one of the few existing resources aimed at applying transdiagnostic treatment principles to target core dysfunctions associated with both anxiety and depression within a single protocol. To our knowledge, this is the first study examining the efficacy of the UP-A adapted as a universal preventive intervention program. Objective The primary aim of this study is to examine whether the Spanish version of the UP-A is more effective than a waitlist (WL) control group in reducing and preventing symptoms of anxiety and depression when employed as a universal, classroom-based preventive intervention. The secondary aim is to investigate changes in a broad range of secondary outcome measures, including negative and positive affect, anxiety sensitivity, emotional avoidance, top problems ratings, school grades, depression and anxiety-related interference, self-esteem, life satisfaction, quality of life, conduct problems, hyperactivity/inattention symptoms, peer problems, prosocial behavior, school adjustment, and discipline problems. Other aims are to assess a range of possible predictors of intervention effects and to examine the feasibility and the acceptability of implementing UP-A in a prevention group format and in a school setting. Methods A cluster, randomized, WL, controlled trial design with classroom as the unit of randomization was used in this study. Five classes including a total of 152 adolescents were randomized to the experimental or WL control groups. Participants in the experimental group received 9 55-minute sessions delivered by advanced doctoral and masters students in clinical psychology. The WL control group will receive the intervention once the 3-month follow-up assessment is completed. Results We have recruited participants to the cluster randomized controlled trial (RCT) and have conducted the intervention with the experimental group. We expect the WL control group to complete the intervention in July 2017. Data analysis will take place during the second semester of 2017. Conclusions We expect the experimental group to outperform the WL control group at post-intervention and 3-month follow-up. We also expect the WL control group to show improvements in primary and secondary outcome measures after receiving the intervention. Results will have implications for researchers, families, and education providers. Trial Registration Clinicaltrials.gov NCT03123991; https://clinicaltrials.gov/ct2/show/NCT03123991 (Archived by WebCite at http://www.webcitation.org/6qp7GIzcR) PMID:28827212

  6. Lysophosphatidic acid (LPA) effects on endometrial carcinoma in vitro proliferation, invasion, and matrix metalloproteinase activity.

    PubMed

    Wang, Feng-qiang; Ariztia, Edgardo V; Boyd, Leslie R; Horton, Faith R; Smicun, Yoel; Hetherington, Jessica A; Smith, Phillip J; Fishman, David A

    2010-04-01

    Lysophosphatidic acid (LPA) has potent growth-regulatory effect in many cell types and has been linked to the in vivo tumor growth and metastasis in several malignancies. The goal of this study was to assess the regulation of (EC) microenvironment by LPA through the examination of its effect on cell proliferation, migration, invasion, uPA activity, and matrix metalloproteinase (MMP) secretion/activation. All experiments were performed in vitro using an EC cell line, HEC-1A. Cell proliferation was determined using the Promega MTS proliferation assay following 48 h of exposures to different concentrations of LPA (0.1, 1.0 and 10.0 microM). Cell invasion was assessed using a modified Boyden chamber assay with collagen I coated on the membrane. HEC-1A motility was examined by Boyden chamber migration assay as well as the scratch wound closure assay on type I collagen. MMP secretion/activation in HEC-1A conditioned medium was detected by gelatin zymography. MMP-7 mRNA expression was determined using real-time PCR. uPA activity was measured using a coupled colorimetric assay. LPA, at the concentrations of 0.1 and 1.0 microM, significantly induced the proliferation of HEC-1A cells (p<0.01). At 10 microM, LPA- induced HEC-1A proliferation to a less extent and showed no significant effect on HEC-1A invasion and migration (p>0.05). Gelatin zymogram showed that HEC-1A cells secreted high levels of MMP-7, while MMP-2 and MMP-9 are barely detectable. In addition, LPA significantly enhanced uPA activity in HEC-1A conditioned medium in a concentration-dependent manner. LPA is a potent modulator of cellular proliferation and invasion for EC cells. It also has the capacity to stimulate the secretion/activity of uPA and MMP-7. Those results suggest that LPA is a bioactive modulator of EC microenvironment and may have a distinct regulation mechanism as observed in epithelial ovarian cancer. Copyright 2009. Published by Elsevier Inc.

  7. Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains

    PubMed Central

    2012-01-01

    Background Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA) are sexually transmitted bacteria among humans implicated in a variety of disease states including but not limited to: nongonococcal urethritis, infertility, adverse pregnancy outcomes, chorioamnionitis, and bronchopulmonary dysplasia in neonates. There are 10 distinct serotypes of UUR and 4 of UPA. Efforts to determine whether difference in pathogenic potential exists at the ureaplasma serovar level have been hampered by limitations of antibody-based typing methods, multiple cross-reactions and poor discriminating capacity in clinical samples containing two or more serovars. Results We determined the genome sequences of the American Type Culture Collection (ATCC) type strains of all UUR and UPA serovars as well as four clinical isolates of UUR for which we were not able to determine serovar designation. UPA serovars had 0.75−0.78 Mbp genomes and UUR serovars were 0.84−0.95 Mbp. The original classification of ureaplasma isolates into distinct serovars was largely based on differences in the major ureaplasma surface antigen called the multiple banded antigen (MBA) and reactions of human and animal sera to the organisms. Whole genome analysis of the 14 serovars and the 4 clinical isolates showed the mba gene was part of a large superfamily, which is a phase variable gene system, and that some serovars have identical sets of mba genes. Most of the differences among serovars are hypothetical genes, and in general the two species and 14 serovars are extremely similar at the genome level. Conclusions Comparative genome analysis suggests UUR is more capable of acquiring genes horizontally, which may contribute to its greater virulence for some conditions. The overwhelming evidence of extensive horizontal gene transfer among these organisms from our previous studies combined with our comparative analysis indicates that ureaplasmas exist as quasi-species rather than as stable serovars in their native environment. Therefore, differential pathogenicity and clinical outcome of a ureaplasmal infection is most likely not on the serovar level, but rather may be due to the presence or absence of potential pathogenicity factors in an individual ureaplasma clinical isolate and/or patient to patient differences in terms of autoimmunity and microbiome. PMID:22646228

  8. Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains.

    PubMed

    Paralanov, Vanya; Lu, Jin; Duffy, Lynn B; Crabb, Donna M; Shrivastava, Susmita; Methé, Barbara A; Inman, Jason; Yooseph, Shibu; Xiao, Li; Cassell, Gail H; Waites, Ken B; Glass, John I

    2012-05-30

    Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA) are sexually transmitted bacteria among humans implicated in a variety of disease states including but not limited to: nongonococcal urethritis, infertility, adverse pregnancy outcomes, chorioamnionitis, and bronchopulmonary dysplasia in neonates. There are 10 distinct serotypes of UUR and 4 of UPA. Efforts to determine whether difference in pathogenic potential exists at the ureaplasma serovar level have been hampered by limitations of antibody-based typing methods, multiple cross-reactions and poor discriminating capacity in clinical samples containing two or more serovars. We determined the genome sequences of the American Type Culture Collection (ATCC) type strains of all UUR and UPA serovars as well as four clinical isolates of UUR for which we were not able to determine serovar designation. UPA serovars had 0.75-0.78 Mbp genomes and UUR serovars were 0.84-0.95 Mbp. The original classification of ureaplasma isolates into distinct serovars was largely based on differences in the major ureaplasma surface antigen called the multiple banded antigen (MBA) and reactions of human and animal sera to the organisms. Whole genome analysis of the 14 serovars and the 4 clinical isolates showed the mba gene was part of a large superfamily, which is a phase variable gene system, and that some serovars have identical sets of mba genes. Most of the differences among serovars are hypothetical genes, and in general the two species and 14 serovars are extremely similar at the genome level. Comparative genome analysis suggests UUR is more capable of acquiring genes horizontally, which may contribute to its greater virulence for some conditions. The overwhelming evidence of extensive horizontal gene transfer among these organisms from our previous studies combined with our comparative analysis indicates that ureaplasmas exist as quasi-species rather than as stable serovars in their native environment. Therefore, differential pathogenicity and clinical outcome of a ureaplasmal infection is most likely not on the serovar level, but rather may be due to the presence or absence of potential pathogenicity factors in an individual ureaplasma clinical isolate and/or patient to patient differences in terms of autoimmunity and microbiome.

  9. Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist.

    PubMed

    Yu, Peng; Li, Shengjie; Zhang, Zhifei; Wen, Xiaolong; Quan, Wei; Tian, Qilong; Gao, Chuang; Su, Wanqiang; Zhang, Jianning; Jiang, Rongcai

    2017-10-01

    Progesterone (P4) has the potential therapeutic effects for traumatic brain injury (TBI) whose recovery depended on the enhanced angiogenesis. Endothelial progenitor cell (EPC) plays an essential role in vascular biology. We previously demonstrated that P4 administration improved circulating EPC level and neurological recovery of rat with TBI. Here, we hypothesized that P4 augmented angiogenic potential of EPC and the angiogenesis-related neurorestoration after TBI through classical progesterone receptor (PR). EPC derived from rats were stimulated with graded concentrations (0, 10 -10 , 10 -9 , 5 × 10 -9 , 10 -8 , 10 -7  mol/L) of P4 or 10 -6  mol/L ulipristal acetate (UPA, a PR antagonist). Male rats were subjected to cortical impact injury and treated with (i) DMSO (dimethyl sulfoxide), (ii) P4 and (iii) P4 and UPA. It showed that P4 improved the angiogenic potential of EPC, including tube formation, adhesion, migration and vascular endothelial growth factor secretion, in a dose-dependent fashion with the maximal effect achieved at 10 -9  mol/L P4. High concentration (10 -7  mol/L) of P4 impaired the angiogenic potential of EPC. Notably, 10 -6  mol/L UPA antagonized the stimulatory effects of 10 -9  mol/L P4. After administrating P4, a significant improvement of neurological function and the restoration of the leaked blood-brain barrier were observed as well as a reduction of the brain water content. Both vessel density and expression of occludin of vessels were increased. When UPA was administered with P4, the neural restoration and angiogenesis were all reversed. Western blot showed that 10 -9  mol/L P4 increased the content of PRA and PRB of EPC, while 10 -7  mol/L P4 reduced the content of both PR isoforms, but there was no change found in the TBI rats. It may suggest that P4-mediated angiogenic activity of EPC and angiogenesis in TBI rats were antagonized by PR antagonist. © 2017 John Wiley & Sons Ltd.

  10. Landsat-1 and Landsat-2 flight evaluation

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The flight performance of Landsat 1 and Landsat 2 is analyzed. Flight operations of the satellites are briefly summarized. Other topics discussed include: orbital parameters; power subsystem; attitude control subsystem; command/clock subsystem; telemetry subsystem; orbit adjust subsystem; magnetic moment compensating assembly; unified s-band/premodulation processor; electrical interface subsystem; thermal subsystem; narrowband tape recorders; wideband telemetry subsystem; attitude measurement sensor; wideband video tape recorders; return beam vidicon; multispectral scanner subsystem; and data collection subsystem.

  11. Compilation of Abstracts of Theses Submitted by Candidates for Degrees.

    DTIC Science & Technology

    1984-06-01

    Management System for the TI - 59 Programmable Calculator Kersh, T. B. Signal Processor Interface 65 CPT, USA Simulation of the AN/SPY-lA Radar...DESIGN AND IMPLEMENTATION OF A BASIC CROSS-COMPILER AND VIRTUAL MEMORY MANAGEMENT SYSTEM FOR THE TI - 59 PROGRAMMABLE CALCULATOR Mark R. Kindl Captain...Academy, 1974 The instruction set of the TI - 59 Programmable Calculator bears a close similarity to that of an assembler. Though most of the calculator

  12. System for Suppressing Vibration in Turbomachine Components

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R. (Inventor); Provenza, Andrew J. (Inventor); Choi, Benjamin B. (Inventor); Bakhle, Milind A. (Inventor); Min, James B (Inventor); Stefko, George L. (Inventor); Kussmann, John A (Inventor); Fougere, Alan J (Inventor)

    2013-01-01

    Disclosed is a system for suppressing vibration and noise mitigation in structures such as blades in turbomachinery. The system includes flexible piezoelectric patches which are secured on or imbedded in turbomachinery blades which, in one embodiment, comprises eight (8) fan blades. The system further includes a capacitor plate coupler and a power transfer apparatus, which may both be arranged into one assembly, that respectively transfer data and power. Each of the capacitive plate coupler and power transfer apparatus is configured so that one part is attached to a fixed member while another part is attached to a rotatable member with an air gap there between. The system still further includes a processor that has 16 channels, eight of which serve as sensor channels, and the remaining eight, serving as actuation channels. The processor collects and analyzes the sensor signals and, in turn, outputs corrective signals for vibration/noise suppression of the turbine blades.

  13. KSC01padig006

    NASA Image and Video Library

    2001-01-03

    KENNEDY SPACE CENTER, Fla. -- Under wispy white morning clouds, Space Shuttle Atlantis approaches Launch Pad 39A, which shows the Rotating Service Structure open (left) and the Fixed Service Structure (right). At the RSS, the payload canister is being lifted up to the Payload Changeout Room. This is the Shuttle’s second attempt at rollout. Jan. 2 a failed computer processor on the crawler transporter aborted the rollout and the Shuttle was returned to the Vehicle Assembly Building using a secondary computer processor on the vehicle. Atlantis will fly on mission STS-98, the seventh construction flight to the International Space Station, carrying the U.S. Laboratory, named Destiny. The lab will have five system racks already installed inside the module. After delivery of electronics in the lab, electrically powered attitude control for Control Moment Gyroscopes will be activated. Atlantis is scheduled for launch no earlier than Jan. 19, 2001, with a crew of five

  14. Demonstration program for Omega receiver prototype microcomputer data processing

    NASA Technical Reports Server (NTRS)

    Lilley, R. W.

    1976-01-01

    The JOLT (TM) commercial microcomputer, based on the MOS Technology 6502 processor chip, for use in Omega navigation system is evaluated. A computer program was prepared in hand-assembled code to demonstrate receiver operation. The processor provides binary processing with interrupts enabled, a carriage return is given to initialize the teleprinter, and a jump is performed to enter the program loop to wait for an interrupt. The program loop operates continuously testing the interrupt flag. The interrupt routine reads the receiver status word and determines whether the current time-slot is the A slot. If so, the interrupt flag, which is also the data index pointer, is reset to zero. The status word is stored in the status buffer. If the time-slot is not A, the interrupt flag/pointer is incremented by one to index the phase and status to the proper buffer words for later use by the print routine.

  15. 1996 national fleet safety survey

    DOT National Transportation Integrated Search

    2011-08-01

    This report presents the test plan for collecting and analyzing data survey and interview data for the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) ...

  16. 5-Benzylglycinyl-Amiloride Kills Proliferating and Nonproliferating Malignant Glioma Cells through Caspase-Independent Necroptosis Mediated by Apoptosis-Inducing Factor

    PubMed Central

    Pasupuleti, Nagarekha; Leon, Leonardo; Carraway, Kermit L.

    2013-01-01

    5′–Βenzylglycinyl-amiloride (UCD38B) and glycinyl-amiloride (UCD74A) are cell-permeant and cell-impermeant derivatives of amiloride, respectively, and used here to identify the cellular mechanisms of action underlying their antiglioma effects. UCD38B comparably kills proliferating and nonproliferating gliomas cells when cell cycle progression is arrested either by cyclin D1 siRNA or by acidification. Cell impermeant UCD74A inhibits plasmalemmal urokinase plasminogen activator (uPA) and the type 1 sodium-proton exchanger with potencies analogous to UCD38B, but is cytostatic. In contrast, UCD38B targets intracellular uPA causing mistrafficking of uPA into perinuclear mitochondria, reducing the mitochondrial membrane potential, and followed by the release of apoptotic inducible factor (AIF). AIF nuclear translocation is followed by a caspase-independent necroptotic cell death. Reduction in AIF expression by siRNA reduces the antiglioma cytotoxic effects of UCD38B, while not activating the caspase pathway. Ultrastructural changes shortly following treatment with UCD38B demonstrate dilation of endoplasmic reticulum (ER) and mitochondrial swelling followed by nuclear condensation within hours consistent with a necroptotic cell death differing from apoptosis and from autophagy. These drug mechanism of action studies demonstrate that UCD38B induces a cell cycle-independent, caspase-independent necroptotic glioma cell death that is mediated by AIF and independent of poly (ADP-ribose) polymerase and H2AX activation. PMID:23241369

  17. Teaching Climate Change Science to Undergradutes with Diverse & Digital Pedagogical Techniquees

    NASA Astrophysics Data System (ADS)

    Kauffman, C.; Brey, J. A.; Nugnes, K. A.; Weinbeck, R. S.; Geer, I. W.

    2015-12-01

    California University of Pennsylvania (CalUPA) is unique relative to other undergraduate geoscience programs in that their climate science offerings are varied and inter-woven into an existing meteorology degree program, which aligns with the guidelines established by the American Meteorological Society (AMS). In addition to the rigorous meteorological requirements, the program strives to increase students' climate literacy. At the introductory course level, students are required to use the educational resources offered by the AMS—specifically their weather and climate studies materials, which have recently transitioned to a digital format. The Earth Sciences Program at CalUPA recently incorporated these new digital resources into a climatology course with novel pedagogical variants. These teaching strategies were well received by students and may benefit other climatology courses at similar institutions. For example, students were tasked with expounding upon textbook content from 'Topic In Depth' segments; they were required to present tangential climate topics in a digital presentation. Moreover, students mined the scientific literature listed at the end of each chapter in the text to identify climate scientists immersed in social media. Students were then required to follow these scientists and engage each other within a social media platform. Finally, as a culminating experience, students were required to create digital portfolios (e.g., infographic) related to climate science and the AMS materials. This presentation will further detail CalUPA's climatological course offerings and detail how the AMS resources were connected to course requirements listed herein.

  18. Real world data of 1473 patients treated with ulipristal acetate for uterine fibroids: Premya study results.

    PubMed

    Fernandez, Hervé; Schmidt, Torsten; Powell, Martin; Costa, Ana Patrícia Freitas; Arriagada, Pablo; Thaler, Christian

    2017-01-01

    To characterize and describe treatment with Ulipristal acetate (UPA) in a pre-operative setting and to evaluate the safety, effectiveness, and Health Related Quality of Life (HRQoL) outcomes in a population treated according to standard clinical practice in the EU. Multi-centre, prospective, non-interventional study (PREMYA) of patients diagnosed with moderate to severe symptoms of uterine fibroids and undergoing a pre-operative treatment with UPA (Esmya ® ) at 73 clinical practice sites within the EU. Patients were followed during UPA treatment and for 12 months after treatment discontinuation for a total of 15 months follow-up. Data was collected every 3 months in accordance with standard care visits. A total of 1568 women were enrolled, of whom 1473 were found to be eligible for data analysis. Only 38.8% of patients underwent surgery, of which the majority were of a conservative/minimally invasive nature. Physicians' assessments of patients' overall symptomatic change, as measured on the Clinical Global Impression-Improvement (CGI-I) scale, indicated that 60% of patients were much improved or very much improved at 3 months. Pain and quality of life after treatment cessation remain lower than baseline during the entire period of follow-up CONCLUSIONS: The majority of patients do not undergo surgery immediately after treatment cessation. Quality of life and pain are highly improved by Esmya ® treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Busch, Susann; Renaud, Stephen J.; Schleussner, Ekkehard

    The intracellular signaling molecule mammalian target of rapamycin (mTOR) is essential for cell growth and proliferation. It is involved in mouse embryogenesis, murine trophoblast outgrowth and linked to tumor cell invasiveness. In order to assess the role of mTOR in human trophoblast invasion we analyzed the in vitro invasiveness of HTR-8/SVneo immortalized first-trimester trophoblast cells in conjunction with enzyme secretion upon mTOR inhibition and knockdown of mTOR protein expression. Additionally, we also tested the capability of mTOR to trigger signal transducer and activator of transcription (STAT)-3 by its phosphorylation status. Rapamycin inhibited mTOR kinase activity as demonstrated with a lowermore » phosphorylation level of the mTOR substrate p70 S6 kinase (S6K). With the use of rapamycin and siRNA-mediated mTOR knockdown we could show that cell proliferation, invasion and secretion of matrix-metalloproteinases (MMP)-2 and -9, urokinase-like plasminogen activator (uPA) and its major physiological uPA inhibitor (PAI)-1 were inhibited. While tyrosine phosphorylation of STAT3 was unaffected by mTOR inhibition and knockdown, serine phosphorylation was diminished. We conclude that mTOR signaling is one major mechanism in a tightly regulated network of intracellular signal pathways including the JAK/STAT system to regulate invasion in human trophoblast cells by secretion of enzymes that remodel the extra-cellular matrix (ECM) such as MMP-2, -9, uPA and PAI-1. Dysregulation of mTOR may contribute to pregnancy-related pathologies caused through impaired trophoblast invasion.« less

  20. Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.

    PubMed

    Diamandis, M; Adam, F; Kahr, W H A; Wang, P; Chorneyko, K A; Arsenault, A L; Rivard, G E; Hayward, C P M

    2006-05-01

    The Quebec platelet disorder (QPD) is inherited and characterized by delayed-onset bleeding following hemostatic challenge. Other characteristics include increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets in the setting of normal to increased u-PA in plasma. There is also consumption of platelet plasminogen activator inhibitor-1 and increased generation of plasmin in platelets accompanied by proteolysis of stored alpha-granule proteins, including Factor V. Although fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood and platelets on clot lysis have not been evaluated. We used thromboelastography (TEG), biochemical evaluations of whole blood clot lysis, assessments of clot ultrastructure, and perfusion of blood over preformed fibrin to gain insights into the disturbed hemostasis in the QPD. Thromboelastography was not sensitive to the increased u-PA in QPD blood. However, there was abnormal plasmin generation in QPD whole blood clots, generated at low shear, with biochemical evidence of increased fibrinolysis. The incorporation of QPD platelets into a forming clot led to progressive disruption of fibrin and platelet aggregates unless drugs were added to inhibit plasmin. In whole blood perfusion studies, QPD platelets showed normal adherence to fibrin, but their adhesion was followed by accelerated fibrinolysis. The QPD is associated with "gain-of-function" abnormalities that increase the lysis of forming or preformed clots. These findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding.

  1. Implementation of a robotic flexible assembly system

    NASA Technical Reports Server (NTRS)

    Benton, Ronald C.

    1987-01-01

    As part of the Intelligent Task Automation program, a team developed enabling technologies for programmable, sensory controlled manipulation in unstructured environments. These technologies include 2-D/3-D vision sensing and understanding, force sensing and high speed force control, 2.5-D vision alignment and control, and multiple processor architectures. The subsequent design of a flexible, programmable, sensor controlled robotic assembly system for small electromechanical devices is described using these technologies and ongoing implementation and integration efforts. Using vision, the system picks parts dumped randomly in a tray. Using vision and force control, it performs high speed part mating, in-process monitoring/verification of expected results and autonomous recovery from some errors. It is programmed off line with semiautomatic action planning.

  2. High-speed assembly language (80386/80387) programming for laser spectra scan control and data acquisition providing improved resolution water vapor spectroscopy

    NASA Technical Reports Server (NTRS)

    Allen, Robert J.

    1988-01-01

    An assembly language program using the Intel 80386 CPU and 80387 math co-processor chips was written to increase the speed of data gathering and processing, and provide control of a scanning CW ring dye laser system. This laser system is used in high resolution (better than 0.001 cm-1) water vapor spectroscopy experiments. Laser beam power is sensed at the input and output of white cells and the output of a Fabry-Perot. The assembly language subroutine is called from Basic, acquires the data and performs various calculations at rates greater than 150 faster than could be performed by the higher level language. The width of output control pulses generated in assembly language are 3 to 4 microsecs as compared to 2 to 3.7 millisecs for those generated in Basic (about 500 to 1000 times faster). Included are a block diagram and brief description of the spectroscopy experiment, a flow diagram of the Basic and assembly language programs, listing of the programs, scope photographs of the computer generated 5-volt pulses used for control and timing analysis, and representative water spectrum curves obtained using these programs.

  3. Algorithms and Application of Sparse Matrix Assembly and Equation Solvers for Aeroacoustics

    NASA Technical Reports Server (NTRS)

    Watson, W. R.; Nguyen, D. T.; Reddy, C. J.; Vatsa, V. N.; Tang, W. H.

    2001-01-01

    An algorithm for symmetric sparse equation solutions on an unstructured grid is described. Efficient, sequential sparse algorithms for degree-of-freedom reordering, supernodes, symbolic/numerical factorization, and forward backward solution phases are reviewed. Three sparse algorithms for the generation and assembly of symmetric systems of matrix equations are presented. The accuracy and numerical performance of the sequential version of the sparse algorithms are evaluated over the frequency range of interest in a three-dimensional aeroacoustics application. Results show that the solver solutions are accurate using a discretization of 12 points per wavelength. Results also show that the first assembly algorithm is impractical for high-frequency noise calculations. The second and third assembly algorithms have nearly equal performance at low values of source frequencies, but at higher values of source frequencies the third algorithm saves CPU time and RAM. The CPU time and the RAM required by the second and third assembly algorithms are two orders of magnitude smaller than that required by the sparse equation solver. A sequential version of these sparse algorithms can, therefore, be conveniently incorporated into a substructuring for domain decomposition formulation to achieve parallel computation, where different substructures are handles by different parallel processors.

  4. Atlanta congestion reduction demonstration national evaluation plan.

    DOT National Transportation Integrated Search

    2011-04-01

    This report provides an analytic framework for evaluating the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) and CRD Programs. The Atlanta CRD project...

  5. Hazardous materials risk assessment : phase I

    DOT National Transportation Integrated Search

    2011-08-01

    This report presents the test plan for collecting and analyzing transit system data for the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) and CRD Pro...

  6. DSS command software update

    NASA Technical Reports Server (NTRS)

    Stinnett, W. G.

    1980-01-01

    The modifications, additions, and testing results for a version of the Deep Space Station command software, generated for support of the Voyager Saturn encounter, are discussed. The software update requirements included efforts to: (1) recode portions of the software to permit recovery of approximately 2000 words of memory; (2) correct five Voyager Ground data System liens; (3) provide capability to automatically turn off the command processor assembly local printer during periods of low activity; and (4) correct anomalies existing in the software.

  7. Elan4/SPARC V9 Cross Loader and Dynamic Linker

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    anf Fabien Lebaillif-Delamare, Fabrizio Petrini

    2004-10-25

    The Elan4/Sparc V9 Croos Loader and Liner is a part of the Linux system software that allows the dynamic loading and linking of user code in the network interface Quadrics QsNETII, also called as Elan4 Quadrics. Elan44 uses a thread processor that is based on the assembly instruction set of the Sparc V9. All this software is integrated as a Linux kernel module in the Linux 2.6.5 release.

  8. Initial Kernel Timing Using a Simple PIM Performance Model

    NASA Technical Reports Server (NTRS)

    Katz, Daniel S.; Block, Gary L.; Springer, Paul L.; Sterling, Thomas; Brockman, Jay B.; Callahan, David

    2005-01-01

    This presentation will describe some initial results of paper-and-pencil studies of 4 or 5 application kernels applied to a processor-in-memory (PIM) system roughly similar to the Cascade Lightweight Processor (LWP). The application kernels are: * Linked list traversal * Sun of leaf nodes on a tree * Bitonic sort * Vector sum * Gaussian elimination The intent of this work is to guide and validate work on the Cascade project in the areas of compilers, simulators, and languages. We will first discuss the generic PIM structure. Then, we will explain the concepts needed to program a parallel PIM system (locality, threads, parcels). Next, we will present a simple PIM performance model that will be used in the remainder of the presentation. For each kernel, we will then present a set of codes, including codes for a single PIM node, and codes for multiple PIM nodes that move data to threads and move threads to data. These codes are written at a fairly low level, between assembly and C, but much closer to C than to assembly. For each code, we will present some hand-drafted timing forecasts, based on the simple PIM performance model. Finally, we will conclude by discussing what we have learned from this work, including what programming styles seem to work best, from the point-of-view of both expressiveness and performance.

  9. miR-23b as a potential tumor suppressor and its regulation by DNA methylation in cervical cancer.

    PubMed

    Campos-Viguri, Gabriela Elizabeth; Jiménez-Wences, Hilda; Peralta-Zaragoza, Oscar; Torres-Altamirano, Gricenda; Soto-Flores, Diana Guillermina; Hernández-Sotelo, Daniel; Alarcón-Romero, Luz Del Carmen; Jiménez-López, Marco Antonio; Illades-Aguiar, Berenice; Fernández-Tilapa, Gloria

    2015-01-01

    The aberrant expression of miR-23b is involved in the development and progression of cancer. The aim of this study was to evaluate the potential role of methylation in the silencing of miR-23b in cervical cancer cell lines and to determine its expression in stages of malignant progression and in cervical cancer tissues HPV16-positive. The methylation of the miR-23b promoter was determined in HeLa, SiHa, CaSki and C33A cells using a Human Cancer miRNA EpiTectMethyl II Signature PCR Array®. The cells were treated with 5-Aza-2'-deoxycytidine, and the expression of miR-23b, uPa, c-Met and Zeb1 was determined by qRT-PCR. miR-92a and GAPDH were used as controls. The expression of miR-23b was determined in cervical scrapes and biopsies of women without squamous intraepithelial lesions, with precursor lesions and with cervical cancer, all were HPV16-positive. The Fisher exact and Mann-Whitney tests were used to compare the differences of the expression of miR-23b, uPa, c-Met and Zeb1 among cell groups, and the difference among patients, respectively. The association between the expression of miR-23b and cervical cancer was determined by logistic regression with a confidence level of 95 %. A value of p < 0.05 was considered statistically significant. In C33A, HeLa and CaSki cells, methylation was associated with decreased expression of miR-23b. After treatment with 5-Aza-CdR, the expression of miR-23b increased in all cell lines and the expression of c-Met decreased in HeLa cells, while uPa and Zeb1 decreased in C33A and CaSki cells. In SiHa cells the expression of uPa, c-Met and Zeb1 increased. The expression of miR-23b decreased in relation to the increase in the severity of the lesion and was significantly lower in cervical cancer. In women with premalignant lesions HPV16-positive, decreased levels of miR-23b increased the risk of cervical cancer (OR = 36, 95 % CI = 6.7-192.6, p < 0.05). The results suggest that the expression of miR-23b is regulated by the methylation of its promoter and is possible that this microRNA influence the expression of uPa, c-Met and Zeb1 in cervical cancer cells lines. In women with premalignant lesions and cervical cancer infected with HPV16, the expression level of miR-23b agree with a tumor suppressor gene.

  10. The Brain's Router: A Cortical Network Model of Serial Processing in the Primate Brain

    PubMed Central

    Zylberberg, Ariel; Fernández Slezak, Diego; Roelfsema, Pieter R.; Dehaene, Stanislas; Sigman, Mariano

    2010-01-01

    The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100–500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a “router” network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates. PMID:20442869

  11. Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions

    PubMed Central

    Cunningham, Orla; Andolfo, Annapaola; Santovito, Maria Lisa; Iuzzolino, Lucia; Blasi, Francesco; Sidenius, Nicolai

    2003-01-01

    The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion. PMID:14609946

  12. Genistein modifies liver fibrosis and improves liver function by inducing uPA expression and proteolytic activity in CCl4-treated rats.

    PubMed

    Salas, Alfonso Leija; Montezuma, Tania Díaz; Fariña, German Garrido; Reyes-Esparza, Jorge; Rodríguez-Fragoso, Lourdes

    2008-01-01

    To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease. (c) 2008 S. Karger AG, Basel.

  13. Ulipristal acetate prior to in vitro fertilization in a female patient affected by uterine fibroids: a case report.

    PubMed

    Lo Monte, G; Piva, I; Graziano, A; Engl, B; Marci, R

    2016-01-01

    Uterine leiomyomatosis and especially submucosal myomas hamper the outcomes of Assisted Reproductive Techniques (ART). Even though surgical treatment eliminates gross anatomical anomalies, medical treatment should be encouraged to improve the overall structure of the uterus, thereby enabling ART. We report the case of an infertile female patient suffering from symptomatic uterine fibromatosis, who received 5 mg/day ulipristal acetate (UPA), a selective progesterone receptor modulator (SPRMs), for three months before and after hysteroscopic myomectomy. Uterine bleeding reduced on the eight days of treatment, with a subsequent improvement of pelvic pain. Under transvaginal ultrasound the uterus appeared globally enlarged with a diffuse leiomyomatosis of the myometrial layer. Saline infusion showed a markedly distorted cavity due two submucosal myomas (sized 31 × 24 mm and 21 × 19 mm, respectively) and one intramural myoma (37 × 34 mm). After three months the size of the myomas was reduced by 30-40%, allowing the hysteroscopic removal of the submucosal fibroids and the bigger intramural one. The smaller fibroids involving the myometrial layer were instead too diffused to be removed. At the conclusion of the subsequent cycle of UPA, the overall appearance of the cavity had improved, and the endometrial layer was regular, allowing the patient to undergo in vitro fertilization (IVF). There was no adverse effect related to treatment, and the endometrial biopsy did not reveal any histologic change. UPA seems to have a triple effect: it ensures prompt symptom relief, it reduces the size of the myomas enabling surgery and it improves the morphology of the uterus.

  14. A Cyclic Peptidic Serine Protease Inhibitor: Increasing Affinity by Increasing Peptide Flexibility

    PubMed Central

    Jiang, Longguang; Paaske, Berit; Kromann-Hansen, Tobias; Jensen, Jan K.; Sørensen, Hans Peter; Liu, Zhuo; Nielsen, Jakob T.; Christensen, Anni; Hosseini, Masood; Sørensen, Kasper K.; Nielsen, Niels Christian; Jensen, Knud J.; Huang, Mingdong; Andreasen, Peter A.

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase-type plasminogen activator (uPA). We used X-ray crystal structure analysis, site-directed mutagenesis, liquid state NMR, surface plasmon resonance analysis, and isothermal titration calorimetry and wild type and engineered variants of murine and human uPA. We demonstrate that Arg6 inserts into the S1 specificity pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending on changes in both P1 - S1 and exosite interactions. Site-directed mutagenesis showed that exosite interactions, while still supporting high affinity binding, differed substantially between different uPA variants. Surprisingly, high affinity binding was facilitated by Ala-substitution of Asp9 of the peptide, in spite of a less favorable binding entropy and loss of a polar interaction. We conclude that increased flexibility of the peptide allows more favorable exosite interactions, which, in combination with the use of novel Arg analogues as P1 residues, can be used to manipulate the affinity and specificity of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden. PMID:25545505

  15. The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke

    PubMed Central

    Jeanneret, Valerie; Yepes, Manuel

    2016-01-01

    Advances in neurocritical care and interventional neuroradiology have led to a significant decrease in acute ischemic stroke (AIS) mortality. In contrast, due to the lack of an effective therapeutic strategy to promote neuronal recovery among AIS survivors, cerebral ischemia is still a leading cause of disability in the world. Ischemic stroke has a harmful impact on synaptic structure and function, and plasticity-mediated synaptic recovery is associated with neurological improvement following an AIS. Dendritic spines (DSs) are specialized dendritic protrusions that receive most of the excitatory input in the brain. The deleterious effect of cerebral ischemia on DSs morphology and function has been associated with impaired synaptic transmission and neurological deterioration. However, these changes are reversible if cerebral blood flow is restored on time, and this recovery has been associated with neurological improvement following an AIS. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are two serine proteases that besides catalyzing the conversion of plasminogen into plasmin in the intravascular and pericellular environment, respectively, are also are efficient inductors of synaptic plasticity. Accordingly, recent evidence indicates that both, tPA and uPA, protect DSs from the metabolic stress associated with the ischemic injury, and promote their morphological and functional recovery during the recovery phase from an AIS. Here we will review data indicating that plasticity-induced changes in DSs and the associated post-synaptic density play a pivotal role in the recovery process from AIS, making special emphasis on the role of tPA and uPA in this process. PMID:26846991

  16. Fish oil decreases matrix metalloproteinases in knee synovia of dogs with inflammatory joint disease.

    PubMed

    Hansen, Rodney A; Harris, Mary A; Pluhar, G Elizabeth; Motta, Tatiana; Brevard, Sean; Ogilvie, Gregory K; Fettman, Martin J; Allen, Kenneth G D

    2008-02-01

    This study was designed to determine whether dietary fish oil affects the expression and activity of matrix metalloproteinases (MMP), tissue inhibitors of MMP-2 (TIMP-2) and urokinase plasminogen activator (uPA) in synovial fluid from dogs with spontaneously occurring stifle (knee) instability in a single hind limb resulting from acute cranial cruciate ligament (CCL) injury. Two groups of 12 dogs were fed diets from 1 week prior to surgery on the affected knee to 56 days post-surgery. The fish oil and control diets provided 90 and 4.5 mg, respectively, of combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/kg body weight per day. Plasma and synovial fluid, from both surgical and nonsurgical knee joints, were obtained at start of the diet (-7), surgery day (0) and 7, 14, 28 and 56 days post-surgery. Plasma total EPA and DHA were significantly increased, and plasma total arachidonic acid (AA) was significantly decreased by the fish oil diet. In synovial fluid from the nonsurgical knee, fish oil treatment significantly decreased proMMP-2 expression at Days 7 and 14, and proMMP-9 expression at Day 56, and uPA activity at 28 days and significantly increased TIMP-2 expression at Days 7 and 28. There were no differences in MMP expression or activity, TIMP-2 expression and uPA activity in the surgical joint synovial fluid at any time throughout the study. These results suggest that dietary fish oil may exert beneficial effects on synovial fluid MMP and TIMP-2 equilibrium in the uninjured stifle of dogs with unilateral CCL injury.

  17. LANDSAT-2 and LANDSAT-3 Flight evaluation report

    NASA Technical Reports Server (NTRS)

    Winchester, T. W.

    1978-01-01

    Flight performance analysis of LANDSAT 2 and LANDSAT 3 are presented for the period July 1978 to October 1978. Spacecraft operations and orbital parameters are summarized for each spacecraft. Data are provided on the performance and operation of the following subsystems onboard the spacecraft: power; attitude control; command/clock; telemetry; orbit adjust; magnetic moment compensating assembly; unified S band/premodulation processor; electrical interface; thermal narrowband tape recorders; wideband telemetry; attitude measurement sensor; wideband video tape recorders; return beam vidicon; multispectral scanner subsystem; and data collections.

  18. Function algorithms for MPP scientific subroutines, volume 1

    NASA Technical Reports Server (NTRS)

    Gouch, J. G.

    1984-01-01

    Design documentation and user documentation for function algorithms for the Massively Parallel Processor (MPP) are presented. The contract specifies development of MPP assembler instructions to perform the following functions: natural logarithm; exponential (e to the x power); square root; sine; cosine; and arctangent. To fulfill the requirements of the contract, parallel array and solar implementations for these functions were developed on the PDP11/34 Program Development and Management Unit (PDMU) that is resident at the MPP testbed installation located at the NASA Goddard facility.

  19. The high energy astronomy observatories

    NASA Technical Reports Server (NTRS)

    Neighbors, A. K.; Doolittle, R. F.; Halpers, R. E.

    1977-01-01

    The forthcoming NASA project of orbiting High Energy Astronomy Observatories (HEAO's) designed to probe the universe by tracing celestial radiations and particles is outlined. Solutions to engineering problems concerning HEAO's which are integrated, yet built to function independently are discussed, including the onboard digital processor, mirror assembly and the thermal shield. The principle of maximal efficiency with minimal cost and the potential capability of the project to provide explanations to black holes, pulsars and gamma-ray bursts are also stressed. The first satellite is scheduled for launch in April 1977.

  20. Commercial truck driver fatigue, alertness, and countermeasures survey

    DOT National Transportation Integrated Search

    2011-08-01

    This report presents the test plan for collecting and analyzing cost and benefit data for the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) and CRD P...

  1. Improvements in Symbol Sign Design To Aid Older Drivers

    DOT National Transportation Integrated Search

    2012-08-01

    This report presents the Traffic System Data Test Plan for the national evaluation of the Los Angeles County Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) Pr...

  2. Risk-based evaluation of commercial motor vehicle roadside violations : process and results

    DOT National Transportation Integrated Search

    2010-09-01

    This report provides an analytic framework for evaluating the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) and CRD Programs. The Atlanta CRD project...

  3. Emergency contraception: which is the best?

    PubMed

    Mittal, Suneeta

    2016-12-01

    Emergency contraception is a safe and effective method to prevent an unwanted pregnancy after an unprotected or inadequately protected sexual intercourse. Several methods for emergency contraception (EC) are currently registered in many countries for use in an emergency to prevent a pregnancy following an unprotected, possibly fertile intercourse or after a contraceptive accident like condom rupture. Different methods have varying modes of action, time frame of efficacy, dosage schedule and unwanted effects. Since several methods are available it is important to decide the best method. In this article the available literature on emergency contraception has been reviewed and an attempt has been made to discuss the need for emergency contraception and compare different options for emergency contraception in terms of their efficacy in pregnancy prevention, their safety profile and unwanted side effects. EC repeated use and initiating a regular method after EC use are also discussed. Emergency contraceptive methods include copper Intra-uterine devices (IUD) and different types of pills like estrogen progestin combination pill (Yuzpe Regimen), Progestin only pill (LNG), antiprogestin pill (Mifepristone), and progesterone modulator Uripristal Acetate (UPA). There is a marginal difference in the mechanism of action, efficacy including time frame and ability to protect from pregnancy with regular doses in obese women, drug interactions and side effects. These are discussed in detail. Copper IUD is the most effective emergency contraceptive with advantage of providing continued contraception. However, it cannot be used universally due to lack of infrastructure and a trained provider as well as not being suitable option for women at risk of sexually transmitted infections. Amongst different pills LNG is more effective with fewer side effects than Yuzpe regimen. LNG and UPA are comparable with similar efficacy and side effect profile. UPA has a wider window of efficacy, in LNG efficacy declines after 72 hours. UPA is more suitable for obese women. Mifepristone is effective but is registered as EC pill only in few countries and use is limited as it is also used as an abortion pill. Yuzpe regimen is the least effective of all contraceptive pills as EC, and works only till 72 hours of unprotected sex, but is useful in places where dedicated methods are not available, as it is easily accessible. Any combined pill can be used in this regimen except triphasic pill.

  4. In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells.

    PubMed Central

    de Vries, J. E.; Dinjens, W. N.; De Bruyne, G. K.; Verspaget, H. W.; van der Linden, E. P.; de Bruïne, A. P.; Mareel, M. M.; Bosman, F. T.; ten Kate, J.

    1995-01-01

    In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell lines were tumorigenic in both sites. SW1116, SW480 and SW620 did not show local invasive in the NCI-H716 and LS174T cells were both invasive in the caecum, but only NCI-H716 was invasive in the subcutis. HT29 and 5583 (S and E) cells were invasive in the caecum and from that site metastatic to the lungs and/or the liver. HT29 and 5583S cells were both invasive in the subcutis, but 5583E cells were not. Of each category of in vivo behaviour in the caecum, one cell line was further investigated with regard to invasion in vitro (into embryonic chick heart fragments), E-cadherin expression in vivo and in vitro and in vitro production of u-PA and t-PA. These parameters were chosen in view of their purported role in extracellular matrix degradation and intercellular adhesion, which are all involved in the invasive and metastatic cascade. Invasion in vitro was not predictive for invasion or metastasis in vivo. In the cell line which showed invasion in embryonic chick heart tissue, heterogeneous E-cadherin expression was observed in vitro together with a relatively high production of u-PA. The non-invasive cell lines showed in vitro homogeneous expression of E-cadherin with a relatively low production of u-PA. In vivo expression of E-cadherin was either absent or heterogeneous. We conclude that: (1) colorectal carcinoma xenografts show site-specific modification of in vivo invasive and metastatic behaviour; (2) invasion in vitro does not correlate with invasion and metastasis in vivo; (3) in vitro non-invasion might be associated with homogeneous E-cadherin expression and low production of u-PA; (4) E-cadherin expression in vitro differs from E-cadherin expression in vivo. The results support the notion that the microenvironment in which cancer cells grow is one of the factors involved in the regulation of invasive and metastatic behaviour. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7841040

  5. San Francisco urban partnership agreement, national evaluation : content analysis test plan.

    DOT National Transportation Integrated Search

    2011-06-01

    This report presents the test plan for collecting and analyzing information on outreach activities, media coverage, : and reactions of the public, policy makers, and other groups to the UPA projects for the San Francisco Urban : Partnership Agreement...

  6. Minnesota : innovative choices for congestion relief.

    DOT National Transportation Integrated Search

    2013-01-01

    All of the Minnesota UPA projects are in operation. The first project, the Transit Advantage Bus Bypass at the Highway 77/Highway 62 intersection, was implemented in December 2008. Most of the transit projects and the expansion of the existing high-o...

  7. Test Program of the "Combined Data and Power Management Infrastructure"

    NASA Astrophysics Data System (ADS)

    Eickhoff, Jens; Fritz, Michael; Witt, Rouven; Bucher, Nico; Roser, Hans-Peter

    2013-08-01

    As already published in previous DASIA papers, the University of Stuttgart, Germany, is developing an advanced 3-axis stabilized small satellite applying industry standards for command/control techniques and Onboard Software design. This satellite furthermore features an innovative hybrid architecture of Onboard Computer and Power Control and Distribution Unit. One of the main challenges was the development of an ultra-compact and performing Onboard Computer (OBC), which was intended to support an RTEMS operating system, a PUS standard based Onboard Software (OBSW) and CCSDS standard based ground/space communication. The developed architecture (see [1, 2, 3]) is called a “Combined Onboard Data and Power Management Infrastructure” - CDPI. It features: The OBC processor boards based on a LEON3FT architecture - from Aeroflex Inc., USA The I/O Boards for all OBC digital interfaces to S/C equipment (digital RIU) - from 4Links Ltd. UK CCSDS TC/TM decoder/encoder boards - with same HW design as I/O boards - just with limited number of interfaces. HW from 4Links Ltd, UK, driver SW and IP-Core from Aeroflex Gaisler, SE Analog RIU functions via enhanced PCDU from Vectronic Aerospace, D OBC reconfiguration unit functions via Common Controller - here in PCDU [4] The CDPI overall assembly is meanwhile complete and a exhaustive description can be found in [5]. The EM test campaign including the HW/SW compatibility testing is finalized. This comprises all OBC EM units, OBC EM assembly and the EM PCDU. The unit test program for the FM Processor-Boards and Power-Boards of the OBC are completed and the unit tests of FM I/O-Boards and CCSDS-Boards have been completed by 4Links at the assembly house. The subsystem tests of the assembled OBC also are completed and the overall System tests of the CDPI with system reconfiguration in diverse possible FDIR cases also reach the last steps. Still ongoing is the subsequent integration of the CDPI with the satellite's avionics components encompassing TTC, AOCS, Power and Payload Control. This paper provides a full picture of the test campaign. Further details can be taken from

  8. Development of an Ion Thruster and Power Processor for New Millennium's Deep Space 1 Mission

    NASA Technical Reports Server (NTRS)

    Sovey, James S.; Hamley, John A.; Haag, Thomas W.; Patterson, Michael J.; Pencil, Eric J.; Peterson, Todd T.; Pinero, Luis R.; Power, John L.; Rawlin, Vincent K.; Sarmiento, Charles J.; hide

    1997-01-01

    The NASA Solar Electric Propulsion Technology Applications Readiness Program (NSTAR) will provide a single-string primary propulsion system to NASA's New Millennium Deep Space 1 Mission which will perform comet and asteroid flybys in the years 1999 and 2000. The propulsion system includes a 30-cm diameter ion thruster, a xenon feed system, a power processing unit, and a digital control and interface unit. A total of four engineering model ion thrusters, three breadboard power processors, and a controller have been built, integrated, and tested. An extensive set of development tests has been completed along with thruster design verification tests of 2000 h and 1000 h. An 8000 h Life Demonstration Test is ongoing and has successfully demonstrated more than 6000 h of operation. In situ measurements of accelerator grid wear are consistent with grid lifetimes well in excess of the 12,000 h qualification test requirement. Flight hardware is now being assembled in preparation for integration, functional, and acceptance tests.

  9. The Fermilab lattice supercomputer project

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fischler, M.; Atac, R.; Cook, A.

    1989-02-01

    The ACPMAPS system is a highly cost effective, local memory MIMD computer targeted at algorithm development and production running for gauge theory on the lattice. The machine consists of a compound hypercube of crates, each of which is a full crossbar switch containing several processors. The processing nodes are single board array processors based on the Weitek XL chip set, each with a peak power of 20 MFLOPS and supported by 8 MBytes of data memory. The system currently being assembled has a peak power of 5 GFLOPS, delivering performance at approximately $250/MFLOP. The system is programmable in C andmore » Fortran. An underpinning of software routines (CANOPY) provides an easy and natural way of coding lattice problems, such that the details of parallelism, and communication and system architecture are transparent to the user. CANOPY can easily be ported to any single CPU or MIMD system which supports C, and allows the coding of typical applications with very little effort. 3 refs., 1 fig.« less

  10. Performance tuning of N-body codes on modern microprocessors: I. Direct integration with a hermite scheme on x86_64 architecture

    NASA Astrophysics Data System (ADS)

    Nitadori, Keigo; Makino, Junichiro; Hut, Piet

    2006-12-01

    The main performance bottleneck of gravitational N-body codes is the force calculation between two particles. We have succeeded in speeding up this pair-wise force calculation by factors between 2 and 10, depending on the code and the processor on which the code is run. These speed-ups were obtained by writing highly fine-tuned code for x86_64 microprocessors. Any existing N-body code, running on these chips, can easily incorporate our assembly code programs. In the current paper, we present an outline of our overall approach, which we illustrate with one specific example: the use of a Hermite scheme for a direct N2 type integration on a single 2.0 GHz Athlon 64 processor, for which we obtain an effective performance of 4.05 Gflops, for double-precision accuracy. In subsequent papers, we will discuss other variations, including the combinations of N log N codes, single-precision implementations, and performance on other microprocessors.

  11. Automatic maintenance payload on board of a Mexican LEO microsatellite

    NASA Astrophysics Data System (ADS)

    Vicente-Vivas, Esaú; García-Nocetti, Fabián; Mendieta-Jiménez, Francisco

    2006-02-01

    Few research institutions from Mexico work together to finalize the integration of a technological demonstration microsatellite called Satex, aiming the launching of the first ever fully designed and manufactured domestic space vehicle. The project is based on technical knowledge gained in previous space experiences, particularly in developing GASCAN automatic experiments for NASA's space shuttle, and in some support obtained from the local team which assembled the México-OSCAR-30 microsatellites. Satex includes three autonomous payloads and a power subsystem, each one with a local microcomputer to provide intelligent and dedicated control. It also contains a flight computer (FC) with a pair of full redundancies. This enables the remote maintenance of processing boards from the ground station. A fourth communications payload depends on the flight computer for control purposes. A fifth payload was decided to be developed for the satellite. It adds value to the available on-board computers and extends the opportunity for a developing country to learn and to generate domestic space technology. Its aim is to provide automatic maintenance capabilities for the most critical on-board computer in order to achieve continuous satellite operations. This paper presents the virtual computer architecture specially developed to provide maintenance capabilities to the flight computer. The architecture is periodically implemented by software with a small amount of physical processors (FC processors) and virtual redundancies (payload processors) to emulate a hybrid redundancy computer. Communications among processors are accomplished over a fault-tolerant LAN. This allows a versatile operating behavior in terms of data communication as well as in terms of distributed fault tolerance. Obtained results, payload validation and reliability results are also presented.

  12. Development Of A Three-Dimensional Circuit Integration Technology And Computer Architecture

    NASA Astrophysics Data System (ADS)

    Etchells, R. D.; Grinberg, J.; Nudd, G. R.

    1981-12-01

    This paper is the first of a series 1,2,3 describing a range of efforts at Hughes Research Laboratories, which are collectively referred to as "Three-Dimensional Microelectronics." The technology being developed is a combination of a unique circuit fabrication/packaging technology and a novel processing architecture. The packaging technology greatly reduces the parasitic impedances associated with signal-routing in complex VLSI structures, while simultaneously allowing circuit densities orders of magnitude higher than the current state-of-the-art. When combined with the 3-D processor architecture, the resulting machine exhibits a one- to two-order of magnitude simultaneous improvement over current state-of-the-art machines in the three areas of processing speed, power consumption, and physical volume. The 3-D architecture is essentially that commonly referred to as a "cellular array", with the ultimate implementation having as many as 512 x 512 processors working in parallel. The three-dimensional nature of the assembled machine arises from the fact that the chips containing the active circuitry of the processor are stacked on top of each other. In this structure, electrical signals are passed vertically through the chips via thermomigrated aluminum feedthroughs. Signals are passed between adjacent chips by micro-interconnects. This discussion presents a broad view of the total effort, as well as a more detailed treatment of the fabrication and packaging technologies themselves. The results of performance simulations of the completed 3-D processor executing a variety of algorithms are also presented. Of particular pertinence to the interests of the focal-plane array community is the simulation of the UNICORNS nonuniformity correction algorithms as executed by the 3-D architecture.

  13. Design of an ITS-Level advanced traffic management system: a human factors perspective

    DOT National Transportation Integrated Search

    2012-07-01

    This report presents the Ridesharing Data Test Plan for the national evaluation of the Los Angeles (L.A.) County Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA...

  14. Eye-activity measures of fatigue and napping as a fatigue countermeasure : tech brief.

    DOT National Transportation Integrated Search

    2011-08-01

    This report presents the test plan for collecting and analyzing safety data for the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) and CRD Programs. T...

  15. Miami urban partnership agreement (UPA) Pines Boulevard transit signal priority evaluation .report.

    DOT National Transportation Integrated Search

    2011-09-01

    The Miami Urban Partnership Agreement included the conversion of high occupancy vehicle (HOV) lanes on I-95 to high occupancy toll : (HOT) lanes and additional express bus service. It also included funding for the installation of transit signal prior...

  16. Petascale self-consistent electromagnetic computations using scalable and accurate algorithms for complex structures

    NASA Astrophysics Data System (ADS)

    Cary, John R.; Abell, D.; Amundson, J.; Bruhwiler, D. L.; Busby, R.; Carlsson, J. A.; Dimitrov, D. A.; Kashdan, E.; Messmer, P.; Nieter, C.; Smithe, D. N.; Spentzouris, P.; Stoltz, P.; Trines, R. M.; Wang, H.; Werner, G. R.

    2006-09-01

    As the size and cost of particle accelerators escalate, high-performance computing plays an increasingly important role; optimization through accurate, detailed computermodeling increases performance and reduces costs. But consequently, computer simulations face enormous challenges. Early approximation methods, such as expansions in distance from the design orbit, were unable to supply detailed accurate results, such as in the computation of wake fields in complex cavities. Since the advent of message-passing supercomputers with thousands of processors, earlier approximations are no longer necessary, and it is now possible to compute wake fields, the effects of dampers, and self-consistent dynamics in cavities accurately. In this environment, the focus has shifted towards the development and implementation of algorithms that scale to large numbers of processors. So-called charge-conserving algorithms evolve the electromagnetic fields without the need for any global solves (which are difficult to scale up to many processors). Using cut-cell (or embedded) boundaries, these algorithms can simulate the fields in complex accelerator cavities with curved walls. New implicit algorithms, which are stable for any time-step, conserve charge as well, allowing faster simulation of structures with details small compared to the characteristic wavelength. These algorithmic and computational advances have been implemented in the VORPAL7 Framework, a flexible, object-oriented, massively parallel computational application that allows run-time assembly of algorithms and objects, thus composing an application on the fly.

  17. GaAs Supercomputing: Architecture, Language, And Algorithms For Image Processing

    NASA Astrophysics Data System (ADS)

    Johl, John T.; Baker, Nick C.

    1988-10-01

    The application of high-speed GaAs processors in a parallel system matches the demanding computational requirements of image processing. The architecture of the McDonnell Douglas Astronautics Company (MDAC) vector processor is described along with the algorithms and language translator. Most image and signal processing algorithms can utilize parallel processing and show a significant performance improvement over sequential versions. The parallelization performed by this system is within each vector instruction. Since each vector has many elements, each requiring some computation, useful concurrent arithmetic operations can easily be performed. Balancing the memory bandwidth with the computation rate of the processors is an important design consideration for high efficiency and utilization. The architecture features a bus-based execution unit consisting of four to eight 32-bit GaAs RISC microprocessors running at a 200 MHz clock rate for a peak performance of 1.6 BOPS. The execution unit is connected to a vector memory with three buses capable of transferring two input words and one output word every 10 nsec. The address generators inside the vector memory perform different vector addressing modes and feed the data to the execution unit. The functions discussed in this paper include basic MATRIX OPERATIONS, 2-D SPATIAL CONVOLUTION, HISTOGRAM, and FFT. For each of these algorithms, assembly language programs were run on a behavioral model of the system to obtain performance figures.

  18. Use of effective contraception 6 months after emergency contraception with a copper intrauterine device or ulipristal acetate - a prospective observational cohort study.

    PubMed

    Envall, Niklas; Groes Kofoed, Nina; Kopp-Kallner, Helena

    2016-08-01

    Emergency contraception must be followed by the use of an effective method of contraception in order to reduce future risk of unintended pregnancies. Provision of long-acting reversible contraception (LARC) is highly effective in this regard. The aim of our study was to compare use of an effective method of contraception 6 months following insertion of a copper intrauterine device (Cu-IUD) or intake of ulipristal acetate (UPA) for emergency contraception (EC). Women (n = 79) presenting with need for EC at an outpatient midwifery clinic chose either Cu-IUD or UPA according to preference. Follow up was 3 and 6 months later through telephone interviews. Primary outcome was use of an effective contraceptive method at the 6-month follow up. Secondary outcomes included use of an effective contraceptive method at 3 months follow up and acceptability of Cu-IUD. A total of 30/36 (83.3%) women who opted for Cu-IUD for EC used an effective contraceptive method 6 months after their first visit compared with 18/31 (58.1%) women who opted for UPA (p = 0.03). In the Cu-IUD group 28/36 (77.8%) were still using Cu-IUD at 6 months and 31/36 (86%) stated that they would recommend the Cu-IUD to others as an EC method. Significantly more women who chose Cu-IUD for EC used an effective method for contraception at the 6-month follow up. The results of this study support increased use of Cu-IUDs for EC. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  19. Experience with oral emergency contraception since the OTC switch in Germany.

    PubMed

    Kiechle, Marion; Neuenfeldt, Miriam

    2017-03-01

    In March 2015, the oral emergency contraceptives levonorgestrel (LNG) and ulipristal acetate (UPA) were released from prescription-only status in Germany. The main research question is to analyse whether the OTC status of oral emergency contraceptives has an influence on the patterns of use. All information is based on searches for public domain sources on emergency contraception. Searches were made for scientific publications, statistics, and surveys. Due to additional active ingredient properties, UPA is superior to LNG in terms of ovulation-inhibiting effect. Since the OTC switch, demand for oral emergency contraceptives has risen by almost 50%, especially at weekends when sexual encounters and thus contraceptive failures are most frequent. However, the age distribution of the users has not changed as a result of the OTC switch. Doctors still play an important role in advising on emergency contraception after the removal of the prescription-only requirement. Pregnancies despite emergency contraception are terminated in more than half of the cases. In federal states with higher rates of use of the morning-after pill, fewer terminations of pregnancy were performed. As a result of the OTC switch, more women and girls use the morning-after pill after unprotected intercourse and the time between unprotected intercourse and taking the oral emergency contraceptive decreases. This is of great advantage in terms of the mechanism of action. UPA is used more frequently than LNG. Only half of all people aged between 16 and 39 years in Germany are aware of the morning-after pill and 94% of women who had a pregnancy terminated in 2015 did not use any emergency contraception after the unprotected intercourse. In the population, there is still a great need for information and education on contraception and emergency contraception.

  20. Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells

    PubMed Central

    Alfano, Daniela; Gorrasi, Anna; Li Santi, Anna; Ricci, Patrizia; Montuori, Nunzia; Selleri, Carmine; Ragno, Pia

    2015-01-01

    The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3′untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo. PMID:26082201

  1. Protease-sensitive, polymer-caged liposomes: a method for making highly targeted liposomes using triggered release.

    PubMed

    Basel, Matthew T; Shrestha, Tej B; Troyer, Deryl L; Bossmann, Stefan H

    2011-03-22

    Liposomes have become useful and well-known drug delivery vehicles because of their ability to entrap drugs without chemically modifying them and to deliver them somewhat selectively to tumorous tissue via the enhanced permeation and retention (EPR) effect. Although useful, liposome preparations are still less than ideal because of imperfect specificity, slow release kinetics in the tumor, and leakiness prior to reaching the tumor site. Cancer-associated proteases (CAPs), which are differentially expressed in tumors, have also gained traction recently as a method for tumor targeting and drug delivery. By combining the EPR effect with CAPs sensitivity, a much more specific liposome can be produced. The method described here creates an improved liposome system that can target more specifically, with faster release kinetics and lower general leaking, by deliberately producing a very unstable liposome (loaded with hyperosmotic vehicle) that is subsequently stabilized by a cross-linked polymer shell containing consensus sequences for cancer-associated proteases (protease-triggered, caged liposomes). A cholesterol-anchored, graft copolymer, composed of a short peptide sequence for urokinase plasminogen activator (uPA) and poly(acrylic acid), was synthesized and incorporated into liposomes prepared at high osmolarities. Upon cross-linking of the polymers, the protease-triggered, caged liposomes showed significant resistance to osmotic swelling and leaking of contents. Protease-triggered, caged liposomes also showed significant and substantial differential release of contents in the presence of uPA, while bare liposomes showed no differential effect in the presence of uPA. Thus a protease-sensitive liposome system with fast release kinetics was developed that could be used for more specific targeting to tumors.

  2. A needs index for mental health care.

    PubMed

    Glover, G R; Robin, E; Emami, J; Arabscheibani, G R

    1998-02-01

    The study aimed to develop a mental illness needs index to help local managers, district purchasers and national policy makers in allocating resources. Formulae were developed by regression analysis using 1991 census data to predict the period prevalence of acute psychiatric admission from electoral wards. Census variables used were chosen on the basis of an established association with mental illness rates. Data from one English Health Service region were analysed for patterns common to wards at hospital catchment area level and patterns common to district health authorities at regional level. The North East Thames region was chosen as the setting for the study, with 7096 patients being admitted during 1991. In most, but not all, catchment areas reasonable prediction of the pattern of admission prevalence was possible using the variables chosen. However, different population characteristics predicted admission prevalence in rural and urban areas. Prediction methods based on one or two variables are thus unlikely to work in both settings. A Mental Illness Needs Index (MINI) based on social isolation, poverty, unemployment, permanent sickness and temporary and insecure housing predicted differences in admission prevalence between wards at catchment area level better than Jarman's Underprivileged Area (UPA) score [1] and between districts at regional level better than the UPA score and comparably to the York Psychiatric Index [2] (adjusted r2 at regional level (MINI 0.82, UPA 0.53, York index 0.70). District admission prevalence rates vary by a factor of three between rural and inner city areas; this difference may not fully reflect the variation in the cost of providing care. It did not prove possible to incorporate factors related to bed availability in the models used; reasons for this are discussed. Data covering other aspects of mental health care in addition to hospital admission are needed for more satisfactory modelling.

  3. The Effect of Levonorgestrel on Fibrinolytic Factors in Human Endometrial Endothelial Cells.

    PubMed

    Pakrashi, Tarita; Taylor, Joelle E; Nelson, Ashley; Archer, David F; Jacot, Terry

    2016-11-01

    The levonorgestrel-releasing intrauterine system is considered a highly effective treatment of heavy menstrual bleeding (HMB). While LNG has established effects on the stromal and glandular compartments of the endometrial tissue, its effect on the endometrial endothelial cells has not been investigated. We examined whether LNG regulates fibrinolytic factors, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) secreted by human endometrial endothelial cells (HEECs) and determined the steroid receptor through which LNG exerts its effect on the endothelium. The HEECs were treated with LNG or progesterone and levels of tPA and plasminogen activator inhibitor 1 (PAI-1) measured. The HEECs were specifically examined for the presence of androgen receptors through Western blot. Levonorgestrel ± flutamide were added to HEECs and the levels of tPA and uPA were examined. An enzyme-linked immunosorbent assay performed on culture media confirmed a statistically significant decrease in tPA levels in cells treated with LNG (77.80% ± 8.0% of control; n = 5, P < .05 vs control) but not progesterone. The androgen receptor (110 kDa) was detected in HEEC lysates. The decrease in tPA was blocked by the addition of flutamide (101.3% ± 16% of control), a classic nonsteroidal androgen receptor blocker. There was no change in uPA or PAI-1 levels in cells treated with LNG. Levonorgestrel decreases tPA levels through the androgen receptor in HEECs. Thus, LNG inhibits tPA secretion by the endometrial endothelial cell. This response suggests reduction in HMB with LNG-IUS could reflect an LNG-mediated promotion of hemostasis. © The Author(s) 2016.

  4. Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress

    PubMed Central

    Tian, Runxia; Wong, Jenny S.; He, John C.; Campbell, Kirk N.

    2016-01-01

    Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA). In vivo inhibition of uPA mitigates Plg activation and development of FSGS in several proteinuric models of renal disease including 5/6 nephrectomy. Here, we show that Plg is markedly increased in the urine in two murine models of proteinuric kidney disease associated with podocyte injury: Tg26 HIV-associated nephropathy and the Cd2ap−/− model of FSGS. We show that human podocytes express uPA and three Plg receptors: uPAR, tPA, and Plg-RKT. We demonstrate that Plg treatment of podocytes specifically upregulates NADPH oxidase isoforms NOX2/NOX4 and increases production of mitochondrial-dependent superoxide anion (O2−) that promotes endothelin-1 synthesis. Plg via O2− also promotes expression of the B scavenger receptor CD36 and subsequent increased intracellular cholesterol uptake resulting in podocyte apoptosis. Taken together, our findings suggest that following disruption of the glomerular filtration barrier at the onset of proteinuric disease, podocytes are exposed to Plg resulting in further injury mediated by oxidative stress. We suggest that chronic exposure to Plg could serve as a “second hit” in glomerular disease and that Plg is potentially an attractive target for therapeutic intervention. PMID:27335373

  5. Regulation of intrapleural fibrinolysis by urokinase-α-macroglobulin complexes in tetracycline-induced pleural injury in rabbits

    PubMed Central

    Mazar, Andrew P.; Koenig, Kathy; Kurdowska, Anna K.; Idell, Steven

    2009-01-01

    The proenzyme single-chain urokinase plasminogen activator (scuPA) more effectively resolved intrapleural loculations in rabbits with tetracycline (TCN)-induced loculation than a range of clinical doses of two-chain uPA (Abbokinase) and demonstrated a trend toward greater efficacy than single-chain tPA (Activase) (Idell S et al., Exp Lung Res 33: 419, 2007.). scuPA more slowly generates durable intrapleural fibrinolytic activity than Abbokinase or Activase, but the interactions of these agents with inhibitors in pleural fluids (PFs) have been poorly understood. PFs from rabbits with TCN-induced pleural injury treated with intrapleural scuPA, its inactive Ser195Ala mutant, Abbokinase, Activase, or vehicle, were analyzed to define the mechanism by which scuPA induces durable fibrinolysis. uPA activity was elevated in PFs of animals treated with scuPA, correlated with the ability to clear pleural loculations, and resisted (70–80%) inhibition by PAI-1. α-macroglobulin (αM) but not urokinase receptor complexes immunoprecipitated from PFs of scuPA-treated rabbits retained uPA activity that resists PAI-1 and activates plasminogen. Conversely, little plasminogen activating or enzymatic activity resistant to PAI-1 was detectable in PFs of rabbits treated with Abbokinase or Activase. Consistent with these findings, PAI-1 interacts with scuPA much slower than with Activase or Abbokinase in vitro. An equilibrium between active and inactive scuPA (kon = 4.3 h−1) limits the rate of its inactivation by PAI-1, favoring formation of complexes with αM. These observations define a newly recognized mechanism that promotes durable intrapleural fibrinolysis via formation of αM/uPA complexes. These complexes promote uPA-mediated plasminogen activation in scuPA-treated rabbits with TCN-induced pleural injury. PMID:19666776

  6. HIF-2α Expression Regulates Sprout Formation into 3D Fibrin Matrices in Prolonged Hypoxia in Human Microvascular Endothelial Cells.

    PubMed

    Nauta, Tessa D; Duyndam, Monique C A; Weijers, Ester M; van Hinsbergh, Victor M W; Koolwijk, Pieter

    2016-01-01

    During short-term hypoxia, Hypoxia Inducible Factors (particular their subunits HIF-1α and HIF-2α) regulate the expression of many genes including the potent angiogenesis stimulator VEGF. However, in some pathological conditions chronic hypoxia occurs and is accompanied by reduced angiogenesis. We investigated the effect of prolonged hypoxia on the proliferation and sprouting ability of human microvascular endothelial cells and the involvement of the HIFs and Dll4/Notch signaling. Human microvascular endothelial cells (hMVECs), cultured at 20% oxygen for 14 days and seeded on top of 3D fibrin matrices, formed sprouts when stimulated with VEGF-A/TNFα. In contrast, hMVECs precultured at 1% oxygen for 14 days were viable and proliferative, but did not form sprouts into fibrin upon VEGF-A/TNFα stimulation at 1% oxygen. Silencing of HIF-2α with si-RNA partially restored the inhibition of endothelial sprouting, whereas HIF-1α or HIF-3α by si-RNA had no effect. No involvement of Dll4/Notch pathway in the inhibitory effect on endothelial sprouting by prolonged hypoxia was found. In addition, hypoxia decreased the production of urokinase-type plasminogen activator (uPA), needed for migration and invasion, without a significant effect on its inhibitor PAI-1. This was independent of HIF-2α, as si-HIF-2α did not counteract uPA reduction. Prolonged culturing of hMVECs at 1% oxygen inhibited endothelial sprouting into fibrin. Two independent mechanisms contribute. Silencing of HIF-2α with si-RNA partially restored the inhibition of endothelial sprouting pointing to a HIF-2α-dependent mechanism. In addition, reduction of uPA contributed to reduced endothelial tube formation in a fibrin matrix during prolonged hypoxia.

  7. Contemporary approaches to congestion pricing : lessons learned from the national evaluation of congestion pricing strategies at six sites.

    DOT National Transportation Integrated Search

    2015-08-01

    This document represents the final report of the national evaluation of congestion reduction strategies at six sites that received federal funding under the Urban Partnership Agreement (UPA) and Congestion Reduction Demonstration (CRD) programs. The ...

  8. JPRS Report, Soviet Union, Political Affairs.

    DTIC Science & Technology

    1988-12-06

    bilingual and trilingual national literatures (Belgian, Swiss...) which testify to the fact that the people themselves are heterogeneous in their lan...Schools were opened and commercial and medical JPRS-UPA-88-056 06 December 1988 37 REGIONAL ISSUES services were improved. At the borderline of the

  9. Anti-Urokinase Receptor Antisense Oligonucleotide (uPAR-aODN) to Prevent and Cure Long-Term Space Exploration-Related Retinal Pathological Angiogenesis

    NASA Astrophysics Data System (ADS)

    Lazzarano, Stefano; Lulli, Matteo; Fibbi, Gabriella; Margheri, Francesca; Papucci, Laura; Serrati, Simona; Witort, Ewa; Chilla, Anastasia; Lapucci, Andrea; Donnini, Martino; Quaglierini, Paolo; Romiti, Alice; Specogna, Rebecca; Del Rosso, Mario; Capaccioli, Sergio

    2008-06-01

    Angiogenesis underlies a variety of physiological processes and its possible deregulation during long term space exploration needs to be investigated. Angiogenesis is a multistep process of new blood capillary formation, where degradation of the extracellular matrix (ECM) by proteolytic enzymes, including uPA (urokinase plasminogen activator) and opening the way to migration of endothelial cells (EC), is critical. Plasminogen activation system regulates angiogenesis by both uPA-driven ECM degradation and uPA receptor (uPAR). Microgravity and low dose irradiations promote tissue neoangiogeenesis and neovascularization is often common occurence in ophthalmologic pathologies. We have designed and patented the uPAR antisense oligonucleotide (aODN) and evaluated its antiangiogenetic activity by EC cellular migration and capillary morphogenesis assays. The uPAR aODN treatment caused a 75% inhibition of human microvascular EC migration and a complete inhibition of capillary morphogenesis, suggesting its therapeutic application to prevent neoangiogenesis-related ophthalmologic pathologies during space exploration.

  10. A personal computer-based, multitasking data acquisition system

    NASA Technical Reports Server (NTRS)

    Bailey, Steven A.

    1990-01-01

    A multitasking, data acquisition system was written to simultaneously collect meteorological radar and telemetry data from two sources. This system is based on the personal computer architecture. Data is collected via two asynchronous serial ports and is deposited to disk. The system is written in both the C programming language and assembler. It consists of three parts: a multitasking kernel for data collection, a shell with pull down windows as user interface, and a graphics processor for editing data and creating coded messages. An explanation of both system principles and program structure is presented.

  11. FTIR spectrometer with solid-state drive system

    DOEpatents

    Rajic, Slobodan; Seals, Roland D.; Egert, Charles M.

    1999-01-01

    An FTIR spectrometer (10) and method using a solid-state drive system with thermally responsive members (27) that are subject to expansion upon heating and to contraction upon cooling. Such members (27) are assembled in the device (10) so as to move an angled, reflective surface (22) a small distance. The sample light beam (13) is received at a detector (24) along with a reference light beam (13) and there it is combined into a resulting signal. This allows the "interference" between the two beams to occur for spectral analysis by a processor (29).

  12. Software for System for Controlling a Magnetically Levitated Rotor

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R. (Inventor)

    2004-01-01

    In a rotor assembly having a rotor supported for rotation by magnetic bearings, a processor controlled by software or firmware controls the generation of force vectors that position the rotor relative to its bearings in a 'bounce' mode in which the rotor axis is displaced from the principal axis defined between the bearings and a 'tilt' mode in which the rotor axis is tilted or inclined relative to the principal axis. Waveform driven perturbations are introduced to generate force vectors that excite the rotor in either the 'bounce' or 'tilt' modes.

  13. Landsat-1 and Landsat-2 evaluation report, 23 January 1975 to 23 April 1975

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A description of the work accomplished with the Landsat-1 and Landsat-2 satellites during the period 23 Jan. - 23 Apr. 1975 was presented. The following information was given for each satellite: operational summary, orbital parameters, power subsystem, attitude control subsystem, command/clock subsystem, telemetry subsystem, orbit adjust subsystem, magnetic moment compensating assembly, unified S-band/premodulation processor, electrical interface subsystem, thermal subsystem, narrowband tape recorders, wideband telemetry subsystem, attitude measurement sensor, wideband video tape recorders, return beam vidicon, multispectral scanner subsystem, and data collection subsystem.

  14. System for Controlling a Magnetically Levitated Rotor

    NASA Technical Reports Server (NTRS)

    Morrison, Carlos R. (Inventor)

    2006-01-01

    In a rotor assembly having a rotor supported for rotation by magnetic bearings, a processor controlled by software or firmware controls the generation of force vectors that position the rotor relative to its bearings in a "bounce" mode in which the rotor axis is displaced from the principal axis defined between the bearings and a "tilt" mode in which the rotor axis is tilted or inclined relative to the principal axis. Waveform driven perturbations are introduced to generate force vectors that excite the rotor in either the "bounce" or "tilt" modes.

  15. TRACALS Evaluation Report. Initial Evaluation Report (AN/GPN-24) Nellis AFB, Nevada, 10 December 1979-6 Mar 1980.

    DTIC Science & Technology

    1980-05-16

    Scott AFB, IL 62225 1 1842 EEG /EEIT, Scott AFB, IL 62225 1 1843 EES/EIELT, H-ickam AFB, H-I 96853 1 1844 EES/EIELT, Griffiss AFB, NY 13441 I HQ AFCC/DAPL...Time Control TDC Target Data Computer TO Technical Order TRACALS Traffic Cortrol and Landing Systems TSDA Transfer Switch Drawer Assembly TWT Traveling...the designated targets. The error detector outputs are fed to the TDC to update the beam position data during the next track interval. (b) Processor

  16. Boxing It Up-a Cross-curricular Approach.

    ERIC Educational Resources Information Center

    Till, Wesley

    1996-01-01

    Reports on a class project that examined the manufacture of boxes and packaging to teach about design and technology. The class discovered basic manufacturing techniques by examining and disassembling cereal boxes. Field trips to stores provided more examples. Appraises the children's final projects and discusses acquiring materials. (MJP)

  17. Monoclonal Antibody Testing for Cancer Metastasis

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Malignant cells are characterized by the ability to invade surrounding normal tissues. Tumor invasion is abetted by proteolytic enzymes that have been correlated with recurrent disease and metastasis. These enzymes are involved in a cascade of proteolytic interactions with other enzymes and inhibitors which allow cancer cells to dissolve surrounding extracellular matrix, thereby enabling the cells to rapidly invade adjacent tissues and migrate to metastatic sites distant from the primary tumor. Among these proteases are the plasminogen activators (PA), collagenase IV, faminase, and in some cases cathepsin D, which together mediate key steps in the invasion process of metastasis. Cells which have the selective advantage for invasion and metastasis are those capable of regulating their proteolytic activity and proliferation. Cells in the process of invasion would be probably down-regulated for proliferation, but subsequent to attachment and adhesion at a distant site, would then be in a proliferative mode, up-regulating DNA replication. Urokinase (uPA) can be present in the tissues in several molecular forms. The inactive proenzyme is a single chain protein (scuPA) that is cleaved at Lys. 158 to form the double chain, high molecular weight active form (HMW-uPA) of 54 kD. A low molecular weight form (LMW-uPA) can also be produced by cleavage of the HMW-U PA at Lys. 135 - Lys. 136 giving a 35 kD active enzyme. Recently, it has been shown that the HMW active form of urokinase, bound to the tumor cell membrane, is responsible for the local lysis of the extracellular matrix, hence the tissue invasion mechanism for metastasis (Andreasen et al, 19861. Receptor- (membrane) bound uPA is twice as efficient (catalytically) as free fluid-phase uPA. Tho unbound uPA and the LMW form is not responsible for most of the local dissolution of extracellular matrix in the immediate vicinity of the metastatic tumor cell. High levels of urokinase (greater than 3.49 ng/mg of total protein) extracted from breast tumor tissues have recently been shown, together with plasminogen activator inhibitor 1 (PAI-1), to be a good prognostic indicator for high risk of recurrence and shorter patient survival times. In this project, we have attempted to develop immunocytochemical methodologies for the clinical assessment of the expression of urokinase plasminogen activator, which has been implicated to be important for initial steps in tumor invasion, and to relate it to cell proliferation and DNA replication at the single-cell level.

  18. Airborne Optical Communications Demonstrator Design And Preflight Test Results

    NASA Technical Reports Server (NTRS)

    Biswas, Abhijit; Page, N.; Neal, J.; Zhu, D.; Wright, M.; Ovtiz, G.; Farr, W. H.; Hernnzati, H.

    2005-01-01

    A second generation optical communications demonstrator (OCD-2) intended for airborne applications like air-to-ground and air-to-air optical links is under development at JPL. This development provides the capability for unidirectional high data rate (2.5-Gbps) transmission at 1550-nm, with the ability to receive an 810-nm beacon to aid acquisition pointing and tracking. The transmitted beam width is nominally 200-(micro)rad. A 3x3 degree coarse field-of-view (FOV) acquisition sensor with a much smaller 3-mrad FOV tracking sensor is incorporated. The OCD-2 optical head will be integrated to a high performance gimbal turret assembly capable of providing pointing stability of 5- microradians from an airborne platform. Other parts of OCD-2 include a cable harness, connecting the optical head in the gimbal turret assembly to a rugged electronics box. The electronics box will house: command and control processors, laser transmitter, data-generation-electronics, power conversion/distribution hardware and state-of-health monitors. The entire assembly will be integrated and laboratory tested prior to a planned flight demonstrations.

  19. Power estimation on functional level for programmable processors

    NASA Astrophysics Data System (ADS)

    Schneider, M.; Blume, H.; Noll, T. G.

    2004-05-01

    In diesem Beitrag werden verschiedene Ansätze zur Verlustleistungsschätzung von programmierbaren Prozessoren vorgestellt und bezüglich ihrer Übertragbarkeit auf moderne Prozessor-Architekturen wie beispielsweise Very Long Instruction Word (VLIW)-Architekturen bewertet. Besonderes Augenmerk liegt hierbei auf dem Konzept der sogenannten Functional-Level Power Analysis (FLPA). Dieser Ansatz basiert auf der Einteilung der Prozessor-Architektur in funktionale Blöcke wie beispielsweise Processing-Unit, Clock-Netzwerk, interner Speicher und andere. Die Verlustleistungsaufnahme dieser Bl¨ocke wird parameterabhängig durch arithmetische Modellfunktionen beschrieben. Durch automatisierte Analyse von Assemblercodes des zu schätzenden Systems mittels eines Parsers können die Eingangsparameter wie beispielsweise der erzielte Parallelitätsgrad oder die Art des Speicherzugriffs gewonnen werden. Dieser Ansatz wird am Beispiel zweier moderner digitaler Signalprozessoren durch eine Vielzahl von Basis-Algorithmen der digitalen Signalverarbeitung evaluiert. Die ermittelten Schätzwerte für die einzelnen Algorithmen werden dabei mit physikalisch gemessenen Werten verglichen. Es ergibt sich ein sehr kleiner maximaler Schätzfehler von 3%. In this contribution different approaches for power estimation for programmable processors are presented and evaluated concerning their capability to be applied to modern digital signal processor architectures like e.g. Very Long InstructionWord (VLIW) -architectures. Special emphasis will be laid on the concept of so-called Functional-Level Power Analysis (FLPA). This approach is based on the separation of the processor architecture into functional blocks like e.g. processing unit, clock network, internal memory and others. The power consumption of these blocks is described by parameter dependent arithmetic model functions. By application of a parser based automized analysis of assembler codes of the systems to be estimated the input parameters of the Correspondence to: H. Blume (blume@eecs.rwth-aachen.de) arithmetic functions like e.g. the achieved degree of parallelism or the kind and number of memory accesses can be computed. This approach is exemplarily demonstrated and evaluated applying two modern digital signal processors and a variety of basic algorithms of digital signal processing. The resulting estimation values for the inspected algorithms are compared to physically measured values. A resulting maximum estimation error of 3% is achieved.

  20. Comprehensive Truck Size and Weight (TS&W) Study. Phase 1-synthesis, working paper 8 : logistics and truck size and weight regulations

    DOT National Transportation Integrated Search

    2012-04-01

    This report presents the Safety Data Test Plan for the national evaluation of the Los Angeles County Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) Program. T...

  1. Comprehensive Truck Size and Weight (TS&W) Study. Phase 1-synthesis, working paper 10 : enforcement and truck size and weight regulations

    DOT National Transportation Integrated Search

    2012-04-01

    This report presents the Content Analysis Test Plan for the national evaluation of the Los Angeles County Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban Partnership Agreement (UPA) Progr...

  2. Safety impacts of the I-35W improvements done under Minnesota's urban partnership agreement (UPA) project : final report.

    DOT National Transportation Integrated Search

    2017-06-01

    As part of an Urban Partnership Agreement project, the Minnesota Department of Transportation added lanes : and began operating a priced dynamic shoulder lane (PDSL) on parts of Interstate 35W. Following the opening of : these improvements, the frequ...

  3. GPS Block 2R Time Standard Assembly (TSA) architecture

    NASA Technical Reports Server (NTRS)

    Baker, Anthony P.

    1990-01-01

    The underlying philosophy of the Global Positioning System (GPS) 2R Time Standard Assembly (TSA) architecture is to utilize two frequency sources, one fixed frequency reference source and one system frequency source, and to couple the system frequency source to the reference frequency source via a sample data loop. The system source is used to provide the basic clock frequency and timing for the space vehicle (SV) and it uses a voltage controlled crystal oscillator (VCXO) with high short term stability. The reference source is an atomic frequency standard (AFS) with high long term stability. The architecture can support any type of frequency standard. In the system design rubidium, cesium, and H2 masers outputting a canonical frequency were accommodated. The architecture is software intensive. All VCXO adjustments are digital and are calculated by a processor. They are applied to the VCXO via a digital to analog converter.

  4. Control of a Glove-Based Grasp Assist Device

    NASA Technical Reports Server (NTRS)

    Bergelin, Bryan J (Inventor); Ihrke, Chris A. (Inventor); Davis, Donald R. (Inventor); Linn, Douglas Martin (Inventor); Sanders, Adam M (Inventor); Askew, R. Scott (Inventor); Laske, Evan (Inventor); Ensley, Kody (Inventor)

    2015-01-01

    A grasp assist system includes a glove and sleeve. The glove includes a digit, i.e., a finger or thumb, and a force sensor. The sensor measures a grasping force applied to an object by an operator wearing the glove. The glove contains a tendon connected at a first end to the digit. The sleeve has an actuator assembly connected to a second end of the tendon and a controller in communication with the sensor. The controller includes a configuration module having selectable operating modes and a processor that calculates a tensile force to apply to the tendon for each of the selectable operating modes to assist the grasping force in a manner that differs for each of the operating modes. A method includes measuring the grasping force, selecting the mode, calculating the tensile force, and applying the tensile force to the tendon using the actuator assembly.

  5. Conference on Real-Time Computer Applications in Nuclear, Particle and Plasma Physics, 6th, Williamsburg, VA, May 15-19, 1989, Proceedings

    NASA Technical Reports Server (NTRS)

    Pordes, Ruth (Editor)

    1989-01-01

    Papers on real-time computer applications in nuclear, particle, and plasma physics are presented, covering topics such as expert systems tactics in testing FASTBUS segment interconnect modules, trigger control in a high energy physcis experiment, the FASTBUS read-out system for the Aleph time projection chamber, a multiprocessor data acquisition systems, DAQ software architecture for Aleph, a VME multiprocessor system for plasma control at the JT-60 upgrade, and a multiasking, multisinked, multiprocessor data acquisition front end. Other topics include real-time data reduction using a microVAX processor, a transputer based coprocessor for VEDAS, simulation of a macropipelined multi-CPU event processor for use in FASTBUS, a distributed VME control system for the LISA superconducting Linac, a distributed system for laboratory process automation, and a distributed system for laboratory process automation. Additional topics include a structure macro assembler for the event handler, a data acquisition and control system for Thomson scattering on ATF, remote procedure execution software for distributed systems, and a PC-based graphic display real-time particle beam uniformity.

  6. Bottom-up construction of artificial molecules for superconducting quantum processors

    NASA Astrophysics Data System (ADS)

    Poletto, Stefano; Rigetti, Chad; Gambetta, Jay M.; Merkel, Seth; Chow, Jerry M.; Corcoles, Antonio D.; Smolin, John A.; Rozen, Jim R.; Keefe, George A.; Rothwell, Mary B.; Ketchen, Mark B.; Steffen, Matthias

    2012-02-01

    Recent experiments on transmon qubits capacitively coupled to superconducting 3-dimensional cavities have shown coherence times much longer than transmons coupled to more traditional planar resonators. For the implementation of a quantum processor this approach has clear advantages over traditional techniques but it poses the challenge of scalability. We are currently implementing multi-qubits experiments based on a bottom-up scaling approach. First, transmon qubits are fabricated on individual chips and are independently characterized. Second, an artificial molecule is assembled by selecting a particular set of previously characterized single-transmon chips. We present recent data on a two-qubit artificial molecule constructed in this way. The two qubits are chosen to generate a strong Z-Z interaction by matching the 0-1 transition energy of one qubit with the 1-2 transition of the other. Single qubit manipulations and state tomography cannot be done with ``traditional'' single tone microwave pulses but instead specifically shaped pulses have to be simultaneously applied on both qubits. Coherence times, coupling strength, and optimal pulses for decoupling the two qubits and perform state tomography are presented

  7. Biomedical engineering tasks. [electrode development for electrocardiography and electroencephalography

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Electrocardiographic and vectorcardiographic bioinstrumentation work centered on the development of a new electrode system harness for Project Skylab. Evaluation of several silver electrode configurations proved superior impedance voltage performance for silver/silver chloride electrodes mounted flush by using a paste adhesive. A portable ECG processor has been designed and a breadboard unit has been built to sample ECG input data at a rate of 500 samples per second for arrhythmia detection. A small real time display driver program has been developed for statistical analysis on selected QPS features. Engineering work on a sleep monitoring cap assembly continued.

  8. Vaginal ring delivery of selective progesterone receptor modulators for contraception

    PubMed Central

    Jensen, Jeffrey T.

    2013-01-01

    Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) are under development to address limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing, and therefore might improve the effectiveness of contraception. The principle contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1–2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6–7 ng/mL. PMID:23040126

  9. Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer.

    PubMed

    Xiong, Ting; Liu, Xiao-Wang; Huang, Xue-Long; Xu, Xiong-Feng; Xie, Wei-Quan; Zhang, Su-Jun; Tu, Jian

    2018-05-01

    Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro . Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

  10. Peroxisome Proliferator-Activated Receptor-γ Ligands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System

    PubMed Central

    Carter, Jennifer C.; Church, Frank C.

    2011-01-01

    We investigated peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands effect on cell motility and the plasminogen activator system using normal MCF-10A and malignant MCF-10CA1 cell lines. Ciglitazone reduced both wound-induced migration and chemotaxis. However, the effect was not reversed with pretreatment of cells with the PPAR-γ-specific antagonist GW9662. Immunoblot analysis of conditioned media showed ciglitazone decreased plasminogen activator inhibitor-1 (PAI-1) in both cell lines; this effect was also unaltered by PPAR-γ antagonism. Alternatively, treatment with the ω-6 fatty acid arachidonic acid (ArA), but not the ω-3 fatty acid docosahexanoic acid, increased both MCF-10A cell migration and cell surface uPA activity. Pretreatment with a PPAR-γ antagonist reversed these effects, suggesting that ArA mediates its effect on cell motility and uPA activity through PPAR-γ activation. Collectively, the data suggest PPAR-γ ligands have a differential effect on normal and malignant cell migration and the plasminogen activation system, resulting from PPAR-γ-dependent and PPAR-γ-independent effects. PMID:22131991

  11. Inner clot diffusion and permeation during fibrinolysis.

    PubMed Central

    Diamond, S L; Anand, S

    1993-01-01

    A model of fibrinolysis was developed using multicomponent convection-diffusion equations with homogeneous reaction and heterogeneous adsorption and reaction. Fibrin is the dissolving stationary phase and plasminogen, tissue plasminogen activator (tPA), urokinase (uPA), and plasmin are the soluble mobile species. The model is based on an accurate molecular description of the fibrin fiber and protofibril structure and contains no adjustable parameters and one phenomenological parameter estimated from experiment. The model can predict lysis fronts moving across fibrin clots (fine or coarse fibers) of various densities under different administration regimes using uPA and tPA. We predict that pressure-driven permeation is the major mode of transport that allows for kinetically significant thrombolysis during clinical situations. Without permeation, clot lysis would be severely diffusion limited and would require hundreds of minutes. Adsorption of tPA to fibrin under conditions of permeation was a nonequilibrium process that tended to front load clots with tPA. Protein engineering efforts to design optimal thrombolytics will likely be affected by the permeation processes that occur during thrombolysis. PMID:8312497

  12. Inhibitory Effects of North American Wild Rice on Monocyte Adhesion and Inflammatory Modulators in Low-Density Lipoprotein Receptor-Knockout Mice.

    PubMed

    Moghadasian, Mohammed H; Zhao, Ruozhi; Ghazawwi, Nora; Le, Khuong; Apea-Bah, Franklin B; Beta, Trust; Shen, Garry X

    2017-10-18

    The present study examined the effects of wild rice on monocyte adhesion, inflammatory and fibrinolytic mediators in low-density lipoprotein receptor-knockout (LDLr-KO) mice. Male LDLr-KO mice received a cholesterol (0.06%, w/w)-supplemented diet with or without white or wild rice (60%, w/w) for 20 weeks. White rice significantly increased monocyte adhesion and abundances of monocyte chemoattractant protein-1, tissue necrosis factor-α, intracellular cell adhesion molecule-1, plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), and uPA receptor in aortae and hearts of LDLr-KO mice compared to the control diet. Wild rice inhibited monocyte adhesion to the aorta, atherosclerosis, and abundances of the inflammatory and fibrinolytic regulators in the cardiovascular tissue of LDLr-KO mice compared to white rice. White or wild rice did not significantly alter the levels of cholesterol, triglycerides, or antioxidant enzymes in plasma. The anti-atherosclerotic effect of wild rice may result from its inhibition on monocyte adhesion and inflammatory modulators in LDLr-KO mice.

  13. Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2.

    PubMed

    Finckh, U; van Hadeln, K; Müller-Thomsen, T; Alberici, A; Binetti, G; Hock, C; Nitsch, R M; Stoppe, G; Reiss, J; Gal, A

    2003-08-01

    Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin. Plasmin is involved in processing of amyloid precursor protein and degrades secreted and aggregated amyloid-beta, a hallmark of Alzheimer disease (AD). PLAU, the gene encoding uPA, maps to chromosome 10q22.2 between two regions showing linkage to late-onset AD (LOAD). We genotyped a frequent C/T single nucleotide polymorphism in codon 141 of PLAU (P141L) in 347 patients with LOAD and 291 control subjects. LOAD was associated with homozygous C/C PLAU genotype in the whole sample (chi2=15.7, P=0.00039, df 2), as well as in all sub-samples stratified by gender or APOE epsilon4 carrier status (chi2> or = 6.84, P< or =0.033, df 2). Odds ratio for LOAD due to homozygosity C/C was 1.89 (95% confidence interval 1.37-2.61). PLAU is a promising new candidate gene for LOAD, with allele C (P141) being a recessive risk allele or allele T (L141) conferring protection.

  14. Population-dynamics focussed rapid rural mapping and characterisation of the peri-urban interface of Kampala, Uganda

    PubMed Central

    Makita, K.; Fèvre, E.M.; Waiswa, C.; Bronsvoort, M.D.C.; Eisler, M.C.; Welburn, S.C.

    2010-01-01

    In developing countries, cities are rapidly expanding and urban and peri-urban agriculture (UPA) has an important role in feeding these growing urban populations; however such agriculture also carries public health risks such as zoonotic disease transmission. It is important to assess the role of UPA in food security and public health risks to make evidence-based decisions on policies. Describing and mapping the peri-urban interface (PUI) are the essential first steps for such an assessment. Kampala, the capital city of Uganda is a rapidly expanding city where the PUI has not previously been mapped or properly described. In this paper we provide a spatial representation of the entire PUI of Kampala economic zone and determine the socio-economic factors related with peri-urbanicity using a population-dynamics focussed rapid rural mapping. This fills a technical gap of rapid rural mapping and offers a simple and rapid methodology for describing the PUI which can be applied in any city in developing countries for wide range of studies. PMID:22210972

  15. Summary of Documentation for DYNA3D-ParaDyn's Software Quality Assurance Regression Test Problems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zywicz, Edward

    The Software Quality Assurance (SQA) regression test suite for DYNA3D (Zywicz and Lin, 2015) and ParaDyn (DeGroot, et al., 2015) currently contains approximately 600 problems divided into 21 suites, and is a required component of ParaDyn’s SQA plan (Ferencz and Oliver, 2013). The regression suite allows developers to ensure that software modifications do not unintentionally alter the code response. The entire regression suite is run prior to permanently incorporating any software modification or addition. When code modifications alter test problem results, the specific cause must be determined and fully understood before the software changes and revised test answers can bemore » incorporated. The regression suite is executed on LLNL platforms using a Python script and an associated data file. The user specifies the DYNA3D or ParaDyn executable, number of processors to use, test problems to run, and other options to the script. The data file details how each problem and its answer extraction scripts are executed. For each problem in the regression suite there exists an input deck, an eight-processor partition file, an answer file, and various extraction scripts. These scripts assemble a temporary answer file in a specific format from the simulation results. The temporary and stored answer files are compared to a specific level of numerical precision, and when differences are detected the test problem is flagged as failed. Presently, numerical results are stored and compared to 16 digits. At this accuracy level different processor types, compilers, number of partitions, etc. impact the results to various degrees. Thus, for consistency purposes the regression suite is run with ParaDyn using 8 processors on machines with a specific processor type (currently the Intel Xeon E5530 processor). For non-parallel regression problems, i.e., the two XFEM problems, DYNA3D is used instead. When environments or platforms change, executables using the current source code and the new resource are created and the regression suite is run. If differences in answers arise, the new answers are retained provided that the differences are inconsequential. This bootstrap approach allows the test suite answers to evolve in a controlled manner with a high level of confidence. Developers also run the entire regression suite with (serial) DYNA3D. While these results normally differ from the stored (parallel) answers, abnormal termination or wildly different values are strong indicators of potential issues.« less

  16. Comparison of potential diatom 'barcode' genes (the 18S rRNA gene and ITS, COI, rbcL) and their effectiveness in discriminating and determining species taxonomy in the Bacillariophyta.

    PubMed

    Guo, Liliang; Sui, Zhenghong; Zhang, Shu; Ren, Yuanyuan; Liu, Yuan

    2015-04-01

    Diatoms form an enormous group of photoautotrophic micro-eukaryotes and play a crucial role in marine ecology. In this study, we evaluated typical genes to determine whether they were effective at different levels of diatom clustering analysis to assess the potential of these regions for barcoding taxa. Our test genes included nuclear rRNA genes (the nuclear small-subunit rRNA gene and the 5.8S rRNA gene+ITS-2), a mitochondrial gene (cytochrome c-oxidase subunit 1, COI), a chloroplast gene [ribulose-1,5-biphosphate carboxylase/oxygenase large subunit (rbcL)] and the universal plastid amplicon (UPA). Calculated genetic divergence was highest for the internal transcribed spacer (ITS; 5.8S+ITS-2) (p-distance of 1.569, 85.84% parsimony-informative sites) and COI (6.084, 82.14%), followed by the 18S rRNA gene (0.139, 57.69%), rbcL (0.120, 42.01%) and UPA (0.050, 14.97%), which indicated that ITS and COI were highly divergent compared with the other tested genes, and that their nucleotide compositions were variable within the whole group of diatoms. Bayesian inference (BI) analysis showed that the phylogenetic trees generated from each gene clustered diatoms at different phylogenetic levels. The 18S rRNA gene was better than the other genes in clustering higher diatom taxa, and both the 18S rRNA gene and rbcL performed well in clustering some lower taxa. The COI region was able to barcode species of some genera within the Bacillariophyceae. ITS was a potential marker for DNA based-taxonomy and DNA barcoding of Thalassiosirales, while species of Cyclotella, Skeletonema and Stephanodiscus gathered in separate clades, and were paraphyletic with those of Thalassiosira. Finally, UPA was too conserved to serve as a diatom barcode. © 2015 IUMS.

  17. Enterolactone Suppresses Proliferation, Migration and Metastasis of MDA-MB-231 Breast Cancer Cells Through Inhibition of uPA Induced Plasmin Activation and MMPs-Mediated ECM Remodeling

    PubMed Central

    Mali, Aniket V; Joshi, Asavari A; Hegde, Mahabaleshwar V; Kadam, Shivajirao S

    2017-01-01

    Background: To enhance their own survival, tumor cells can manipulate their microenvironment through remodeling of the extra cellular matrix (ECM). The urokinase-type plasminogen activator (uPA) system catalyzes plasmin production which further mediates activation of matrix metalloproteinases (MMPs) and plays an important role in breast cancer invasion and metastasis through ECM remodeling. This provides a potential target for therapeutic intervention of breast cancer treatment. Enterolactone (EL) is derived from dietary flax lignans in the human body and is known to have anti-breast cancer activity. We here investigated molecular and cellular mechanisms of EL action on the uPA-plasmin-MMPs system. Methods: MTT and trypan blue dye exclusion assays, anchorage-dependent clonogenic assays and wound healing assays were carried out to study effects on cell proliferation and viability, clonogenicity and migration capacity, respectively. Real-time PCR was employed to study gene expression and gelatin zymography was used to assess MMP-2 and MMP-9 activities. All data were statistically analysed and presented as mean ± SEM values. Results: All the findings collectively demonstrated anticancer and antimetastatic potential of EL with antiproliferative, antimigratory and anticlonogenic cellular mechanisms. EL was found to exhibit multiple control of plasmin activation by down-regulating uPA expression and also up-regulating its natural inhibitor, PAI-1, at the mRNA level. Further, EL was found to down-regulate expression of MMP-2 and MMP-9 genes, and up-regulate TIMP-1 and TIMP-2; natural inhibitors of MMP-2 and MMP-9, respectively. This may be as a consequence of inhibition of plasmin activation, resulting in robust control over migration and invasion of breast cancer cells during metastasis. Conclusions: EL suppresses proliferation, migration and metastasis of MDA-MB-231 breast cancer cells by inhibiting induced ECM remodeling by the ‘uPA-plasmin-MMPs system’. PMID:28545187

  18. Curcumin Attenuates Staurosporine-Mediated Death of Retinal Ganglion Cells

    PubMed Central

    Burugula, Balabharathi; Ganesh, Bhagyalaxmi S.

    2011-01-01

    Purpose. Staurosporine (SS) causes retinal ganglion cell (RGC) death in vivo, but the underlying mechanisms have been unclear. Since previous studies on RGC-5 cells indicated that SS induces cell death by elevating proteases, this study was undertaken to investigate whether SS induces RGC loss by elevating proteases in the retina, and curcumin prevents SS-mediated death of RGCs. Methods. Transformed mouse retinal ganglion-like cells (RGC-5) were treated with 2.0 μM SS and various doses of curcumin. Two optimal doses of SS (12.5 and 100 nM) and curcumin (2.5 and 10 μM) were injected into the vitreous of C57BL/6 mice. Matrix metalloproteinase (MMP)-9, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) activities were assessed by zymography assays. Viability of RGC-5 cells was assessed by MTT assays. RGC and amacrine cell loss in vivo was assessed by immunostaining with Brn3a and ChAT antibodies, respectively. Frozen retinal cross sections were immunostained for nuclear factor-κB (NF-κB). Results. Staurosporine induced uPA and tPA levels in RGC-5 cells, and MMP-9, uPA, and tPA levels in the retinas and promoted the death of RGC-5 cells in vitro and RGCs and amacrine cells in vivo. In contrast, curcumin attenuated RGC and amacrine cell loss, despite elevated levels of proteases. An NF-κB inhibitory peptide reversed curcumin-mediated protective effect on RGC-5 cells, but did not inhibit protease levels. Curcumin did not inhibit protease levels in vivo, but attenuated RGC and amacrine cell loss by restoring NF-κB expression. Conclusions. The results show that curcumin attenuates RGC and amacrine cell death despite elevated levels of proteases and raises the possibility that it may be used as a plausible adjuvant therapeutic agent to prevent the loss of these cells in retinal degenerative conditions. PMID:21498608

  19. Epsilon-aminocaproic acid prevents high glucose and insulin induced-invasiveness in MDA-MB-231 breast cancer cells, modulating the plasminogen activator system.

    PubMed

    Viedma-Rodríguez, Rubí; Martínez-Hernández, María Guadalupe; Flores-López, Luis Antonio; Baiza-Gutman, Luis Arturo

    2018-01-01

    Obesity and type II diabetes mellitus have contributed to the increase of breast cancer incidence worldwide. High glucose concentration promotes the proliferation of metastatic cells, favoring the activation of the plasminogen/plasmin system, thus contributing to tumor progression. The efficient formation of plasmin is dependent on the binding of plasminogen to the cell surface. We studied the effect of ε-aminocaproic acid (EACA), an inhibitor of the binding of plasminogen to cell surface, on proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and plasminogen activation system, in metastatic MDA-MB-231 breast cancer cells grown in a high glucose microenvironment and treated with insulin. MDA-MB-231 cells were treated with EACA 12.5 mmol/L under high glucose 30 mmol/L (HG) and high glucose and insulin 80 nmol/L (HG-I) conditions, evaluating: cell population growth, % of viability, migratory, and invasive abilities, as well as the expression of uPA, its receptor (uPAR), and its inhibitor (PAI-1), by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, MMP-2 and MMP-9 mRNAs were evaluated by RT-PCR. Markers of EMT were evaluated by Western blot. Additionally, the presence of active uPA was studied by gel zymography, using casein-plasminogen as substrates. EACA prevented the increase in cell population, migration and invasion induced by HG and insulin, which was associated with the inhibition of EMT and the attenuation of HG- and insulin-dependent expression of uPA, uPAR, PAI-1, MMP-2, MMP-9, α-enolase (ENO A), and HCAM. The interaction of plasminogen to the cell surface and plasmin formation are mediators of the prometastasic action of hyperglycemia and insulin, potentially, EACA can be employed in the prevention and as adjuvant treatment of breast tumorigenesis promoted by hyperglycemia and insulin.

  20. A case control study on the structural equation model of the mechanism of coagulation and fibrinolysis imbalance in chronic schistosomiasis.

    PubMed

    Le, Aiping; Zhang, Lunli; Liu, Wei; Li, Xiaopeng; Ren, Jianwei; Ning, An

    2017-02-01

    A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90). FVIII, PAP, D-D, tPA, and uPA plasma levels were significantly higher in the chronic group than in the control group and were also significantly higher in the advanced group. However, AT-III, PC, PS, AT, PLG, and PAI1 plasma levels in the advanced and chronic groups were significantly lower than those in the control group. With progression of disease in patients with schistosomiasis japonica, a hypercoagulable state is induced by the coagulation-anticoagulation imbalance, eventually leading to patients with high levels of D-D. Furthermore, we established a structural equation model path of a "chronic schistosomiasis disease stage-(coagulation-anticoagulation-fibrinolysis)-D-D." By using analysis of moment structures (AMOS), it was shown that the chronic schistosomiasis stage was positively related to factor VIII and had negative correlation with AT-III; a good positive correlation with PAP, tPA, and uPA; and a good negative correlation with PLG and PAI1. In addition, our results show that the path coefficient of anticoagulation-fibrinolysis system to the chronic stage of schistosomiasis or D-D levels was significantly higher than that of the coagulation system. In conclusion, the coagulation and fibrinolysis imbalance in patients with chronic schistosomiasis, especially with advanced schistosomiasis, is due to the progression of disease stages.

  1. Distributed processor allocation for launching applications in a massively connected processors complex

    DOEpatents

    Pedretti, Kevin

    2008-11-18

    A compute processor allocator architecture for allocating compute processors to run applications in a multiple processor computing apparatus is distributed among a subset of processors within the computing apparatus. Each processor of the subset includes a compute processor allocator. The compute processor allocators can share a common database of information pertinent to compute processor allocation. A communication path permits retrieval of information from the database independently of the compute processor allocators.

  2. Feasibility and Effects of Short Activity Breaks for Increasing Preschool-Age Children's Physical Activity Levels

    ERIC Educational Resources Information Center

    Alhassan, Sofiya; Nwaokelemeh, Ogechi; Mendoza, Albert; Shitole, Sanyog; Puleo, Elaine; Pfeiffer, Karin A.; Whitt-Glover, Melicia C.

    2016-01-01

    Background: We examined the effects of short bouts of structured physical activity (SBS-PA) implemented within the classroom setting as part of designated gross-motor playtime on preschoolers PA. Methods: Preschools were randomized to SBS-PA (centers, N = 5; participants, N = 141) or unstructured free playtime (UPA) (centers, N = 5; participants,…

  3. A new version of the CADNA library for estimating round-off error propagation in Fortran programs

    NASA Astrophysics Data System (ADS)

    Jézéquel, Fabienne; Chesneaux, Jean-Marie; Lamotte, Jean-Luc

    2010-11-01

    The CADNA library enables one to estimate, using a probabilistic approach, round-off error propagation in any simulation program. CADNA provides new numerical types, the so-called stochastic types, on which round-off errors can be estimated. Furthermore CADNA contains the definition of arithmetic and relational operators which are overloaded for stochastic variables and the definition of mathematical functions which can be used with stochastic arguments. On 64-bit processors, depending on the rounding mode chosen, the mathematical library associated with the GNU Fortran compiler may provide incorrect results or generate severe bugs. Therefore the CADNA library has been improved to enable the numerical validation of programs on 64-bit processors. New version program summaryProgram title: CADNA Catalogue identifier: AEAT_v1_1 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAT_v1_1.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 28 488 No. of bytes in distributed program, including test data, etc.: 463 778 Distribution format: tar.gz Programming language: Fortran NOTE: A C++ version of this program is available in the Library as AEGQ_v1_0 Computer: PC running LINUX with an i686 or an ia64 processor, UNIX workstations including SUN, IBM Operating system: LINUX, UNIX Classification: 6.5 Catalogue identifier of previous version: AEAT_v1_0 Journal reference of previous version: Comput. Phys. Commun. 178 (2008) 933 Does the new version supersede the previous version?: Yes Nature of problem: A simulation program which uses floating-point arithmetic generates round-off errors, due to the rounding performed at each assignment and at each arithmetic operation. Round-off error propagation may invalidate the result of a program. The CADNA library enables one to estimate round-off error propagation in any simulation program and to detect all numerical instabilities that may occur at run time. Solution method: The CADNA library [1-3] implements Discrete Stochastic Arithmetic [4,5] which is based on a probabilistic model of round-off errors. The program is run several times with a random rounding mode generating different results each time. From this set of results, CADNA estimates the number of exact significant digits in the result that would have been computed with standard floating-point arithmetic. Reasons for new version: On 64-bit processors, the mathematical library associated with the GNU Fortran compiler may provide incorrect results or generate severe bugs with rounding towards -∞ and +∞, which the random rounding mode is based on. Therefore a particular definition of mathematical functions for stochastic arguments has been included in the CADNA library to enable its use with the GNU Fortran compiler on 64-bit processors. Summary of revisions: If CADNA is used on a 64-bit processor with the GNU Fortran compiler, mathematical functions are computed with rounding to the nearest, otherwise they are computed with the random rounding mode. It must be pointed out that the knowledge of the accuracy of the stochastic argument of a mathematical function is never lost. Restrictions: CADNA requires a Fortran 90 (or newer) compiler. In the program to be linked with the CADNA library, round-off errors on complex variables cannot be estimated. Furthermore array functions such as product or sum must not be used. Only the arithmetic operators and the abs, min, max and sqrt functions can be used for arrays. Additional comments: In the library archive, users are advised to read the INSTALL file first. The doc directory contains a user guide named ug.cadna.pdf which shows how to control the numerical accuracy of a program using CADNA, provides installation instructions and describes test runs. The source code, which is located in the src directory, consists of one assembly language file (cadna_rounding.s) and eighteen Fortran language files. cadna_rounding.s is a symbolic link to the assembly file corresponding to the processor and the Fortran compiler used. This assembly file contains routines which are frequently called in the CADNA Fortran files to change the rounding mode. The Fortran language files contain the definition of the stochastic types on which the control of accuracy can be performed, CADNA specific functions (for instance to enable or disable the detection of numerical instabilities), the definition of arithmetic and relational operators which are overloaded for stochastic variables and the definition of mathematical functions which can be used with stochastic arguments. The examples directory contains seven test runs which illustrate the use of the CADNA library and the benefits of Discrete Stochastic Arithmetic. Running time: The version of a code which uses CADNA runs at least three times slower than its floating-point version. This cost depends on the computer architecture and can be higher if the detection of numerical instabilities is enabled. In this case, the cost may be related to the number of instabilities detected.

  4. Enabling Graph Appliance for Genome Assembly

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Singh, Rina; Graves, Jeffrey A; Lee, Sangkeun

    2015-01-01

    In recent years, there has been a huge growth in the amount of genomic data available as reads generated from various genome sequencers. The number of reads generated can be huge, ranging from hundreds to billions of nucleotide, each varying in size. Assembling such large amounts of data is one of the challenging computational problems for both biomedical and data scientists. Most of the genome assemblers developed have used de Bruijn graph techniques. A de Bruijn graph represents a collection of read sequences by billions of vertices and edges, which require large amounts of memory and computational power to storemore » and process. This is the major drawback to de Bruijn graph assembly. Massively parallel, multi-threaded, shared memory systems can be leveraged to overcome some of these issues. The objective of our research is to investigate the feasibility and scalability issues of de Bruijn graph assembly on Cray s Urika-GD system; Urika-GD is a high performance graph appliance with a large shared memory and massively multithreaded custom processor designed for executing SPARQL queries over large-scale RDF data sets. However, to the best of our knowledge, there is no research on representing a de Bruijn graph as an RDF graph or finding Eulerian paths in RDF graphs using SPARQL for potential genome discovery. In this paper, we address the issues involved in representing a de Bruin graphs as RDF graphs and propose an iterative querying approach for finding Eulerian paths in large RDF graphs. We evaluate the performance of our implementation on real world ebola genome datasets and illustrate how genome assembly can be accomplished with Urika-GD using iterative SPARQL queries.« less

  5. A real-time programming system.

    PubMed

    Townsend, H R

    1979-03-01

    The paper describes a Basic Operating and Scheduling System (BOSS) designed for a small computer. User programs are organised as self-contained modular 'processes' and the way in which the scheduler divides the time of the computer equally between them, while arranging for any process which has to respond to an interrupt from a peripheral device to be given the necessary priority, is described in detail. Next the procedures provided by the operating system to organise communication between processes are described, and how they are used to construct dynamically self-modifying real-time systems. Finally, the general philosophy of BOSS and applications to a multi-processor assembly are discussed.

  6. Risetime distortion of Shuttle Ku-band payload 50 MBPS data due to coaxial cable skin effects

    NASA Technical Reports Server (NTRS)

    Schadelbauer, S.; Vang, H. A.

    1980-01-01

    This paper discusses distortion of digital signals generated in the Space Shuttle Ku-band communications systems. Specifically, the degradation considered is due to coaxial cables which interface data and clock from a source located in the payload bay to the KuSPA (Ku-Band Signal Processor Assembly) located in the avionics bay of the Shuttle. Due to the length (nearly 100 feet) and relatively narrow bandwidth of the cable, the clock and data waveforms are significantly affected by this transmission medium. This paper presents a closed form model that closely approximates the distortion of the waveforms measured in laboratory tests.

  7. LLL 8080 BASIC-II interpreter user's manual

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McGoldrick, P.R.; Dickinson, J.; Allison, T.G.

    1978-04-03

    Scientists are finding increased applications for microprocessors as process controllers in their experiments. However, while microprocessors are small and inexpensive, they are difficult to program in machine or assembly language. A high-level language is needed to enable scientists to develop their own microcomputer programs for their experiments on location. Recognizing this need, LLL contracted to have such a language developed. This report describes the resulting LLL BASIC interpreter, which opeates with LLL's 8080-based MCS-8 microcomputer system. All numerical operations are done using Advanced Micro Device's Am9511 arithmetic processor chip or optionally by using a software simulation of that chip. 1more » figure.« less

  8. Concept report: Microprocessor control of electrical power system

    NASA Technical Reports Server (NTRS)

    Perry, E.

    1977-01-01

    An electrical power system which uses a microprocessor for systems control and monitoring is described. The microprocessor controlled system permits real time modification of system parameters for optimizing a system configuration, especially in the event of an anomaly. By reducing the components count, the assembling and testing of the unit is simplified, and reliability is increased. A resuable modular power conversion system capable of satisfying a large percentage of space applications requirements is examined along with the programmable power processor. The PC global controller which handles systems control and external communication is analyzed, and a software description is given. A systems application summary is also included.

  9. Embedded mobile farm robot for identification of diseased plants

    NASA Astrophysics Data System (ADS)

    Sadistap, S. S.; Botre, B. A.; Pandit, Harshavardhan; Chandrasekhar; Rao, Adesh

    2013-07-01

    This paper presents the development of a mobile robot used in farms for identification of diseased plants. It puts forth two of the major aspects of robotics namely automated navigation and image processing. The robot navigates on the basis of the GPS (Global Positioning System) location and data obtained from IR (Infrared) sensors to avoid any obstacles in its path. It uses an image processing algorithm to differentiate between diseased and non-diseased plants. A robotic platform consisting of an ARM9 processor, motor drivers, robot mechanical assembly, camera and infrared sensors has been used. Mini2440 microcontroller has been used wherein Embedded linux OS (Operating System) is implemented.

  10. A strongly interacting polaritonic quantum dot

    NASA Astrophysics Data System (ADS)

    Jia, Ningyuan; Schine, Nathan; Georgakopoulos, Alexandros; Ryou, Albert; Clark, Logan W.; Sommer, Ariel; Simon, Jonathan

    2018-06-01

    Polaritons are promising constituents of both synthetic quantum matter1 and quantum information processors2, whose properties emerge from their components: from light, polaritons draw fast dynamics and ease of transport; from matter, they inherit the ability to collide with one another. Cavity polaritons are particularly promising as they may be confined and subjected to synthetic magnetic fields controlled by cavity geometry3, and furthermore they benefit from increased robustness due to the cavity enhancement in light-matter coupling. Nonetheless, until now, cavity polaritons have operated only in a weakly interacting mean-field regime4,5. Here we demonstrate strong interactions between individual cavity polaritons enabled by employing highly excited Rydberg atoms as the matter component of the polaritons. We assemble a quantum dot composed of approximately 150 strongly interacting Rydberg-dressed 87Rb atoms in a cavity, and observe blockaded transport of photons through it. We further observe coherent photon tunnelling oscillations, demonstrating that the dot is zero-dimensional. This work establishes the cavity Rydberg polariton as a candidate qubit in a photonic information processor and, by employing multiple resonator modes as the spatial degrees of freedom of a photonic particle, the primary ingredient to form photonic quantum matter6.

  11. System for clinical photometric stereo endoscopy

    NASA Astrophysics Data System (ADS)

    Durr, Nicholas J.; González, Germán.; Lim, Daryl; Traverso, Giovanni; Nishioka, Norman S.; Vakoc, Benjamin J.; Parot, Vicente

    2014-02-01

    Photometric stereo endoscopy is a technique that captures information about the high-spatial-frequency topography of the field of view simultaneously with a conventional color image. Here we describe a system that will enable photometric stereo endoscopy to be clinically evaluated in the large intestine of human patients. The clinical photometric stereo endoscopy system consists of a commercial gastroscope, a commercial video processor, an image capturing and processing unit, custom synchronization electronics, white light LEDs, a set of four fibers with diffusing tips, and an alignment cap. The custom pieces that come into contact with the patient are composed of biocompatible materials that can be sterilized before use. The components can then be assembled in the endoscopy suite before use. The resulting endoscope has the same outer diameter as a conventional colonoscope (14 mm), plugs into a commercial video processor, captures topography and color images at 15 Hz, and displays the conventional color image to the gastroenterologist in real-time. We show that this system can capture a color and topographical video in a tubular colon phantom, demonstrating robustness to complex geometries and motion. The reported system is suitable for in vivo evaluation of photometric stereo endoscopy in the human large intestine.

  12. Performance Evaluation of the ISS Water Processor Multifiltration Beds

    NASA Technical Reports Server (NTRS)

    Bowman, Elizabeth M.; Carter, Layne; Wilson, Mark; Cole, Harold; Orozco, Nicole; Snowdon, Doug

    2012-01-01

    The ISS Water Processor Assembly (WPA) produces potable water from a waste stream containing humidity condensate and urine distillate. The primary treatment process is achieved in the Multifiltration Bed, which includes adsorbent media and ion exchange resin for the removal of dissolved organic and inorganic contaminants. The first Multifiltration Bed was replaced on ISS in July 2010 after initial indication of inorganic breakthrough. This bed was returned to ground in July 2011 for an engineering investigation. The water resident in the bed was analyzed for various parameters to evaluate adsorbent loading, performance of the ion exchange resin, microbial activity, and generation of leachates from the ion exchange resin. Portions of the adsorbent media and ion exchange resin were sampled and subsequently desorbed to identify the primary contaminants removed at various points in the bed. In addition, an unused Multifiltration Bed was evaluated after two years in storage to assess the generation of leachates during storage. This assessment was performed to evaluate the possibility that these leachates are impacting performance of the Catalytic Reactor located downstream of the Multifiltration Bed. The results of these investigations and implications to the operation of the WPA on ISS are documented in this paper.

  13. Live interactive computer music performance practice

    NASA Astrophysics Data System (ADS)

    Wessel, David

    2002-05-01

    A live-performance musical instrument can be assembled around current lap-top computer technology. One adds a controller such as a keyboard or other gestural input device, a sound diffusion system, some form of connectivity processor(s) providing for audio I/O and gestural controller input, and reactive real-time native signal processing software. A system consisting of a hand gesture controller; software for gesture analysis and mapping, machine listening, composition, and sound synthesis; and a controllable radiation pattern loudspeaker are described. Interactivity begins in the set up wherein the speaker-room combination is tuned with an LMS procedure. This system was designed for improvisation. It is argued that software suitable for carrying out an improvised musical dialog with another performer poses special challenges. The processes underlying the generation of musical material must be very adaptable, capable of rapid changes in musical direction. Machine listening techniques are used to help the performer adapt to new contexts. Machine learning can play an important role in the development of such systems. In the end, as with any musical instrument, human skill is essential. Practice is required not only for the development of musically appropriate human motor programs but for the adaptation of the computer-based instrument as well.

  14. Back to the Future: The Congress Party’s Upset Victory in India’s 14th General Elections

    DTIC Science & Technology

    2004-06-01

    stance on all regional and global issues even as it pursues closer strategic and economic engagement with the USA.” However, the final draft, at the...maintain the independence of India’s foreign policy position on all regional and global issues . The UPA is committed to deepening ties with Russia and

  15. [Community vegetable gardens as a health promotion activity: an experience in Primary Healthcare Units].

    PubMed

    Costa, Christiane Gasparini Araújo; Garcia, Mariana Tarricone; Ribeiro, Silvana Maria; Salandini, Marcia Fernanda de Sousa; Bógus, Cláudia Maria

    2015-10-01

    Urban and peri-urban agriculture (UPA) is being practiced in different settings, contributing to the improvement of health in communities and healthier environments. In order to identify the meanings and implications of the practice of UPA in Primary Healthcare Units (PHU) as an activity of health promotion (HP), and to what extent its therapeutic dimension characterizes it as an activity aligned with complementary and integrative practices (CIP), a qualitative cross-sectional study was performed in Embu das Artes, State of São Paulo. From the analysis, the following main themes arose: health concept, health outcomes, the return to traditional practices and habits and the reorientation of health services. It was possible to identify the close link between the cultivation of vegetable gardens and HP guidelines and fields of action, such as creating healthier environments, boosting community actions, developing personal skills, stimulating autonomy and empowerment and demands for the reorientation of services. The garden activities, set up in PHU areas, proved to be an implementation strategy of CIP. The conclusion reached is that vegetable gardening activities in community gardens are seen to be health promotion practices that integrate key elements of CIP.

  16. Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development.

    PubMed

    Nelson, Anita L

    2015-01-01

    As efforts are made to continue to increase the safety of contraceptive methods, those without estrogen have attracted new attention. Progestin-only options are available in many delivery systems, but most cause disturbed bleeding patterns. For gynecologic patients, selective progesterone receptor modulators (SPRMs) have been approved for medical abortion, for ovulation suppression in emergency contraception, and for the treatment of heavy menstrual bleeding due to leiomyoma. This article discusses the role of SPRMs in controlling fertility on an ongoing basis with particular emphasis on mifepristone and ulipristal acetate (UPA), since none of the other compounds has progressed out of early Phase I - II testing. It also discusses important information about the mechanisms of action and safety of these two SPRMs. Of all the investigational hormone agonist/antagonists, SPRMs have demonstrated the greatest potential as ongoing female contraceptives. They have the ability to suppress ovulation after initiation of the luteinizing hormone (LH) surge without affecting ovarian production of estrogen or inducing any significant metabolic changes. SPRMs may well be able to provide longer term contraception as oral agents, vaginal rings, and perhaps even intrauterine devices. UPA has the greatest promise. Current research needs to be expanded.

  17. N2 non-thermal atmospheric pressure plasma promotes wound healing in vitro and in vivo: Potential modulation of adhesion molecules and matrix metalloproteinase-9.

    PubMed

    Kang, Sung Un; Choi, Jae Won; Chang, Jae Won; Kim, Kang Il; Kim, Yeon Soo; Park, Ju Kyeong; Kim, Yang Eun; Lee, Yun Sang; Yang, Sang Sik; Kim, Chul-Ho

    2017-02-01

    Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N 2 optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment. We also showed that NTP treatment increased Slug and TCF8/ZEB1 expression and decreased that of E-cadherin, suggesting induction of the epithelial-to-mesenchymal transition (EMT). The effect of N 2 NTP was verified on rat wound model. Taken together, these results suggest that N 2 NTP promotes wound healing by inducing the EMT and activating the MMP-9/uPA system. These findings show the therapeutic potential of NTP for skin wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Structural Basis of Interaction between Urokinase-Type Plasminogen Activator and Its Receptor

    PubMed Central

    Barinka, Cyril; Parry, Graham; Callahan, Jennifer; Shaw, David E.; Kuo, Alice; Bdeir, Khalil; Cines, Douglas B.; Mazar, Andrew; Lubkowski, Jacek

    2009-01-01

    Summary Recent studies indicate that binding of urokinase-type plasminogen activator (uPA) to its high affinity receptor (uPAR), orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known as to the exact mode of uPAR-uPA interactions and the presumed conformational changes that accompanying uPA-uPAR engagement. Here we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell surface anchoring sequence, in complex with the amino terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 Å. We also report the 1.9 Å crystal structure of the free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR-uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding. PMID:16979660

  19. Lanthanide-doped NaScF4 nanoprobes: crystal structure, optical spectroscopy and biodetection

    NASA Astrophysics Data System (ADS)

    Ai, Yu; Tu, Datao; Zheng, Wei; Liu, Yongsheng; Kong, Jintao; Hu, Ping; Chen, Zhuo; Huang, Mingdong; Chen, Xueyuan

    2013-06-01

    Trivalent lanthanide ions (Ln3+)-doped inorganic nanoparticles (NPs) as potential luminescent bioprobes have been attracting tremendous interest because of their unique upconversion (UC) and downconversion (DC) luminescence properties. NaScF4, as an important host material, has been rarely reported and its crystal structure remains unclear. Herein, based on the single crystal X-ray diffraction, the space group of NaScF4 crystals was determined to be P31 containing multiple sites of Sc3+ with crystallographic site symmetry of C1, which was verified by high-resolution photoluminescence spectroscopy of Eu3+ at low temperature (10 K). Furthermore, monodisperse and size-controllable NaScF4:Ln3+ NPs were synthesized via a facile thermal decomposition method. The biotinylated NaScF4:Er3+/Yb3+ NPs were demonstrated for their applications as a heterogeneous UC luminescence bioprobe to detect avidin with a detection limit of 180 pM. After bioconjugation with amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), NaScF4:Ln3+ NPs also exhibited specific recognition of cancer cells overexpressed with uPA receptor (uPAR, an important marker of tumor biology and metastasis), showing great potentials in tumor-targeted bioimaging.Trivalent lanthanide ions (Ln3+)-doped inorganic nanoparticles (NPs) as potential luminescent bioprobes have been attracting tremendous interest because of their unique upconversion (UC) and downconversion (DC) luminescence properties. NaScF4, as an important host material, has been rarely reported and its crystal structure remains unclear. Herein, based on the single crystal X-ray diffraction, the space group of NaScF4 crystals was determined to be P31 containing multiple sites of Sc3+ with crystallographic site symmetry of C1, which was verified by high-resolution photoluminescence spectroscopy of Eu3+ at low temperature (10 K). Furthermore, monodisperse and size-controllable NaScF4:Ln3+ NPs were synthesized via a facile thermal decomposition method. The biotinylated NaScF4:Er3+/Yb3+ NPs were demonstrated for their applications as a heterogeneous UC luminescence bioprobe to detect avidin with a detection limit of 180 pM. After bioconjugation with amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), NaScF4:Ln3+ NPs also exhibited specific recognition of cancer cells overexpressed with uPA receptor (uPAR, an important marker of tumor biology and metastasis), showing great potentials in tumor-targeted bioimaging. Electronic supplementary information (ESI) available: Crystallographic data (CCDC 931481) in CIF format. EDX analysis of NaScF4:Er3+/Yb3+ NPs. 10 K PL excitation spectra of NaScF4:Eu3+ microcrystals. Selected bond lengths and angles for NaScF4 crystals. Atomic coordinates and equivalent isotropic displacement parameters for NaScF4 crystals. UC quantum yield data of NaScF4:Er3+/Yb3+ NPs. See DOI: 10.1039/c3nr01529g

  20. Efficiency of static core turn-off in a system-on-a-chip with variation

    DOEpatents

    Cher, Chen-Yong; Coteus, Paul W; Gara, Alan; Kursun, Eren; Paulsen, David P; Schuelke, Brian A; Sheets, II, John E; Tian, Shurong

    2013-10-29

    A processor-implemented method for improving efficiency of a static core turn-off in a multi-core processor with variation, the method comprising: conducting via a simulation a turn-off analysis of the multi-core processor at the multi-core processor's design stage, wherein the turn-off analysis of the multi-core processor at the multi-core processor's design stage includes a first output corresponding to a first multi-core processor core to turn off; conducting a turn-off analysis of the multi-core processor at the multi-core processor's testing stage, wherein the turn-off analysis of the multi-core processor at the multi-core processor's testing stage includes a second output corresponding to a second multi-core processor core to turn off; comparing the first output and the second output to determine if the first output is referring to the same core to turn off as the second output; outputting a third output corresponding to the first multi-core processor core if the first output and the second output are both referring to the same core to turn off.

  1. Calibrating thermal behavior of electronics

    DOEpatents

    Chainer, Timothy J.; Parida, Pritish R.; Schultz, Mark D.

    2017-07-11

    A method includes determining a relationship between indirect thermal data for a processor and a measured temperature associated with the processor, during a calibration process, obtaining the indirect thermal data for the processor during actual operation of the processor, and determining an actual significant temperature associated with the processor during the actual operation using the indirect thermal data for the processor during actual operation of the processor and the relationship.

  2. Calibrating thermal behavior of electronics

    DOEpatents

    Chainer, Timothy J.; Parida, Pritish R.; Schultz, Mark D.

    2016-05-31

    A method includes determining a relationship between indirect thermal data for a processor and a measured temperature associated with the processor, during a calibration process, obtaining the indirect thermal data for the processor during actual operation of the processor, and determining an actual significant temperature associated with the processor during the actual operation using the indirect thermal data for the processor during actual operation of the processor and the relationship.

  3. Calibrating thermal behavior of electronics

    DOEpatents

    Chainer, Timothy J.; Parida, Pritish R.; Schultz, Mark D.

    2017-01-03

    A method includes determining a relationship between indirect thermal data for a processor and a measured temperature associated with the processor, during a calibration process, obtaining the indirect thermal data for the processor during actual operation of the processor, and determining an actual significant temperature associated with the processor during the actual operation using the indirect thermal data for the processor during actual operation of the processor and the relationship.

  4. Safety data for levonorgestrel, ulipristal acetate and Yuzpe regimens for emergency contraception.

    PubMed

    Jatlaoui, Tara C; Riley, Halley; Curtis, Kathryn M

    2016-02-01

    The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) provide recommendations for use of emergency contraceptive pills (ECPs), including levonorgestrel (LNG) and combined oral contraceptives (COCs). A new ECP formulation, ulipristal acetate (UPA), is now available worldwide. To determine whether LNG, UPA or COC (Yuzpe) ECPs are safe for women with certain characteristics or medical conditions, we searched the PubMed and Cochrane databases for articles published from date of inception until May 2015 pertaining to the safety of LNG, UPA or Yuzpe ECP use. For direct evidence, we considered studies that looked at safety outcomes among women with certain medical conditions or characteristics taking ECPs compared with women not taking ECPs. For indirect evidence, we considered studies that reported pharmacokinetic (PK) data for ECP use among women with certain medical conditions or characteristics and studies that reported safety outcomes among healthy women taking ECPs. Five studies provided direct evidence; of these five studies, four examined LNG or Yuzpe use among pregnant or breastfeeding women, and one reported risk of ectopic pregnancy among women repeatedly using LNG ECPs. Poor pregnancy outcomes were rare among pregnant women who used LNG or Yuzpe ECPs during the conception cycle or early pregnancy. Breastfeeding outcomes did not differ between women exposed to LNG ECP and those unexposed, and there was no increased risk of ectopic pregnancy versus intrauterine pregnancy after repeated use of LNG ECPs compared with nonuse. Forty-five studies provided indirect evidence. One PK study demonstrated that LNG passes into breastmilk but in minimal quantities. In addition, nine studies examined pregnancy outcomes following ECP failure among healthy women, and 35 articles reported adverse events. Studies suggest that serious adverse events are rare among women taking any of these ECP formulations. Evidence on safety of ECPs among women with characteristics or medical conditions listed within WHO and CDC family planning guidance is limited. However, both direct and indirect evidence for our study question did not suggest any special safety concerns for the use of ECPs among women with particular medical conditions or personal characteristics, such as pregnancy, lactation or frequent ECP use. Published by Elsevier Inc.

  5. Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility.

    PubMed

    Marí-Alexandre, Josep; Barceló-Molina, Moisés; Belmonte-López, Elisa; García-Oms, Javier; Estellés, Amparo; Braza-Boïls, Aitana; Gilabert-Estellés, Juan

    2018-04-01

    To define the microRNA (miRNA) profile and its relationship with cytokines content in peritoneal fluid (PF) from endometriosis patients. Case-control study. University hospital, research institute. One hundred twenty-six women with endometriosis (EPF) and 45 control women (CPF). MiRNA arrays were prepared from six EPF and six CPF. Quantitative reverse transcription-polymerase chain reaction validation of nine selected miRNAs (miR-29c-3p, -106b-3p, -130a-3p, -150-5p, -185-5p, -195-5p, -451a, -486-5p, and -1343-5p) was performed. Vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-3 (MMP3), tissue inhibitor of metalloproteinases type 1 (TIMP-1), interleukin (IL)-6, IL-8, IL-17A, macrophage inflammatory protein 1β (MIP1beta), platelet-derived growth factor α-polypeptide A, and regulated on activation, normal T cell expressed and secreted (RANTES) were quantified by ELISA and MILLIPLEX. MiRNA arrays showed 126 miRNAs differentially expressed (fold change ±1.2) (78 down-regulated, 48 up-regulated) in EPF. Validation showed higher levels of miR-106b-3p, -451a, -486-5p, IL-6, IL-8, uPA, and TIMP-1 in EPF. In menstrual phase, EPF presented up-regulation of miR-106b-3p, -130a-3p, -150-5p, -185-5p, -451a, -486-5p, VEGF-A, IL-8, MIF 1β, uPA, and PAI-1 compared with other phases; however, CPF did not. MiRNA-486-5p was up-regulated in sterile EPF compared with sterile controls, and VEGF-A, IL-8, and TIMP-1 were increased in sterile and fertile EPF compared with fertile CPF. MiRNAs seem to be involved in the peritoneal alterations in endometriosis, suggesting new mechanisms by which ectopic lesions could implant in endometriosis patients; and to serve as biomarkers for fertility outcome prediction. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Role of p53–fibrinolytic system cross-talk in the regulation of quartz-induced lung injury

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bhandary, Yashodhar P.; Shetty, Shwetha K.; Marudamuthu, Amarnath S.

    2015-03-01

    Silica is the major component of airborne dust generated by wind, manufacturing and/or demolition. Chronic occupational inhalation of silica dust containing crystalline quartz is by far the predominant form of silicosis in humans. Silicosis is a progressive lung disease that typically arises after a very long latency and is a major occupational concern with no known effective treatment. The mechanism of silicosis is not clearly understood. However, silicosis is associated with increased cell death, expression of redox enzymes and pro-fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and disruption of alveolar fibrinolysis is often associated with both acutemore » and chronic lung injuries, we explored whether p53-mediated changes in the urokinase-type plasminogen activator (uPA) system contributes to silica-induced lung injury. We further sought to determine whether caveolin-1 scaffolding domain peptide (CSP), which inhibits p53 expression, mitigates lung injury associated with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA expression and prevents AEC apoptosis by suppressing p53, which is otherwise induced in mice exposed to silica. The process involves CSP-mediated inhibition of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations suggest that changes in the p53–uPA fibrinolytic system cross-talk contribute to lung injury caused by inhalation of silica dust containing crystalline quartz and is protected by CSP by targeting this pathway. - Highlights: • Chronic exposure to quartz dusts is a major cause of lung injury and silicosis. • The survival of patients with silicosis is bleak due to lack of effective treatments. • This study defines a new role of p53–uPA cross-talk in quartz-induced lung injury. • Targeting the p53–uPA system inhibits ATII cell/lung injury due to quartz exposure.« less

  7. A combined remote sensing and modeling based approach to identify sustainable pathways for urban and peri-urban agriculture in China

    NASA Astrophysics Data System (ADS)

    Wattenbach, M.; Delgado, J. M.; Roessner, S.; Bochow, M.; Güntner, A.; Kropp, J.; Cantu Ros, A. G.; Hattermann, F.; Kolbe, T.; Sodoudi, S.; Cubasch, U. Ulrich; Zeitz, J.; Ross, L.; Böckel, K.; Fang, C.; Bo, L.; Pan, G.

    2012-04-01

    As the world's biggest economy, China is becoming the biggest consumer of resources globally. Given this trend, the over-proportional fast increase in urbanization presents China with fundamental problems. Among the most urgent ones is the increasing loss of agricultural land as urbanization takes place in the most productive regions along the coast. The latter is being responsible for a shift in agriculture production towards climatically less favorable areas. At the same time, the loss of green areas in and around growing cities is increasing the effect of the urban heat island. The perception of the potential risks related to this phenomenon, in the context of climate change, has led the Shanghai city administration to increase its urban-greening efforts, expanding the per capita area of green from 1m2 in 1990 to 12.5m2 in 2008. In this context, this paper aims at identifying the influence of urban and peri-urban agriculture (UPA) on the sustainability of the urban regions of Shanghai and Nanjing. In particular, it focuses on the effects of UPA on the greenhouse gas (GHG) emissions, soil nutrients and water balances, local climate and the structure and functions of the urbanized areas. We propose an interdisciplinary framework combining remote sensing, model simulations and GHG field observations and targeted at identifying "win-win" strategies for sustainable planning pathways showing high potentials for UPA. The framework is based on spatial scenario modeling, automatic classification of urban structure types and on a prototype of a high-quality spatial database consisting of a 3D city model. Dynamic boundary conditions for climate and urban development are provided by state of the art models. These approaches meet the needs of stakeholders and planners in China. A special emphasis is put on interdependencies between small holder farming in the urban and peri-urban zone and climate change adaptation and mitigation strategies focusing on improved management of local water and nutrient cycles. The whole database generated will be structured and made accessible for planners and stakeholders in the form of a 3D city visualization model.

  8. A microprocessor-based control system for the Vienna PDS microdensitometer

    NASA Technical Reports Server (NTRS)

    Jenkner, H.; Stoll, M.; Hron, J.

    1984-01-01

    The Motorola Exorset 30 system, based on a Motorola 6809 microprocessor which serves as control processor for the microdensitometer is presented. User communication and instrument control are implemented in this syatem; data transmission to a host computer is provided via standard interfaces. The Vienna PDS system (VIPS) software was developed in BASIC and M6809 assembler. It provides efficient user interaction via function keys and argument input in a menu oriented environment. All parameters can be stored on, and retrieved from, minifloppy disks, making it possible to set up large scanning tasks. Extensive user information includes continuously updated status and coordinate displays, as well as a real time graphic display during scanning.

  9. Structural weights analysis of advanced aerospace vehicles using finite element analysis

    NASA Technical Reports Server (NTRS)

    Bush, Lance B.; Lentz, Christopher A.; Rehder, John J.; Naftel, J. Chris; Cerro, Jeffrey A.

    1989-01-01

    A conceptual/preliminary level structural design system has been developed for structural integrity analysis and weight estimation of advanced space transportation vehicles. The system includes a three-dimensional interactive geometry modeler, a finite element pre- and post-processor, a finite element analyzer, and a structural sizing program. Inputs to the system include the geometry, surface temperature, material constants, construction methods, and aerodynamic and inertial loads. The results are a sized vehicle structure capable of withstanding the static loads incurred during assembly, transportation, operations, and missions, and a corresponding structural weight. An analysis of the Space Shuttle external tank is included in this paper as a validation and benchmark case of the system.

  10. Silicon nanodisk array with a fin field-effect transistor for time-domain weighted sum calculation toward massively parallel spiking neural networks

    NASA Astrophysics Data System (ADS)

    Tohara, Takashi; Liang, Haichao; Tanaka, Hirofumi; Igarashi, Makoto; Samukawa, Seiji; Endo, Kazuhiko; Takahashi, Yasuo; Morie, Takashi

    2016-03-01

    A nanodisk array connected with a fin field-effect transistor is fabricated and analyzed for spiking neural network applications. This nanodevice performs weighted sums in the time domain using rising slopes of responses triggered by input spike pulses. The nanodisk arrays, which act as a resistance of several giga-ohms, are fabricated using a self-assembly bio-nano-template technique. Weighted sums are achieved with an energy dissipation on the order of 1 fJ, where the number of inputs can be more than one hundred. This amount of energy is several orders of magnitude lower than that of conventional digital processors.

  11. Learning the Art of Electronics

    NASA Astrophysics Data System (ADS)

    Hayes, Thomas C.; Horowitz, Paul

    2016-03-01

    1. DC circuits; 2. RC circuits; 3. Diode circuits; 4. Transistors I; 5. Transistors II; 6. Operational amplifiers I; 7. Operational amplifiers II: nice positive feedback; 8. Operational amplifiers III; 9. Operational amplifiers IV: nasty positive feedback; 10. Operational amplifiers V: PID motor control loop; 11. Voltage regulators; 12. MOSFET switches; 13. Group audio project; 14. Logic gates; 15. Logic compilers, sequential circuits, flip-flops; 16. Counters; 17. Memory: state machines; 18. Analog to digital: phase-locked loop; 19. Microcontrollers and microprocessors I: processor/controller; 20. I/O, first assembly language; 21. Bit operations; 22. Interrupt: ADC and DAC; 23. Moving pointers, serial buses; 24. Dallas Standalone Micro, SiLabs SPI RAM; 25. Toys in the attic; Appendices; Index.

  12. Methods and systems for providing reconfigurable and recoverable computing resources

    NASA Technical Reports Server (NTRS)

    Stange, Kent (Inventor); Hess, Richard (Inventor); Kelley, Gerald B (Inventor); Rogers, Randy (Inventor)

    2010-01-01

    A method for optimizing the use of digital computing resources to achieve reliability and availability of the computing resources is disclosed. The method comprises providing one or more processors with a recovery mechanism, the one or more processors executing one or more applications. A determination is made whether the one or more processors needs to be reconfigured. A rapid recovery is employed to reconfigure the one or more processors when needed. A computing system that provides reconfigurable and recoverable computing resources is also disclosed. The system comprises one or more processors with a recovery mechanism, with the one or more processors configured to execute a first application, and an additional processor configured to execute a second application different than the first application. The additional processor is reconfigurable with rapid recovery such that the additional processor can execute the first application when one of the one more processors fails.

  13. Mechanism controller system for the optical spectroscopic and infrared remote imaging system instrument on board the Rosetta space mission

    NASA Astrophysics Data System (ADS)

    Castro Marín, J. M.; Brown, V. J. G.; López Jiménez, A. C.; Rodríguez Gómez, J.; Rodrigo, R.

    2001-05-01

    The optical, spectroscopic infrared remote imaging system (OSIRIS) is an instrument carried on board the European Space Agency spacecraft Rosetta that will be launched in January 2003 to study in situ the comet Wirtanen. The electronic design of the mechanism controller board (MCB) system of the two OSIRIS optical cameras, the narrow angle camera, and the wide angle camera, is described here. The system is comprised of two boards mounted on an aluminum frame as part of an electronics box that contains the power supply and the digital processor unit of the instrument. The mechanisms controlled by the MCB for each camera are the front door assembly and a filter wheel assembly. The front door assembly for each camera is driven by a four phase, permanent magnet stepper motor. Each filter wheel assembly consists of two, eight filter wheels. Each wheel is driven by a four phase, variable reluctance stepper motor. Each motor, for all the assemblies, also contains a redundant set of four stator phase windings that can be energized separately or in parallel with the main windings. All stepper motors are driven in both directions using the full step unipolar mode of operation. The MCB also performs general housekeeping data acquisition of the OSIRIS instrument, i.e., mechanism position encoders and temperature measurements. The electronic design application used is quite new due to use of a field programmable gate array electronic devices that avoid the use of the now traditional system controlled by microcontrollers and software. Electrical tests of the engineering model have been performed successfully and the system is ready for space qualification after environmental testing. This system may be of interest to institutions involved in future space experiments with similar needs for mechanisms control.

  14. Rectangular Array Of Digital Processors For Planning Paths

    NASA Technical Reports Server (NTRS)

    Kemeny, Sabrina E.; Fossum, Eric R.; Nixon, Robert H.

    1993-01-01

    Prototype 24 x 25 rectangular array of asynchronous parallel digital processors rapidly finds best path across two-dimensional field, which could be patch of terrain traversed by robotic or military vehicle. Implemented as single-chip very-large-scale integrated circuit. Excepting processors on edges, each processor communicates with four nearest neighbors along paths representing travel to north, south, east, and west. Each processor contains delay generator in form of 8-bit ripple counter, preset to 1 of 256 possible values. Operation begins with choice of processor representing starting point. Transmits signals to nearest neighbor processors, which retransmits to other neighboring processors, and process repeats until signals propagated across entire field.

  15. Buffered coscheduling for parallel programming and enhanced fault tolerance

    DOEpatents

    Petrini, Fabrizio [Los Alamos, NM; Feng, Wu-chun [Los Alamos, NM

    2006-01-31

    A computer implemented method schedules processor jobs on a network of parallel machine processors or distributed system processors. Control information communications generated by each process performed by each processor during a defined time interval is accumulated in buffers, where adjacent time intervals are separated by strobe intervals for a global exchange of control information. A global exchange of the control information communications at the end of each defined time interval is performed during an intervening strobe interval so that each processor is informed by all of the other processors of the number of incoming jobs to be received by each processor in a subsequent time interval. The buffered coscheduling method of this invention also enhances the fault tolerance of a network of parallel machine processors or distributed system processors

  16. Flight design system level C requirements. Solid rocket booster and external tank impact prediction processors. [space transportation system

    NASA Technical Reports Server (NTRS)

    Seale, R. H.

    1979-01-01

    The prediction of the SRB and ET impact areas requires six separate processors. The SRB impact prediction processor computes the impact areas and related trajectory data for each SRB element. Output from this processor is stored on a secure file accessible by the SRB impact plot processor which generates the required plots. Similarly the ET RTLS impact prediction processor and the ET RTLS impact plot processor generates the ET impact footprints for return-to-launch-site (RTLS) profiles. The ET nominal/AOA/ATO impact prediction processor and the ET nominal/AOA/ATO impact plot processor generate the ET impact footprints for non-RTLS profiles. The SRB and ET impact processors compute the size and shape of the impact footprints by tabular lookup in a stored footprint dispersion data base. The location of each footprint is determined by simulating a reference trajectory and computing the reference impact point location. To insure consistency among all flight design system (FDS) users, much input required by these processors will be obtained from the FDS master data base.

  17. JPRS Report, Soviet Union, Political Affairs.

    DTIC Science & Technology

    1989-05-19

    8217; For protocol , in the small office of the chairman of the May 1988 Mazurov interview, see JPRS-UPA-88-047, All-Union Council of War and Labor...the increase in murder, premeditated serious bodily injury , robberies, crime within the republic. In Tashkent, for example, thefts, and rapes. Almost...have been uncovered. One of them, the Yakubov and tated serious bodily injury , almost every tenth murder, Boloshin gang (a total 33 criminals

  18. Molecular Disruption of Breast Tumor Angiogenesis

    DTIC Science & Technology

    2004-07-01

    human breast cancer . During the period of this grant, we carried out studies to confirm that targeted ablation of PAI- 1 gene expression resulted in a...microvessel endothelial cells. Breast cancer -derived factors (TGF-P, EGF)were found to be important contributors of continued PAI-I expression and long...various culture model systems implicated both urokinase plasminogen activator (uPA) and its fast-acting type-i inhibitor (PAl-l) as necessary to achieve

  19. JPRS Report, Soviet Union, Political Affairs.

    DTIC Science & Technology

    1989-10-03

    18000602 Moscow PRA VDA in Russian 2 Aug 88 p 3 [Article by I . Zarakhovich and T . Trukhacheva, journal- ists, and Ye. Sokolova, member, Central Council...QTJAUn INSP1CH3B t Soviet Union Political Affairs JPRS-UPA-88-044 CONTENTS 03 OCTOBER 1989 PARTY, STATE AFFAIRS History of Formation of Nagorno...Advocated //. Zarakhovich, T . Trukhacheva; PRAVDA, 2 Aug 88] 86 REGIONAL ISSUES Biologist on Costs of Pollution Control Measures [A. Valentey

  20. JPRS Report. Soviet Union: Political Affairs.

    DTIC Science & Technology

    1990-07-10

    following three essential features: voluntary member- ship; self -management; and a permanent nature. All NATIONAL PARTY AND STATE AFFAIRS JPRS-UPA-90-040...voluntary, self -managed, permanently functioning association of citizens organized on a not- for-profit basis. This wording, which takes in the basic...problems which had long been present in the depths of society, including a most serious one—national self -preservation. As soon as the possibility of

  1. Emergency contraception: clinical outcomes.

    PubMed

    Glasier, Anna

    2013-03-01

    Emergency contraception (EC) is widely used to prevent unwanted pregnancy. This review considers the safety and efficacy of three commonly used methods -- levonorgestrel (LNG-EC), ulipristal acetate (UPA) and the copper intrauterine device. All are extremely safe, and side effects are minimal. Concerns about increased risks of ectopic pregnancy after EC use have proved unfounded, and possible teratogenic effects seem unlikely. Although the true effectiveness of EC is impossible to estimate, recent research suggests that LNG-EC prevents around 50% of expected pregnancies in women using the method within 72 h of intercourse, whereas UPA appeared to prevent almost two thirds of pregnancies. Emergency intrauterine device insertion probably prevents over 95% of pregnancies. However, although improved accessibility of EC has clearly led to increased use, it does not appear to have had any public health benefit in reducing unintended pregnancy rates. Most of the data on sexual behavior following improved access to EC do not show any detrimental effect on subsequent use of other more effective methods of contraception or on the incidence of unintended pregnancy or sexually transmitted infection. However, unless these other methods of contraception are also made easily available from pharmacies, improved access to EC risks unlinking its use with use of subsequent ongoing contraception. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth.

    PubMed

    Ehnman, M; Li, H; Fredriksson, L; Pietras, K; Eriksson, U

    2009-01-29

    Members of the platelet-derived growth factor (PDGF) family are mitogens for cells of mesenchymal origin and have important functions during embryonic development, blood vessel maturation, fibrotic diseases and cancer. In contrast to the two classical PDGFs, the novel and less well-characterized members, PDGF-CC and PDGF-DD, are latent factors that need to be processed extracellularly by activating proteases, before they can mediate PDGF receptor activation. Here, we elucidate the structural requirements for urokinase plasminogen activator (uPA)-mediated activation of PDGF-DD, as well as the intricate interplay with uPA receptor (uPAR) signalling. Furthermore, we show that activated PDGF-DD, in comparison to latent, more potently transforms NIH/3T3 cells in vitro. Conversely, xenograft studies in nude mice demonstrate that cells expressing latent PDGF-DD are more tumorigenic than those expressing activated PDGF-DD. These findings imply that a fine-tuned proteolytic activation, in the local milieu, controls PDGF-DD bioavailability. Moreover, we suggest that proteolytic activation of PDGF-DD reveals a retention motif mediating interactions with pericellular components. Our proposed mechanism, where uPA not only generates active PDGF-DD, but also regulates its spatial distribution, provides novel insights into the biological function of PDGF-DD.

  3. Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-Enolase.

    PubMed

    López-Alemany, Roser; Longstaff, Colin; Hawley, Stephen; Mirshahi, Massoud; Fábregas, Pere; Jardí, Merce; Merton, Elizabeth; Miles, Lindsey A; Félez, Jordi

    2003-04-01

    Localization of plasmin activity on leukocyte surfaces plays a critical role in fibrinolysis as well as in pathological and physiological processes in which cells must degrade the extracellular matrix in order to migrate. The binding of plasminogen to leukocytic cell lines induces a 30- to 80-fold increase in the rate of plasminogen activation by tissue-type (tPA) and urokinase-type (uPA) plasminogen activators. In the present study we have examined the role of alpha-enolase in plasminogen activation on the cell surface. We produced and characterized a monoclonal antibody (MAb) 11G1 against purified alpha-enolase, which abrogated about 90% of cell-dependent plasminogen activation by either uPA or tPA on leukocytoid cell lines of different lineages: B-lymphocytic, T-lymphocytic, granulocytic, and monocytic cells. In addition, MAb 11G1 also blocked enhancement of plasmin formation by peripheral blood neutrophils and monocytes. In contrast, MAb 11G1 did not affect plasmin generation in the presence of fibrin, indicating that this antibody did not interact with fibrinolytic components in the absence of cells. These data suggest that, although leukocytic cells display several molecules that bind plasminogen, alpha-enolase is responsible for the majority of the promotion of plasminogen activation on the surfaces of leukocytic cells. Copyright 2003 Wiley-Liss, Inc.

  4. Lanthanide-doped NaScF4 nanoprobes: crystal structure, optical spectroscopy and biodetection.

    PubMed

    Ai, Yu; Tu, Datao; Zheng, Wei; Liu, Yongsheng; Kong, Jintao; Hu, Ping; Chen, Zhuo; Huang, Mingdong; Chen, Xueyuan

    2013-07-21

    Trivalent lanthanide ions (Ln(3+))-doped inorganic nanoparticles (NPs) as potential luminescent bioprobes have been attracting tremendous interest because of their unique upconversion (UC) and downconversion (DC) luminescence properties. NaScF4, as an important host material, has been rarely reported and its crystal structure remains unclear. Herein, based on the single crystal X-ray diffraction, the space group of NaScF4 crystals was determined to be P31 containing multiple sites of Sc(3+) with crystallographic site symmetry of C1, which was verified by high-resolution photoluminescence spectroscopy of Eu(3+) at low temperature (10 K). Furthermore, monodisperse and size-controllable NaScF4:Ln(3+) NPs were synthesized via a facile thermal decomposition method. The biotinylated NaScF4:Er(3+)/Yb(3+) NPs were demonstrated for their applications as a heterogeneous UC luminescence bioprobe to detect avidin with a detection limit of 180 pM. After bioconjugation with amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), NaScF4:Ln(3+) NPs also exhibited specific recognition of cancer cells overexpressed with uPA receptor (uPAR, an important marker of tumor biology and metastasis), showing great potentials in tumor-targeted bioimaging.

  5. Flexural behavior of reinforced concrete beam with polymer coated pumice

    NASA Astrophysics Data System (ADS)

    Nainggolan, Christin Remayanti; Wijatmiko, Indradi; Wibowo, Ari

    2017-09-01

    Sustainable development has become an important issue due to the increasing consideration of preserving the nature. Many alternative for coarse aggregate replacement have been investigated ranging from natural and fabricated aggregates. In this study, natural aggregate pumice was investigated since it offers lower density that give paramount benefit in reducing total building weight and hence reducing the earthquake excitation effect and optimizing the structural dimension. However, the characteristic of porous surfaces of pumice causes excessive water absorption during concrete mixing process. Therefore, to reduce the additional water, the pumice aggregates were coated with polymer. The tested specimens consisted of normal concrete beams (NCB), uncoated pumice aggregate concrete beam (UPA) and polymer coated pumice aggregate concrete beam (PCP). The objective of the research was to obtain the effect of coating on the pumice aggregate to the flexural behavior of concrete beams. The lateral load-displacement behavior, ductility and collapse mechanism were studied. The results showed that there were only marginal drop on the load-carrying capacity of the pumice aggregate beam compared to those of normal beam. Additionally, the ductility coefficient of specimens UPA and PCP decreased of 11,97% and 14,03% respectively compared to NCB, and the ultimate load capacity decreased less than 1%. Overall, the pumice aggregate showed good characteristic for replacing normal coarse aggregate.

  6. An Atmospheric General Circulation Model with Chemistry for the CRAY T3E: Design, Performance Optimization and Coupling to an Ocean Model

    NASA Technical Reports Server (NTRS)

    Farrara, John D.; Drummond, Leroy A.; Mechoso, Carlos R.; Spahr, Joseph A.

    1998-01-01

    The design, implementation and performance optimization on the CRAY T3E of an atmospheric general circulation model (AGCM) which includes the transport of, and chemical reactions among, an arbitrary number of constituents is reviewed. The parallel implementation is based on a two-dimensional (longitude and latitude) data domain decomposition. Initial optimization efforts centered on minimizing the impact of substantial static and weakly-dynamic load imbalances among processors through load redistribution schemes. Recent optimization efforts have centered on single-node optimization. Strategies employed include loop unrolling, both manually and through the compiler, the use of an optimized assembler-code library for special function calls, and restructuring of parts of the code to improve data locality. Data exchanges and synchronizations involved in coupling different data-distributed models can account for a significant fraction of the running time. Therefore, the required scattering and gathering of data must be optimized. In systems such as the T3E, there is much more aggregate bandwidth in the total system than in any particular processor. This suggests a distributed design. The design and implementation of a such distributed 'Data Broker' as a means to efficiently couple the components of our climate system model is described.

  7. Data communication through multiple physical media: applications to munitions

    NASA Astrophysics Data System (ADS)

    Dhadwal, Harbans S.; Rastegar, Jahangir; Feng, Dake; Kwok, Philip

    2015-05-01

    Electronic systems comprising of subassemblies, distributed across different physical media, require seamless communication between processors and sensors embedded in the disparate volumes. For example, smart munitions systems embed sensors and other key control electronics, throughout the structure, in vastly different physical media. In addition to the obvious space constraints, these structures are subjected to high G forces during launch. Thus, communications through wire harnesses becomes cumbersome, make assembly process and testing difficult, and challenging to make survive high G firing. Here we focus on an approach that takes advantage of the partial optical transparency of epoxy material commonly used in potting electronic components in munitions, as well as the wave guiding that is possible through the body of the munitions wall which is made from composite materials. Experimental results show that a wireless optical link, connecting various parts of the distributed system, is possible at near IR frequencies. Data can be rapidly parsed between a processor, sensors and actuators. We present experimental data for a commercial epoxy system, which is used to embed a number of IrDA devices inside the cone of 120 mm mortar shell. IrDA devices using the FIR data rates establish point-to-point communication through various media, representative of the environment inside the 120 mm mortar cone.

  8. Generating unstructured nuclear reactor core meshes in parallel

    DOE PAGES

    Jain, Rajeev; Tautges, Timothy J.

    2014-10-24

    Recent advances in supercomputers and parallel solver techniques have enabled users to run large simulations problems using millions of processors. Techniques for multiphysics nuclear reactor core simulations are under active development in several countries. Most of these techniques require large unstructured meshes that can be hard to generate in a standalone desktop computers because of high memory requirements, limited processing power, and other complexities. We have previously reported on a hierarchical lattice-based approach for generating reactor core meshes. Here, we describe efforts to exploit coarse-grained parallelism during reactor assembly and reactor core mesh generation processes. We highlight several reactor coremore » examples including a very high temperature reactor, a full-core model of the Korean MONJU reactor, a ¼ pressurized water reactor core, the fast reactor Experimental Breeder Reactor-II core with a XX09 assembly, and an advanced breeder test reactor core. The times required to generate large mesh models, along with speedups obtained from running these problems in parallel, are reported. A graphical user interface to the tools described here has also been developed.« less

  9. Assessment of Service Life for Regenerative ECLSS Resin Beds

    NASA Technical Reports Server (NTRS)

    Cloud, Dale L.; Keilich, Maria C.; Polis, Peter C.; Yanczura, Stephen J.

    2013-01-01

    The International Space Station (ISS) Water Processor Assembly (WPA) and Oxygen Generation Assembly (OGA) manage and process water at various levels of cleanliness for multiple purposes. The effluent of theWPA and the influent of the OGA require water at very high levels of purity. The bulk of the water purification that occurs in both systems is performed by consumable activated carbon and ion exchange resin beds. Replacement beds must be available on orbit in order to continue the ISS critical processes of water purification and oxygen generation. Various hurdles exist in order to ensure viable spare resin beds. These include the characteristics of resin beds such as: storage environment, shelf life requirements, microbial growth, and variations in the levels and species of contaminants the beds are required to remove. Careful consideration has been given to match water models, bed capacities and spares traffic models to ensure that spares are always viable. The results of these studies and considerations, in particular, how shelf life requirements affect resin bed life management, are documented in this paper.

  10. Gas-Liquid Two-Phase Flows Through Packed Bed Reactors in Microgravity

    NASA Technical Reports Server (NTRS)

    Motil, Brian J.; Balakotaiah, Vemuri

    2001-01-01

    The simultaneous flow of gas and liquid through a fixed bed of particles occurs in many unit operations of interest to the designers of space-based as well as terrestrial equipment. Examples include separation columns, gas-liquid reactors, humidification, drying, extraction, and leaching. These operations are critical to a wide variety of industries such as petroleum, pharmaceutical, mining, biological, and chemical. NASA recognizes that similar operations will need to be performed in space and on planetary bodies such as Mars if we are to achieve our goals of human exploration and the development of space. The goal of this research is to understand how to apply our current understanding of two-phase fluid flow through fixed-bed reactors to zero- or partial-gravity environments. Previous experiments by NASA have shown that reactors designed to work on Earth do not necessarily function in a similar manner in space. Two experiments, the Water Processor Assembly and the Volatile Removal Assembly have encountered difficulties in predicting and controlling the distribution of the phases (a crucial element in the operation of this type of reactor) as well as the overall pressure drop.

  11. Integration of In-Flight and Post-Flight Water Monitoring Resources in Addressing the U.S. Water Processor Assembly Total Organic Carbon (TOC) Anomaly

    NASA Technical Reports Server (NTRS)

    Straub, John E., II; McCly, J. Torin

    2011-01-01

    Beginning in June of 2010, the total organic carbon (TOC) concentration in the U.S. Water Processor Assembly (WPA) product water started to increase. A surprisingly consistent upward TOC trend was observed through weekly ISS total organic carbon analyzer (TOCA) monitoring. As TOC is a general organic compound indicator, return of water archive samples was needed to make better-informed crew health decisions on the specific compounds of concern and to aid in WPA troubleshooting. TOCA-measured TOC was more than halfway to the health-based screening limit of 3,000 g/L before archive samples were returned. Archive samples were returned on 22 Soyuz in September 2010 and on ULF5 in November of 2010. The samples were subjected to extensive analysis. Although TOC was confirmed to be elevated, somewhat surprisingly, none of the typical target compounds were detected at high levels. After some solid detective work, it was confirmed that the TOC was associated with a compound known as dimethylsilanediol (DMSD). DMSD is believed to be a breakdown product of siloxanes which are thought to be ubiquitous in the ISS atmosphere. A toxicological limit was set for DMSD and a forward plan was developed for conducting operations in the context of understanding the composition of the TOC measured in flight. This required careful consideration of existing ISS flight rules, coordination with ISS stakeholders, and development of a novel approach for the blending of inflight TOCA data with archive results to protect crew health. Among other challenges, team members had to determine how to utilize TOCA readings when making decisions about crew consumption of WPA water. This involved balancing very real concerns associated with the assumption that TOC would continue to be comprised of only DMSD. Demonstrated teamwork, multidisciplinary awareness, and innovative problem-solving were required to respond effectively to this anomaly.

  12. Coding, testing and documentation of processors for the flight design system

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The general functional design and implementation of processors for a space flight design system are briefly described. Discussions of a basetime initialization processor; conic, analytical, and precision coasting flight processors; and an orbit lifetime processor are included. The functions of several utility routines are also discussed.

  13. The computational structural mechanics testbed generic structural-element processor manual

    NASA Technical Reports Server (NTRS)

    Stanley, Gary M.; Nour-Omid, Shahram

    1990-01-01

    The usage and development of structural finite element processors based on the CSM Testbed's Generic Element Processor (GEP) template is documented. By convention, such processors have names of the form ESi, where i is an integer. This manual is therefore intended for both Testbed users who wish to invoke ES processors during the course of a structural analysis, and Testbed developers who wish to construct new element processors (or modify existing ones).

  14. Highly parallel reconfigurable computer architecture for robotic computation having plural processor cells each having right and left ensembles of plural processors

    NASA Technical Reports Server (NTRS)

    Fijany, Amir (Inventor); Bejczy, Antal K. (Inventor)

    1994-01-01

    In a computer having a large number of single-instruction multiple data (SIMD) processors, each of the SIMD processors has two sets of three individual processor elements controlled by a master control unit and interconnected among a plurality of register file units where data is stored. The register files input and output data in synchronism with a minor cycle clock under control of two slave control units controlling the register file units connected to respective ones of the two sets of processor elements. Depending upon which ones of the register file units are enabled to store or transmit data during a particular minor clock cycle, the processor elements within an SIMD processor are connected in rings or in pipeline arrays, and may exchange data with the internal bus or with neighboring SIMD processors through interface units controlled by respective ones of the two slave control units.

  15. System and method for representing and manipulating three-dimensional objects on massively parallel architectures

    DOEpatents

    Karasick, Michael S.; Strip, David R.

    1996-01-01

    A parallel computing system is described that comprises a plurality of uniquely labeled, parallel processors, each processor capable of modelling a three-dimensional object that includes a plurality of vertices, faces and edges. The system comprises a front-end processor for issuing a modelling command to the parallel processors, relating to a three-dimensional object. Each parallel processor, in response to the command and through the use of its own unique label, creates a directed-edge (d-edge) data structure that uniquely relates an edge of the three-dimensional object to one face of the object. Each d-edge data structure at least includes vertex descriptions of the edge and a description of the one face. As a result, each processor, in response to the modelling command, operates upon a small component of the model and generates results, in parallel with all other processors, without the need for processor-to-processor intercommunication.

  16. Switch for serial or parallel communication networks

    DOEpatents

    Crosette, D.B.

    1994-07-19

    A communication switch apparatus and a method for use in a geographically extensive serial, parallel or hybrid communication network linking a multi-processor or parallel processing system has a very low software processing overhead in order to accommodate random burst of high density data. Associated with each processor is a communication switch. A data source and a data destination, a sensor suite or robot for example, may also be associated with a switch. The configuration of the switches in the network are coordinated through a master processor node and depends on the operational phase of the multi-processor network: data acquisition, data processing, and data exchange. The master processor node passes information on the state to be assumed by each switch to the processor node associated with the switch. The processor node then operates a series of multi-state switches internal to each communication switch. The communication switch does not parse and interpret communication protocol and message routing information. During a data acquisition phase, the communication switch couples sensors producing data to the processor node associated with the switch, to a downlink destination on the communications network, or to both. It also may couple an uplink data source to its processor node. During the data exchange phase, the switch couples its processor node or an uplink data source to a downlink destination (which may include a processor node or a robot), or couples an uplink source to its processor node and its processor node to a downlink destination. 9 figs.

  17. Switch for serial or parallel communication networks

    DOEpatents

    Crosette, Dario B.

    1994-01-01

    A communication switch apparatus and a method for use in a geographically extensive serial, parallel or hybrid communication network linking a multi-processor or parallel processing system has a very low software processing overhead in order to accommodate random burst of high density data. Associated with each processor is a communication switch. A data source and a data destination, a sensor suite or robot for example, may also be associated with a switch. The configuration of the switches in the network are coordinated through a master processor node and depends on the operational phase of the multi-processor network: data acquisition, data processing, and data exchange. The master processor node passes information on the state to be assumed by each switch to the processor node associated with the switch. The processor node then operates a series of multi-state switches internal to each communication switch. The communication switch does not parse and interpret communication protocol and message routing information. During a data acquisition phase, the communication switch couples sensors producing data to the processor node associated with the switch, to a downlink destination on the communications network, or to both. It also may couple an uplink data source to its processor node. During the data exchange phase, the switch couples its processor node or an uplink data source to a downlink destination (which may include a processor node or a robot), or couples an uplink source to its processor node and its processor node to a downlink destination.

  18. Conditions for space invariance in optical data processors used with coherent or noncoherent light.

    PubMed

    Arsenault, H R

    1972-10-01

    The conditions for space invariance in coherent and noncoherent optical processors are considered. All linear optical processors are shown to belong to one of two types. The conditions for space invariance are more stringent for noncoherent processors than for coherent processors, so that a system that is linear in coherent light may be nonlinear in noncoherent light. However, any processor that is linear in noncoherent light is also linear in the coherent limit.

  19. Broadcasting collective operation contributions throughout a parallel computer

    DOEpatents

    Faraj, Ahmad [Rochester, MN

    2012-02-21

    Methods, systems, and products are disclosed for broadcasting collective operation contributions throughout a parallel computer. The parallel computer includes a plurality of compute nodes connected together through a data communications network. Each compute node has a plurality of processors for use in collective parallel operations on the parallel computer. Broadcasting collective operation contributions throughout a parallel computer according to embodiments of the present invention includes: transmitting, by each processor on each compute node, that processor's collective operation contribution to the other processors on that compute node using intra-node communications; and transmitting on a designated network link, by each processor on each compute node according to a serial processor transmission sequence, that processor's collective operation contribution to the other processors on the other compute nodes using inter-node communications.

  20. LANDSAT-D flight segment operations manual. Appendix B: OBC software operations

    NASA Technical Reports Server (NTRS)

    Talipsky, R.

    1981-01-01

    The LANDSAT 4 satellite contains two NASA standard spacecraft computers and 65,536 words of memory. Onboard computer software is divided into flight executive and applications processors. Both applications processors and the flight executive use one or more of 67 system tables to obtain variables, constants, and software flags. Output from the software for monitoring operation is via 49 OBC telemetry reports subcommutated in the spacecraft telemetry. Information is provided about the flight software as it is used to control the various spacecraft operations and interpret operational OBC telemetry. Processor function descriptions, processor operation, software constraints, processor system tables, processor telemetry, and processor flow charts are presented.

  1. Managing Power Heterogeneity

    NASA Astrophysics Data System (ADS)

    Pruhs, Kirk

    A particularly important emergent technology is heterogeneous processors (or cores), which many computer architects believe will be the dominant architectural design in the future. The main advantage of a heterogeneous architecture, relative to an architecture of identical processors, is that it allows for the inclusion of processors whose design is specialized for particular types of jobs, and for jobs to be assigned to a processor best suited for that job. Most notably, it is envisioned that these heterogeneous architectures will consist of a small number of high-power high-performance processors for critical jobs, and a larger number of lower-power lower-performance processors for less critical jobs. Naturally, the lower-power processors would be more energy efficient in terms of the computation performed per unit of energy expended, and would generate less heat per unit of computation. For a given area and power budget, heterogeneous designs can give significantly better performance for standard workloads. Moreover, even processors that were designed to be homogeneous, are increasingly likely to be heterogeneous at run time: the dominant underlying cause is the increasing variability in the fabrication process as the feature size is scaled down (although run time faults will also play a role). Since manufacturing yields would be unacceptably low if every processor/core was required to be perfect, and since there would be significant performance loss from derating the entire chip to the functioning of the least functional processor (which is what would be required in order to attain processor homogeneity), some processor heterogeneity seems inevitable in chips with many processors/cores.

  2. Multi-Core Processor Memory Contention Benchmark Analysis Case Study

    NASA Technical Reports Server (NTRS)

    Simon, Tyler; McGalliard, James

    2009-01-01

    Multi-core processors dominate current mainframe, server, and high performance computing (HPC) systems. This paper provides synthetic kernel and natural benchmark results from an HPC system at the NASA Goddard Space Flight Center that illustrate the performance impacts of multi-core (dual- and quad-core) vs. single core processor systems. Analysis of processor design, application source code, and synthetic and natural test results all indicate that multi-core processors can suffer from significant memory subsystem contention compared to similar single-core processors.

  3. Simulink/PARS Integration Support

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vacaliuc, B.; Nakhaee, N.

    2013-12-18

    The state of the art for signal processor hardware has far out-paced the development tools for placing applications on that hardware. In addition, signal processors are available in a variety of architectures, each uniquely capable of handling specific types of signal processing efficiently. With these processors becoming smaller and demanding less power, it has become possible to group multiple processors, a heterogeneous set of processors, into single systems. Different portions of the desired problem set can be assigned to different processor types as appropriate. As software development tools do not keep pace with these processors, especially when multiple processors ofmore » different types are used, a method is needed to enable software code portability among multiple processors and multiple types of processors along with their respective software environments. Sundance DSP, Inc. has developed a software toolkit called “PARS”, whose objective is to provide a framework that uses suites of tools provided by different vendors, along with modeling tools and a real time operating system, to build an application that spans different processor types. The software language used to express the behavior of the system is a very high level modeling language, “Simulink”, a MathWorks product. ORNL has used this toolkit to effectively implement several deliverables. This CRADA describes this collaboration between ORNL and Sundance DSP, Inc.« less

  4. SPECIAL ISSUE ON OPTICAL PROCESSING OF INFORMATION: Optoelectronic processors with scanning CCD photodetectors

    NASA Astrophysics Data System (ADS)

    Esepkina, N. A.; Lavrov, A. P.; Anan'ev, M. N.; Blagodarnyi, V. S.; Ivanov, S. I.; Mansyrev, M. I.; Molodyakov, S. A.

    1995-10-01

    Two new types of optoelectronic radio-signal processors were investigated. Charge-coupled device (CCD) photodetectors are used in these processors under continuous scanning conditions, i.e. in a time delay and storage mode. One of these processors is based on a CCD photodetector array with a reference-signal amplitude transparency and the other is an adaptive acousto-optical signal processor with linear frequency modulation. The processor with the transparency performs multichannel discrete—analogue convolution of an input signal with a corresponding kernel of the transformation determined by the transparency. If a light source is an array of light-emitting diodes of special (stripe) geometry, the optical stages of the processor can be made from optical fibre components and the whole processor then becomes a rigid 'sandwich' (a compact hybrid optoelectronic microcircuit). A report is given also of a study of a prototype processor with optical fibre components for the reception of signals from a system with antenna aperture synthesis, which forms a radio image of the Earth.

  5. System and method for representing and manipulating three-dimensional objects on massively parallel architectures

    DOEpatents

    Karasick, M.S.; Strip, D.R.

    1996-01-30

    A parallel computing system is described that comprises a plurality of uniquely labeled, parallel processors, each processor capable of modeling a three-dimensional object that includes a plurality of vertices, faces and edges. The system comprises a front-end processor for issuing a modeling command to the parallel processors, relating to a three-dimensional object. Each parallel processor, in response to the command and through the use of its own unique label, creates a directed-edge (d-edge) data structure that uniquely relates an edge of the three-dimensional object to one face of the object. Each d-edge data structure at least includes vertex descriptions of the edge and a description of the one face. As a result, each processor, in response to the modeling command, operates upon a small component of the model and generates results, in parallel with all other processors, without the need for processor-to-processor intercommunication. 8 figs.

  6. Shared performance monitor in a multiprocessor system

    DOEpatents

    Chiu, George; Gara, Alan G.; Salapura, Valentina

    2012-07-24

    A performance monitoring unit (PMU) and method for monitoring performance of events occurring in a multiprocessor system. The multiprocessor system comprises a plurality of processor devices units, each processor device for generating signals representing occurrences of events in the processor device, and, a single shared counter resource for performance monitoring. The performance monitor unit is shared by all processor cores in the multiprocessor system. The PMU comprises: a plurality of performance counters each for counting signals representing occurrences of events from one or more the plurality of processor units in the multiprocessor system; and, a plurality of input devices for receiving the event signals from one or more processor devices of the plurality of processor units, the plurality of input devices programmable to select event signals for receipt by one or more of the plurality of performance counters for counting, wherein the PMU is shared between multiple processing units, or within a group of processors in the multiprocessing system. The PMU is further programmed to monitor event signals issued from non-processor devices.

  7. Implementation of kernels on the Maestro processor

    NASA Astrophysics Data System (ADS)

    Suh, Jinwoo; Kang, D. I. D.; Crago, S. P.

    Currently, most microprocessors use multiple cores to increase performance while limiting power usage. Some processors use not just a few cores, but tens of cores or even 100 cores. One such many-core microprocessor is the Maestro processor, which is based on Tilera's TILE64 processor. The Maestro chip is a 49-core, general-purpose, radiation-hardened processor designed for space applications. The Maestro processor, unlike the TILE64, has a floating point unit (FPU) in each core for improved floating point performance. The Maestro processor runs at 342 MHz clock frequency. On the Maestro processor, we implemented several widely used kernels: matrix multiplication, vector add, FIR filter, and FFT. We measured and analyzed the performance of these kernels. The achieved performance was up to 5.7 GFLOPS, and the speedup compared to single tile was up to 49 using 49 tiles.

  8. Ordering of guarded and unguarded stores for no-sync I/O

    DOEpatents

    Gara, Alan; Ohmacht, Martin

    2013-06-25

    A parallel computing system processes at least one store instruction. A first processor core issues a store instruction. A first queue, associated with the first processor core, stores the store instruction. A second queue, associated with a first local cache memory device of the first processor core, stores the store instruction. The first processor core updates first data in the first local cache memory device according to the store instruction. The third queue, associated with at least one shared cache memory device, stores the store instruction. The first processor core invalidates second data, associated with the store instruction, in the at least one shared cache memory. The first processor core invalidates third data, associated with the store instruction, in other local cache memory devices of other processor cores. The first processor core flushing only the first queue.

  9. Automated system for analyzing the activity of individual neurons

    NASA Technical Reports Server (NTRS)

    Bankman, Isaac N.; Johnson, Kenneth O.; Menkes, Alex M.; Diamond, Steve D.; Oshaughnessy, David M.

    1993-01-01

    This paper presents a signal processing system that: (1) provides an efficient and reliable instrument for investigating the activity of neuronal assemblies in the brain; and (2) demonstrates the feasibility of generating the command signals of prostheses using the activity of relevant neurons in disabled subjects. The system operates online, in a fully automated manner and can recognize the transient waveforms of several neurons in extracellular neurophysiological recordings. Optimal algorithms for detection, classification, and resolution of overlapping waveforms are developed and evaluated. Full automation is made possible by an algorithm that can set appropriate decision thresholds and an algorithm that can generate templates on-line. The system is implemented with a fast IBM PC compatible processor board that allows on-line operation.

  10. Rapid solution of large-scale systems of equations

    NASA Technical Reports Server (NTRS)

    Storaasli, Olaf O.

    1994-01-01

    The analysis and design of complex aerospace structures requires the rapid solution of large systems of linear and nonlinear equations, eigenvalue extraction for buckling, vibration and flutter modes, structural optimization and design sensitivity calculation. Computers with multiple processors and vector capabilities can offer substantial computational advantages over traditional scalar computer for these analyses. These computers fall into two categories: shared memory computers and distributed memory computers. This presentation covers general-purpose, highly efficient algorithms for generation/assembly or element matrices, solution of systems of linear and nonlinear equations, eigenvalue and design sensitivity analysis and optimization. All algorithms are coded in FORTRAN for shared memory computers and many are adapted to distributed memory computers. The capability and numerical performance of these algorithms will be addressed.

  11. Electronics reliability fracture mechanics. Volume 1: Causes of failures of shop replaceable units and hybrid microcircuits

    NASA Astrophysics Data System (ADS)

    Kallis, J.; Buechler, D.; Erickson, J.; Westerhuyzen, D. V.; Strokes, R.

    1992-05-01

    This is the first of two volumes. The other volume (WL-TR-91-3119) is 'Fracture Mechanics'. The objective of the Electronics Reliability Fracture Mechanics (ERFM) program was to develop and demonstrate a life prediction technique for electronic assemblies, when subjected to environmental stress of vibration and thermal cycling, based upon the mechanical properties of the materials and packaging configurations which make up an electronic system. A detailed investigation was performed of the following two shop replaceable units (SRUs): Timing and Control Module (P/N 3562102) and Linear Regulator Module (P/N 3569800). The SRUs are in the Programmable Signal Processor (3137042) Line Replaceable Unit (LRU) of the Hughes AN/APG-63 Radar for the F-15 Aircraft.

  12. Solving a four-destination traveling salesman problem using Escherichia coli cells as biocomputers.

    PubMed

    Esau, Michael; Rozema, Mark; Zhang, Tuo Huang; Zeng, Dawson; Chiu, Stephanie; Kwan, Rachel; Moorhouse, Cadence; Murray, Cameron; Tseng, Nien-Tsu; Ridgway, Doug; Sauvageau, Dominic; Ellison, Michael

    2014-12-19

    The Traveling Salesman Problem involves finding the shortest possible route visiting all destinations on a map only once before returning to the point of origin. The present study demonstrates a strategy for solving Traveling Salesman Problems using modified E. coli cells as processors for massively parallel computing. Sequential, combinatorial DNA assembly was used to generate routes, in the form of plasmids made up of marker genes, each representing a path between destinations, and short connecting linkers, each representing a given destination. Upon growth of the population of modified E. coli, phenotypic selection was used to eliminate invalid routes, and statistical analysis was performed to successfully identify the optimal solution. The strategy was successfully employed to solve a four-destination test problem.

  13. Electrochemical sensing using voltage-current time differential

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woo, Leta Yar-Li; Glass, Robert Scott; Fitzpatrick, Joseph Jay

    2017-02-28

    A device for signal processing. The device includes a signal generator, a signal detector, and a processor. The signal generator generates an original waveform. The signal detector detects an affected waveform. The processor is coupled to the signal detector. The processor receives the affected waveform from the signal detector. The processor also compares at least one portion of the affected waveform with the original waveform. The processor also determines a difference between the affected waveform and the original waveform. The processor also determines a value corresponding to a unique portion of the determined difference between the original and affected waveforms.more » The processor also outputs the determined value.« less

  14. Accuracy requirements of optical linear algebra processors in adaptive optics imaging systems

    NASA Technical Reports Server (NTRS)

    Downie, John D.; Goodman, Joseph W.

    1989-01-01

    The accuracy requirements of optical processors in adaptive optics systems are determined by estimating the required accuracy in a general optical linear algebra processor (OLAP) that results in a smaller average residual aberration than that achieved with a conventional electronic digital processor with some specific computation speed. Special attention is given to an error analysis of a general OLAP with regard to the residual aberration that is created in an adaptive mirror system by the inaccuracies of the processor, and to the effect of computational speed of an electronic processor on the correction. Results are presented on the ability of an OLAP to compete with a digital processor in various situations.

  15. Modeling heterogeneous processor scheduling for real time systems

    NASA Technical Reports Server (NTRS)

    Leathrum, J. F.; Mielke, R. R.; Stoughton, J. W.

    1994-01-01

    A new model is presented to describe dataflow algorithms implemented in a multiprocessing system. Called the resource/data flow graph (RDFG), the model explicitly represents cyclo-static processor schedules as circuits of processor arcs which reflect the order that processors execute graph nodes. The model also allows the guarantee of meeting hard real-time deadlines. When unfolded, the model identifies statically the processor schedule. The model therefore is useful for determining the throughput and latency of systems with heterogeneous processors. The applicability of the model is demonstrated using a space surveillance algorithm.

  16. Parallel processor for real-time structural control

    NASA Astrophysics Data System (ADS)

    Tise, Bert L.

    1993-07-01

    A parallel processor that is optimized for real-time linear control has been developed. This modular system consists of A/D modules, D/A modules, and floating-point processor modules. The scalable processor uses up to 1,000 Motorola DSP96002 floating-point processors for a peak computational rate of 60 GFLOPS. Sampling rates up to 625 kHz are supported by this analog-in to analog-out controller. The high processing rate and parallel architecture make this processor suitable for computing state-space equations and other multiply/accumulate-intensive digital filters. Processor features include 14-bit conversion devices, low input-to-output latency, 240 Mbyte/s synchronous backplane bus, low-skew clock distribution circuit, VME connection to host computer, parallelizing code generator, and look- up-tables for actuator linearization. This processor was designed primarily for experiments in structural control. The A/D modules sample sensors mounted on the structure and the floating- point processor modules compute the outputs using the programmed control equations. The outputs are sent through the D/A module to the power amps used to drive the structure's actuators. The host computer is a Sun workstation. An OpenWindows-based control panel is provided to facilitate data transfer to and from the processor, as well as to control the operating mode of the processor. A diagnostic mode is provided to allow stimulation of the structure and acquisition of the structural response via sensor inputs.

  17. Testing and operating a multiprocessor chip with processor redundancy

    DOEpatents

    Bellofatto, Ralph E; Douskey, Steven M; Haring, Rudolf A; McManus, Moyra K; Ohmacht, Martin; Schmunkamp, Dietmar; Sugavanam, Krishnan; Weatherford, Bryan J

    2014-10-21

    A system and method for improving the yield rate of a multiprocessor semiconductor chip that includes primary processor cores and one or more redundant processor cores. A first tester conducts a first test on one or more processor cores, and encodes results of the first test in an on-chip non-volatile memory. A second tester conducts a second test on the processor cores, and encodes results of the second test in an external non-volatile storage device. An override bit of a multiplexer is set if a processor core fails the second test. In response to the override bit, the multiplexer selects a physical-to-logical mapping of processor IDs according to one of: the encoded results in the memory device or the encoded results in the external storage device. On-chip logic configures the processor cores according to the selected physical-to-logical mapping.

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reed, D.A.; Grunwald, D.C.

    The spectrum of parallel processor designs can be divided into three sections according to the number and complexity of the processors. At one end there are simple, bit-serial processors. Any one of thee processors is of little value, but when it is coupled with many others, the aggregate computing power can be large. This approach to parallel processing can be likened to a colony of termites devouring a log. The most notable examples of this approach are the NASA/Goodyear Massively Parallel Processor, which has 16K one-bit processors, and the Thinking Machines Connection Machine, which has 64K one-bit processors. At themore » other end of the spectrum, a small number of processors, each built using the fastest available technology and the most sophisticated architecture, are combined. An example of this approach is the Cray X-MP. This type of parallel processing is akin to four woodmen attacking the log with chainsaws.« less

  19. Synthesis and characterization of an 111In-labeled peptide for the in vivo localization of human cancers expressing the urokinase-type plasminogen activator receptor (uPAR)

    PubMed Central

    Liu, Dijie; Overbey, Douglas; Watkinson, Lisa; Giblin, Michael F.

    2009-01-01

    This study describes the synthesis and preliminary biologic evaluation of an 111Inlabeled peptide antagonist of the urokinase-type plasminogen activator receptor (uPAR) as a potential probe for assessing metastatic potential of human breast cancer in vivo. The peptide (NAc-dD-CHA-F-dS-dR-Y-L-W-S-βAla)2-K-K(DOTA)-NH2 was synthesized and conjugated with the DOTA chelating moiety via conventional Solid-Phase Peptide Synthesis (SPPS), purified by reversed-phase HPLC, and characterized by MALDI-TOF MS and receptor binding assay. In vitro receptor binding studies demonstrated an IC50 of 240 ± 125 nM for the peptide, compared with IC50’s of 0.44 ± 0.02 and 0.75 ± 0.01 nM for the amino terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA) and full-length uPA, respectively. In vivo biodistribution studies were carried out using SCID mice bearing MDA-MB-231 human breast cancer xenografts. Biodistribution data was collected at 1, 4, and 24 hr post-injection of 111In-DOTA-peptide, and compared with data obtained using a scrambled control peptide, as well as with data obtained using wild-type ATF radiolabeled with I-125. Biodistribution studies showed rapid elimination of the 111In-labeled peptide from the blood pool, with 0.12 ± 0.06% ID/g remaining in blood at 4 hr pi. Elimination was seen primarily via the renal/urinary route, with 83.9 ± 2.2%ID in the urine at the same timepoint. Tumor uptake at this time was 0.53 ± 0.11%ID/g, resulting in tumor: blood and tumor: muscle ratios of 4.2 and 9.4, respectively. Uptake in tumor was significantly higher than that obtained using a scrambled control peptide that showed no specific binding to uPAR (p < 0.05). In vitro and ex vivo results both suggested that the magnitude of tumor-specific binding was reduced in this model by endogenous expression of uPA. The results indicate that radiolabeled peptide uPAR antagonists may find application in the imaging and therapy of uPAR-expressing breast cancers in vivo. PMID:19354275

  20. [The effect of urokinase on hepatic fibrogenesis in rats].

    PubMed

    Wu, Xi-run; Wang, Qi; Wang, Ling; Shi, Shui-sheng; Guo, Wen-dong

    2009-12-01

    To investigate the effect of urokinase on hepatic fibrogenesis in rats. Hepatic fibrosis was induced in rats by complex pathogenic factors including subcutaneous injections of carbon tetrachloride, alcohol and cholesterol feeding. Animals were randomly divided into 3 groups: normal control group, hepatic fibrosis group (complex pathogenic factors for 6 weeks), UK prevention group (complex pathogenic factors+UK for 6 weeks). The animals were sacrificed at the end of week 6. The expression of alpha-SMA, uPA, PAI-1, TGFb1, TIMP-1, collagen type I and type III proteins in hepatic fibrosis tissue was detected by immunohistochemistry, the expression of PAI-1 and TGFb1 mRNA in the hepatic fibrosis tissue was quantified by real time RT-PCR. The serum levels of hyaluronicacid (HA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (TBil) and the content of liver hydroxyproline (Hyp) were detected using ELISA kits. The serum ALT, AST, TBil, HA and the content of liver Hyp were (46.66+/-6.30) U/L, (126.26+/-31.65) U/L, (31.11+/-4.20) micromol/L, (109.70+/-18.81) microg/L and (0.98+/-0.09) mg/(g liver), respectively, in UK prevention group, which were significantly lower than those [(101.57+/-11.97) U/L, (205.89+/-56.26) U/L, (67.75+/-2.75) micromol/L, (184.43+/-32.36) microg/L and (1.65+/-0.16) mg/(g liver), respectively] in hepatic fibrosis group (q = 3.3801-20.0061, P < 0.01). The levels of a-SMA, collagen type I, type III, TIMP-1, PAI-1, TGFb1 proteins were (299.27+/-37.36), (210.05+/-27.17), (192.94+/-24.48), (213.70+/-32.21), (204.25+/-17.92), (205.97+/-23.81), respectively, in UK prevention group, which were significantly lower than those [(418.83+/-30.21), (323.77+/-21.53), (302.37+/-31.43), (376.63+/-25.19), (313.53+/-26.67) and (327.42+/-36.75), respectively] in hepatic fibrosis group. The level of uPA protein was increased, and the expression of PAI-1, TGFb1 mRNA in hepatic fibrosis tissue was decreased in UK prevention group. In the early stage of hepatic fibrogenesis, urokinase can attenuate the progression of rat hepatic fibrosis via upregulation of uPA, downregulation of TGFb1, and inhibition of HSC activation.

  1. Electrochemical sensing using comparison of voltage-current time differential values during waveform generation and detection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woo, Leta Yar-Li; Glass, Robert Scott; Fitzpatrick, Joseph Jay

    2018-01-02

    A device for signal processing. The device includes a signal generator, a signal detector, and a processor. The signal generator generates an original waveform. The signal detector detects an affected waveform. The processor is coupled to the signal detector. The processor receives the affected waveform from the signal detector. The processor also compares at least one portion of the affected waveform with the original waveform. The processor also determines a difference between the affected waveform and the original waveform. The processor also determines a value corresponding to a unique portion of the determined difference between the original and affected waveforms.more » The processor also outputs the determined value.« less

  2. Hybrid Electro-Optic Processor

    DTIC Science & Technology

    1991-07-01

    This report describes the design of a hybrid electro - optic processor to perform adaptive interference cancellation in radar systems. The processor is...modulator is reported. Included is this report is a discussion of the design, partial fabrication in the laboratory, and partial testing of the hybrid electro ... optic processor. A follow on effort is planned to complete the construction and testing of the processor. The work described in this report is the

  3. JPRS Report, Science & Technology, Europe.

    DTIC Science & Technology

    1991-04-30

    processor in collaboration with Intel . The processor , christened Touchstone, will be used as the core of a parallel computer with 2,000 processors . One of...ELECTRONIQUE HEBDO in French 24 Jan 91 pp 14-15 [Article by Claire Remy: "Everything Set for Neural Signal Processors " first paragraph is ELECTRONIQUE...paving the way for neural signal processors in so doing. The principal advantage of this specific circuit over a neuromimetic software program is

  4. Processor register error correction management

    DOEpatents

    Bose, Pradip; Cher, Chen-Yong; Gupta, Meeta S.

    2016-12-27

    Processor register protection management is disclosed. In embodiments, a method of processor register protection management can include determining a sensitive logical register for executable code generated by a compiler, generating an error-correction table identifying the sensitive logical register, and storing the error-correction table in a memory accessible by a processor. The processor can be configured to generate a duplicate register of the sensitive logical register identified by the error-correction table.

  5. The CSM testbed matrix processors internal logic and dataflow descriptions

    NASA Technical Reports Server (NTRS)

    Regelbrugge, Marc E.; Wright, Mary A.

    1988-01-01

    This report constitutes the final report for subtask 1 of Task 5 of NASA Contract NAS1-18444, Computational Structural Mechanics (CSM) Research. This report contains a detailed description of the coded workings of selected CSM Testbed matrix processors (i.e., TOPO, K, INV, SSOL) and of the arithmetic utility processor AUS. These processors and the current sparse matrix data structures are studied and documented. Items examined include: details of the data structures, interdependence of data structures, data-blocking logic in the data structures, processor data flow and architecture, and processor algorithmic logic flow.

  6. Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-abdominal Adhesions, and Arterial Injuries

    DTIC Science & Technology

    2008-04-01

    small-cell lung cancer; TFP1, transferrin pseudogene 1; TGFβ, transforming growth factor-β; TNF, tumour- necrosis factor; uPA, urokinase-type plasminogen...Cell 79, 315–328 (1994). 23. Frater-Schroder, M., Risau, W., Hallmann, R., Gautschi, P. & Bohlen, P. Tumor necrosis factor type α, a potent inhibitor...relatively thin (skin) or avascular (cartilage) tissues, where post- implantation vascularization from the host is sufficient. To overcome the problem

  7. Novel gene C17orf37 in Prostate Cancer Progression and Metastasis: A Prospective Biomarker

    DTIC Science & Technology

    2010-05-01

    15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON a...UPA and VEGF. These results were reported in an original article. Ongoing experiments: Currently we are performing in vivo xenograft studies in...Activation of multiple cancer- associated genes at the ERBB2 amplicon in breast cancer. Endocr Relat Cancer 13: 39. Kelly P, Stemmle LN , Madden JF

  8. Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration.

    PubMed

    Chang, Yung-Ming; Ye, Chi-Xin; Ho, Tsung-Jung; Tsai, Te-Neng; Chiu, Ping-Ling; Tsai, Chin-Chuan; Lin, Yueh-Min; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang

    2014-05-01

    This study investigates the molecular mechanisms by which Alpiniae oxyphyllae fructus (AOF) promotes neuron regeneration. A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of AOF extract (0-200 mg/ml). We investigated the role of MAPK (ERK1/2, JNK and p38) pathways for AOF-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in RSC96 Schwann cells. The results showed that AOF increased the expressions of uPA, tPA, MMP-9, and MAPKs in vivo. In vitro, our results show that treatment with AOF extract induces ERK1/2, JNK, and p38 phosphorylation to activate the downstream PAs and MMPs signaling expression. AOF-stimulated ERK1/2, JNK, and p38 phosphorylation attenuated by individual pretreatment with siRNAs or inhibitors (U0126, SP600125 and SB203580), resulting in migration and uPA-related signal pathway inhibition. Taken together our data suggests the MAPKs (ERK1/2, JNK and p38), PAs (uPA, tPA), MMP (MMP2, MMP9) regenerative and migration signaling pathway of Schwann cells regulated by AOF extract might play a major role in Schwann cell migration and damaged peripheral nerve regeneration.

  9. Loss or Inhibition of uPA or MMP-9 Attenuates LV Remodeling and Dysfunction after Acute Pressure Overload in Mice

    PubMed Central

    Heymans, Stephane; Lupu, Florea; Terclavers, Sven; Vanwetswinkel, Bjorn; Herbert, Jean-Marc; Baker, Andrew; Collen, Desire; Carmeliet, Peter; Moons, Lieve

    2005-01-01

    Left ventricular (LV) hypertrophy is a natural response of the heart to increased pressure loading, but accompanying fibrosis and dilatation may result in irreversible life-threatening heart failure. Matrix metalloproteinases (MMPs) have been invoked in various cardiac diseases, however, direct genetic evidence for a role of the plasminogen activator (PA) and MMP systems in pressure overload-induced LV hypertrophy and in heart failure is lacking. Therefore, the consequences of transverse aortic banding (TAB) were analyzed in mice lacking tissue-type PA (t-PA−/−), urokinase-type PA (u-PA−/−), or gelatinase-B (MMP-9−/−), and in wild-type (WT) mice after adenoviral gene transfer of the PA-inhibitor PAI-1 or the MMP-inhibitor TIMP-1. TAB elevated LV pressure comparably in all genotypes. In WT and t-PA−/− mice, cardiomyocyte hypertrophy was associated with myocardial fibrosis, LV dilatation and dysfunction, and pump failure after 7 weeks. In contrast, in u-PA−/− mice or in WT mice after PAI-1- and TIMP-1-gene transfer, cardiomyocyte hypertrophy was moderate and only minimally associated with cardiac fibrosis and LV dilatation, resulting in better preservation of pump function. Deficiency of MMP-9 had an intermediate effect. These findings suggest that the use of u-PA- or MMP-inhibitors might preserve cardiac pump function in LV pressure overloading. PMID:15631996

  10. Council tax valuation band of patient residence and clinical contacts in a general practice

    PubMed Central

    Beale, Norman; Taylor, Gordon; Straker-Cook, Dawn; Peart, Carole; Gwynne, Mark

    2005-01-01

    Background There is a dearth of data relating UK general practice workload to personal and social markers of individual patients. Aim To test whether there is a significant association between general practice patient contact rates and the council tax valuation band of their residential address. Design of study Cross-sectional analyses using data recorded, over 1 year, for over 3300 general practice patients. Setting One medium-sized group practice in an industrialised English market town. Method Face-to-face contacts between the patients and the doctors and nurses in the practice were compared by patient age, sex, registration period, distance from surgery, Underprivileged Area 8 (UPA8) score, and council tax valuation band. Results Patient sex, age, recent registration, distance from surgery, and council tax valuation band were each significantly associated with face-to-face contact rate in univariate analyses. UPA8 score was not significantly associated with contact rates. On multivariate testing, sex, age, recent registration, and council tax valuation band remained significantly associated with contact rates. The last is a new finding. Conclusion Council tax valuation bands predict contact rate in general practice; the lower the band, the higher the contact rate. Council tax valuation band could be a useful marker of workload that is linked to socioeconomic status. This is a pilot study and multipractice research is advocated. PMID:15667763

  11. Applications of three DNA barcodes in assorting intertidal red macroalgal flora in Qingdao, China

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaobo; Pang, Shaojun; Shan, Tifeng; Liu, Feng

    2013-03-01

    This study is part of the endeavor to construct a comprehensive DNA barcoding database for common seaweeds in China. Identifications of red seaweeds, which have simple morphology and anatomy, are sometimes difficult solely depending on morphological characteristics. In recent years, DNA barcode technique has become a more and more effective tool to help solve some of the taxonomic difficulties. Some DNA markers such as COI (cytochrome oxidase subunit I) are proposed as standardized DNA barcodes for all seaweed species. In this study, COI, UPA (universal plastid amplicon, domain V of 23S rRNA), and ITS (nuclear internal transcribed spacer) were employed to analyze common species of intertidal red seaweeds in Qingdao (119.3°-121°E, 35.35°-37.09°N). The applicability of using one or a few combined barcodes to identify red seaweed species was tested. The results indicated that COI is a sensitive marker at species level. However, not all the tested species gave PCR amplification products due to lack of the universal primers. The second barcode UPA had effective universal primers but needed to be tested for the effectiveness of resolving closely related species. More than one ITS sequence types were found in some species in this investigation, which might lead to confusion in further analysis. Therefore ITS sequence is not recommended as a universal barcode for seaweeds identification.

  12. Parallel processor for real-time structural control

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tise, B.L.

    1992-01-01

    A parallel processor that is optimized for real-time linear control has been developed. This modular system consists of A/D modules, D/A modules, and floating-point processor modules. The scalable processor uses up to 1,000 Motorola DSP96002 floating-point processors for a peak computational rate of 60 GFLOPS. Sampling rates up to 625 kHz are supported by this analog-in to analog-out controller. The high processing rate and parallel architecture make this processor suitable for computing state-space equations and other multiply/accumulate-intensive digital filters. Processor features include 14-bit conversion devices, low input-output latency, 240 Mbyte/s synchronous backplane bus, low-skew clock distribution circuit, VME connection tomore » host computer, parallelizing code generator, and look-up-tables for actuator linearization. This processor was designed primarily for experiments in structural control. The A/D modules sample sensors mounted on the structure and the floating-point processor modules compute the outputs using the programmed control equations. The outputs are sent through the D/A module to the power amps used to drive the structure's actuators. The host computer is a Sun workstation. An Open Windows-based control panel is provided to facilitate data transfer to and from the processor, as well as to control the operating mode of the processor. A diagnostic mode is provided to allow stimulation of the structure and acquisition of the structural response via sensor inputs.« less

  13. 7 CFR 1435.310 - Sharing processors' allocations with producers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Flexible Marketing Allotments For Sugar § 1435.310 Sharing processors' allocations with producers. (a) Every sugar beet and sugarcane processor must provide CCC a certification that: (1) The processor...

  14. 7 CFR 1435.310 - Sharing processors' allocations with producers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Flexible Marketing Allotments For Sugar § 1435.310 Sharing processors' allocations with producers. (a) Every sugar beet and sugarcane processor must provide CCC a certification that: (1) The processor...

  15. 7 CFR 1435.310 - Sharing processors' allocations with producers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Flexible Marketing Allotments For Sugar § 1435.310 Sharing processors' allocations with producers. (a) Every sugar beet and sugarcane processor must provide CCC a certification that: (1) The processor...

  16. 7 CFR 1435.310 - Sharing processors' allocations with producers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Flexible Marketing Allotments For Sugar § 1435.310 Sharing processors' allocations with producers. (a) Every sugar beet and sugarcane processor must provide CCC a certification that: (1) The processor...

  17. 7 CFR 1435.310 - Sharing processors' allocations with producers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Flexible Marketing Allotments For Sugar § 1435.310 Sharing processors' allocations with producers. (a) Every sugar beet and sugarcane processor must provide CCC a certification that: (1) The processor...

  18. 40 CFR 791.45 - Processors.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) When a test rule or subsequent Federal Register notice pertaining to a test rule expressly obligates processors as well as manufacturers to assume direct testing and data reimbursement responsibilities. (2... processors voluntarily agree to reimburse manufacturers for a portion of test costs. Only those processors...

  19. Interprocessor bus switching system for simultaneous communication in plural bus parallel processing system

    DOEpatents

    Atac, R.; Fischler, M.S.; Husby, D.E.

    1991-01-15

    A bus switching apparatus and method for multiple processor computer systems comprises a plurality of bus switches interconnected by branch buses. Each processor or other module of the system is connected to a spigot of a bus switch. Each bus switch also serves as part of a backplane of a modular crate hardware package. A processor initiates communication with another processor by identifying that other processor. The bus switch to which the initiating processor is connected identifies and secures, if possible, a path to that other processor, either directly or via one or more other bus switches which operate similarly. If a particular desired path through a given bus switch is not available to be used, an alternate path is considered, identified and secured. 11 figures.

  20. Method and structure for skewed block-cyclic distribution of lower-dimensional data arrays in higher-dimensional processor grids

    DOEpatents

    Chatterjee, Siddhartha [Yorktown Heights, NY; Gunnels, John A [Brewster, NY

    2011-11-08

    A method and structure of distributing elements of an array of data in a computer memory to a specific processor of a multi-dimensional mesh of parallel processors includes designating a distribution of elements of at least a portion of the array to be executed by specific processors in the multi-dimensional mesh of parallel processors. The pattern of the designating includes a cyclical repetitive pattern of the parallel processor mesh, as modified to have a skew in at least one dimension so that both a row of data in the array and a column of data in the array map to respective contiguous groupings of the processors such that a dimension of the contiguous groupings is greater than one.

  1. Interprocessor bus switching system for simultaneous communication in plural bus parallel processing system

    DOEpatents

    Atac, Robert; Fischler, Mark S.; Husby, Donald E.

    1991-01-01

    A bus switching apparatus and method for multiple processor computer systems comprises a plurality of bus switches interconnected by branch buses. Each processor or other module of the system is connected to a spigot of a bus switch. Each bus switch also serves as part of a backplane of a modular crate hardware package. A processor initiates communication with another processor by identifying that other processor. The bus switch to which the initiating processor is connected identifies and secures, if possible, a path to that other processor, either directly or via one or more other bus switches which operate similarly. If a particular desired path through a given bus switch is not available to be used, an alternate path is considered, identified and secured.

  2. Improved Dynamic Modeling of the Cascade Distillation Subsystem and Analysis of Factors Affecting Its Performance

    NASA Technical Reports Server (NTRS)

    Perry, Bruce A.; Anderson, Molly S.

    2015-01-01

    The Cascade Distillation Subsystem (CDS) is a rotary multistage distiller being developed to serve as the primary processor for wastewater recovery during long-duration space missions. The CDS could be integrated with a system similar to the International Space Station Water Processor Assembly to form a complete water recovery system for future missions. A preliminary chemical process simulation was previously developed using Aspen Custom Modeler® (ACM), but it could not simulate thermal startup and lacked detailed analysis of several key internal processes, including heat transfer between stages. This paper describes modifications to the ACM simulation of the CDS that improve its capabilities and the accuracy of its predictions. Notably, the modified version can be used to model thermal startup and predicts the total energy consumption of the CDS. The simulation has been validated for both NaC1 solution and pretreated urine feeds and no longer requires retuning when operating parameters change. The simulation was also used to predict how internal processes and operating conditions of the CDS affect its performance. In particular, it is shown that the coefficient of performance of the thermoelectric heat pump used to provide heating and cooling for the CDS is the largest factor in determining CDS efficiency. Intrastage heat transfer affects CDS performance indirectly through effects on the coefficient of performance.

  3. Variable word length encoder reduces TV bandwith requirements

    NASA Technical Reports Server (NTRS)

    Sivertson, W. E., Jr.

    1965-01-01

    Adaptive variable resolution encoding technique provides an adaptive compression pseudo-random noise signal processor for reducing television bandwidth requirements. Complementary processors are required in both the transmitting and receiving systems. The pretransmission processor is analog-to-digital, while the postreception processor is digital-to-analog.

  4. Accelerating molecular dynamic simulation on the cell processor and Playstation 3.

    PubMed

    Luttmann, Edgar; Ensign, Daniel L; Vaidyanathan, Vishal; Houston, Mike; Rimon, Noam; Øland, Jeppe; Jayachandran, Guha; Friedrichs, Mark; Pande, Vijay S

    2009-01-30

    Implementation of molecular dynamics (MD) calculations on novel architectures will vastly increase its power to calculate the physical properties of complex systems. Herein, we detail algorithmic advances developed to accelerate MD simulations on the Cell processor, a commodity processor found in PlayStation 3 (PS3). In particular, we discuss issues regarding memory access versus computation and the types of calculations which are best suited for streaming processors such as the Cell, focusing on implicit solvation models. We conclude with a comparison of improved performance on the PS3's Cell processor over more traditional processors. (c) 2008 Wiley Periodicals, Inc.

  5. Allocating application to group of consecutive processors in fault-tolerant deadlock-free routing path defined by routers obeying same rules for path selection

    DOEpatents

    Leung, Vitus J [Albuquerque, NM; Phillips, Cynthia A [Albuquerque, NM; Bender, Michael A [East Northport, NY; Bunde, David P [Urbana, IL

    2009-07-21

    In a multiple processor computing apparatus, directional routing restrictions and a logical channel construct permit fault tolerant, deadlock-free routing. Processor allocation can be performed by creating a linear ordering of the processors based on routing rules used for routing communications between the processors. The linear ordering can assume a loop configuration, and bin-packing is applied to this loop configuration. The interconnection of the processors can be conceptualized as a generally rectangular 3-dimensional grid, and the MC allocation algorithm is applied with respect to the 3-dimensional grid.

  6. Communications systems and methods for subsea processors

    DOEpatents

    Gutierrez, Jose; Pereira, Luis

    2016-04-26

    A subsea processor may be located near the seabed of a drilling site and used to coordinate operations of underwater drilling components. The subsea processor may be enclosed in a single interchangeable unit that fits a receptor on an underwater drilling component, such as a blow-out preventer (BOP). The subsea processor may issue commands to control the BOP and receive measurements from sensors located throughout the BOP. A shared communications bus may interconnect the subsea processor and underwater components and the subsea processor and a surface or onshore network. The shared communications bus may be operated according to a time division multiple access (TDMA) scheme.

  7. An Efficient Functional Test Generation Method For Processors Using Genetic Algorithms

    NASA Astrophysics Data System (ADS)

    Hudec, Ján; Gramatová, Elena

    2015-07-01

    The paper presents a new functional test generation method for processors testing based on genetic algorithms and evolutionary strategies. The tests are generated over an instruction set architecture and a processor description. Such functional tests belong to the software-oriented testing. Quality of the tests is evaluated by code coverage of the processor description using simulation. The presented test generation method uses VHDL models of processors and the professional simulator ModelSim. The rules, parameters and fitness functions were defined for various genetic algorithms used in automatic test generation. Functionality and effectiveness were evaluated using the RISC type processor DP32.

  8. Experimental testing of the noise-canceling processor.

    PubMed

    Collins, Michael D; Baer, Ralph N; Simpson, Harry J

    2011-09-01

    Signal-processing techniques for localizing an acoustic source buried in noise are tested in a tank experiment. Noise is generated using a discrete source, a bubble generator, and a sprinkler. The experiment has essential elements of a realistic scenario in matched-field processing, including complex source and noise time series in a waveguide with water, sediment, and multipath propagation. The noise-canceling processor is found to outperform the Bartlett processor and provide the correct source range for signal-to-noise ratios below -10 dB. The multivalued Bartlett processor is found to outperform the Bartlett processor but not the noise-canceling processor. © 2011 Acoustical Society of America

  9. A High Performance VLSI Computer Architecture For Computer Graphics

    NASA Astrophysics Data System (ADS)

    Chin, Chi-Yuan; Lin, Wen-Tai

    1988-10-01

    A VLSI computer architecture, consisting of multiple processors, is presented in this paper to satisfy the modern computer graphics demands, e.g. high resolution, realistic animation, real-time display etc.. All processors share a global memory which are partitioned into multiple banks. Through a crossbar network, data from one memory bank can be broadcasted to many processors. Processors are physically interconnected through a hyper-crossbar network (a crossbar-like network). By programming the network, the topology of communication links among processors can be reconfigurated to satisfy specific dataflows of different applications. Each processor consists of a controller, arithmetic operators, local memory, a local crossbar network, and I/O ports to communicate with other processors, memory banks, and a system controller. Operations in each processor are characterized into two modes, i.e. object domain and space domain, to fully utilize the data-independency characteristics of graphics processing. Special graphics features such as 3D-to-2D conversion, shadow generation, texturing, and reflection, can be easily handled. With the current high density interconnection (MI) technology, it is feasible to implement a 64-processor system to achieve 2.5 billion operations per second, a performance needed in most advanced graphics applications.

  10. Rapid prototyping and evaluation of programmable SIMD SDR processors in LISA

    NASA Astrophysics Data System (ADS)

    Chen, Ting; Liu, Hengzhu; Zhang, Botao; Liu, Dongpei

    2013-03-01

    With the development of international wireless communication standards, there is an increase in computational requirement for baseband signal processors. Time-to-market pressure makes it impossible to completely redesign new processors for the evolving standards. Due to its high flexibility and low power, software defined radio (SDR) digital signal processors have been proposed as promising technology to replace traditional ASIC and FPGA fashions. In addition, there are large numbers of parallel data processed in computation-intensive functions, which fosters the development of single instruction multiple data (SIMD) architecture in SDR platform. So a new way must be found to prototype the SDR processors efficiently. In this paper we present a bit-and-cycle accurate model of programmable SIMD SDR processors in a machine description language LISA. LISA is a language for instruction set architecture which can gain rapid model at architectural level. In order to evaluate the availability of our proposed processor, three common baseband functions, FFT, FIR digital filter and matrix multiplication have been mapped on the SDR platform. Analytical results showed that the SDR processor achieved the maximum of 47.1% performance boost relative to the opponent processor.

  11. New Modular Ultrasonic Signal Processing Building Blocks for Real-Time Data Acquisition and Post Processing

    NASA Astrophysics Data System (ADS)

    Weber, Walter H.; Mair, H. Douglas; Jansen, Dion

    2003-03-01

    A suite of basic signal processors has been developed. These basic building blocks can be cascaded together to form more complex processors without the need for programming. The data structures between each of the processors are handled automatically. This allows a processor built for one purpose to be applied to any type of data such as images, waveform arrays and single values. The processors are part of Winspect Data Acquisition software. The new processors are fast enough to work on A-scan signals live while scanning. Their primary use is to extract features, reduce noise or to calculate material properties. The cascaded processors work equally well on live A-scan displays, live gated data or as a post-processing engine on saved data. Researchers are able to call their own MATLAB or C-code from anywhere within the processor structure. A built-in formula node processor that uses a simple algebraic editor may make external user programs unnecessary. This paper also discusses the problems associated with ad hoc software development and how graphical programming languages can tie up researchers writing software rather than designing experiments.

  12. Array processor architecture connection network

    NASA Technical Reports Server (NTRS)

    Barnes, George H. (Inventor); Lundstrom, Stephen F. (Inventor); Shafer, Philip E. (Inventor)

    1982-01-01

    A connection network is disclosed for use between a parallel array of processors and a parallel array of memory modules for establishing non-conflicting data communications paths between requested memory modules and requesting processors. The connection network includes a plurality of switching elements interposed between the processor array and the memory modules array in an Omega networking architecture. Each switching element includes a first and a second processor side port, a first and a second memory module side port, and control logic circuitry for providing data connections between the first and second processor ports and the first and second memory module ports. The control logic circuitry includes strobe logic for examining data arriving at the first and the second processor ports to indicate when the data arriving is requesting data from a requesting processor to a requested memory module. Further, connection circuitry is associated with the strobe logic for examining requesting data arriving at the first and the second processor ports for providing a data connection therefrom to the first and the second memory module ports in response thereto when the data connection so provided does not conflict with a pre-established data connection currently in use.

  13. 21 CFR 892.1900 - Automatic radiographic film processor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automatic radiographic film processor. 892.1900... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1900 Automatic radiographic film processor. (a) Identification. An automatic radiographic film processor is a device intended to be used to...

  14. 21 CFR 892.1900 - Automatic radiographic film processor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automatic radiographic film processor. 892.1900... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1900 Automatic radiographic film processor. (a) Identification. An automatic radiographic film processor is a device intended to be used to...

  15. 21 CFR 892.1900 - Automatic radiographic film processor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automatic radiographic film processor. 892.1900... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1900 Automatic radiographic film processor. (a) Identification. An automatic radiographic film processor is a device intended to be used to...

  16. 21 CFR 892.1900 - Automatic radiographic film processor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automatic radiographic film processor. 892.1900... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1900 Automatic radiographic film processor. (a) Identification. An automatic radiographic film processor is a device intended to be used to...

  17. 7 CFR 1160.108 - Fluid milk processor.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Fluid milk processor. 1160.108 Section 1160.108... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order Definitions § 1160.108 Fluid milk processor. (a) Fluid milk processor means any person who...

  18. 7 CFR 1160.108 - Fluid milk processor.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Fluid milk processor. 1160.108 Section 1160.108... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order Definitions § 1160.108 Fluid milk processor. (a) Fluid milk processor means any person who...

  19. 7 CFR 1160.108 - Fluid milk processor.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Fluid milk processor. 1160.108 Section 1160.108... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order Definitions § 1160.108 Fluid milk processor. (a) Fluid milk processor means any person who...

  20. 21 CFR 892.1900 - Automatic radiographic film processor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automatic radiographic film processor. 892.1900... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1900 Automatic radiographic film processor. (a) Identification. An automatic radiographic film processor is a device intended to be used to...

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