Capabilities and Testing of the Fission Surface Power Primary Test Circuit (FSP-PTC)

NASA Technical Reports Server (NTRS)

Garber, Anne E.

2007-01-01

An actively pumped alkali metal flow circuit, designed and fabricated at the NASA Marshall Space Flight Center, is currently undergoing testing in the Early Flight Fission Test Facility (EFF-TF). Sodium potassium (NaK), which was used in the SNAP-10A fission reactor, was selected as the primary coolant. Basic circuit components include: simulated reactor core, NaK to gas heat exchanger, electromagnetic (EM) liquid metal pump, liquid metal flowmeter, load/drain reservoir, expansion reservoir, test section, and instrumentation. Operation of the circuit is based around a 37-pin partial-array core (pin and flow path dimensions are the same as those in a full core), designed to operate at 33 kWt. NaK flow rates of greater than 1 kg/sec may be achieved, depending upon the power applied to the EM pump. The heat exchanger provides for the removal of thermal energy from the circuit, simulating the presence of an energy conversion system. The presence of the test section increases the versatility of the circuit. A second liquid metal pump, an energy conversion system, and highly instrumented thermal simulators are all being considered for inclusion within the test section. This paper summarizes the capabilities and ongoing testing of the Fission Surface Power Primary Test Circuit (FSP-PTC).

Thermally Simulated 32kW Direct-Drive Gas-Cooled Reactor: Design, Assembly, and Test

NASA Astrophysics Data System (ADS)

Godfroy, Thomas J.; Kapernick, Richard J.; Bragg-Sitton, Shannon M.

2004-02-01

One of the power systems under consideration for nuclear electric propulsion is a direct-drive gas-cooled reactor coupled to a Brayton cycle. In this system, power is transferred from the reactor to the Brayton system via a circulated closed loop gas. To allow early utilization, system designs must be relatively simple, easy to fabricate, and easy to test using non-nuclear heaters to closely mimic heat from fission. This combination of attributes will allow pre-prototypic systems to be designed, fabricated, and tested quickly and affordably. The ability to build and test units is key to the success of a nuclear program, especially if an early flight is desired. The ability to perform very realistic non-nuclear testing increases the success probability of the system. In addition, the technologies required by a concept will substantially impact the cost, time, and resources required to develop a successful space reactor power system. This paper describes design features, assembly, and test matrix for the testing of a thermally simulated 32kW direct-drive gas-cooled reactor in the Early Flight Fission - Test Facility (EFF-TF) at Marshall Space Flight Center. The reactor design and test matrix are provided by Los Alamos National Laboratories.

Stainless Steel NaK-Cooled Circuit (SNaKC) Fabrication and Assembly

NASA Technical Reports Server (NTRS)

Godfroy, Thomas J.

2007-01-01

An actively pumped Stainless Steel NaK Circuit (SNaKC) has been designed and fabricated by the Early Flight Fission Test Facility (EFF-TF) team at NASA's Marshall Space Flight Center. This circuit uses the eutectic mixture of sodium and potassium (NaK) as the working fluid building upon the experience and accomplishments of the SNAP reactor program from the late 1960's The SNaKC enables valuable experience and liquid metal test capability to be gained toward the goal of designing and building an affordable surface power reactor. The basic circuit components include a simulated reactor core a NaK to gas heat exchanger, an electromagnetic (EM) liquid metal pump, a liquid metal flow meter, an expansion reservoir and a drain/fill reservoir To maintain an oxygen free environment in the presence of NaK, an argon system is utilized. A helium and nitrogen system are utilized for core, pump, and heat exchanger operation. An additional rest section is available to enable special component testing m an elevated temperature actively pumped liquid metal environment. This paper summarizes the physical build of the SNaKC the gas and pressurization systems, vacuum systems, as well as instrumentation and control methods.

Plans for an ERL Test Facility at CERN

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

Jensen, Erik; Bruning, O S; Calaga, Buchi Rama Rao

2014-12-01

The baseline electron accelerator for LHeC and one option for FCC-he is an Energy Recovery Linac. To prepare and study the necessary key technologies, CERNhas started – in collaboration with JLAB and Mainz University – the conceptual design of an ERL Test Facility (ERL-TF). Staged construction will allow the study under different conditions with up to 3 passes, beam energies of up to about 1 GeV and currents of up to 50 mA. The design and development of superconducting cavity modules, including coupler and HOM damper designs, are also of central importance for other existing and future accelerators and theirmore » tests are at the heart of the current ERL-TF goals. However, the ERL-TF could also provide a unique infrastructure for several applications that go beyond developing and testing the ERL technology at CERN. In addition to experimental studies of beam dynamics, operational and reliability issues in an ERL, it could equally serve for quench tests of superconducting magnets, as physics experimental facility on its own right or as test stand for detector developments. This contribution will describe the goals and the concept of the facility and the status of the R&D.« less

Transient Approximation of SAFE-100 Heat Pipe Operation

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Reid, Robert S.

2005-01-01

Engineers at Los Alamos National Laboratory (LANL) have designed several heat pipe cooled reactor concepts, ranging in power from 15 kWt to 800 kWt, for both surface power systems and nuclear electric propulsion systems. The Safe, Affordable Fission Engine (SAFE) is now being developed in a collaborative effort between LANL and NASA Marshall Space Flight Center (NASA/MSFC). NASA is responsible for fabrication and testing of non-nuclear, electrically heated modules in the Early Flight Fission Test Facility (EFF-TF) at MSFC. In-core heat pipes must be properly thawed as the reactor power starts. Computational models have been developed to assess the expected operation of a specific heat pipe design during start-up, steady state operation, and shutdown. While computationally intensive codes provide complete, detailed analyses of heat pipe thaw, a relatively simple. concise routine can also be applied to approximate the response of a heat pipe to changes in the evaporator heat transfer rate during start-up and power transients (e.g., modification of reactor power level) with reasonably accurate results. This paper describes a simplified model of heat pipe start-up that extends previous work and compares the results to experimental measurements for a SAFE-100 type heat pipe design.

Sodium Heat Pipe Module Processing For the SAFE-100 Reactor Concept

NASA Technical Reports Server (NTRS)

Martin, James; Salvail, Pat

2003-01-01

To support development and hardware-based testing of various space reactor concepts, the Early Flight Fission-Test Facility (EFF-TF) team established a specialized glove box unit with ancillary systems to handle/process alkali metals. Recently, these systems have been commissioned with sodium supporting the fill of stainless steel heat pipe modules for use with a 100 kW thermal heat pipe reactor design. As part of this effort, procedures were developed and refined to govern each segment of the process covering: fill, leak check, vacuum processing, weld closeout, and final "wet in". A series of 316 stainless steel modules, used as precursors to the actual 321 stainless steel modules, were filled with 35 +/- 1 grams of sodium using a known volume canister to control the dispensed mass. Each module was leak checked to less than10(exp -10) std cc/sec helium and vacuum conditioned at 250 C to assist in the removal of trapped gases. A welding procedure was developed to close out the fill stem preventing external gases from entering the evacuated module. Finally the completed modules were vacuum fired at 750 C allowing the sodium to fully wet the internal surface and wick structure of the heat pipe module.

Sodium Heat Pipe Module Processing For the SAFE-100 Reactor Concept

NASA Astrophysics Data System (ADS)

Martin, James; Salvail, Pat

2004-02-01

To support development and hardware-based testing of various space reactor concepts, the Early Flight Fission-Test Facility (EFF-TF) team established a specialized glove box unit with ancillary systems to handle/process alkali metals. Recently, these systems have been commissioned with sodium supporting the fill of stainless steel heat pipe modules for use with a 100 kW thermal heat pipe reactor design. As part of this effort, procedures were developed and refined to govern each segment of the process covering: fill, leak check, vacuum processing, weld closeout, and final ``wet in''. A series of 316 stainless steel modules, used as precursors to the actual 321 stainless steel modules, were filled with 35 +/-1 grams of sodium using a known volume canister to control the dispensed mass. Each module was leak checked to <10-10 std cc/sec helium and vacuum conditioned at 250 °C to assist in the removal of trapped gases. A welding procedure was developed to close out the fill stem preventing external gases from entering the evacuated module. Finally the completed modules were vacuum fired at 750 °C allowing the sodium to fully wet the internal surface and wick structure of the heat pipe module.

Preliminary Evaluation of Convective Heat Transfer in a Water Shield for a Surface Power Reactor

NASA Technical Reports Server (NTRS)

Pearson J. Boise; Reid, Robert S.

2007-01-01

As part of the Vision for Space Exploration, the end of the next decade will bring man back to the surface of the moon. A crucial issue for the establishment of human presence on the moon will be the availability of compact power sources. This presence could require greater than 10's of kWt's in follow on years. Nuclear reactors are well suited to meet the needs for power generation on the lunar or Martian surface. Radiation shielding is a key component of any surface power reactor system. Several competing concepts exist for lightweight, safe, robust shielding systems such as a water shield, lithium hydride (LiH), and boron carbide. Water offers several potential advantages, including reduced cost, reduced technical risk, and reduced mass. Water has not typically been considered for space reactor applications because of the need for gravity to fix the location of any vapor that could form radiation streaming paths. The water shield concept relies on the predictions of passive circulation of the shield water by natural convection to adequately cool the shield. This prediction needs to be experimentally evaluated, especially for shields with complex geometries. NASA Marshall Space Flight Center has developed the experience and facilities necessary to do this evaluation in its Early Flight Fission - Test Facility (EFF-TF).

Cool-Down and Current Test Results of the KSTAR Prototype TF Coil

NASA Astrophysics Data System (ADS)

Oh, Y. K.; Lee, S.; Chu, Y.; Park, K. R.; Yonekawa, H.; Baek, S. H.; Cho, K. W.; Park, Y. M.; Kim, M. K.; Chang, H. S.; Kim, Y. S.; Chang, Y. B.; Lee, Y. J.; Kim, W. C.; Kim, K.; Kwag, S. W.; Lee, S. H.; Yang, S. H.; Lee, S. J.; Bak, J. S.; Lee, G. S.

2004-06-01

A prototype toroidal field (TF) coil, TF00 coil, of the Korea Superconducting Tokamak Advanced Research (KSTAR) project has been assembled and tested at the coil test facility in Korea Basic Science Institute (KBSI). The TF00 coil is a real-sized TF coil made of Nb3Sn superconducting cable-in-conduit conductor (CICC). The coil test was conducted by several campaigns according to the objectives. The first campaign, which was carried out by Jan. 2003, has objectives of cooling the coil into operating temperature and finding any defect in the coil such as cold leaks. From the results of the first campaign experiment, any defect in the coil was not found. The second campaign, which was carried out by Aug. 2003, has objectives to get the operating characteristics according to the current ramp up and discharge operations. In this paper, the coil test results are introduced as well as the details of the coil test system setup.

Thermal-hydraulic analysis of the coil test facility for CFETR.

PubMed

Ren, Yong; Liu, Xiaogang; Li, Junjun; Wang, Zhaoliang; Qiu, Lilong; Du, Shijun; Li, Guoqiang; Gao, Xiang

2016-01-01

Performance test of the China Fusion Engineering Test Reactor (CFETR) central solenoid (CS) and toroidal field (TF) insert coils is of great importance to evaluate the CFETR magnet performance in relevant operation conditions. The superconducting magnet of the coil test facility for CFETR is being designed with the aim of providing a background magnetic field to test the CFETR CS insert and TF insert coils. The superconducting magnet consists of the inner module with Nb 3 Sn coil and the outer module with NbTi coil. The superconducting magnet is designed to have a maximum magnetic field of 12.59 T and a stored energy of 436.6 MJ. An active quench protection circuit and the positive temperature coefficient dump resistor were adopted to transfer the stored magnetic energy. The temperature margin behavior of the test facility for CFETR satisfies the design criteria. The quench analysis of the test facility shows that the cable temperature and the helium pressure inside the jacket are within the design criteria.

Major Range and Test Facility Base Summary of Capabilities.

DTIC Science & Technology

1983-06-01

TEST CHART NATIONAL BUREAU OF STANDARDS 1963 A 3,i 4, S °.I i L -. ~ . % o,. ° . - ° . - . .I ¢ PHOTOGRAPH THIS SHEET LEVEL INVENTORY DOCUMENT...NUMBER DOD 3200.11-D 4. TTLE(~dS..tt~t@) S TYPE Of REPORT a PERIO’ COVERED Major Range and Test Facility Base Summary Reference Maerial of Capabilities...Electronic Warfare, Command, Control Communications and Intelligence (C31) Surveillance, Jammers, Radar, Test Facility ZG5 ABETW ACT f~ a "Afie Afr- s 444 eF~f

Analysis of seasonal strain measurements in asphalt materials under accelerated pavement testing and comparing field performance and laboratory measured binder tension properties : technical summary report.

DOT National Transportation Integrated Search

2009-06-01

Since 1996, the Louisiana Department of Transportation and Development (LADOTD) has : utilized the Louisiana Transportation and Research Centers (LTRCs) Accelerated Loading : Facility (ALF) at the Pavement Research Facility to determine the eff...

Operational experience with the supercritical helium during the TF coils tests campaign of SST-1

NASA Astrophysics Data System (ADS)

Panchal, Rohitkumar Natvarlal; Patel, Rakesh; Tank, Jignesh; Mahesuria, Gaurang; Sonara, Dashrath; Tanna, Vipul; Patel, Jayant; Srikanth, G. L. N.; Singh, Manoj; Patel, Ketan; Christian, Dikens; Garg, Atul; Bairagi, Nitn; Gupta, Manoj Kumar; Nimavat, Hiren; Shah, Pankil; Sharma, Rajiv; Pradhan, Subrata

2012-06-01

Under the 'SST-1 mission mandate' recently, all the sixteen Steady State Superconducting Tokamak (SST-1) Toroidal Field (TF) magnets have been successfully tested at their nominal currents of 10000 A in cold under supercritical helium (SHe) flow conditions. The TF magnets test campaign have begun in an experimental cryostat since June 2010 with the SST-1 Helium cryogenics facility, which is a 1.3 kW at 4.5 K helium refrigerator-cum-liquefier (HRL) system. The HRL provides ~300 g-s-1supercritical helium (SHe) with cold circulator (CC) as well as ~ 60 g-s-1 without cold circulator to fulfill the forced flow cooling requirements of SST- 1 magnets. In case of single TF coil tests, we can adjust HRL process parameters such that an adequate amount of required supercritical helium is available without the cold circulator. In this paper, the complete process is describing the Process Flow Diagram (PFD) of 1.3 kW at 4.5 K HRL, techniques to generate supercritical helium without using the cold-circulator and the results of the cooldown, steady state characteristics and experience of supercritical helium operations during the TF coils test campaign have been discussed.

Work with Us | Photovoltaic Research | NREL

Science.gov Websites

Research Facility (SERF) Science and Technology Facility (S&TF) Outdoor Test Facility (OTF) Energy the Hands On Photovoltaic Experience (HOPE). Photo of a researcher in a lab Photovoltaic research and related activities occur in various locations across the NREL campus, including the Solar Energy Research

Experimental Fuels Facility Re-categorization Based on Facility Segmentation

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

Reiss, Troy P.; Andrus, Jason

The Experimental Fuels Facility (EFF) (MFC-794) at the Materials and Fuels Complex (MFC) located on the Idaho National Laboratory (INL) Site was originally constructed to provide controlled-access, indoor storage for radiological contaminated equipment. Use of the facility was expanded to provide a controlled environment for repairing contaminated equipment and characterizing, repackaging, and treating waste. The EFF facility is also used for research and development services, including fuel fabrication. EFF was originally categorized as a LTHC-3 radiological facility based on facility operations and facility radiological inventories. Newly planned program activities identified the need to receive quantities of fissionable materials in excessmore » of the single parameter subcritical limit in ANSI/ANS-8.1, “Nuclear Criticality Safety in Operations with Fissionable Materials Outside Reactors” (identified as “criticality list” quantities in DOE-STD-1027-92, “Hazard Categorization and Accident Analysis Techniques for Compliance with DOE Order 5480.23, Nuclear Safety Analysis Reports,” Attachment 1, Table A.1). Since the proposed inventory of fissionable materials inside EFF may be greater than the single parameter sub-critical limit of 700 g of U-235 equivalent, the initial re-categorization is Hazard Category (HC) 2 based upon a potential criticality hazard. This paper details the facility hazard categorization performed for the EFF. The categorization was necessary to determine (a) the need for further safety analysis in accordance with LWP-10802, “INL Facility Categorization,” and (b) compliance with 10 Code of Federal Regulations (CFR) 830, Subpart B, “Safety Basis Requirements.” Based on the segmentation argument presented in this paper, the final hazard categorization for the facility is LTHC-3. Department of Energy Idaho (DOE-ID) approval of the final hazard categorization determined by this hazard assessment document (HAD) was required per the DOE-ID Supplemental Guidance for DOE-STD-1027-92 based on the proposed downgrade of the initial facility categorization of Hazard Category 2.« less

Experimental Evaluation of a Water Shield for a Surface Power Reactor

NASA Technical Reports Server (NTRS)

Pearson, J. Boise; Reid, Robert S.

2006-01-01

As part of the Vision for Space Exploration the end of the next decade will bring man back to the surface of the moon. One of the most critical issues for the establishment of human presence on the moon will be the availability of compact power sources. The establishment of man on the moon will require power from greater than 10's of kWt's in follow on years. Nuclear reactors are extremely we11 suited to meet the needs for power generation on the lunar or Martian surface. reactor system. Several competing concepts exist for lightweight, safe, robust shielding systems such as a water shield, lithium hydride (LiH), Boron Carbide, and others. Water offers several potential advantages, including reduced cost, reduced technical risk, and reduced mass. Water has not typically been considered for space reactor applications because of the need for gravity to remove the potential for radiation streaming paths. The water shield concept relies on predictions of passive circulation of the shield water by natural convection to adequately cool the shield. This prediction needs to be experimentally evaluated, especially for shields with complex geometries. MSFC has developed the experience and fac necessary to do this evaluation in the Early Flight Fission - Test Facility (EFF-TF).

Testing of Liquid Metal Components for Nuclear Surface Power Systems

NASA Technical Reports Server (NTRS)

Polzin, Kurt A.; Godfroy, Thomas J.; Pearson, J. Boise

2010-01-01

The Early Flight Fission Test Facility (EFF-TF) was established by the Marshall Space Flight Center (MSFC) to provide a capability for performing hardware-directed activities to support multiple in-space nuclear reactor concepts by using a non-nuclear test methodology. This includes fabrication and testing at both the module/component level and near prototypic reactor configurations. The EFF-TF is currently supporting an effort to develop an affordable fission surface power (AFSP) system that could be deployed on the Lunar surface. The AFSP system is presently based on a pumped liquid metal-cooled (Sodium-Potassium eutectic, NaK-78) reactor design. This design was derived from the only fission system that the United States has deployed for space operation, the Systems for Nuclear Auxiliary Power (SNAP) 10A reactor, which was launched in 1965. Two prototypical components recently tested at MSFC were a pair of Stirling power conversion units that would be used in a reactor system to convert heat to electricity, and an annular linear induction pump (ALIP) that uses travelling electromagnetic fields to pump the liquid metal coolant through the reactor loop. First ever tests were conducted at MSFC to determine baseline performance of a pair of 1 kW Stirling convertors using NaK as the hot side working fluid. A special test rig was designed and constructed and testing was conducted inside a vacuum chamber at MSFC. This test rig delivered pumped NaK for the hot end temperature to the Stirlings and water as the working fluid on the cold end temperature. These test were conducted through a hot end temperature range between 400 to 550C in increments of 50 C and a cold end temperature range from 30 to 70 C in 20 C increments. Piston amplitudes were varied from 6 to 1 1mm in .5 mm increments. A maximum of 2240 Watts electric was produced at the design point of 550 hot end, 40 C cold end with a piston amplitude of 10.5mm. This power level was reached at a gross thermal efficiency of 28%. A baseline performance map was established for the pair of 1kW Stirling convertors. The performance data will then be used for design modification to the Stirling convertors. The ALIP tested at MSFC has no moving parts and no direct electrical connections to the liquid metal containing components. Pressure is developed by the interaction of the magnetic field produced by the stator and the current which flows as a result of the voltage induced in the liquid metal contained in the pump duct. Flow is controlled by variation of the voltage supplied to the pump windings. Under steady-state conditions, pump performance is measured for flow rates from 0.5-4.3 kg/s. The pressure rise developed by the pump to support these flow rates is roughly 5-65 kPa. The RMS input voltage (phase-to-phase voltage) ranges from 5-120 V, while the frequency can be varied arbitrarily up to 60 Hz. Performance is quantified at different loop temperature levels from 50 C up to 650 C, which is the peak operating temperature of the proposed AFSP reactor. The transient response of the pump is also evaluated to determine its behavior during startup and shut-down procedures.

Field analysis for explosives: TNT and RDX

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

Elcoate, W.; Mapes, J.

The EPA has listed as hazardous many of the compounds used in the production of ammunitions and other explosive ordnance. The contamination of soil with TNT (2,4,6-trinitrotoluene), the major component of many munitions formulations and to a lesser degree RDX (hexhydro-1,3,5-trinitro-1,3,5-trizine) is a significant problem at many ammunition manufacturing facilities, depots, and ordnance disposal sites. Field test kits for explosives TNT and RDX (hexhydro-1,3,5-trinitro-1,3,5-triazine) were developed based on the methods of T.F. Jenkins and M.E. Walsh and T.F Jenkins. EnSys Environmental Products, Inc. with technical support from T.F. Jenkins took the original TNT procedure, modified it for easier field use,more » performed validation studies to ensure that it met or exceeded the method specifications for both the T.F. Jenkins and SW-846 methods, and developed an easy to use test format for the field testing of TNT. The RDX procedure has gone through the development cycle and is presently in the field validation phase. This paper describes the test protocol and performance characteristics of the TNT test procedure.« less

A Randomized Implementation Study of Trauma-Focused Cognitive Behavioral Therapy for Adjudicated Teens in Residential Treatment Facilities.

PubMed

Cohen, Judith A; Mannarino, Anthony P; Jankowski, Kay; Rosenberg, Stanley; Kodya, Suzanne; Wolford, George L

2016-05-01

Adjudicated youth in residential treatment facilities (RTFs) have high rates of trauma exposure and post-traumatic stress disorder (PTSD). This study evaluated strategies for implementing trauma-focused cognitive behavioral therapy (TF-CBT) in RTF. Therapists (N = 129) treating adjudicated youth were randomized by RTF program (N = 18) to receive one of the two TF-CBT implementation strategies: (1) web-based TF-CBT training + consultation (W) or (2) W + 2 day live TF-CBT workshop + twice monthly phone consultation (W + L). Youth trauma screening and PTSD symptoms were assessed via online dashboard data entry using the University of California at Los Angeles PTSD Reaction Index. Youth depressive symptoms were assessed with the Mood and Feelings Questionnaire-Short Version. Outcomes were therapist screening; TF-CBT engagement, completion, and fidelity; and youth improvement in PTSD and depressive symptoms. The W + L condition resulted in significantly more therapists conducting trauma screening (p = .0005), completing treatment (p = .03), and completing TF-CBT with fidelity (p = .001) than the W condition. Therapist licensure significantly impacted several outcomes. Adjudicated RTF youth receiving TF-CBT across conditions experienced statistically and clinically significant improvement in PTSD (p = .001) and depressive (p = .018) symptoms. W + L is generally superior to W for implementing TF-CBT in RTF. TF-CBT is effective for improving trauma-related symptoms in adjudicated RTF youth. Implementation barriers are discussed. © The Author(s) 2016.

A Randomized Implementation Study of Trauma-Focused Cognitive Behavioral Therapy for Adjudicated Teens in Residential Treatment Facilities

PubMed Central

Cohen, Judith A.; Mannarino, Anthony P.; Jankowski, Kay; Rosenberg, Stanley; Kodya, Suzanne; Wolford, George L.

2016-01-01

Adjudicated youth in residential treatment facilities (RTFs) have high rates of trauma exposure and post-traumatic stress disorder (PTSD). This study evaluated strategies for implementing trauma-focused cognitive behavioral therapy (TF-CBT) in RTF. Therapists (N = 129) treating adjudicated youth were randomized by RTF program (N = 18) to receive one of the two TF-CBT implementation strategies: (1) web-based TF-CBT training + consultation (W) or (2) W + 2 day live TF-CBT workshop + twice monthly phone consultation (W + L). Youth trauma screening and PTSD symptoms were assessed via online dashboard data entry using the University of California at Los Angeles PTSD Reaction Index. Youth depressive symptoms were assessed with the Mood and Feelings Questionnaire–Short Version. Outcomes were therapist screening; TF-CBT engagement, completion, and fidelity; and youth improvement in PTSD and depressive symptoms. The W + L condition resulted in significantly more therapists conducting trauma screening (p = .0005), completing treatment (p = .03), and completing TF-CBT with fidelity (p = .001) than the W condition. Therapist licensure significantly impacted several outcomes. Adjudicated RTF youth receiving TF-CBT across conditions experienced statistically and clinically significant improvement in PTSD (p = .001) and depressive (p = .018) symptoms. W + L is generally superior to W for implementing TF-CBT in RTF. TF-CBT is effective for improving trauma-related symptoms in adjudicated RTF youth. Implementation barriers are discussed. PMID:26747845

Present Status of the KSTAR Superconducting Magnet System Development

NASA Astrophysics Data System (ADS)

Kim, Keeman; H, K. Park; K, R. Park; B, S. Lim; S, I. Lee; M, K. Kim; Y, Chu; W, H. Chung; S, H. Baek; J Y, Choi; H, Yonekawa; A, Chertovskikh; Y, B. Chang; J, S. Kim; C, S. Kim; D, J. Kim; N, H. Song; K, P. Kim; Y, J. Song; I, S. Woo; W, S. Han; D, K. Lee; Y, K. Oh; K, W. Cho; J, S. Park; G, S. Lee; H, J. Lee; T, K. Ko; S, J. Lee

2004-10-01

The mission of Korea Superconducting Tokamak Advanced Research (KSTAR) project is to develop an advanced steady-state superconducting tokamak for establishing a scientific and technological basis for an attractive fusion reactor. Because one of the KSTAR mission is to achieve a steady-state operation, the use of superconducting coils is an obvious choice for the magnet system. The KSTAR superconducting magnet system consists of 16 Toroidal Field (TF) coils and 14 Poloidal Field (PF) coils. Internally-cooled Cable-In-Conduit Conductors (CICC) are put into use in both the TF and PF coil systems. The TF coil system provides a field of 3.5 T at the plasma center and the PF coil system is able to provide a flux swing of 17 V-sec. The major achievement in KSTAR magnet-system development includes the development of CICC, the development of a full-size TF model coil, the development of a coil system for background magnetic-field generation, the construction of a large-scale superconducting magnet and CICC test facility. TF and PF coils are in the stage of fabrication to pave the way for the scheduled completion of KSTAR by the end of 2006.

Evaluation of surface antigen TF1.17 in feline Tritrichomonas foetus isolates.

PubMed

Gould, E N; Corbeil, L B; Kania, S A; Tolbert, M K

2017-09-15

Tritrichomonas foetus (T. foetus) is a flagellated protozoa that infects the distal ileum and proximal colon of domestic cats, as well as the urogenital tract of cattle. Feline trichomonosis is recognized as a prevalent cause of chronic diarrhea in cats worldwide. The suspected route of transmission is fecal-oral, with cats in densely crowded environments at highest risk for infection. Thus, the recommended strategy for minimizing spread of infection is to identify and isolate T. foetus-positive cats from the general population. Rapid identification of infected cats can be challenging due to the inability to accurately and quickly detect the organism in samples at point of care facilities. Thus, identification of targets for use in development of a novel diagnostic test, as well as a vaccine or therapy for T. foetus infection is a significant area of research. Despite a difference in organ tropism between T. foetus genotypes, evidence exists for conserved virulence factors between feline and bovine T. foetus. The bovine T. foetus surface antigen, TF1.17, is an adhesin that is conserved across isolates. Vaccination with the purified antigen results in amelioration of cytopathogenicity and more rapid clearance of infection in cattle. We previously showed that three feline isolates of T. foetus were positive for TF1.17 antigen so we further hypothesized that TF1.17 is conserved across feline T. foetus isolates and that this antigen would represent an attractive target for development of a novel diagnostic test or therapy for feline trichomonosis. In these studies, we used monoclonal antibodies previously generated against 1.15 and 1.17 epitopes of the bovine T. foetus TF1.17 antigen, to evaluate for the presence and role of TF1.17 in the cytopathogenicity of feline T. foetus. A previously validated in vitro co-culture approach was used to model feline T. foetus infection. Immunoblotting, immunofluorescence assays, and flow cytometric analysis confirmed the presence and surface localization of antigen TF1.17 across all feline T. foetus isolates tested. Antigen TF1.17 was notably absent in the presumably nonpathogenic intestinal trichomonad, Pentatrichomonas hominis, a parasite that can be confused microscopically with T. foetus. Similar to bovine trichomoniasis, TF1.17 was found to promote T. foetus adhesion to the intestinal epithelium. These results support further characterization and development of the TF1.17 antigen as a possible target for the diagnosis and prevention of feline T. foetus infection. Copyright © 2017 Elsevier B.V. All rights reserved.

LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant-like activity.

PubMed

Ortmann, Caroline Flach; Abelaira, Helena Mendes; Réus, Gislaine Zilli; Ignácio, Zuleide Maria; Chaves, Vitor Clasen; Dos Santos, Talitha Caldas; de Carvalho, Pâmela; Carlessi, Anelise Scussel; Bruchchen, Livia; Danielski, Lucineia G; Cardoso, Simone Gonçalves; de Campos, Angela Machado; Petronilho, Fabricia; Rebelo, Joyce; Dos Santos Morais, Meline Oliveira; Vuolo, Francieli; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Quevedo, João; Reginatto, Flávio Henrique

2017-11-01

There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by the forced swimming test, splash test and open field test. EFF-Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya. Quantitatively, EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosyl flavonoids. In addition, EFF-Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF-Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF-Cp exerts antidepressant-like effects with its antioxidant properties. Copyright © 2017 John Wiley & Sons, Ltd.

Constellation Training Facility Support

NASA Technical Reports Server (NTRS)

Flores, Jose M.

2008-01-01

The National Aeronautics and Space Administration is developing the next set of vehicles that will take men back to the moon under the Constellation Program. The Constellation Training Facility (CxTF) is a project in development that will be used to train astronauts, instructors, and flight controllers on the operation of Constellation Program vehicles. It will also be used for procedure verification and validation of flight software and console tools. The CxTF will have simulations for the Crew Exploration Vehicle (CEV), Crew Module (CM), CEV Service Module (SM), Launch Abort System (LAS), Spacecraft Adapter (SA), Crew Launch Vehicle (CLV), Pressurized Cargo Variant CM, Pressurized Cargo Variant SM, Cargo Launch Vehicle, Earth Departure Stage (EDS), and the Lunar Surface Access Module (LSAM). The Facility will consist of part-task and full-task trainers, each with a specific set of mission training capabilities. Part task trainers will be used for focused training on a single vehicle system or set of related systems. Full task trainers will be used for training on complete vehicles and all of its subsystems. Support was provided in both software development and project planning areas of the CxTF project. Simulation software was developed for the hydraulic system of the Thrust Vector Control (TVC) of the ARES I launch vehicle. The TVC system is in charge of the actuation of the nozzle gimbals for navigation control of the upper stage of the ARES I rocket. Also, software was developed using C standards to send and receive data to and from hand controllers to be used in CxTF cockpit simulations. The hand controllers provided movement in all six rotational and translational axes. Under Project Planning & Control, support was provided to the development and maintenance of integrated schedules for both the Constellation Training Facility and Missions Operations Facilities Division. These schedules maintain communication between projects in different levels. The CxTF support provided is one that requires continuous maintenance since the project is still on initial development phases.

Novel Use of Water Soluble "Aquapour" As A Temporary Spacer During Coil Winding For The NSTX-U Centerstack

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

Mardenfeld, Michael

A major facility upgrade to the National Spherical Torus eXperiment (NSTX-U) is currently underway at Princeton Plasma Physics Laboratory (PPPL). A key component of NSTX-U is the fabrication of a new, higher field centerstack (CS). In order to simultaneously provide robust joints between the inner and outer legs of the Toroidal Field Coils (TF) and minimize radial build, the NSTX-U CS design requires that the Ohmic Heating solenoid (OH) be wound directly on the inner TF bundle. To protect the OH against thermal expansion stress during scenarios where the inner TF bundle is hot but the OH is relatively cool,more » the completed CS will have a 0.100 inch annular gap between the outer diameter of the TF bundle and the inner diameter of the OH solenoid. "Aquapour", a proprietary material produced by the Advanced Ceramics Manufacturing Company will be used during manufacture to produce this gap. After the TF bundle is vacuum pressure impregnated and cured, a cylindrical "clam shell" mold will be assembled around it, and a slurry of powdered Aquapour and water will be pumped into the annular space between the mold and TF bundle. Subsequent baking will turn the Aquapour solid, and a protective layer of wet lay-up fiberglass and resin will be added. The OH solenoid will be wound directly on this wet lay-up shell. After vacuum pressure impregnation of the OH, the water soluble Aquapour will be washed away, leaving the required radial clearance between the TF and OH. This paper will describe prototyping and testing of this process, and plans for use on the actual CS fabrication.« less

Metallographic autopsies of full-scale ITER prototype cable-in-conduit conductors after full cyclic testing in SULTAN: III. The importance of strand surface roughness in long twist pitch conductors

DOE PAGES

Sanabria, Charlie; Lee, Peter J.; Starch, William; ...

2016-05-31

As part of the ITER conductor qualification process, 3 m long Cable-in-Conduit Conductors (CICCs) were tested at the SULTAN facility under conditions simulating ITER operation so as to establish the current sharing temperature, T cs, as a function of multiple full Lorentz force loading cycles. After a comprehensive evaluation of both the Toroidal Field (TF) and the Central Solenoid (CS) conductors, it was found that T cs degradation was common in long twist pitch TF conductors while short twist pitch CS conductors showed some T cs increase. However, one kind of TF conductors containing superconducting strand fabricated by the Bochvarmore » Institute of Inorganic Materials (VNIINM) avoided T cs degradation despite having long twist pitch. In our earlier metallographic autopsies of long and short twist pitch CS conductors, we observed a substantially greater transverse strand movement under Lorentz force loading for long twist pitch conductors, while short twist pitch conductors had negligible transverse movement. With help from the literature, we concluded that the transverse movement was not the source of T cs degradation but rather an increase of the compressive strain in the Nb 3Sn filaments possibly induced by longitudinal movement of the wires. Like all TF conductors this TF VNIINM conductor showed large transverse motions under Lorentz force loading, but Tcs actually increased, as in all short twist pitch CS conductors. We here propose that the high surface roughness of the VNIINM strand may be responsible for the suppression of the compressive strain enhancement (characteristic of long twist pitch conductors). Furthermore, it appears that increasing strand surface roughness could improve the performance of long twist pitch CICCs.« less

Metallographic autopsies of full-scale ITER prototype cable-in-conduit conductors after full cyclic testing in SULTAN: III. The importance of strand surface roughness in long twist pitch conductors

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

Sanabria, Charlie; Lee, Peter J.; Starch, William

As part of the ITER conductor qualification process, 3 m long Cable-in-Conduit Conductors (CICCs) were tested at the SULTAN facility under conditions simulating ITER operation so as to establish the current sharing temperature, T cs, as a function of multiple full Lorentz force loading cycles. After a comprehensive evaluation of both the Toroidal Field (TF) and the Central Solenoid (CS) conductors, it was found that T cs degradation was common in long twist pitch TF conductors while short twist pitch CS conductors showed some T cs increase. However, one kind of TF conductors containing superconducting strand fabricated by the Bochvarmore » Institute of Inorganic Materials (VNIINM) avoided T cs degradation despite having long twist pitch. In our earlier metallographic autopsies of long and short twist pitch CS conductors, we observed a substantially greater transverse strand movement under Lorentz force loading for long twist pitch conductors, while short twist pitch conductors had negligible transverse movement. With help from the literature, we concluded that the transverse movement was not the source of T cs degradation but rather an increase of the compressive strain in the Nb 3Sn filaments possibly induced by longitudinal movement of the wires. Like all TF conductors this TF VNIINM conductor showed large transverse motions under Lorentz force loading, but Tcs actually increased, as in all short twist pitch CS conductors. We here propose that the high surface roughness of the VNIINM strand may be responsible for the suppression of the compressive strain enhancement (characteristic of long twist pitch conductors). Furthermore, it appears that increasing strand surface roughness could improve the performance of long twist pitch CICCs.« less

Improvement of COBRA-TF for modeling of PWR cold- and hot-legs during reactor transients

NASA Astrophysics Data System (ADS)

Salko, Robert K.

COBRA-TF is a two-phase, three-field (liquid, vapor, droplets) thermal-hydraulic modeling tool that has been developed by the Pacific Northwest Laboratory under sponsorship of the NRC. The code was developed for Light Water Reactor analysis starting in the 1980s; however, its development has continued to this current time. COBRA-TF still finds wide-spread use throughout the nuclear engineering field, including nuclear-power vendors, academia, and research institutions. It has been proposed that extension of the COBRA-TF code-modeling region from vessel-only components to Pressurized Water Reactor (PWR) coolant-line regions can lead to improved Loss-of-Coolant Accident (LOCA) analysis. Improved modeling is anticipated due to COBRA-TF's capability to independently model the entrained-droplet flow-field behavior, which has been observed to impact delivery to the core region[1]. Because COBRA-TF was originally developed for vertically-dominated, in-vessel, sub-channel flow, extension of the COBRA-TF modeling region to the horizontal-pipe geometries of the coolant-lines required several code modifications, including: • Inclusion of the stratified flow regime into the COBRA-TF flow regime map, along with associated interfacial drag, wall drag and interfacial heat transfer correlations, • Inclusion of a horizontal-stratification force between adjacent mesh cells having unequal levels of stratified flow, and • Generation of a new code-input interface for the modeling of coolant-lines. The sheer number of COBRA-TF modifications that were required to complete this work turned this project into a code-development project as much as it was a study of thermal-hydraulics in reactor coolant-lines. The means for achieving these tasks shifted along the way, ultimately leading the development of a separate, nearly completely independent one-dimensional, two-phase-flow modeling code geared toward reactor coolant-line analysis. This developed code has been named CLAP, for Coolant-Line-Analysis Package. Versions were created that were both coupled to COBRA-TF and standalone, with the most recent version being a standalone code. This code performs a separate, simplified, 1-D solution of the conservation equations while making special considerations for coolant-line geometry and flow phenomena. The end of this project saw a functional code package that demonstrates a stable numerical solution and that has gone through a series of Validation and Verification tests using the Two-Phase Testing Facility (TPTF) experimental data[2]. The results indicate that CLAP is under-performing RELAP5-MOD3 in predicting the experimental void of the TPTF facility in some cases. There is no apparent pattern, however, to point to a consistent type of case that the code fails to predict properly (e.g., low-flow, high-flow, discharging to full vessel, or discharging to empty vessel). Pressure-profile predictions are sometimes unrealistic, which indicates that there may be a problem with test-case boundary conditions or with the coupling of continuity and momentum equations in the solution algorithm. The code does predict the flow regime correctly for all cases with the stratification-force model off. Turning the stratification model on can cause the low-flow case void profiles to over-react to the force and the flow regime to transition out of stratified flow. The code would benefit from an increased amount of Validation & Verification testing. The development of CLAP was significant, as it is a cleanly written, logical representation of the reactor coolant-line geometry. It is stable and capable of modeling basic flow physics in the reactor coolant-line. Code development and debugging required the temporary removal of the energy equation and mass-transfer terms in governing equations. The reintroduction of these terms will allow future coupling to RELAP and re-coupling with COBRA-TF. Adding in more applicable entrainment and de-entrainment models would allow the capture of more advanced physics in the coolant-line that can be expected during Loss-of-Coolant Accident. One of the package's benefits is its ability to be used as a platform for future coolant-line model development and implementation, including capturing of the important de-entrainment behavior in reactor hot-legs (steam-binding effect) and flow convection in the upper-plenum region of the vessel.

Transfer of radionuclides to plants of natural ecosystems at the Semipalatinsk Test Site.

PubMed

Larionova, N V; Lukashenko, S N; Kabdyrakova, A M; Kunduzbayeva, A Ye; Panitskiy, A V; Ivanova, A R

2018-06-01

A systematic study devoted to 137 Cs, 90 Sr, 241 Am, 239+240 Pu radionuclides in vegetation cover from several spots of the Semipalatinsk test site (STS) is summarised in this paper, highlighting the main findings obtained. The analysed spots are characterized by various types of radioactive contamination. Transfer factors (Tf) required for the quantitative description of the radionuclides transition from the soil to aboveground plant parts were determined, being found that, on average, the minimum Tf for all the radionuclides concerned were determined on the "Experimental Field" ground, followed by the determined ones in the "plumes" of radioactive fallout and in the conditionally "background" territories analysed. The highest transfer factors were characteristic of zones of radioactive streamflows and places of warfare radioactive agent (WRA) tests. On the other hand, ordering the radionuclide transferring factors in descending order, the following sequence was obtained: 90 Sr Tf > Cs Tf >  239+240 Pu Tf >  241 Am Tf, with the 90 Sr Tf, on the average, exceeding the 137 Cs Tf by 8 times and exceeding the 239+240 Pu Tf by up 16 times. 239+240 Pu Tf values were up to 3 times higher than the 241 Am Tf. The exception to the indicated radionuclide Tf descending order corresponded to places of WRA tests where Tf of radionuclides of interest by plants follows the sequence 90 Sr >  239+240 Pu >  137 Cs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determining thyroid {sup 131}I effective half-life for the treatment planning of Graves' disease

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

Willegaignon, Jose; Sapienza, Marcelo T.; Barberio Coura Filho, George

2013-02-15

Purpose: Thyroid {sup 131}I effective half-life (T{sub eff}) is an essential parameter in patient therapy when accurate radiation dose is desirable for producing an intended therapeutic outcome. Multiple {sup 131}I uptake measurements and resources from patients themselves and from nuclear medicine facilities are requisites for determining T{sub eff}, these being limiting factors when implementing the treatment planning of Graves' disease (GD) in radionuclide therapy. With the aim of optimizing this process, this study presents a practical, propitious, and accurate method of determining T{sub eff} for dosimetric purposes. Methods: A total of 50 patients with GD were included in this prospectivemore » study. Thyroidal {sup 131}I uptake was measured at 2-h, 6-h, 24-h, 48-h, 96-h, and 220-h postradioiodine administration. T{sub eff} was calculated by considering sets of two measured points (24-48-h, 24-96-h, and 24-220-h), sets of three (24-48-96-h, 24-48-220-h, and 24-96-220-h), and sets of four (24-48-96-220-h). Results: When considering all the measured points, the representative T{sub eff} for all the patients was 6.95 ({+-}0.81) days, whereas when using such sets of points as (24-220-h), (24-96-220-h), and (24-48-220-h), this was 6.85 ({+-}0.81), 6.90 ({+-}0.81), and 6.95 ({+-}0.81) days, respectively. According to the mean deviations 2.2 ({+-}2.4)%, 2.1 ({+-}2.0)%, and 0.04 ({+-}0.09)% found in T{sub eff}, calculated based on all the measured points in time, and with methods using the (24-220-h), (24-48-220-h), and (24-96-220-h) sets, respectively, no meaningful statistical difference was noted among the three methods (p > 0.500, t test). Conclusions: T{sub eff} obtained from only two thyroid {sup 131}I uptakes measured at 24-h and 220-h, besides proving to be sufficient, accurate enough, and easily applicable, attributes additional major cost-benefits for patients, and facilitates the application of the method for dosimetric purposes in the treatment planning of Graves' disease.« less

Magnet Design Considerations for Fusion Nuclear Science Facility

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

Zhai, Y.; Kessel, C.; El-Guebaly, L.

2016-06-01

The Fusion Nuclear Science Facility (FNSF) is a nuclear confinement facility that provides a fusion environment with components of the reactor integrated together to bridge the technical gaps of burning plasma and nuclear science between the International Thermonuclear Experimental Reactor (ITER) and the demonstration power plant (DEMO). Compared with ITER, the FNSF is smaller in size but generates much higher magnetic field, i.e., 30 times higher neutron fluence with three orders of magnitude longer plasma operation at higher operating temperatures for structures surrounding the plasma. Input parameters to the magnet design from system code analysis include magnetic field of 7.5more » T at the plasma center with a plasma major radius of 4.8 m and a minor radius of 1.2 m and a peak field of 15.5 T on the toroidal field (TF) coils for the FNSF. Both low-temperature superconductors (LTS) and high-temperature superconductors (HTS) are considered for the FNSF magnet design based on the state-of-the-art fusion magnet technology. The higher magnetic field can be achieved by using the high-performance ternary restacked-rod process Nb3Sn strands for TF magnets. The circular cable-in-conduit conductor (CICC) design similar to ITER magnets and a high-aspect-ratio rectangular CICC design are evaluated for FNSF magnets, but low-activation-jacket materials may need to be selected. The conductor design concept and TF coil winding pack composition and dimension based on the horizontal maintenance schemes are discussed. Neutron radiation limits for the LTS and HTS superconductors and electrical insulation materials are also reviewed based on the available materials previously tested. The material radiation limits for FNSF magnets are defined as part of the conceptual design studies for FNSF magnets.« less

Magnet design considerations for Fusion Nuclear Science Facility

DOE PAGES

Zhai, Yuhu; Kessel, Chuck; El-guebaly, Laila; ...

2016-02-25

The Fusion Nuclear Science Facility (FNSF) is a nuclear confinement facility to provide a fusion environment with components of the reactor integrated together to bridge the technical gaps of burning plasma and nuclear science between ITER and the demonstration power plant (DEMO). Compared to ITER, the FNSF is smaller in size but generates much higher magnetic field, 30 times higher neutron fluence with 3 orders of magnitude longer plasma operation at higher operating temperatures for structures surrounding the plasma. Input parameters to the magnet design from system code analysis include magnetic field of 7.5 T at the plasma center withmore » plasma major radius of 4.8 m and minor radius of 1.2 m, and a peak field of 15.5 T on the TF coils for FNSF. Both low temperature superconductor (LTS) and high temperature superconductor (HTS) are considered for the FNSF magnet design based on the state-of-the-art fusion magnet technology. The higher magnetic field can be achieved by using the high performance ternary Restack Rod Process (RRP) Nb3Sn strands for toroidal field (TF) magnets. The circular cable-in-conduit conductor (CICC) design similar to ITER magnets and a high aspect ratio rectangular CICC design are evaluated for FNSF magnets but low activation jacket materials may need to be selected. The conductor design concept and TF coil winding pack composition and dimension based on the horizontal maintenance schemes are discussed. Neutron radiation limits for the LTS and HTS superconductors and electrical insulation materials are also reviewed based on the available materials previously tested. As a result, the material radiation limits for FNSF magnets are defined as part of the conceptual design studies for FNSF magnets.« less

The implementation and operation of a variable-response electronic throttle control system for a TF-104G aircraft

NASA Technical Reports Server (NTRS)

Neal, Bradford; Sengupta, Upal

1989-01-01

During some flight programs, researchers have encountered problems in the throttle response characteristics of high-performance aircraft. To study and to help solve these problems, the National Aeronautics and Space Administration Ames Research Center's Dryden Flight Research Facility (Ames-Dryden) conducted a study using a TF-104G airplane modified with a variable-response electronic throttle control system. Ames-Dryden investigated the effects of different variables on engine response and handling qualities. The system provided transport delay, lead and lag filters, second-order lags, command rate and position limits, and variable gain between the pilot's throttle command and the engine fuel controller. These variables could be tested individually or in combination. Ten research flights were flown to gather data on engine response and to obtain pilot ratings of the various system configurations. The results should provide design criteria for engine-response characteristics. The variable-response throttle components and how they were installed in the TF-104G aircraft are described. How the variable-response throttle was used in flight and some of the results of using this system are discussed.

Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms.

PubMed

Kwon, Seok-Joon; Zhang, Fuming; Dordick, Jonathan S; Sonstein, William J; Linhardt, Robert J

2015-10-01

A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo-transferrin (aTF) biomarker, without interference from serum sialo-transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two-step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Qualitative Study Investigating Experiences, Perceptions, and Healthcare System Performance in Relation to the Surveillance of Typhoid Fever in Madagascar.

PubMed

Pach, Alfred; Warren, Michelle; Chang, Irene; Im, Justin; Nichols, Chelsea; Meyer, Christian G; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; von Kalckreuth, Vera; Baker, Stephen; Rabezanahary, Henintsoa; Rakotondrainiarivelo, Jean Philibert; Raminosoa, Tiana Mirana; Rakotozandrindrainy, Raphaël; Marks, Florian

2016-03-15

The burden of typhoid fever (TF) in sub-Saharan Africa is largely unknown but is increasingly thought to be high, given that water and sanitary conditions remain unimproved in many countries. To address this gap in information, the Typhoid Fever Surveillance in Africa Program (TSAP) founded a surveillance system for TF in 10 African countries. This study was a component of the TSAP surveillance project in Madagascar. The study entailed a qualitative assessment of patients' experiences and perceptions of services for febrile symptoms at the studies' rural and urban sentinel public health clinics. The study examined influences on the use of these facilities, alternative sources of care, and providers' descriptions of medical consultations and challenges in providing services. Data were collected through semistructured and open-ended individual interviews and a focus group with patients, caregivers, and medical personnel. Thirty-three patients and 12 healthcare providers participated in the data collection across the 2 healthcare facilities. The quality of services, cost, and travel distance were key factors that enabled access to and use of these clinics. Divergent healthcare-seeking patterns were related to variability in the care utilized, socioeconomic status, and potential distance from the facilities : These factors influenced delivery of care, patient access, and the health facilities' capacity to identify cases of febrile illness such as TF. This approach provided an in-depth investigation and understanding of healthcare-seeking behavior at the study facilities, and factors that facilitated or acted as barriers to their use. Our findings demonstrate the relevance of these public health clinics as sites for the surveillance of TF in their role as central healthcare sources for families and communities within these rural and urban areas of Madagascar. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability.

PubMed

Zakeri-Milani, Parvin; Barzegar-Jalali, Mohammad; Azimi, Mandana; Valizadeh, Hadi

2009-09-01

The solubility and dissolution rate of active ingredients are of major importance in preformulation studies of pharmaceutical dosage forms. In the present study, passively absorbed drugs are classified based on their intrinsic dissolution rate (IDR) and their intestinal permeabilities. IDR was determined by measuring the dissolution of a non-disintegrating disk of drug, and effective intestinal permeability of tested drugs in rat jejunum was determined using single perfusion technique. The obtained intrinsic dissolution rate values were in the range of 0.035-56.8 mg/min/cm(2) for tested drugs. The minimum and maximum intestinal permeabilities in rat intestine were determined to be 1.6 x 10(-5) and 2 x 10(-4)cm/s, respectively. Four classes of drugs were defined: Category I: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR>1(mg/min/cm(2)), Category II: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)), Category III: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR>1 (mg/min/cm(2)) and Category IV: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)). According to the results obtained and proposed classification of drugs, it is concluded that drugs could be categorized correctly based on their IDR and intestinal permeability values.

Engine installation effects of four civil transport airplanes : Wallops Flight Facility study

DOT National Transportation Integrated Search

2003-10-31

This report examines the effects of airplane geometrical configuration on the acoustic directivity characteristics and on the propagation of airplane noise. This effect of airplane geometry is referred to in this report as engine installation effe...

Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area.

PubMed

Khanna, Ashish; Khanna, Menka; Gill, Karamjit Singh

2015-11-01

Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas.

Influence of high altitude on the burning behaviour of typical combustibles and the related responses of smoke detectors in compartments

PubMed Central

Zeng, Yi; Fang, Jun; Zhang, Yong-Ming

2018-01-01

The effect of altitude on typical combustible burning and related smoke detector response signals was investigated by comparison experiments at altitudes of 40 m and 3650 m based on EN54 standard tests. Point-type light scattering photoelectric smoke detectors and ionization smoke detectors were used for four kinds of EN54 fire tests, including two kinds of smouldering fires with wood (test fire no. 2 in EN54 standard or TF2) and cotton (TF3), and two kinds of flaming fires with polyurethane (TF4) and n-heptane (TF5). First, the influence of altitude or ambient pressure on mass loss for smouldering combustion (TF2 or TF3) was insignificant, while a significant decrease in the mass burning rate was found for flaming tests (TF4 and TF5) as reported in our previous studies. Second, for photoelectric smoke detectors in flaming fire tests, the effect of altitude was similar to that of the burning rate, whereas for the ionization smoke detectors, the response signal at high altitudes was shown to be ‘enhanced’ by the detection principle of the ionization chamber, leading to an even larger value than at normal altitude for smouldering conditions. Third, to provide a reference for smoke detector design in high-altitude areas, the differences between signal speed in rising and peak values at two locations are discussed. Also, relationship between ion chamber signals and smoke optical densities are presented by utilization of an ionization smoke detector and smoke concentration meter. Moreover, a hierarchical diagram is illustrated to provide a better understanding of the effects of altitude on combustible burning behaviour and the mechanisms of detector response. PMID:29765695

Influence of high altitude on the burning behaviour of typical combustibles and the related responses of smoke detectors in compartments.

PubMed

Tu, Ran; Zeng, Yi; Fang, Jun; Zhang, Yong-Ming

2018-04-01

The effect of altitude on typical combustible burning and related smoke detector response signals was investigated by comparison experiments at altitudes of 40 m and 3650 m based on EN54 standard tests. Point-type light scattering photoelectric smoke detectors and ionization smoke detectors were used for four kinds of EN54 fire tests, including two kinds of smouldering fires with wood (test fire no. 2 in EN54 standard or TF2) and cotton (TF3), and two kinds of flaming fires with polyurethane (TF4) and n -heptane (TF5). First, the influence of altitude or ambient pressure on mass loss for smouldering combustion (TF2 or TF3) was insignificant, while a significant decrease in the mass burning rate was found for flaming tests (TF4 and TF5) as reported in our previous studies. Second, for photoelectric smoke detectors in flaming fire tests, the effect of altitude was similar to that of the burning rate, whereas for the ionization smoke detectors, the response signal at high altitudes was shown to be 'enhanced' by the detection principle of the ionization chamber, leading to an even larger value than at normal altitude for smouldering conditions. Third, to provide a reference for smoke detector design in high-altitude areas, the differences between signal speed in rising and peak values at two locations are discussed. Also, relationship between ion chamber signals and smoke optical densities are presented by utilization of an ionization smoke detector and smoke concentration meter. Moreover, a hierarchical diagram is illustrated to provide a better understanding of the effects of altitude on combustible burning behaviour and the mechanisms of detector response.

38 CFR 39.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... FOR ESTABLISHMENT, EXPANSION, AND IMPROVEMENT OF VETERANS' CEMETERIES (Eff. until 7-16-10) General Provisions § 39.2 Definitions. For the purpose of this part: (a) Establishment means the process of site... of gravesites and other cemeterial facilities. (c) Improvement means the enhancement of a cemetery...

Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

PubMed

Lin, Zeng-Mao; Zhao, Jian-Xin; Duan, Xue-Ning; Zhang, Lan-Bo; Ye, Jing-Ming; Xu, Ling; Liu, Yin-Hua

2014-01-01

This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Central blood pressure in children and adolescents: non-invasive development and testing of novel transfer functions.

PubMed

Cai, T Y; Qasem, A; Ayer, J G; Butlin, M; O'Meagher, S; Melki, C; Marks, G B; Avolio, A; Celermajer, D S; Skilton, M R

2017-12-01

Central blood pressure can be estimated from peripheral pulses in adults using generalised transfer functions (TF). We sought to create and test age-specific non-invasively developed TFs in children, with comparison to a pre-existing adult TF. We studied healthy children from two sites at two time points, 8 and 14 years of age, split by site into development and validation groups. Radial and carotid pressure waveforms were obtained by applanation tonometry. Central systolic pressure was derived from carotid waveforms calibrated to brachial mean and diastolic pressures. Age-specific TFs created in the development groups (n=50) were tested in the validation groups aged 8 (n=137) and 14 years (n=85). At 8 years of age, the age-specific TF estimated 82, 99 and 100% of central systolic pressure values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF overestimated central systolic pressure by 2.2 (s.d. 3.7) mm Hg, compared to being underestimated by 5.6 (s.d. 3.9) mm Hg with the adult TF. At 14 years of age, the age-specific TF estimated 60, 87 and 95% of values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF underestimated central systolic pressure by 0.5 (s.d. 6.7) mm Hg, while the adult TF underestimated it by 6.8 (s.d. 6.0) mm Hg. In conclusion, age-specific TFs more accurately predict central systolic pressure measured at the carotid artery in children than an existing adult TF.

Vertical Plane Oscillation Experiments on a Series of Two-Dimensional SWATH Demi-Hull Sections

DTIC Science & Technology

1988-08-01

32 21. Example of repeatability of hydrodynamic coefficients for the Z1 gage, and wave TF1 , for model A...waves heights from probes 1 and 2 were divided by the heave oscillation amplitude to define radiated wave transfer functions , TF1 and TF2...delta2) and TF1 and TF2 are presented versus kB/2 on a single page for each combination of draft and amplitude tested. The plots are followed by the

Theaflavins in black tea and catechins in green tea are equally effective antioxidants.

PubMed

Leung, L K; Su, Y; Chen, R; Zhang, Z; Huang, Y; Chen, Z Y

2001-09-01

Green tea catechins, including (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG), are oxidized and dimerized during the manufacture of black tea and oolong tea to form orange-red pigments, theaflavins (TF), a mixture of theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B) and theaflavin-3,3'-digallate (TF3). The present study was designed to compare the antioxidant activities of individual TF with that of each catechin using human LDL oxidation as a model. All catechins and TF tested inhibited Cu(+2)-mediated LDL oxidation. Analysis of the thiobarbituric acid-reactive substances (TBARS) and conjugated dienes produced during LDL oxidation revealed that the antioxidant activity was in the order: TF3 > ECG > EGCG > or = TF2B > or = TF2A > TF1 > or = EC > EGC. Four TF derivatives also demonstrated a dose-dependent antioxidant activity in Cu(+2)-mediated LDL oxidation at concentrations of 5-40 micromol/L. These results demonstrate that the TF present in black tea possess at least the same antioxidant potency as catechins present in green tea, and that the conversion of catechins to TF during fermentation in making black tea does not alter significantly their free radical-scavenging activity.

The Influence of Team Functioning and Workload on Sustainability of Trauma-Focused Evidence-Based Psychotherapies.

PubMed

Mohr, David C; Rosen, Craig S; Schnurr, Paula P; Orazem, Robert J; Noorbaloochi, Siamak; Clothier, Barbara A; Eftekhari, Afsoon; Bernardy, Nancy C; Chard, Kathleen M; Crowley, Jill J; Cook, Joan M; Kehle-Forbes, Shannon M; Ruzek, Josef I; Sayer, Nina A

2018-05-25

It has been over a decade since the U.S. Department of Veterans Affairs (VA) began formal dissemination and implementation of two trauma-focused evidence-based psychotherapies (TF-EBPs). The objective of this study was to examine the sustainability of the TF-EBPs and determine whether team functioning and workload were associated with TF-EBP sustainability. This observational study used VA administrative data for 6,251 patients with posttraumatic stress disorder (PTSD) and surveys from 78 providers from 10 purposefully selected PTSD clinical teams located in nine VA medical centers. The outcome was sustainability of TF-EBPs, which was based on British National Health System Sustainability Index scores (possible scores range from 0 to 100.90). Primary predictors included team functioning, workload, and TB-EBP reach to patients with PTSD. Multiple linear regression models were used to examine the influence of team functioning and workload on TF-EBP sustainability after adjustment for covariates that were significantly associated with sustainability. Sustainability Index scores ranged from 53.15 to 100.90 across the 10 teams. Regression models showed that after adjustment for patient and facility characteristics, team functioning was positively associated (B=9.16, p<.001) and workload was negatively associated (B=-.28, p<.05) with TF-EBP sustainability. There was considerable variation across teams in TF-EBP sustainability. The contribution of team functioning and workload to the sustainability of evidence-based mental health care warrants further study.

Relationship between rabbit transferrin electrophoretic patterns and plasma iron concentrations.

PubMed

Zaragoza, P; Arana, A; Amorena, B

1987-01-01

Rabbit transferrin (Tf) was studied electrophoretically using 1141 blood samples from individuals belonging to seven populations (Spanish Common, Spanish Giant, Butterfly, Lyoné de Bourgogne, New Zealand White, Californian and New Zealand White X Californian hybrids). No Tf polymorphism was found by starch gel electrophoresis, but six patterns, differing in the presence and/or intensity of three bands ('a', anodic; 'b', intermediate; and 'c', cathodic) were observed by polyacrylamide gel electrophoresis. No genetic model could explain these patterns, since they reflect differences in plasma Tf iron content. The electrophoretic test allowed a direct observation of the relative in vivo levels of the different Tf molecular species; saturated (band 'a', Fe2Tf); semi-saturated (band 'b', Fe1Tf); and without iron (band 'c' Fe0Tf, apotransferrin). The degree of iron saturation of Tf varied among individuals and throughout the individual's life. Specifically, in pregnant females, Fe2Tf and Fe1Tf are generally observed, except in late pregnancy (from day 25 to parturition), when mainly apotransferrin is observed. Significantly, within 24 h post-partum, high levels of Fe2Tf are reached in the female's serum.

Operational analysis of shared lane markings and green bike lanes on roadways with speeds greater than 35 mph : [summary].

DOT National Transportation Integrated Search

2014-01-01

In this project, University of North Florida : researchers analyzed how shared lane markings : (sharrows), wide curb lanes, standard and : buffered bike lanes, and green bike lanes affected : operations of bicycle facilities. Three measures : of effe...

Scoping and sensitivity analyses for the Demonstration Tokamak Hybrid Reactor (DTHR)

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

Sink, D.A.; Gibson, G.

1979-03-01

The results of an extensive set of parametric studies are presented which provide analytical data of the effects of various tokamak parameters on the performance and cost of the DTHR (Demonstration Tokamak Hybrid Reactor). The studies were centered on a point design which is described in detail. Variations in the device size, neutron wall loading, and plasma aspect ratio are presented, and the effects on direct hardware costs, fissile fuel production (breeding), fusion power production, electrical power consumption, and thermal power production are shown graphically. The studies considered both ignition and beam-driven operations of DTHR and yielded results based onmore » two empirical scaling laws presently used in reactor studies. Sensitivity studies were also made for variations in the following key parameters: the plasma elongation, the minor radius, the TF coil peak field, the neutral beam injection power, and the Z/sub eff/ of the plasma.« less

Transverse heat transfer coefficient in the dual channel ITER TF CICCs Part II. Analysis of transient temperature responses observed during a heat slug propagation experiment

NASA Astrophysics Data System (ADS)

Lewandowska, Monika; Herzog, Robert; Malinowski, Leszek

2015-01-01

A heat slug propagation experiment in the final design dual channel ITER TF CICC was performed in the SULTAN test facility at EPFL-CRPP in Villigen PSI. We analyzed the data resulting from this experiment to determine the equivalent transverse heat transfer coefficient hBC between the bundle and the central channel of this cable. In the data analysis we used methods based on the analytical solutions of a problem of transient heat transfer in a dual-channel cable, similar to Renard et al. (2006) and Bottura et al. (2006). The observed experimental and other limits related to these methods are identified and possible modifications proposed. One result from our analysis is that the hBC values obtained with different methods differ by up to a factor of 2. We have also observed that the uncertainties of hBC in both methods considered are much larger than those reported earlier.

Membrane triangles with corner drilling freedoms. III - Implementation and performance evaluation

NASA Technical Reports Server (NTRS)

Felippa, Carlos A.; Alexander, Scott

1992-01-01

This paper completes a three-part series on the formulation of 3-node, 9-dof membrane triangles with corner drilling freedoms based on parametrized variational principles. The first four sections cover element implementation details including determination of optimal parameters and treatment of distributed loads. Then three elements of this type, labeled ALL, FF and EFF-ANDES, are tested on standard plane stress problems. ALL represents numerically integrated versions of Allman's 1988 triangle; FF is based on the free formulation triangle presented by Bergan and Felippa in 1985; and EFF-ANDES represent two different formulations of the optimal triangle derived in Parts I and II. The numerical studies indicate that the ALL, FF and EFF-ANDES elements are comparable in accuracy for elements of unitary aspect ratios. The ALL elements are found to stiffen rapidly in inplane bending for high aspect ratios, whereas the FF and EFF elements maintain accuracy. The EFF and ANDES implementations have a moderate edge in formation speed over the FF.

Facile Method and Novel Dielectric Material Using a Nanoparticle-Doped Thermoplastic Elastomer Composite Fabric for Triboelectric Nanogenerator Applications.

PubMed

Zhang, Zhi; Chen, Ying; Debeli, Dereje Kebebew; Guo, Jian Sheng

2018-04-18

The trends toward flexible and wearable electronic devices give rise to the attention of triboelectric nanogenerators (TENGs) which can gather tiny energy from human body motions. However, to accommodate the needs, wearable electronics are still facing challenges for choosing a better dielectric material to improve their performance and practicability. As a kind of synthetic rubber, the thermoplastic elastomer (TPE) contains many advantages such as lightweight, good flexibility, high tear strength, and friction resistance, accompanied by good adhesion with fabrics, which is an optimal candidate of dielectric materials. Herein, a novel nanoparticle (NP)-doped TPE composite fabric-based TENG (TF-TENG) has been developed, which operates based on the NP-doped TPE composite fabric using a facile coating method. The performances of the TENG device are systematically investigated under various thicknesses of TPE films, NP kinds, and doping mass. After being composited with a Cu NP-doped TPE film, the TPE composite fabric exhibited superior elastic behavior and good bending property, along with excellent flexibility. Moreover, a maximum output voltage of 470 V, a current of 24 μA, and a power of 12 mW under 3 MΩ can be achieved by applying a force of 60 N on the TF-TENG. More importantly, the TF-TENG can be successfully used to harvest biomechanical energy from human body and provides much more comfort. In general, the TF-TENG has great application prospects in sustainable wearable devices owing to its lightweight, flexibility, and high mechanical properties.

Quantification of Endospore-Forming Firmicutes by Quantitative PCR with the Functional Gene spo0A

PubMed Central

Bueche, Matthieu; Wunderlin, Tina; Roussel-Delif, Ludovic; Junier, Thomas; Sauvain, Loic; Jeanneret, Nicole

2013-01-01

Bacterial endospores are highly specialized cellular forms that allow endospore-forming Firmicutes (EFF) to tolerate harsh environmental conditions. EFF are considered ubiquitous in natural environments, in particular, those subjected to stress conditions. In addition to natural habitats, EFF are often the cause of contamination problems in anthropogenic environments, such as industrial production plants or hospitals. It is therefore desirable to assess their prevalence in environmental and industrial fields. To this end, a high-sensitivity detection method is still needed. The aim of this study was to develop and evaluate an approach based on quantitative PCR (qPCR). For this, the suitability of functional genes specific for and common to all EFF were evaluated. Seven genes were considered, but only spo0A was retained to identify conserved regions for qPCR primer design. An approach based on multivariate analysis was developed for primer design. Two primer sets were obtained and evaluated with 16 pure cultures, including representatives of the genera Bacillus, Paenibacillus, Brevibacillus, Geobacillus, Alicyclobacillus, Sulfobacillus, Clostridium, and Desulfotomaculum, as well as with environmental samples. The primer sets developed gave a reliable quantification when tested on laboratory strains, with the exception of Sulfobacillus and Desulfotomaculum. A test using sediment samples with a diverse EFF community also gave a reliable quantification compared to 16S rRNA gene pyrosequencing. A detection limit of about 104 cells (or spores) per gram of initial material was calculated, indicating this method has a promising potential for the detection of EFF over a wide range of applications. PMID:23811505

Linearly Supporting Feature Extraction for Automated Estimation of Stellar Atmospheric Parameters

NASA Astrophysics Data System (ADS)

Li, Xiangru; Lu, Yu; Comte, Georges; Luo, Ali; Zhao, Yongheng; Wang, Yongjun

2015-05-01

We describe a scheme to extract linearly supporting (LSU) features from stellar spectra to automatically estimate the atmospheric parameters {{T}{\\tt{eff} }}, log g, and [Fe/H]. “Linearly supporting” means that the atmospheric parameters can be accurately estimated from the extracted features through a linear model. The successive steps of the process are as follow: first, decompose the spectrum using a wavelet packet (WP) and represent it by the derived decomposition coefficients; second, detect representative spectral features from the decomposition coefficients using the proposed method Least Absolute Shrinkage and Selection Operator (LARS)bs; third, estimate the atmospheric parameters {{T}{\\tt{eff} }}, log g, and [Fe/H] from the detected features using a linear regression method. One prominent characteristic of this scheme is its ability to evaluate quantitatively the contribution of each detected feature to the atmospheric parameter estimate and also to trace back the physical significance of that feature. This work also shows that the usefulness of a component depends on both the wavelength and frequency. The proposed scheme has been evaluated on both real spectra from the Sloan Digital Sky Survey (SDSS)/SEGUE and synthetic spectra calculated from Kurucz's NEWODF models. On real spectra, we extracted 23 features to estimate {{T}{\\tt{eff} }}, 62 features for log g, and 68 features for [Fe/H]. Test consistencies between our estimates and those provided by the Spectroscopic Parameter Pipeline of SDSS show that the mean absolute errors (MAEs) are 0.0062 dex for log {{T}{\\tt{eff} }} (83 K for {{T}{\\tt{eff} }}), 0.2345 dex for log g, and 0.1564 dex for [Fe/H]. For the synthetic spectra, the MAE test accuracies are 0.0022 dex for log {{T}{\\tt{eff} }} (32 K for {{T}{\\tt{eff} }}), 0.0337 dex for log g, and 0.0268 dex for [Fe/H].

Single-shot Z(eff) dense plasma diagnostic through simultaneous refraction and attenuation measurements with a Talbot-Lau x-ray moiré deflectometer.

PubMed

Valdivia, M P; Stutman, D; Finkenthal, M

2015-04-01

The Talbot-Lau x-ray moiré deflectometer is a powerful plasma diagnostic capable of delivering simultaneous refraction and attenuation information through the accurate detection of x-ray phase shift and intensity. The diagnostic can provide the index of refraction n=1-δ+iβ of an object (dense plasma, for example) placed in the x-ray beam by independently measuring both δ and β, which are directly related to the electron density n(e) and the attenuation coefficient μ, respectively. Since δ and β depend on the effective atomic number Z(eff), a map can be obtained from the ratio between phase and absorption images acquired in a single shot. The Talbot-Lau x-ray moiré deflectometer and its corresponding data acquisition and processing are briefly described to illustrate how the above is achieved; Z(eff) values of test objects within the 4-12 range were obtained experimentally through simultaneous refraction and attenuation measurements. We show that Z(eff) mapping of objects does not require previous knowledge of sample length or shape. The determination of Z(eff) from refraction and attenuation measurements with moiré deflectometry could be of high interest to various domains of high energy density research, such as shocked materials and inertial confinement fusion experiments, as well as material science and nondestructive testing.

Evaluation of speciated VOC emission factors for Air Force hush houses

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

Sullivan, P.D.; Stevens, D.K.

1997-12-31

Data published in: ``Engine and Hush House Emissions from a TF30-P109 Jet Engine Tested at Cannon Air Force Base, NM`` by Radian Corporation and ``Aircraft Emissions. Characterization: TF41-A2, TF30-P103 , and TF30-P109 Engines`` by Battelle are reviewed and compared. Specifically CO, NO{sub x}, and VOC emission factors using EPA Method 19 are addressed, with comparisons between JP-4 and JP-8 jet fuels. CO and NO{sub x} emissions for JP-4 and JP-8 jet fuels were found to be essentially the same. VOC emission data exhibited high variability. Problems inherent in speciated VOC emission testing are discussed. A limiting of speciated VOC emissionmore » testing, with emission factor estimation based on fuel content is proposed.« less

The aesthetic impact of enamel fluorosis on Irish adolescents.

PubMed

Browne, Deirdre; Whelton, Helen; O'Mullane, Denis; Tavener, Jacqueline; Flannery, Edel

2011-04-01

To assess the impact of differing degrees of enamel fluorosis on dental aesthetics according to Irish adolescents. The same participants also aesthetically rated other variations in dental appearances including a carious lesion, bleached teeth and a demarcated opacity. One hundred and fifty adolescents examined seven identical template photographs of an attractive dental smile displaying varying levels of enamel fluorosis (TF1, TF2, TF3), a demarcated opacity, no fluorosis (TF0), anterior caries and very white or bleached teeth. By indicating their level of agreement or disagreement with five statements on a five-point Likert scale, the participants rated the aesthetic acceptability of each of the photographs. Using paired t-tests with the Bonferroni correction, it was found that the photographs depicting the very white teeth and anterior caries were rated as the most and least aesthetically pleasing images, respectively. There was no significant difference in the ratings of the photographs displaying TF0, TF1 and TF2 levels of fluorosis indicating that these photographs were viewed similarly (P>0.002). The remaining two photographs (TF3 and the demarcated opacity) were rated similarly and significantly worse (P<0.002) than the photographs showing no or low grades of fluorosis (TF0, TF1 and TF2). TF3 level of fluorosis represented the break point at which enamel fluorosis became aesthetically objectionable to these participants. Low grades of fluorosis (TF1 and TF2) were rated similarly to the photograph depicting no fluorosis (TF0). © 2011 John Wiley & Sons A/S.

Cutting efficiency of nickel-titanium rotary and reciprocating instruments after prolonged use.

PubMed

Gambarini, Gianluca; Giansiracusa Rubini, Alessio; Sannino, Giampaolo; Di Giorgio, Gianni; Di Giorgio, Fabrizio; Piasecki, Lucila; Al-Sudani, Dina; Plotino, Gianluca; Testarelli, Luca

2016-01-01

The aim of the present study was to compare the cutting efficiency of Twisted File instruments used in continuous rotation or TF Adaptive motion and evaluate if prolonged use significantly affected their cutting ability. 20 new NiTi instruments were used in the present study (TF tip size 35, 0.06 taper; Sybron-Endo, Orange, CA, USA), divided into 2 subgroups of 10 instruments each, depending on which movement was selected on the endodontic motor. Group 1: TF instruments were activated using the program TF continuous rotation at 500 rpm and torque set at 2 N; Group 2: TF instruments were activated using the reciprocating TF Adaptive motion. Cutting efficiency was tested in a device developed to test the cutting ability of endodontic instruments. Each instrument cut 10 plastic blocks (10 uses) and the length of the surface cut in a plastic block after 1 min was measured in a computerized program with a precision of 0.1 mm. Maximum penetration depth was calculated after 1 use and after 10 uses, and mean and standard deviation (SD) of each group was calculated. Data were statistically analyzed with a one-way ANOVA test (P < 0.05). TF instruments used in continuous rotation (Group 1) cut a mean depth of 10.4 mm (SD = 0.6 mm) after the first use and 10.1 mm (SD 1.1 mm) after 10 uses, while TF instruments used with the Adaptive motion cut a mean depth of 9.9 mm (SD = 0.7 mm) after the first use and 9.6 mm (SD = 0.9 mm) after 10 uses. There was no statistically significant difference between the two groups investigated (P > 0.05) nor between instruments after 1 or 10 uses. In conclusion, the TFA motion showed a lateral cutting ability similar to continuous rotation and all tested instruments exhibited the same cutting ability after prolonged use.

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

PubMed

Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

2011-11-01

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

Imminent Engine Failure Probe Investigation.

DTIC Science & Technology

probe signature determination, development of data recording techniques, accumulation of data during durability testing of T56 or TF41 engines and...any other opportunistic gas turbine engine test. The electrostatic probe demonstrated some capability to detect engine distress in TF41 and T56 engines

Computational Identification of Diverse Mechanisms Underlying Transcription Factor-DNA Occupancy

PubMed Central

Cheng, Qiong; Kazemian, Majid; Pham, Hannah; Blatti, Charles; Celniker, Susan E.; Wolfe, Scot A.; Brodsky, Michael H.; Sinha, Saurabh

2013-01-01

ChIP-based genome-wide assays of transcription factor (TF) occupancy have emerged as a powerful, high-throughput method to understand transcriptional regulation, especially on a global scale. This has led to great interest in the underlying biochemical mechanisms that direct TF-DNA binding, with the ultimate goal of computationally predicting a TF's occupancy profile in any cellular condition. In this study, we examined the influence of various potential determinants of TF-DNA binding on a much larger scale than previously undertaken. We used a thermodynamics-based model of TF-DNA binding, called “STAP,” to analyze 45 TF-ChIP data sets from Drosophila embryonic development. We built a cross-validation framework that compares a baseline model, based on the ChIP'ed (“primary”) TF's motif, to more complex models where binding by secondary TFs is hypothesized to influence the primary TF's occupancy. Candidates interacting TFs were chosen based on RNA-SEQ expression data from the time point of the ChIP experiment. We found widespread evidence of both cooperative and antagonistic effects by secondary TFs, and explicitly quantified these effects. We were able to identify multiple classes of interactions, including (1) long-range interactions between primary and secondary motifs (separated by ≤150 bp), suggestive of indirect effects such as chromatin remodeling, (2) short-range interactions with specific inter-site spacing biases, suggestive of direct physical interactions, and (3) overlapping binding sites suggesting competitive binding. Furthermore, by factoring out the previously reported strong correlation between TF occupancy and DNA accessibility, we were able to categorize the effects into those that are likely to be mediated by the secondary TF's effect on local accessibility and those that utilize accessibility-independent mechanisms. Finally, we conducted in vitro pull-down assays to test model-based predictions of short-range cooperative interactions, and found that seven of the eight TF pairs tested physically interact and that some of these interactions mediate cooperative binding to DNA. PMID:23935523

What is the best immunization strategy for protecting African children against invasive Salmonella disease?

PubMed

Jeon, Hyon Jin; Pak, Gi Deok; Im, Justin; Owusu-Dabo, Ellis; Adu-Sarkodie, Yaw; Gassama Sow, Amy; Bassiahi, Abdramane Soura; Gasmelseed, Nagla; Keddy, Karen H; Bjerregaard-Andersen, Morten; Konings, Frank; Aseffa, Abraham; Crump, John A; Chon, Yun; Breiman, Robert F; Park, Se Eun; Cruz Espinoza, Ligia Maria; Seo, Hye Jin; May, Jürgen; Meyer, Christian G; Andrews, Jason R; Panzner, Ursula; von Kalckreuth, Vera; Wierzba, Thomas F; Rakotozandrindrainy, Raphaël; Dougan, Gordon; Levine, Myron M; Hombach, Joachim; Kim, Jerome H; Clemens, John D; Baker, Stephen; Marks, Florian

2018-05-09

The WHO recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons aged ≥6 months to 45 years residing in typhoid fever (TF)-endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations in Africa. The Typhoid Fever Surveillance in Africa Program (TSAP) in 10 sub-Saharan African countries included blood culture-based surveillance in febrile people presenting at healthcare-facilities originating from defined catchment areas. The TF/invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0-10 year-old children in yearly increments. Salmonella Typhi and iNTS were the most frequently isolated pathogens, 135 and 94 cases were identified, respectively. Isolates (12 and 4, respectively) from Ethiopia, Senegal and South Africa were excluded due to person-years of observation (PYO) data absence. 37/123 (30.1%) TF and 71/90 (78.9%) iNTS disease cases occurred among individuals aged <5 years. No TF and 8/90 (8.9%) iNTS-infections were observed in children aged <9 months. The TF incidences (/100,000 PYO) for children aged <1 year and 1-<2 years were 5 and 39, respectively; the highest incidence was 304/100,000 PYO in 4-<5 year-old children. The iNTS incidence in the defined age groups ranged between 81 and 233/100,000 PYO, with the highest incidence in 1-<2 year-old children. Higher TF/iNTS disease incidences were observed in West Africa. The high TF burden observed in TSAP merits TCV introductions. Considering the additional iNTS disease burden, a trivalent vaccine targeting S. Typhi, S. Typhimurium, and S. Enteritidis may be a future solution.

Single-shot Z eff dense plasma diagnostic through simultaneous refraction and attenuation measurements with a Talbot–Lau x-ray moiré deflectometer

DOE PAGES

Valdivia, M. P.; Stutman, D.; Finkenthal, M.

2015-03-23

The Talbot–Lau x-ray moiré deflectometer is a powerful plasma diagnostic capable of delivering simultaneous refraction and attenuation information through the accurate detection of x-ray phase shift and intensity. The diagnostic can provide the index of refraction n=1₋δ + iβ of an object (dense plasma, for example) placed in the x-ray beam by independently measuring both δ and β, which are directly related to the electron density n e and the attenuation coefficient μ respectively. Since δ and β depend on the effective atomic number Z eff, a map can be obtained from the ratio between phase and absorption images acquiredmore » in a single shot. The Talbot–Lau x-ray moiré deflectometer and its corresponding data acquisition and processing are briefly described to illustrate how the above is achieved; Z eff values of test objects within the 4₋12 range were obtained experimentally through simultaneous refraction and attenuation measurements. We show that Z eff mapping of objects does not require previous knowledge of sample length or shape. In conclusion, the determination of Z eff from refraction and attenuation measurements with moiré deflectometry could be of high interest to various domains of high energy density research, such as shocked materials and inertial confinement fusion experiments, as well as material science and nondestructive testing.« less

Single-shot Z eff dense plasma diagnostic through simultaneous refraction and attenuation measurements with a Talbot–Lau x-ray moiré deflectometer

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

Valdivia, M. P.; Stutman, D.; Finkenthal, M.

The Talbot–Lau x-ray moiré deflectometer is a powerful plasma diagnostic capable of delivering simultaneous refraction and attenuation information through the accurate detection of x-ray phase shift and intensity. The diagnostic can provide the index of refraction n=1₋δ + iβ of an object (dense plasma, for example) placed in the x-ray beam by independently measuring both δ and β, which are directly related to the electron density n e and the attenuation coefficient μ respectively. Since δ and β depend on the effective atomic number Z eff, a map can be obtained from the ratio between phase and absorption images acquiredmore » in a single shot. The Talbot–Lau x-ray moiré deflectometer and its corresponding data acquisition and processing are briefly described to illustrate how the above is achieved; Z eff values of test objects within the 4₋12 range were obtained experimentally through simultaneous refraction and attenuation measurements. We show that Z eff mapping of objects does not require previous knowledge of sample length or shape. In conclusion, the determination of Z eff from refraction and attenuation measurements with moiré deflectometry could be of high interest to various domains of high energy density research, such as shocked materials and inertial confinement fusion experiments, as well as material science and nondestructive testing.« less

Transposon integration enhances expression of stress response genes.

PubMed

Feng, Gang; Leem, Young-Eun; Levin, Henry L

2013-01-01

Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress.

Transposon integration enhances expression of stress response genes

PubMed Central

Feng, Gang; Leem, Young-Eun; Levin, Henry L.

2013-01-01

Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress. PMID:23193295

Development of In-Fiber Reflective Bragg Gratings as Shear Stress Monitors in Aerodynamic Facilities

NASA Technical Reports Server (NTRS)

Parmar, Devendra S.; Sprinkle, Danny R.; Singh, Jag J.

1998-01-01

Bragg gratings centered at nominal wavelengths of 1290 nm and 1300 run were inscribed in a 9/125 microns germano-silicate optical fiber, using continuous wave frequency doubled Ar+ laser radiation at 244 nm. Such gratings have been used extensively as temperature and strain monitors in smart structures. They have, however, never been used for measuring aerodynamic shear stresses. As a test of their sensitivity as shear stress monitors, a Bragg fiber attached to a metal plate was subjected to laminar flows in a glass pipe. An easily measurable large flow-induced wavelength shift (Delta Lambda(sub B)) was observed in the Bragg reflected wavelength. Thereafter, the grating was calibrated by making one time, simultaneous measurements of Delta Lambda(sub B) and the coefficient of skin friction (C(sub f)) with a skin friction balance, as a function of flow rates in a subsonic wind tunnel. Onset of fan-induced transition in the tunnel flow provided a unique flow rate for correlating Delta Lambda(sub B) and (C(sub f) values needed for computing effective modulus of rigidity (N(sub eff)) of the fiber attached to the metal plate. This value Of N(sub eff) is expected to remain constant throughout the elastic stress range expected during the Bragg grating aerodynamic tests. It has been used for calculating the value of Cf at various tunnel speeds, on the basis of measured values of Bragg wavelength shifts at those speeds.

Manufacture and Quality Control of Insert Coil with Real ITER TF Conductor

DOE PAGES

Ozeki, H.; Isono, T.; Uno, Y.; ...

2016-03-02

JAEA successfully completed the manufacture of the toroidal field (TF) insert coil (TFIC) for a performance test of the ITER TF conductor in the final design in cooperation with Hitachi, Ltd. The TFIC is a single-layer 8.875-turn solenoid coil with 1.44-m diameter. This will be tested for 68-kA current application in a 13-T external magnetic field. TFIC was manufactured in the following order: winding of the TF conductor, lead bending, fabrication of the electrical termination, heat treatment, turn insulation, installation of the coil into the support mandrel structure, vacuum pressure impregnation (VPI), structure assembly, and instrumentation. Here in this presentation,more » manufacture process and quality control status for the TFIC manufacturing are reported.« less

Prospective Design of Anti‐Transferrin Receptor Bispecific Antibodies for Optimal Delivery into the Human Brain

PubMed Central

Kanodia, JS; Gadkar, K; Bumbaca, D; Zhang, Y; Tong, RK; Luk, W; Hoyte, K; Lu, Y; Wildsmith, KR; Couch, JA; Watts, RJ; Dennis, MS; Ernst, JA; Scearce‐Levie, K; Atwal, JK; Joseph, S

2016-01-01

Anti‐transferrin receptor (TfR)‐based bispecific antibodies have shown promise for boosting antibody uptake in the brain. Nevertheless, there are limited data on the molecular properties, including affinity required for successful development of TfR‐based therapeutics. A complex nonmonotonic relationship exists between affinity of the anti‐TfR arm and brain uptake at therapeutically relevant doses. However, the quantitative nature of this relationship and its translatability to humans is heretofore unexplored. Therefore, we developed a mechanistic pharmacokinetic‐pharmacodynamic (PK‐PD) model for bispecific anti‐TfR/BACE1 antibodies that accounts for antibody‐TfR interactions at the blood‐brain barrier (BBB) as well as the pharmacodynamic (PD) effect of anti‐BACE1 arm. The calibrated model correctly predicted the optimal anti‐TfR affinity required to maximize brain exposure of therapeutic antibodies in the cynomolgus monkey and was scaled to predict the optimal affinity of anti‐TfR bispecifics in humans. Thus, this model provides a framework for testing critical translational predictions for anti‐TfR bispecific antibodies, including choice of candidate molecule for clinical development. PMID:27299941

Performance Testing of a Liquid Metal Pump for In-Space Power Systems

NASA Technical Reports Server (NTRS)

Polzin, Kurt

2011-01-01

Fission surface power (FSP) systems could be used to provide power on the surface of the moon, Mars, or other planets and moons of our solar system. Fission power systems could provide excellent performance at any location, including those near the poles or other permanently shaded regions, and offer the capability to provide on demand power at any time, even at large distances from the sun. Fission-based systems also offer the potential for outposts, crew and science instruments to operate in a power-rich environment. NASA has been exploring technologies with the goal of reducing the cost and technical risk of employing FSP systems. A reference 40 kWe option has been devised that is cost-competitive with alternatives while providing more power for less mass anywhere on the lunar surface. The reference FSP system is also readily extensible for use on Mars, where it would be capable of operating through global dust storms and providing year-round power at any Martian latitude. Detailed development of the FSP concept and the reference mission are documented in various other reports. The development discussed in this paper prepares the way for testing of the Technology Demonstration Unit (TDU), which is a 10 kWe end-to-end test of FSP technologies intended to raise the entire FSP system to technology readiness level (TRL) 6. The Early Flight Fission Test Facility (EFF-TF) was established by NASA s Marshall Space Flight Center (MSFC) to provide a capability for performing hardware-directed activities to support multiple in-space nuclear reactor concepts by using a nonnuclear test methodology. This includes fabrication and testing at both the module/component level and at near prototypic reactor components and configurations allowing for realistic thermal-hydraulic evaluations of systems. The liquid-metal pump associated with the FSP system must be compatible with the liquid NaK coolant and have adequate performance to enable a viable flight system. Idaho National Laboratory (INL) was tasked with the modeling, design, and fabrication of an ALIP suitable for the FSP reference mission. A prototypic ALIP was fabricated under the direction of INL and shipped to MSFC for inclusion in the Technology Demonstration Unit (TDU), a quarter-scale end-to-end reactor simulator system that is scheduled for testing at NASA-GRC. Before inclusion in the TDU, the ALIP was tested in the ALIP test circuit (ATC), which is a rig developed and operated at MSFC for the specific purpose of providing accurate quantification of liquid metal pump performance. Data showing the pump performance curves (pressure, flowrate, and pump efficiency) are presented for various operating power levels, demonstrating the full performance envelope of the pump.

Water-tunnel study results of a TF/A-18 and F/A-18 canopy flow visualization

NASA Technical Reports Server (NTRS)

Johnson, Steven A.; Fisher, David F.

1990-01-01

A water tunnel study examining the influence of canopy shape on canopy and leading edge extension flow patterns was initiated. The F/A-18 single-place canopy model and the TF/A-18 two place canopy model were the study subjects. Plan view and side view photographs showing the flow patterns created by injected colored dye are presented for 0 deg and 5 deg sideslip angles. Photographs taken at angle of attack and sideslip conditions correspond to test departure points found in flight test. Flight experience has shown that the TF/A-18 airplane departs in regions where the F/A-18 airplane is departure-resistant. The study results provide insight into the differences in flow patterns which may influence the resulting aerodynamics of the TF/A-18 and F/A-18 aircraft. It was found that at 0 deg sideslip, the TF/A-18 model has more downward flow on the sides of the canopy than the F/A-18 model. This could be indicative of flow from the leading edge extension (LEX) vortexes impinging on the sides of the wider TF/A-18 canopy. In addition, the TF/A-18 model has larger areas of asymmetric separated and unsteady flow on the LEXs and fuselage, possibly indicating a lateral and directional destabilizing effect at the conditions studied.

Pentoxifylline inhibits hypoxia-induced upregulation of tumor cell tissue factor and vascular endothelial growth factor.

PubMed

Amirkhosravi, A; Meyer, T; Warnes, G; Amaya, M; Malik, Z; Biggerstaff, J P; Siddiqui, F A; Sherman, P; Francis, J L

1998-10-01

Tissue factor (TF), the membrane glycoprotein that initiates blood coagulation, is constitutively expressed by many tumor cells and is implicated in peri-tumor fibrin deposition and hypercoagulability in cancer. Upregulation of tumor TF correlates with enhanced metastatic potential. Furthermore, TF has been colocalized with VEGF in breast cancer, specially at sites of early angiogenesis. There are no data on the effect of hypoxia on tumor cell TF expression. Since hypoxia is known to stimulate VEGF production, we studied whether this also induces tumor cell TF expression. Confluent monolayers of A375 melanoma, MCF-7 breast carcinoma and A549 lung carcinoma were cultured in either 95% air, 5% CO2 (normoxic) or 95% N2, 5% CO2 (hypoxic; 25-30 mmHg) for 24 h. Procoagulant activity (PCA) was measured by amidolytic and clotting assays, surface TF antigen by flow cytometry, early apoptosis by annexin V binding and VEGF levels in culture supernatants by ELISA. Hypoxia significantly increased tumor cell PCA in all three cell lines tested and TF antigen on A375 cells was increased four-fold (P <0.05). Pentoxifylline (PTX), a methylxanthine derivative, significantly inhibited the hypoxia-induced increase in PCA as well as VEGF release in all three cell lines tested. In A375 cells, PTX significantly inhibited TF antigen expression by both normoxic and hypoxic cells. Hypoxia induced a slight (5%) but not significant, increase in early apoptosis. Intravenous injection of hypoxic A375 cells into nude rats produced more pronounced thrombocytopenia (n = 5, P <0.01) and more lung metastases (n = 3, P <0.05) compared to normoxic cells. We conclude that hypoxia increases TF expression by malignant cells which enhances tumor cell-platelet binding and hematogenous metastasis. Hypoxia-induced upregulation of TF appears to parallel that of VEGF, although the mechanism remains unclear.

Search for double beta decay with HPGe detectors at the Gran Sasso underground laboratory

NASA Astrophysics Data System (ADS)

Chkvorets, Oleg

2008-12-01

Neutrinoless double-beta decay is practically the only way to establish the Majorana nature of the neutrino mass and its decay rate provides a probe of an effective neutrino mass. Double beta experiments are long-running underground experiments with specific challenges concerning the background reduction and the long term stability. These problems are addressed in this work for the Heidelberg-Moscow (HdM), GENIUS Test Facility (TF) and GERDA experiments. The HdM experiment collected data with enriched 76Ge high purity (HPGe) detectors from 1990 to 2003. An improved analysis of HdM data is presented, exploiting new calibration and spectral shape measurements with the HdM detectors. GENIUS-TF was a test-facility that verified the feasibility of using bare germanium detectors in liquid nitrogen. The first year results of this experiment are discussed. The GERDA experiment has been designed to further increase the sensitivity by operating bare germanium detectors in a high purity cryogenic liquid, which simultaneously serves as a shielding against background and as a cooling media. In the preparatory stage of GERDA, an external background gamma flux measurement was done at the experimental site in the Hall A of the Gran Sasso laboratory. The characterization of the enriched detectors from the HdM and IGEX experiments was performed in the underground detector laboratory for the GERDA collaboration. Long term stability measurements of a bare HPGe detector in liquid argon were carried out. Based on these measurements, the first lower limit on the half-life of neutrinoless double electron capture of 36Ar was established to be 1.85*10^18 years at 68% C.L.

Fan Noise Test Facility

NASA Image and Video Library

1969-01-21

The Fan Noise Test Facility built at the Lewis Research Center to obtain far-field noise data for the National Aeronautics and Space Administration (NASA) and General Electric Quiet Engine Program. The engine incorporated existing noise reduction methods into an engine of similar power to those that propelled the Boeing 707 or McDonnell-Douglas DC-8 airliner. The new the low-bypass ratio turbofan engines of the 1960s were inherently quieter than their turbojet counterparts, researchers had a better grasp of the noise generation problem, and new acoustic technologies had emerged. Lewis contracted General Electric in 1969 to build and aerodynamically test three experimental engines with 72-inch diameter fans. The engines were then brought to Lewis and tested with an acoustically treated nacelle. This Fan Noise Test Facility was built off of the 10- by 10-Foot Supersonic Wind Tunnel’s Main Compressor and Drive Building. Lewis researchers were able to isolate the fan’s noise during these initial tests by removing the core of the engine. The Lewis test rig drove engines to takeoff tip speeds of 1160 feet per second. The facility was later used to test a series of full-scale model fans and fan noise suppressors to be used with the quiet engine. NASA researchers predicted low-speed single-stage fans without inlet guide vanes and with large spacing between rotors and stators would be quieter. General Electric modified a TF39 turbofan engine by removing the the outer protion of the fan and spacing the blade rows of the inner portion. The tests revealed that the untreated version of the engine generated less noise than was anticipated, and the acoustically treated nacelle substantially reduced engine noise.

Continuous versus bolus tube feeds: Does the modality affect glycemic variability, tube feeding volume, caloric intake, or insulin utilization?

PubMed

Evans, David C; Forbes, Rachel; Jones, Christian; Cotterman, Robert; Njoku, Chinedu; Thongrong, Cattleya; Tulman, David; Bergese, Sergio D; Thomas, Sheela; Papadimos, Thomas J; Stawicki, Stanislaw P

2016-01-01

Enteral nutrition (EN) is very important to optimizing outcomes in critical illness. Debate exists regarding the best strategy for enteral tube feeding (TF), with concerns that bolus TF (BTF) may increase glycemic variability (GV) but result in fewer nutritional interruptions than continuous TF (CTF). This study examines if there is a difference in GV, insulin usage, TF volume, and caloric delivery among intensive care patients receiving BTF versus CTF. We hypothesize that there are no significant differences between CTF and BTF when comparing the above parameters. Prospective, randomized pilot study of critically ill adult patients undergoing percutaneous endoscopic gastrostomy (PEG) placement for EN was performed between March 1, 2012 and May 15, 2014. Patients were randomized to BTF or CTF. Glucose values, insulin use, TF volume, and calories administered were recorded. Data were organized into 12-h epochs for statistical analyses and GV determination. In addition, time to ≥80% nutritional delivery goal, demographics, Acute Physiology and Chronic Health Evaluation II scores, and TF interruptions were examined. When performing BTF versus CTF assessments, continuous parameters were compared using Mann-Whitney U-test or repeated measures t-test, as appropriate. Categorical data were analyzed using Fisher's exact test. No significant demographic or physiologic differences between the CTF (n = 24) and BTF (n = 26) groups were seen. The immediate post-PEG 12-h epoch showed significantly lower GV and median TF volume for patients in the CTF group. All subsequent epochs (up to 18 days post-PEG) showed no differences in GV, insulin use, TF volume, or caloric intake. Insulin use for both groups increased when comparing the first 24 h post-PEG values to measurements from day 8. There were no differences in TF interruptions, time to ≥80% nutritional delivery goal, or hypoglycemic episodes. This study demonstrated no clinically relevant differences in GV, insulin use, TF volume or caloric intake between BTF and CTF groups. Despite some shortcomings, our data suggest that providers should not feel limited to BTF or CTF because of concerns for GV, time to goal nutrition, insulin use, or caloric intake, and should consider other factors such as resource utilization, ease of administration, and/or institutional/patient characteristics.

Properties of a recombinant bovine tissue factor expressed by Silkworm pupae and its performance as an Owren-type prothrombin time reagent for warfarin monitoring.

PubMed

Okuda, Masahiro; Taniguchi, Tomokuni; Takamiya, Osamu

2012-09-01

Tissue factor (TF), or thromboplastin, is a glycoprotein that triggers the extrinsic coagulation pathway. In blood coagulation testing, TF has been used as a natural source for determining Quick prothrombin time (PT) or the Owren PT (OBT). Currently, natural sources are being replaced with recombinant proteins because of their uniform characteristics and the possibility of stable mass production of PT reagents. Because bovine spongiform encephalopathy (BSE)-infected cows are widespread in Japan, we prepared a recombinant bovine TF (rbTF) with a baculovirus expression system using silkworms. To overcome the limitations of natural TF, especially in bovine brain, we expressed a full-length rbTF protein in Silkworm pupae with a baculovirus expression system. Baculovirus inactivation and the presence of DNA fragments in the rbTF fraction were confirmed using Reed-Muench and polymerase chain reaction methods after inactivation with a detergent. The rbTF fraction prepared by an immobilized anti-Silkworm pupae fluid protein Sepharose 4B column was identified as a visible band on western blots with a polyclonal antibody against human TF with cross-reactivity with TFs. The inhibition of the polyclonal antibody against human TF by the clotting assay for PT was identified, and amidolytic biological activity through activated factor VII on S-2288 substrate was observed. In conclusion, the rbTF expressed by the baculovirus system using Silkworm pupae was uniformly specific for bovine TF. The OBT reagent incorporated by this rbTF was similar to those of commercial reagents. It also showed a suitable International Sensitivity Index and reproducibility precision, thereby allowing for diagnostic use. Copyright © 2012 Elsevier Ltd. All rights reserved.

The self primer of the long terminal repeat retrotransposon Tf1 is not removed during reverse transcription.

PubMed

Atwood-Moore, Angela; Yan, Kenneth; Judson, Robert L; Levin, Henry L

2006-08-01

The long terminal repeat retrotransposon Tf1 of Schizosaccharomyces pombe uses a unique mechanism of self priming to initiate reverse transcription. Instead of using a tRNA, Tf1 primes minus-strand synthesis with an 11-nucleotide RNA removed from the 5' end of its own transcript. We tested whether the self primer of Tf1 was similar to tRNA primers in being removed from the cDNA by RNase H. Our analysis of Tf1 cDNA extracted from virus-like particles revealed the surprising observation that the dominant species of cDNA retained the self primer. This suggests that integration of the cDNA relies on mechanisms other than reverse transcription to remove the primer.

AC loss, interstrand resistance and mechanical properties of prototype EU DEMO TF conductors up to 30 000 load cycles

NASA Astrophysics Data System (ADS)

Yagotintsev, K.; Nijhuis, A.

2018-07-01

Two prototype Nb3Sn cable-in-conduit conductors conductors were designed and manufactured for the toroidal field (TF) magnet system of the envisaged European DEMO fusion reactor. The AC loss, contact resistance and mechanical properties of two sample conductors were tested in the Twente Cryogenic Cable Press under cyclic load up to 30 000 cycles. Though both conductors were designed to operate at 82 kA in a background magnetic field of 13.6 T, they reflect different approaches with respect to the magnet winding pack assembly. The first approach is based on react and wind technology while the second is the more common wind and react technology. Each conductor was tested first for AC loss in virgin condition without handling. The impact of Lorentz load during magnet operation was simulated using the cable press. In the press each conductor specimen was subjected to transverse cyclic load up to 30 000 cycles in liquid helium bath at 4.2 K. Here a summary of results for AC loss, contact resistance, conductor deformation, mechanical heat production and conductor stiffness evolution during cycling of the load is presented. Both conductors showed similar mechanical behaviour but quite different AC loss. In comparison with previously tested ITER TF conductors, both DEMO TF conductors possess very low contact resistance resulting in high coupling loss. At the same time, load cycling has limited impact on properties of DEMO TF conductors in comparison with ITER TF conductors.

Facilities and the Air Force Systems Acquisition Process.

DTIC Science & Technology

1985-05-01

INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (it applicable) Sc. ADDRESS (City. State and ZIP Code) 10. SOURCE OF FUNDING NOS. PROGRAM PROJECT TASK WORK UNIT...L- . - - - CHAP T-F< I P f),DUCTr JOti The Air Force is in the midst of its most extensive peacetime force modernization programs ...will answer the following ques- tions: a. Are facility requirements anticipated and ade- quatel% scoped during the early phase of program development so

Pediatric tinea faciei in southern Spain: a 30-year survey.

PubMed

del Boz, Javier; Crespo, Vicente; de Troya, Magdalena

2012-01-01

Tinea faciei (TF) is a common clinical form of tinea in children that is frequently misdiagnosed and treated with corticosteroids. No large case series of TF focusing on children have been published. The aim of this study was to analyze the main epidemiologic, clinical, and microbiologic features of TF in children over a period of 30 years and compare these features with those of other tineas. We undertook a retrospective study of 818 cases of tinea in children at a referral hospital in southern Spain, diagnosed between 1977 and 2006, concentrating for this study on TF. Of the 73 cases of TF diagnosed, 50.7% were in girls. Most children (46.6%) were 4 to 9 years old. At the time of diagnosis, 29.2% of the cases had been treated with topical steroids. The most frequently isolated dermatophyte was Trichophyton mentagrophytes, which was isolated significantly more frequently in TF than in the other tineas. Cases of TF in children were not extremely unusual, emphasizing that TF must be considered in children with inflammatory facial eruptions. This consideration and the more-frequent use of mycologic tests can help achieve the correct diagnosis, when present. © 2011 Wiley Periodicals, Inc.

Can corneal pannus with trachomatous inflammation--follicular be used in combination as an improved specific clinical sign for current ocular Chlamydia trachomatis infection?

PubMed

Derrick, Tamsyn; Holland, Martin J; Cassama, Eunice; Markham-David, Rod; Nabicassa, Meno; Marks, Michael; Bailey, Robin L; Last, Anna R

2016-01-27

Trachoma is a blinding disease caused by conjunctival infection with Chlamydia trachomatis (Ct). Mass drug administration (MDA) for trachoma control is administered based on the population prevalence of the clinical sign of trachomatis inflammation - follicular (TF). However, the prevalence of TF is often much higher than the prevalence of Ct infection. The addition of a clinical sign specific for current ocular Ct infection to TF could save resources by preventing unnecessary additional rounds of MDA. Study participants were aged between 1-9 years and resided on 7 islands of the Bijagos Archipelago, Guinea Bissau. Clinical grades for trachoma and corneal pannus and ocular swab samples were taken from 80 children with TF and from 81 matched controls without clinical evidence of trachoma. Ct infection testing was performed using droplet digital PCR. New pannus was significantly associated with Ct infection after adjustment for TF (P = 0.009, OR = 3.65 (1.4-9.8)). Amongst individuals with TF, individuals with new pannus had significantly more Ct infection than individuals with none or old pannus (75.0% vs 45.5%, Chi(2) P = 0.01). TF and new pannus together provide a highly specific (91.7%), but a poorly sensitive (51.9%) clinical diagnostic test for Ct infection. As we move towards trachoma elimination it may be desirable to use a combined clinical sign (new pannus in addition to TF) that is highly specific for current ocular Ct infection. This would allow national health systems to obtain a more accurate estimate of Ct population prevalence to inform further need for MDA without the expense of Ct molecular diagnostics, which are currently unaffordable in programmatic contexts.

Glycogen Synthase Kinase 3β Promotes the Endocytosis of Transferrin in the African Trypanosome.

PubMed

Guyett, Paul J; Xia, Shuangluo; Swinney, David C; Pollastri, Michael P; Mensa-Wilmot, Kojo

2016-07-08

Human parasite Trypanosoma brucei proliferates in the blood of its host, where it takes up iron via receptor-mediated endocytosis of transferrin (Tf). Mechanisms of Tf endocytosis in the trypanosome are not fully understood. Small molecule lapatinib inhibits Tf endocytosis in T. brucei and associates with protein kinase GSK3β (TbGSK3β). Therefore, we hypothesized that Tf endocytosis may be regulated by TbGSK3β, and we used three approaches (both genetic and small molecule) to test this possibility. First, the RNAi knock-down of TbGSK3β reduced Tf endocytosis selectively, without affecting the uptake of haptaglobin-hemoglobin (Hp-Hb) or bovine serum albumin (BSA). Second, the overexpression of TbGSK3β increased the Tf uptake. Third, small-molecule inhibitors of TbGSK3β, TWS119 (IC50 = 600 nM), and GW8510 (IC50 = 8 nM) reduced Tf endocytosis. Furthermore, TWS119, but not GW8510, selectively blocked Tf uptake. Thus, TWS119 phenocopies the selective endocytosis effects of a TbGSK3β knockdown. Two new inhibitors of TbGSK3β, LY2784544 (IC50 = 0.6 μM) and sorafenib (IC50 = 1.7 μM), were discovered in a focused screen: at low micromolar concentrations, they prevented Tf endocytosis as well as trypanosome proliferation (GI50's were 1.0 and 3.1 μM, respectively). These studies show that (a) TbGSK3β regulates Tf endocytosis, (b) TWS119 is a small-molecule tool for investigating the endocytosis of Tf, (c) endocytosis of GPI-anchored TfR and HpHbR are differentially regulated, and (d) the imidazopyridazine aminopyrazole scaffold of LY2784544 is attractive for a hit-to-lead optimization program in antitrypanosome drug discovery.

The Self Primer of the Long Terminal Repeat Retrotransposon Tf1 Is Not Removed during Reverse Transcription

PubMed Central

Atwood-Moore, Angela; Yan, Kenneth; Judson, Robert L.; Levin, Henry L.

2006-01-01

The long terminal repeat retrotransposon Tf1 of Schizosaccharomyces pombe uses a unique mechanism of self priming to initiate reverse transcription. Instead of using a tRNA, Tf1 primes minus-strand synthesis with an 11-nucleotide RNA removed from the 5′ end of its own transcript. We tested whether the self primer of Tf1 was similar to tRNA primers in being removed from the cDNA by RNase H. Our analysis of Tf1 cDNA extracted from virus-like particles revealed the surprising observation that the dominant species of cDNA retained the self primer. This suggests that integration of the cDNA relies on mechanisms other than reverse transcription to remove the primer. PMID:16873283

Palmitoylation of Sindbis Virus TF Protein Regulates Its Plasma Membrane Localization and Subsequent Incorporation into Virions.

PubMed

Ramsey, Jolene; Renzi, Emily C; Arnold, Randy J; Trinidad, Jonathan C; Mukhopadhyay, Suchetana

2017-02-01

Palmitoylation is a reversible, posttranslational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms that are identical in their N termini but unique in their C termini due to a -1 ribosomal frameshift during translation. In this study, we used cysteine (Cys) mutants to test differential palmitoylation of the Sindbis virus 6K and TF proteins. We modularly mutated the five Cys residues in the identical N termini of 6K and TF, the four additional Cys residues in TF's unique C terminus, or all nine Cys residues in TF. Using these mutants, we determined that TF palmitoylation occurs primarily in the N terminus. In contrast, 6K is not palmitoylated, even on these shared residues. In the C-terminal Cys mutant, TF protein levels increase both in the cell and in the released virion compared to the wild type. In viruses with the N-terminal Cys residues mutated, TF is much less efficiently localized to the plasma membrane, and it is not incorporated into the virion. The three Cys mutants have minor defects in cell culture growth but a high incidence of abnormal particle morphologies compared to the wild-type virus as determined by transmission electron microscopy. We propose a model where the C terminus of TF modulates the palmitoylation of TF at the N terminus, and palmitoylated TF is preferentially trafficked to the plasma membrane for virus budding. Alphaviruses are a reemerging viral cause of arthritogenic disease. Recently, the small 6K and TF proteins of alphaviruses were shown to contribute to virulence in vivo Nevertheless, a clear understanding of the molecular mechanisms by which either protein acts to promote virus infection is missing. The TF protein is a component of budded virions, and optimal levels of TF correlate positively with wild-type-like particle morphology. In this study, we show that the palmitoylation of TF regulates its localization to the plasma membrane, which is the site of alphavirus budding. Mutants in which TF is not palmitoylated display drastically reduced plasma membrane localization, which effectively prevents TF from participating in budding or being incorporated into virus particles. Investigation of the regulation of TF will aid current efforts in the alphavirus field searching for approaches to mitigate alphaviral disease in humans. Copyright © 2017 American Society for Microbiology.

Control of Fretting Fatigue

DTIC Science & Technology

1977-07-01

analysis predicted the location of crack initiation on the fretted surfaces of specimens of Al -4% Cu alloy loaded axially or in bending and the calculated...at least for Al -4 d Cu alloy and three steels tested in air, the macroscopic stress distribution appears to pre- dict the initiation of fretting...and abrasive effe^-s were crucial to the fretting process [Tomlinson, et al .(175)l. The role of these two effects has now been downplayed (i.e

Ovine uterine space restriction alters placental transferrin receptor and fetal iron status during late pregnancy

PubMed Central

Sun, Mary Y.; Habeck, Jason M.; Meyer, Katie M.; Koch, Jill M.; Ramadoss, Jayanth; Blohowiak, Sharon E.; Magness, Ronald R.; Kling, Pamela J.

2013-01-01

Background Fetal growth restriction is reported to be associated with impaired placental iron transport. Transferrin receptor (TfR) is a major placental iron transporter in humans, but is unstudied in sheep. TfR is regulated by both iron and nitric oxide (NO), the molecule produced by endothelial NOS (eNOS). We hypothesized that limited placental development downregulates both placental TfR and eNOS expression, thereby lowering fetal tissue iron. Methods An ovine surgical uterine space restriction (USR) model, combined with multifetal gestation, tested the extremes of uterine and placental adaptation. Blood, tissues, and placentomes from non-space restricted (NSR) singletons were compared to USR fetuses at 120 or 130 days of gestation (GD). Results When expressed proportionate to fetal weight, liver iron content did not differ while renal iron was higher in USR vs. NSR fetuses. Renal TfR protein expression did not differ, but placental TfR expression was lower in USR fetuses at GD130. Placental levels of TfR correlated to eNOS. TfR was localized throughout the placentome, including the hemophagous zone, implicating a role for TfR in ovine placental iron transport. Conclusion In conclusion, fetal iron was regulated in an organ-specific fashion. In USR fetuses, NO-mediated placental adaptations may prevent the normal upregulation of placental TfR at GD130. PMID:23202722

Gastrointestinal tolerance and plasma status of carotenoids, EPA and DHA with a fiber-enriched tube feed in hospitalized patients initiated on tube nutrition: Randomized controlled trial.

PubMed

Jakobsen, L H; Wirth, R; Smoliner, C; Klebach, M; Hofman, Z; Kondrup, J

2017-04-01

During the first days of tube feeding (TF) gastrointestinal (GI) complications are common and administration of sufficient nutrition is a challenge. Not all standard nutritionally complete formulas contain dietary fiber, fish oil or carotenoids, key dietary nutrients for health and wellbeing. The aim of this study was to investigate the effects of a fiber, fish oil and carotenoid enriched TF formula on diarrhea, constipation and nutrient bioavailability. A multi-center randomized, double-blind, controlled, parallel trial compared the effects of a dietary fiber, fish oil and carotenoid-enriched TF formula (test) with an isocaloric non-enriched formula (control) in 51 patients requiring initiation of TF. Incidence of diarrhea and constipation (based on stool frequency and consistency) was recorded daily. Plasma status of EPA, DHA and carotenoids was measured after 7 days. The incidence of diarrhea was lower in patients receiving the test formula compared with the control group (19% vs. 48%, p = 0.034). EPA and DHA status (% of total plasma phospholipids) was higher after 7 days in test compared with control group (EPA: p = 0.002, DHA: p = 0.082). Plasma carotenoid levels were higher after 7 days in the test group compared with control group (lutein: p = 0.024, α-carotene: p = 0.005, lycopene: p = 0.020, β-carotene: p = 0.054). This study suggests that the nutrient-enriched TF formula tested might have a positive effect on GI tolerance with less diarrhea incidence and significantly improved EPA, DHA and carotenoid plasma levels during the initiation of TF in hospitalized patients who are at risk of diarrhea and low nutrient status. This trial was registered at trialregister.nl; registration number 2924. Copyright © 2016. Published by Elsevier Ltd.

Absence of social conditioned place preference in BTBR T+tf/J mice: relevance for social motivation testing in rodent models of autism

PubMed Central

Pearson, Brandon L.; Bettis, Jaclyn K.; Meyza, Ksenia Z.; Yamamoto, Lace Y.; Blanchard, D. Caroline; Blanchard, Robert J.

2012-01-01

A major goal of translation research in autism is to characterize the physiological and psychological processes underlying behavioral abnormalities. Since autism reflects impairments in social motivation, we modified the mouse three-chamber social approach apparatus for use as a social conditioned place preference arena. We paired one of two unique contexts with social interactions in juvenile mice for five or ten conditioning sessions in BTBR T+tf/J mice and a control strain with normal approach behaviors (C57BL/6J) since the BTBR T+tf/J inbred mouse strain displays a variety of behavioral alterations analogous to symptoms of autism spectrum disorders. While C57BL/6J mice formed a conditioned place preference to the context associated with social interactions, particularly those receiving ten days of conditioning, BTBR T+tf/J mice did not. Neither absence of social proximity nor avoidance due to high rates of autogrooming appeared to underlie the impaired positive incentive value of the unconditioned social stimulus in the BTBR T+tf/J strain. These data contribute to a growing body of evidence suggesting that the BTBR T+tf/J strain shows impairments in all diagnostic domains of autism including social motivation. Additionally, social conditioning testing might provide an important social motivation measure in other rodent models of neuropsychiatric disorders characterized by social abnormalities. PMID:22562042

An automatic recording system for the study of escape from fear in rats.

PubMed

Li, Ming; He, Wei

2013-11-01

Escape from fear (EFF) is an active response to a conditioned stimulus (CS) previously paired with an unconditioned fearful stimulus (US), which typically leads to the termination of the CS. In this paradigm, animals acquire two distinct associations: S-S [CS-US] and R-O [response-outcome] through Pavlovian and instrumental conditioning, respectively. The present study describes a computer controlled automatic recording system that captures the development of EFF and allows the determination of the respective roles of S-S and R-O associations in this process. We validated this system by showing that only rats subjected to a simultaneous CS-US conditioning (i.e., CS and US occur together at the beginning of each trial) acquired EFF, not those subjected to an unpaired CS-US conditioning. Paired rats had a progressively increased number of EFF and significantly shorter escape latencies than unpaired rats across the 5-trial blocks on the test day. However, during the conditioning phase, the unpaired rats emitted more 22kHz ultrasonic vocalizations, a validated measure of conditioned reactive fear responses. Our results demonstrate that the acquisition of EFF is contingent upon pairing of the CS with the US, not simply the consequence of a high level of generalized fear. Because this commercially available system is capable of examining both conditioned active and reactive fear responses in a single setup, it could be used to determine the relative roles of S-S and R-O associations in EFF, the neurobiology of conditioned active fear response and neuropharmacology of psychotherapeutic drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Testing the applicability of a benthic foraminiferal-based transfer function for the reconstruction of paleowater depth changes in Rhodes (Greece) during the early Pleistocene.

PubMed

Milker, Yvonne; Weinkauf, Manuel F G; Titschack, Jürgen; Freiwald, Andre; Krüger, Stefan; Jorissen, Frans J; Schmiedl, Gerhard

2017-01-01

We present paleo-water depth reconstructions for the Pefka E section deposited on the island of Rhodes (Greece) during the early Pleistocene. For these reconstructions, a transfer function (TF) using modern benthic foraminifera surface samples from the Adriatic and Western Mediterranean Seas has been developed. The TF model gives an overall predictive accuracy of ~50 m over a water depth range of ~1200 m. Two separate TF models for shallower and deeper water depth ranges indicate a good predictive accuracy of 9 m for shallower water depths (0-200 m) but far less accuracy of 130 m for deeper water depths (200-1200 m) due to uneven sampling along the water depth gradient. To test the robustness of the TF, we randomly selected modern samples to develop random TFs, showing that the model is robust for water depths between 20 and 850 m while greater water depths are underestimated. We applied the TF to the Pefka E fossil data set. The goodness-of-fit statistics showed that most fossil samples have a poor to extremely poor fit to water depth. We interpret this as a consequence of a lack of modern analogues for the fossil samples and removed all samples with extremely poor fit. To test the robustness and significance of the reconstructions, we compared them to reconstructions from an alternative TF model based on the modern analogue technique and applied the randomization TF test. We found our estimates to be robust and significant at the 95% confidence level, but we also observed that our estimates are strongly overprinted by orbital, precession-driven changes in paleo-productivity and corrected our estimates by filtering out the precession-related component. We compared our corrected record to reconstructions based on a modified plankton/benthos (P/B) ratio, excluding infaunal species, and to stable oxygen isotope data from the same section, as well as to paleo-water depth estimates for the Lindos Bay Formation of other sediment sections of Rhodes. These comparisons indicate that our orbital-corrected reconstructions are reasonable and reflect major tectonic movements of Rhodes during the early Pleistocene.

Testing the applicability of a benthic foraminiferal-based transfer function for the reconstruction of paleowater depth changes in Rhodes (Greece) during the early Pleistocene

PubMed Central

Weinkauf, Manuel F. G.; Titschack, Jürgen; Freiwald, Andre; Krüger, Stefan; Jorissen, Frans J.; Schmiedl, Gerhard

2017-01-01

We present paleo-water depth reconstructions for the Pefka E section deposited on the island of Rhodes (Greece) during the early Pleistocene. For these reconstructions, a transfer function (TF) using modern benthic foraminifera surface samples from the Adriatic and Western Mediterranean Seas has been developed. The TF model gives an overall predictive accuracy of ~50 m over a water depth range of ~1200 m. Two separate TF models for shallower and deeper water depth ranges indicate a good predictive accuracy of 9 m for shallower water depths (0–200 m) but far less accuracy of 130 m for deeper water depths (200–1200 m) due to uneven sampling along the water depth gradient. To test the robustness of the TF, we randomly selected modern samples to develop random TFs, showing that the model is robust for water depths between 20 and 850 m while greater water depths are underestimated. We applied the TF to the Pefka E fossil data set. The goodness-of-fit statistics showed that most fossil samples have a poor to extremely poor fit to water depth. We interpret this as a consequence of a lack of modern analogues for the fossil samples and removed all samples with extremely poor fit. To test the robustness and significance of the reconstructions, we compared them to reconstructions from an alternative TF model based on the modern analogue technique and applied the randomization TF test. We found our estimates to be robust and significant at the 95% confidence level, but we also observed that our estimates are strongly overprinted by orbital, precession-driven changes in paleo-productivity and corrected our estimates by filtering out the precession-related component. We compared our corrected record to reconstructions based on a modified plankton/benthos (P/B) ratio, excluding infaunal species, and to stable oxygen isotope data from the same section, as well as to paleo-water depth estimates for the Lindos Bay Formation of other sediment sections of Rhodes. These comparisons indicate that our orbital-corrected reconstructions are reasonable and reflect major tectonic movements of Rhodes during the early Pleistocene. PMID:29166653

Thermal Release of 3He from Tritium Aged LaNi 4.25Al 0.75 Hydride

DOE PAGES

Staack, Gregory C.; Crowder, Mark L.; Klein, James E.

2015-02-01

Recently, the demand for He-3 has increased dramatically due to widespread use in nuclear nonproliferation, cryogenic, and medical applications. Essentially all of the world’s supply of He-3 is created by the radiolytic decay of tritium. The Savannah River Site Tritium Facilities (SRS-TF) utilizes LANA.75 in the tritium process to store hydrogen isotopes. The vast majority of He-3 “born” from tritium stored in LANA.75 is trapped in the hydride metal matrix. The SRS-TF has multiple LANA.75 tritium storage beds that have been retired from service with significant quantities of He-3 trapped in the metal. To support He-3 recovery, the Savannah Rivermore » National Laboratory (SRNL) conducted thermogravimetric analysis coupled with mass spectrometry (TGA-MS) on a tritium aged LANA.75 sample. TGA-MS testing was performed in an argon environment. Prior to testing, the sample was isotopically exchanged with deuterium to reduce residual tritium and passivated with air to alleviate pyrophoric concerns associated with handling the material outside of an inert glovebox. Analyses indicated that gas release from this sample was bimodal, with peaks near 220 and 490°C. The first peak consisted of both He-3 and residual hydrogen isotopes, the second was primarily He-3. The bulk of the gas was released by 600 °C« less

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

Ozeki, H.; Isono, T.; Uno, Y.

JAEA successfully completed the manufacture of the toroidal field (TF) insert coil (TFIC) for a performance test of the ITER TF conductor in the final design in cooperation with Hitachi, Ltd. The TFIC is a single-layer 8.875-turn solenoid coil with 1.44-m diameter. This will be tested for 68-kA current application in a 13-T external magnetic field. TFIC was manufactured in the following order: winding of the TF conductor, lead bending, fabrication of the electrical termination, heat treatment, turn insulation, installation of the coil into the support mandrel structure, vacuum pressure impregnation (VPI), structure assembly, and instrumentation. Here in this presentation,more » manufacture process and quality control status for the TFIC manufacturing are reported.« less

TF34 convertible engine control system design

NASA Technical Reports Server (NTRS)

Gilmore, D. R., Jr.

1984-01-01

The characteristics of the TF34 convertible engine, capable of producing shaft power, thrust, or a combination of both, is investigated with respect to the control system design, development, bench testing, and the anticipated transient response during engine testing at NASA. The modifications to the prototype standard TF34-GE-400 turbofan, made primarily in the fan section, consist of the variable inlet guide vanes and variable exit guide vanes. The control system was designed using classical frequency domain techniques and was based on the anticipated convertible/VTOL airframe requirements. The engine has been run in the fan mode and in the shaft mode, exhibiting a response of 0.14 second to a 5-percent thrust change.

Clausius inequality beyond the weak-coupling limit: the quantum Brownian oscillator.

PubMed

Kim, Ilki; Mahler, Günter

2010-01-01

We consider a quantum linear oscillator coupled at an arbitrary strength to a bath at an arbitrary temperature. We find an exact closed expression for the oscillator density operator. This state is noncanonical but can be shown to be equivalent to that of an uncoupled linear oscillator at an effective temperature T*(eff) with an effective mass and an effective spring constant. We derive an effective Clausius inequality deltaQ*(eff)< or =T*(eff)dS , where deltaQ*(eff) is the heat exchanged between the effective (weakly coupled) oscillator and the bath, and S represents a thermal entropy of the effective oscillator, being identical to the von-Neumann entropy of the coupled oscillator. Using this inequality (for a cyclic process in terms of a variation of the coupling strength) we confirm the validity of the second law. For a fixed coupling strength this inequality can also be tested for a process in terms of a variation of either the oscillator mass or its spring constant. Then it is never violated. The properly defined Clausius inequality is thus more robust than assumed previously.

Evidence for the packaging of multiple copies of Tf1 mRNA into particles and the trans priming of reverse transcription.

PubMed

Haag, A L; Lin, J H; Levin, H L

2000-08-01

Long terminal repeat (LTR)-containing retrotransposons and retroviruses are close relatives that possess similar mechanisms of reverse transcription. The particles of retroviruses package two copies of viral mRNA that both function as templates for the reverse transcription of the element. We studied the LTR-retrotransposon Tf1 of Schizosaccharomyces pombe to test whether multiple copies of transposon mRNA participate in the production of cDNA. Using the unique self-priming property of Tf1, we obtained evidence that multiple copies of Tf1 mRNA were packaged into virus-like particles. By coexpressing two distinct versions of Tf1, we found that the bulk of reverse transcription that was initiated on one mRNA template was subsequently transferred to others. In addition, the first 11 nucleotides of one mRNA were able to prime, in trans, the reverse transcription of another mRNA.

On the Preparation and Testing of Fuel Cell Catalysts Using the Thin Film Rotating Disk Electrode Method.

PubMed

Inaba, Masanori; Quinson, Jonathan; Bucher, Jan Rudolf; Arenz, Matthias

2018-03-16

We present a step-by-step tutorial to prepare proton exchange membrane fuel cell (PEMFC) catalysts, consisting of Pt nanoparticles (NPs) supported on a high surface area carbon, and to test their performance in thin film rotating disk electrode (TF-RDE) measurements. The TF-RDE methodology is widely used for catalyst screening; nevertheless, the measured performance sometimes considerably differs among research groups. These uncertainties impede the advancement of new catalyst materials and, consequently, several authors discussed possible best practice methods and the importance of benchmarking. The visual tutorial highlights possible pitfalls in the TF-RDE testing of Pt/C catalysts. A synthesis and testing protocol to assess standard Pt/C catalysts is introduced that can be used together with polycrystalline Pt disks as benchmark catalysts. In particular, this study highlights how the properties of the catalyst film on the glassy carbon (GC) electrode influence the measured performance in TF-RDE testing. To obtain thin, homogeneous catalyst films, not only the catalyst preparation, but also the ink deposition and drying procedures are essential. It is demonstrated that an adjustment of the ink's pH might be necessary, and how simple control measurements can be used to check film quality. Once reproducible TF-RDE measurements are obtained, determining the Pt loading on the catalyst support (expressed as Pt wt%) and the electrochemical surface area is necessary to normalize the determined reaction rates to either surface area or Pt mass. For the surface area determination, so-called CO stripping, or the determination of the hydrogen underpotential deposition (Hupd) charge, are standard. For the determination of the Pt loading, a straightforward and cheap procedure using digestion in aqua regia with subsequent conversion of Pt(IV) to Pt(II) and UV-vis measurements is introduced.

On the Preparation and Testing of Fuel Cell Catalysts Using the Thin Film Rotating Disk Electrode Method

PubMed Central

Inaba, Masanori; Quinson, Jonathan; Bucher, Jan Rudolf; Arenz, Matthias

2018-01-01

We present a step-by-step tutorial to prepare proton exchange membrane fuel cell (PEMFC) catalysts, consisting of Pt nanoparticles (NPs) supported on a high surface area carbon, and to test their performance in thin film rotating disk electrode (TF-RDE) measurements. The TF-RDE methodology is widely used for catalyst screening; nevertheless, the measured performance sometimes considerably differs among research groups. These uncertainties impede the advancement of new catalyst materials and, consequently, several authors discussed possible best practice methods and the importance of benchmarking. The visual tutorial highlights possible pitfalls in the TF-RDE testing of Pt/C catalysts. A synthesis and testing protocol to assess standard Pt/C catalysts is introduced that can be used together with polycrystalline Pt disks as benchmark catalysts. In particular, this study highlights how the properties of the catalyst film on the glassy carbon (GC) electrode influence the measured performance in TF-RDE testing. To obtain thin, homogeneous catalyst films, not only the catalyst preparation, but also the ink deposition and drying procedures are essential. It is demonstrated that an adjustment of the ink's pH might be necessary, and how simple control measurements can be used to check film quality. Once reproducible TF-RDE measurements are obtained, determining the Pt loading on the catalyst support (expressed as Pt wt%) and the electrochemical surface area is necessary to normalize the determined reaction rates to either surface area or Pt mass. For the surface area determination, so-called CO stripping, or the determination of the hydrogen underpotential deposition (Hupd) charge, are standard. For the determination of the Pt loading, a straightforward and cheap procedure using digestion in aqua regia with subsequent conversion of Pt(IV) to Pt(II) and UV-vis measurements is introduced. PMID:29608166

Performance analysis of the toroidal field ITER production conductors

NASA Astrophysics Data System (ADS)

Breschi, M.; Macioce, D.; Devred, A.

2017-05-01

The production of the superconducting cables for the toroidal field (TF) magnets of the ITER machine has recently been completed at the manufacturing companies selected during the previous qualification phase. The quality assurance/quality control programs that have been implemented to ensure production uniformity across numerous suppliers include performance tests of several conductor samples from selected unit lengths. The short full-size samples (4 m long) were subjected to DC and AC tests in the SULTAN facility at CRPP in Villigen, Switzerland. In a previous work the results of the tests of the conductor performance qualification samples were reported. This work reports the analyses of the results of the tests of the production conductor samples. The results reported here concern the values of current sharing temperature, critical current, effective strain and n-value from the DC tests and the energy dissipated per cycle from the AC loss tests. A detailed comparison is also presented between the performance of the conductors and that of their constituting strands.

Predicting trace organic compound breakthrough in granular activated carbon using fluorescence and UV absorbance as surrogates.

PubMed

Anumol, Tarun; Sgroi, Massimiliano; Park, Minkyu; Roccaro, Paolo; Snyder, Shane A

2015-06-01

This study investigated the applicability of bulk organic parameters like dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254), and total fluorescence (TF) to act as surrogates in predicting trace organic compound (TOrC) removal by granular activated carbon in water reuse applications. Using rapid small-scale column testing, empirical linear correlations for thirteen TOrCs were determined with DOC, UV254, and TF in four wastewater effluents. Linear correlations (R(2) > 0.7) were obtained for eight TOrCs in each water quality in the UV254 model, while ten TOrCs had R(2) > 0.7 in the TF model. Conversely, DOC was shown to be a poor surrogate for TOrC breakthrough prediction. When the data from all four water qualities was combined, good linear correlations were still obtained with TF having higher R(2) than UV254 especially for TOrCs with log Dow>1. Excellent linear relationship (R(2) > 0.9) between log Dow and the removal of TOrC at 0% surrogate removal (y-intercept) were obtained for the five neutral TOrCs tested in this study. Positively charged TOrCs had enhanced removals due to electrostatic interactions with negatively charged GAC that caused them to deviate from removals that would be expected with their log Dow. Application of the empirical linear correlation models to full-scale samples provided good results for six of seven TOrCs (except meprobamate) tested when comparing predicted TOrC removal by UV254 and TF with actual removals for GAC in all the five samples tested. Surrogate predictions using UV254 and TF provide valuable tools for rapid or on-line monitoring of GAC performance and can result in cost savings by extended GAC run times as compared to using DOC breakthrough to trigger regeneration or replacement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reciproc versus Twisted file for root canal filling removal: assessment of apically extruded debris.

PubMed

Altunbas, Demet; Kutuk, Betul; Toyoglu, Mustafa; Kutlu, Gizem; Kustarci, Alper; Er, Kursat

2016-01-01

The aim of this study was to evaluate the amount of apically extruded debris during endodontic retreatment with different file systems. Sixty extracted human mandibular premolar teeth were used in this study. Root canals of the teeth were instrumented and filled before being randomly assigned to three groups. Guttapercha was removed using the Reciproc system, the Twisted File system (TF), and Hedström-files (H-file). Apically extruded debris was collected and dried in pre-weighed Eppendorf tubes. The amount of extruded debris was assessed with an electronic balance. Data were statistically analyzed using one-way ANOVA, Kruskal-Wallis, and Mann-Whitney U tests. The Reciproc and TF systems extruded significantly less debris than the H-file (p<0.05). However, no significant difference was found between the Reciproc and TF systems. All tested file systems caused apical extrusion of debris. Both the rotary file (TF) and the reciprocating single-file (Reciproc) systems were associated with less apical extrusion compared with the H-file.

Comparison of cleaning efficiency and deformation characteristics of Twisted File and ProTaper rotary instruments

PubMed Central

Li, Hang; Zhang, Chenzheng; Li, Qing; Wang, Changning; Song, Yaling

2014-01-01

Objective: The objective of the following study is to compare the cleaning efficiency and deformation characteristics of Twisted File (TF) and ProTaper (PT) nickel-titanium rotary instruments in root canal preparation. Materials and Methods: A total of 52 canals from 26 extracted maxillary first molars were randomly assigned into two groups of each including 13 mesiobuccal and 12 distobuccal (DB) canals. Two DB canals were as blank controls. After preparation with TF and PT, we recorded the preparation time and evaluate the amounts of debris and smear layer at apical, middle and coronal canals under scanning electron microscopy (SEM). Three cross-sections of canals at 3 mm, 5 mm and 7 mm from the apex foramens were scanned before and after preparation under micro-computed tomography. Changes of the cross-section area (CSA) at the three levels were calculated with Photoshop CS4. File deformation was also investigated under SEM. Two groups were statistically compared with Mann-Whitney test and independent sample t-test. Results: Less debris and smear layer were found in coronal regions of canals prepared with TF (P = 0.006, P = 0.001, respectively). TF group displayed more CSA change than PT group (P = 0.045) at cross-sections of 5 mm from the apex foramens and took significantly less preparation time than PT group did (P = 9.06 × 10−28). All five TF files without obvious micro-cracks and two out of 25 PT files with many micro-cracks showed visible unwound deformation. Conclusion: Neither TF nor PT achieves complete cleanliness of canal walls. Their deformation features might indicate different fracture resistance. TF single-file technique would substantially shorten the time of root canal preparation. PMID:24966769

Using the international classification of functioning to examine the impact of trigger finger.

PubMed

Langer, Danit; Maeir, Adina; Michailevich, Michael; Applebaum, Yael; Luria, Shai

2016-12-01

To evaluate the impact of trigger finger (TF) on hand motor function, activity and participation (A&P) and quality of life (QOL), and to evaluate the association between personal factors (age and gender, disease severity) and body functions (dexterity and strength) with A&P and QOL in patients with TF. Sixty-six patients with TF (study group) and 66 healthy volunteers (control group) participated in the study. TF symptoms were graded using the Quinnell classification. A&P was evaluated using the Disabilities of Arm Shoulder and Hand questionnaire and the QOL using the World Health Organization Quality of Life questionnaire. Dexterity was evaluated using the Functional Dexterity Test and the Purdue Pegboard Test; hand strength was evaluated using the Jamar Dynamometer and Pinch Gauge. The comparisons between the study and control groups revealed significant differences in all measures. The study group reported lower perceived QOL, A&P and reduced hand strength and dexterity. Hierarchical regression analyses revealed that (a) the severity of TF contributed significantly to the explained variance of QOL, while demographics and hand functioning did not; (b) demographics, TF severity and hand function all contributed significantly to the explained variance of A&P. The findings of the study point to the importance of addressing the functional implications and QOL of individuals with TF. Implications for Rehabilitation Although trigger finger is considered to be a mild hand pathology, it has a wide-ranging impact on hand functioning, daily activities and quality of life. Clinicians should include assessments of these outcomes in the treatment of individuals with trigger finger. Treatment efficacy should be evaluated with International Classification of Functioning outcomes, and not limited to symptomatology.

Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression.

PubMed

Lindholm, Paul F; Lu, Yi; Adley, Brian P; Vladislav, Tudor; Jovanovic, Borko; Sivapurapu, Neela; Yang, Ximing J; Kajdacsy-Balla, André

2010-11-01

Tissue factor (TF) is a cell surface glycoprotein intricately related to blood coagulation and inflammation. This study was performed to investigate the role of monocyte-lineage cells in prostate cancer cell TF expression and cell invasion. Prostate cancer cell invasion was tested with and without added peripheral blood monocytes or human monocyte-lineage cell lines. TF neutralizing antibodies were used to determine the TF requirement for prostate cancer cell invasion activity. Immunohistochemistry was performed to identify prostate tissue CD68 positive monocyte-derived cells and prostate epithelial TF expression. Co-culture of PC-3, DU145, and LNCaP cells with isolated human monocytes significantly stimulated prostate cancer cell invasion activity. TF expression was greater in highly invasive prostate cancer cells and was induced in PC-3, DU145, and LNCaP cells by co-culture with U-937 cells, but not with THP-1 cells. TF neutralizing antibodies inhibited PC-3 cell invasion in co-cultures with monocyte-lineage U-937 or THP-1 cells. Prostate cancer tissues contained more CD68 positive cells in the stroma and epithelium (145 ± 53/mm(2)) than benign prostate (108 ± 31/mm(2)). Samples from advanced stage prostate cancer tended to contain more CD68 positive cells when compared with lower stage lesions. Prostatic adenocarcinoma demonstrated significantly increased TF expression compared with benign prostatic epithelium. This study shows that co-culture with monocyte-lineage cells induced prostate cancer cell invasion activity. PC-3 invasion and TF expression was induced in co-culture with U-937 cells and partially inhibited with TF neutralizing antibodies.

New clinical insights for transiently evoked otoacoustic emission protocols.

PubMed

Hatzopoulos, Stavros; Grzanka, Antoni; Martini, Alessandro; Konopka, Wieslaw

2009-08-01

The objective of the study was to optimize the area of a time-frequency analysis and then investigate any stable patterns in the time-frequency structure of otoacoustic emissions in a population of 152 healthy adults sampled over one year. TEOAE recordings were collected from 302 ears in subjects presenting normal hearing and normal impedance values. The responses were analyzed by the Wigner-Ville distribution (WVD). The TF region of analysis was optimized by examining the energy content of various rectangular and triangular TF regions. The TEOAE components from the initial and recordings 12 months later were compared in the optimized TF region. The best region for TF analysis was identified with base point 1 at 2.24 ms and 2466 Hz, base point 2 at 6.72 ms and 2466 Hz, and the top point at 2.24 ms and 5250 Hz. Correlation indices from the TF optimized region were higher, and were statistically significant, than the traditional indices in the selected time window. An analysis of the TF data within a 12-month period indicated a 85% TEOAE component similarity in 90% of the tested subjects.

Temporal multiplexing to simulate multifocal intraocular lenses: theoretical considerations

PubMed Central

Akondi, Vyas; Dorronsoro, Carlos; Gambra, Enrique; Marcos, Susana

2017-01-01

Fast tunable lenses allow an effective design of a portable simultaneous vision simulator (SimVis) of multifocal corrections. A novel method of evaluating the temporal profile of a tunable lens in simulating different multifocal intraocular lenses (M-IOLs) is presented. The proposed method involves the characteristic fitting of the through-focus (TF) optical quality of the multifocal component of a given M-IOL to a linear combination of TF optical quality of monofocal lenses viable with a tunable lens. Three different types of M-IOL designs are tested, namely: segmented refractive, diffractive and refractive extended depth of focus. The metric used for the optical evaluation of the temporal profile is the visual Strehl (VS) ratio. It is shown that the time profiles generated with the VS ratio as a metric in SimVis resulted in TF VS ratio and TF simulated images that closely matched the TF VS ratio and TF simulated images predicted with the M-IOL. The effects of temporal sampling, varying pupil size, monochromatic aberrations, longitudinal chromatic aberrations and temporal dynamics on SimVis are discussed. PMID:28717577

Equipped for the Future Research Report: Building the Framework, 1993-1997. EFF Technical Report.

ERIC Educational Resources Information Center

Merrifield, Juliet

This report focuses on the research aspects of the Equipped for the Future (EFF) project that works toward system reform for adult literacy and lifelong learning. Section 1 describes the EFF process 1993-97, the impetus for EFF, and approaches to system reform. Section 2 explores the research processes EFF uses to build a framework that could…

EFF HOT Topics: Strategies and Tools for Teaching with EFF. Volume 4, Number 1, Winter 2005

ERIC Educational Resources Information Center

Bingman, Beth, Ed.

2005-01-01

"EFF HOT (Highlights on Teaching Topics) Topics" is a publication of the EFF (Equipped for the Future) Center for Training and Technical Assistance. Each issue concentrates on a specific topic, highlighting examples of actual practice and offering strategies and tools for using EFF in the classroom. In this issue, "HOT Topics" focuses on the…

Studies on effective atomic numbers for photon energy absorption and electron density of some narcotic drugs in the energy range 1 keV-20 MeV

NASA Astrophysics Data System (ADS)

Gounhalli, Shivraj G.; Shantappa, Anil; Hanagodimath, S. M.

2013-04-01

Effective atomic numbers for photon energy absorption ZPEA,eff, photon interaction ZPI,eff and for electron density Nel, have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for narcotic drugs, such as Heroin (H), Cocaine (CO), Caffeine (CA), Tetrahydrocannabinol (THC), Cannabinol (CBD), Tetrahydrocannabivarin (THCV). The ZPEA,eff, ZPI,eff and Nel values have been found to change with energy and composition of the narcotic drugs. The energy dependence ZPEA,eff, ZPI,eff and Nel is shown graphically. The maximum difference between the values of ZPEA,eff, and ZPI,eff occurs at 30 keV and the significant difference of 2 to 33% for the energy region 5-100 keV for all drugs. The reason for these differences is discussed.

Do the Infrared Emission Features Need UV Excitation? The PAH Model in UV-poor Reflection Nebulae

NASA Astrophysics Data System (ADS)

Li, A.; Draine, B. T.

2001-12-01

One of the major challenges of identifying the 3.3, 6.2, 7.7, 8.6, and 11.3μ m interstellar infrared emission bands with polycyclic aromatic hydrocarbon (PAH) molecules has been the recent detection of these bands in regions with little ultraviolet (UV) illumination since small, neutral PAH molecules have little or no absorption at visible wavelengths and thus are excited primarily by UV photons. The ``astronomical'' PAH model (Li & Draine 2001), incorporating the experimental result that the visual absorption edge shifts to longer wavelength upon ionization and/or as the PAH size increases (Allamandola, Hudgins, & Sandford 1999), is shown to be able to closely reproduce the observed infrared emission bands of vdB 133, a UV-poor reflection nebula (Uchida, Sellgren, & Werner 1998) as well as the 6.2, 7.7, and 11.3μ m band ratios of the UV-deficient ring in the Andromeda galaxy M31 (Pagani et al. 1999). It is also shown that ``astronomical'' PAHs can be heated sufficiently by a T eff=3000 K black-body to emit at 6.2, 7.7, 8.6, and 11.3μ m. Illustrative mid-IR emission spectra are calculated for reflection nebulae illuminated by cool stars with T eff=3600, 4500, 5000 K. These will allow comparison with future Space Infrared Telescope Facility (SIRTF) observations of vdB 135 (T eff=3600 K), vdB 47 (T eff=4500 K), and vdB 101 (T eff=5000 K) (Houck 2001). This research was supported in part by NASA grant NAG5-7030 and NSF grant AST-9619429. { References:} Allamandola, L.J., Hudgins, D.M., & Sandford, S.A. 1999, ApJ, 511, L115 Houck, J.R. 2001, SIRTF Observations of the Mid IR Features in Reflection Nebulae, {\\sf http://sirtf.caltech.edu/ROC/pid19} Li, A., & Draine, B.T. 2001, ApJ, 554, 778 Pagani, L., et al. 1999, A&A, 351, 447 Uchida, K.I., Sellgren, K., & Werner, M.W. 1998, ApJ, 493, L109

Mass Treatment with Azithromycin for Trachoma: When Is One Round Enough? Results from the PRET Trial in The Gambia

PubMed Central

Harding-Esch, Emma M.; Sillah, Ansumana; Edwards, Tansy; Burr, Sarah E.; Hart, John D.; Joof, Hassan; Laye, Mass; Makalo, Pateh; Manjang, Ahmed; Molina, Sandra; Sarr-Sissoho, Isatou; Quinn, Thomas C.; Lietman, Tom; Holland, Martin J.; Mabey, David; West, Sheila K.; Bailey, Robin

2013-01-01

Background The World Health Organization has recommended three rounds of mass drug administration (MDA) with antibiotics in districts where the prevalence of follicular trachoma (TF) is ≥10% in children aged 1–9 years, with treatment coverage of at least 80%. For districts at 5–10% TF prevalence it was recommended that TF be assessed in 1–9 year olds in each community within the district, with three rounds of MDA provided to any community where TF≥10%. Worldwide, over 40 million people live in districts whose TF prevalence is estimated to be between 5 and 10%. The best way to treat these districts, and the optimum role of testing for infection in deciding whether to initiate or discontinue MDA, are unknown. Methods In a community randomized trial with a factorial design, we randomly assigned 48 communities in four Gambian districts, in which the prevalence of trachoma was known or suspected to be above 10%, to receive annual mass treatment with expected coverage of 80–89% (“Standard”), or to receive an additional visit in an attempt to achieve coverage of 90% or more (“Enhanced”). The same 48 communities were randomised to receive mass treatment annually for three years (“3×”), or to have treatment discontinued if Chlamydia trachomatis (Ct) infection was not detected in a sample of children in the community after mass treatment (stopping rule(“SR”)). Primary outcomes were the prevalence of TF and of Ct infection in 0–5 year olds at 36 months. Results The baseline prevalence of TF and of Ct infection in the target communities was 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline (Standard-3×: TF 5.6%, Ct 0.7%; Standard-SR: TF 6.1%, Ct 0.2%; Enhanced-3×: TF 7.4%, Ct 0.9%; and Enhanced-SR: TF 6.2%, Ct 1.2%); or at 36 months (Standard-3×: TF 2.3%, Ct 1.0%; Standard-SR TF 2.5%, Ct 0.2%; Enhanced-3× TF 3.0%, Ct 0.2%; and Enhanced-SR TF 3.2%, Ct 0.7% ). The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0–9 in communities randomised to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. Mean coverage of children in communities randomized to enhanced treatment was 90.0% at baseline and 94.2% and 93.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three. Conclusions The Gambia is close to the elimination target for active trachoma. In districts prioritised for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programmes could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold. PMID:23785525

Fluoride Availability and Stability in Children's Toothpastes in Uruguay.

PubMed

Loureiro, Licet Alvarez; Fager, Anunzziatta Fabruccini; Santos Moreira, Maurício José; Maltz, Marisa; Hashizume, Lina Naomi

2017-05-15

The purpose of this study was to evaluate the availability and stability of fluoride in children's toothpastes in Uruguay. Six commercial brands of children's toothpaste available in Uruguay were tested. Analyses were made when the dentifrices were purchased (fresh samples) and after one year of storage (aged samples). Total fluoride (TF) and total soluble fluoride (TSF) concentrations were determined using an ion specific electrode. Four of the children's dentifrices showed TF concentration similar to that specified on the package. Three products showed similar concentrations of TF and TSF with no variations after the one-year storage period. Two dentifrices showed an initial insoluble fluoride concentration greater than 50 percent, which increased with toothpaste aging. Most tested toothpastes showed a decrease in the soluble fluoride content with aging. The high quantity of insoluble fluoride found in two tested dentifrices may compromise their anti-caries efficacy.

Nuclear fuel management optimization using genetic algorithms

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

DeChaine, M.D.; Feltus, M.A.

1995-07-01

The code independent genetic algorithm reactor optimization (CIGARO) system has been developed to optimize nuclear reactor loading patterns. It uses genetic algorithms (GAs) and a code-independent interface, so any reactor physics code (e.g., CASMO-3/SIMULATE-3) can be used to evaluate the loading patterns. The system is compared to other GA-based loading pattern optimizers. Tests were carried out to maximize the beginning of cycle k{sub eff} for a pressurized water reactor core loading with a penalty function to limit power peaking. The CIGARO system performed well, increasing the k{sub eff} after lowering the peak power. Tests of a prototype parallel evaluation methodmore » showed the potential for a significant speedup.« less

Synthesis, characterization and evaluation of a fluorinated resin monomer with low water sorption.

PubMed

Liu, Xue; Wang, Zengyao; Zhao, Chengji; Bu, Wenhuan; Zhang, Yurong; Na, Hui

2018-01-01

A fluorinated acrylate monomer (4-TF-PQEA) without BPA (bisphenol-A) structure was synthesized and mixed with triethylene glycol dimethacrylate (TEGDMA) to used as dental resin system in order to achieve lower water sorption and reduce human exposure to BPA derivatives. Double bond conversion (DC) was measured using Fourier transform infrared spectroscopy (FTIR). Water sorption (WS), water solution (WL) and depth of cure (DOC) were evaluated according to ISO 4049:2009. Water contact angle (CA) was measured using contact angle analyzer. Polymerization shrinkage (PS) was evaluated according to the Archimedes' principle and ISO 17304:2013. Flexural strength (FS) and flexural modulus (FM) were measured by three-point bending test with a universal testing machine according to ISO 4049:2009. Comprehensive strength (CS) and vickers microhardness (VM) were also investigated. Thermal stability test was measure by Thermogravimetric analyzer. Cytotoxicity of three resin systems was tested through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid) cytotoxicity method according to the ISO 10993-5:2009. Bisphenol-A glycidyl dimethacrylate (Bis-GMA)/ TEGDMA resin system was used as a control. The results show that 4-TF-PQEA/TEGDMA resin system had lower PS, lower WS and higher DC values than those of Bis-GMA/TEGDMA resin system except some mechanical properties, such as FS, FM and CS. Moreover, properties of other 4-TF-PQEA-containing resin systems were also comparable with those of Bis-GMA/TEGDMA resin system. In particular, the overall performance of resin system consisted of 4-TF-PQEA/Bis-GMA/TEGDMA is optimized when the mixture ratio is 30/40/30(wt/wt/wt). Therefore, the 4-TF-PQEA has potential to be used as resin monomer for dental resin composites to achieve lower water sorption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study.

PubMed

Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul

2017-12-01

Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes ( TF , HFE , CBS , BHMT and MTR ) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (p<0.0083). Seven SNPs in the MTHFR gene were associated with homocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels. Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The utility of rat jejunal permeability for biopharmaceutics classification system.

PubMed

Zakeri-Milani, Parvin; Valizadeh, Hadi; Tajerzadeh, Hosnieh; Islambulchilar, Ziba

2009-12-01

The biopharmaceutical classification system has been developed to provide a scientific approach for classifying drug compounds based on their dose/solubility ratio and human intestinal permeability. Therefore in this study a new classification is presented, which is based on a correlation between rat and human intestinal permeability values. In situ technique in rat jejunum was used to determine the effective intestinal permeability of tested drugs. Then three dimensionless parameters--dose number, absorption number, and dissolution number (D(o), A(n), and D(n))--were calculated for each drug. Four classes of drugs were defined, that is, class I, D(0) < 0.5, P(eff(rat)) > 5.09 x 10(-5) cm/s; class II, D(o) > 1, P(eff(rat)) > 5.09 x 10( -5) cm/s; class III, D(0) < 0.5, P(eff(rat)) < 4.2 x 10(-5) cm/s; and class IV, D(o) > 1, P(eff(rat)) < 4.2 x 10(-5) cm/s. A region of borderline drugs (0.5 < D(o) < 1, 4.2 x 10(-5) < P(eff(rat)) < 5.09 x 10(-5) cm/s) was also defined. According to obtained results and proposed classification for drugs, it is concluded that drugs could be categorized correctly based on dose number and their intestinal permeability values in rat model using single-pass intestinal perfusion technique. This classification enables us to remark defined characteristics for intestinal absorption of all four classes using suitable cutoff points for both dose number and rat effective intestinal permeability values.

Evidence for the Packaging of Multiple Copies of Tf1 mRNA into Particles and the trans Priming of Reverse Transcription

PubMed Central

Haag, Amanda Leigh; Lin, Jia-Hwei; Levin, Henry L.

2000-01-01

Long terminal repeat (LTR)-containing retrotransposons and retroviruses are close relatives that possess similar mechanisms of reverse transcription. The particles of retroviruses package two copies of viral mRNA that both function as templates for the reverse transcription of the element. We studied the LTR-retrotransposon Tf1 of Schizosaccharomyces pombe to test whether multiple copies of transposon mRNA participate in the production of cDNA. Using the unique self-priming property of Tf1, we obtained evidence that multiple copies of Tf1 mRNA were packaged into virus-like particles. By coexpressing two distinct versions of Tf1, we found that the bulk of reverse transcription that was initiated on one mRNA template was subsequently transferred to others. In addition, the first 11 nucleotides of one mRNA were able to prime, in trans, the reverse transcription of another mRNA. PMID:10888658

Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus

PubMed Central

Sundaram, Vasavi; Choudhary, Mayank N. K.; Pehrsson, Erica; Xing, Xiaoyun; Fiore, Christopher; Pandey, Manishi; Maricque, Brett; Udawatta, Methma; Ngo, Duc; Chen, Yujie; Paguntalan, Asia; Ray, Tammy; Hughes, Ava; Cohen, Barak A.; Wang, Ting

2017-01-01

Cis-regulatory modules contain multiple transcription factor (TF)-binding sites and integrate the effects of each TF to control gene expression in specific cellular contexts. Transposable elements (TEs) are uniquely equipped to deposit their regulatory sequences across a genome, which could also contain cis-regulatory modules that coordinate the control of multiple genes with the same regulatory logic. We provide the first evidence of mouse-specific TEs that encode a module of TF-binding sites in mouse embryonic stem cells (ESCs). The majority (77%) of the individual TEs tested exhibited enhancer activity in mouse ESCs. By mutating individual TF-binding sites within the TE, we identified a module of TF-binding motifs that cooperatively enhanced gene expression. Interestingly, we also observed the same motif module in the in silico constructed ancestral TE that also acted cooperatively to enhance gene expression. Our results suggest that ancestral TE insertions might have brought in cis-regulatory modules into the mouse genome. PMID:28348391

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: the follow-up study of gastrointestinal cancer patients.

PubMed

Smorodin, Eugeniy-P; Kurtenkov, Oleg-A; Sergeyev, Boris-L; Kodar, Kristel-E; Chuzmarov, Valentin-I; Afanasyev, Vladimir-P

2008-07-21

To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic alphaGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages I-IV without distant metastases were subjected to follow-up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and alphaGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut-off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (c2 = 3.89, all patients; c2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages III-IV (c2 = 4.71, gastric cancer; c2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti-Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

Endocytosis regulates membrane localization and function of the fusogen EFF-1.

PubMed

Smurova, Ksenia; Podbilewicz, Benjamin

2017-07-03

Cell fusion is essential for sexual reproduction and formation of muscles, bones, and placenta. Two families of cell fusion proteins (Syncytins and FFs) have been identified in eukaryotes. Syncytins have been shown to form the giant syncytial trophoblasts in the placenta. The FFs are essential to fuse cells in the skin, reproductive, excretory, digestive and nervous systems in nematodes. EFF-1 (Epithelial Fusion Failure 1), a member of the FF family, is a type I membrane glycoprotein that is essential for most cell fusions in C. elegans. The crystal structure of EFF-1 ectodomain reveals striking structural similarity to class II fusion glycoproteins from enveloped viruses (e.g. dengue and rubella) that mediate virus to cell fusion. We found EFF-1 to be present on the plasma membrane and in RAB-5-positive early endosomes, with EFF-1 recycling between these 2 cell compartments. Only when EFF-1 proteins transiently arrive to the surfaces of 2 adjacent cells do they dynamically interact in trans and mediate membrane fusion. EFF-1 is continuously internalized by receptor-mediated endocytosis via the activity of 2 small GTPases: RAB-5 and Dynamin. Here we propose a model that explains how EFF-1 endocytosis together with interactions in trans can control cell-cell fusion. Kontani et al. showed that vacuolar ATPase (vATPase) mutations result in EFF-1-dependent hyperfusion. 1 We propose that vATPase is required for normal degradation of EFF-1. Failure to degrade EFF-1 results in delayed hyperfusion and mislocalization to organelles that appear to be recycling endosomes. EFF-1 is also required to fuse neurons as part of the repair mechanism following injury and to prune dendrites. We speculate that EFF-1 may regulate neuronal tree like structures via endocytosis. Thus, endocytosis of cell-cell fusion proteins functions to prevent merging of cells and to sculpt organs and neurons.

[Evoked Potential Blind Extraction Based on Fractional Lower Order Spatial Time-Frequency Matrix].

PubMed

Long, Junbo; Wang, Haibin; Zha, Daifeng

2015-04-01

The impulsive electroencephalograph (EEG) noises in evoked potential (EP) signals is very strong, usually with a heavy tail and infinite variance characteristics like the acceleration noise impact, hypoxia and etc., as shown in other special tests. The noises can be described by a stable distribution model. In this paper, Wigner-Ville distribution (WVD) and pseudo Wigner-Ville distribution (PWVD) time-frequency distribution based on the fractional lower order moment are presented to be improved. We got fractional lower order WVD (FLO-WVD) and fractional lower order PWVD (FLO-PWVD) time-frequency distribution which could be suitable for a stable distribution process. We also proposed the fractional lower order spatial time-frequency distribution matrix (FLO-STFM) concept. Therefore, combining with time-frequency underdetermined blind source separation (TF-UBSS), we proposed a new fractional lower order spatial time-frequency underdetermined blind source separation (FLO-TF-UBSS) which can work in a stable distribution environment. We used the FLO-TF-UBSS algorithm to extract EPs. Simulations showed that the proposed method could effectively extract EPs in EEG noises, and the separated EPs and EEG signals based on FLO-TF-UBSS were almost the same as the original signal, but blind separation based on TF-UBSS had certain deviation. The correlation coefficient of the FLO-TF-UBSS algorithm was higher than the TF-UBSS algorithm when generalized signal-to-noise ratio (GSNR) changed from 10 dB to 30 dB and a varied from 1. 06 to 1. 94, and was approximately e- qual to 1. Hence, the proposed FLO-TF-UBSS method might be better than the TF-UBSS algorithm based on second order for extracting EP signal under an EEG noise environment.

FXIa and platelet polyphosphate as therapeutic targets during human blood clotting on collagen/tissue factor surfaces under flow

PubMed Central

Zhu, Shu; Travers, Richard J.; Morrissey, James H.

2015-01-01

Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas platelet-derived polyphosphate (polyP) may potentiate contact or thrombin-feedback pathways. The significance of these mediators in human blood under thrombotic flow conditions on tissue factor (TF) –bearing surfaces remains inadequately resolved. Human blood (corn trypsin inhibitor treated [4 μg/mL]) was tested by microfluidic assay for clotting on collagen/TF at TF surface concentration ([TF]wall) from ∼0.1 to 2 molecules per μm2. Anti-FXI antibodies (14E11 and O1A6) or polyP-binding protein (PPXbd) were used to block FXIIa-dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet-derived polyP, respectively. Fibrin formation was sensitive to 14E11 at 0 to 0.1 molecules per µm2 and sensitive to O1A6 at 0 to 0.2 molecules per µm2. However, neither antibody reduced fibrin generation at ∼2 molecules per µm2 when the extrinsic pathway became dominant. Interestingly, PPXbd reduced fibrin generation at low [TF]wall (0.1 molecules per µm2) but not at zero or high [TF]wall, suggesting a role for polyP distinct from FXIIa activation and requiring low extrinsic pathway participation. Regardless of [TF]wall, PPXbd enhanced fibrin sensitivity to tissue plasminogen activator and promoted clot retraction during fibrinolysis concomitant with an observed PPXbd-mediated reduction of fibrin fiber diameter. This is the first detection of endogenous polyP function in human blood under thrombotic flow conditions. When triggered by low [TF]wall, thrombosis may be druggable by contact pathway inhibition, although thrombolytic susceptibility may benefit from polyP antagonism regardless of [TF]wall. PMID:26136249

Benchmark tests of JENDL-3.2 for thermal and fast reactors

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

Takano, Hideki; Akie, Hiroshi; Kikuchi, Yasuyuki

1994-12-31

Benchmark calculations for a variety of thermal and fast reactors have been performed by using the newly evaluated JENDL-3 Version-2 (JENDL-3.2) file. In the thermal reactor calculations for the uranium and plutonium fueled cores of TRX and TCA, the k{sub eff} and lattice parameters were well predicted. The fast reactor calculations for ZPPR-9 and FCA assemblies showed that the k{sub eff} reactivity worths of Doppler, sodium void and control rod, and reaction rate distribution were in a very good agreement with the experiments.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry.

PubMed

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.

[A study on the diagnostic value of tear film objective scatter index in dry eye].

PubMed

Su, Y D; Liang, Q F; Wang, N L; Antoine, Labbè

2017-09-11

Objective: To study the sensitivity and specificity of tear film objective scatter index to the diagnosis dry eye disease (DED). Methods: A prospective case-controlled study. Fifty-three patients with DED and 32 healthy age- and sex-matched control subjects were included from July to October 2016. All subjects underwent the examinations sequentially as follows: evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index, optical quality detection, lipid layer thickness, tear film breakup time and SchirmerⅠtest. With Optical Quality Analysis SystemⅡ, the values of modulation transfer function cut off, basic objective scatter index (OSI) and total OSI were measured. To eliminate the influence of other refractive media, the tear film OSI (TF-OSI) was calculated, and the difference in TF-OSI between two groups was analyzed with the independent-samples t test. Spearman's correlation analysis was used to detect the correlation of each parameter in the DED group. With the receiver operating characteristic curve and the area under the curve (AUC), the specificity and sensitivity of TF-OSI and other parameters were described to differentiate DED from normal eyes. Results: In the dry eye group, the value of modulation transfer function cut off (32.07±11.95) was significantly lower than the normal group (39.38±9.44, t=- 3.096, P= 0.003) , and the mean value and dispersion of TF-OSI (0.50±0.43, 0.52±0.81) were higher than the normal group (0.21±0.16, 0.12±0.01) ( t= 4.300, P= 0.000, t= 3.546, P= 0.001) . The mean value of TF-OSI had a positive correlation with lipid layer thickness ( r= 0.365, P= 0.007) and dispersion of TF-OSI ( r= 0.581, P= 0.000), and a negative correlation with MTF cut off ( r=- 0.368, P= 0.007). To the diagnostic value of DED, the mean value of TF-OSI had a sensitivity of 0.736, a specificity of 0.762, and the AUC was 0.764. The dispersion of TF-OSI had a sensitivity of 0.811 and a specificity of 0.810, and the AUC was 0.900. Conclusion: In the DED group, the mean value and dispersion of TF-OSI were higher than the normal group. With its advantages, the TF-OSI may be a new method for the auxiliary diagnosis of dry eye. (Chin J Ophthalmol, 2017, 53: 668-674) .

Identification of active miRNA and transcription factor regulatory pathways in human obesity-related inflammation.

PubMed

Zhang, Xi-Mei; Guo, Lin; Chi, Mei-Hua; Sun, Hong-Mei; Chen, Xiao-Wen

2015-03-07

Obesity-induced chronic inflammation plays a fundamental role in the pathogenesis of metabolic syndrome (MS). Recently, a growing body of evidence supports that miRNAs are largely dysregulated in obesity and that specific miRNAs regulate obesity-associated inflammation. We applied an approach aiming to identify active miRNA-TF-gene regulatory pathways in obesity. Firstly, we detected differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) from mRNA and miRNA expression profiles, respectively. Secondly, by mapping the DEGs and DEmiRs to the curated miRNA-TF-gene regulatory network as active seed nodes and connect them with their immediate neighbors, we obtained the potential active miRNA-TF-gene regulatory subnetwork in obesity. Thirdly, using a Breadth-First-Search (BFS) algorithm, we identified potential active miRNA-TF-gene regulatory pathways in obesity. Finally, through the hypergeometric test, we identified the active miRNA-TF-gene regulatory pathways that were significantly related to obesity. The potential active pathways with FDR < 0.0005 were considered to be the active miRNA-TF regulatory pathways in obesity. The union of the active pathways is visualized and identical nodes of the active pathways were merged. We identified 23 active miRNA-TF-gene regulatory pathways that were significantly related to obesity-related inflammation.

EFF Voice, Winter 2002.

ERIC Educational Resources Information Center

EFF Voice, 2002

2002-01-01

This newsletter reports on the activities of Equipped for the Future (EFF), which is a National Institute for Literacy initiative. EFF helps Temporary Assistance for Needy Families (TANF) recipients build the skills needed to balance work and home and make a successful transition to work. The article "EFF Frames Family Literacy Programs"…

Biomechanical comparison of straight DCP and helical plates for fixation of transverse and oblique bone fractures.

PubMed

Aksakal, Bunyamin; Gurger, Murat; Say, Yakup; Yilmaz, Erhan

2014-01-01

Biomechanical comparison of straight DCP and helical plates for fixation of transversal and oblique tibial bone fractures were analyzed and compared to each other by axial compression, bending and torsion tests. An in vitro osteosynthesis of transverse (TF) and oblique bone fracture (OF) fixations have been analysed on fresh sheep tibias by using the DCP and helical compression plates (HP). Statistically significant differences were found for both DCP and helical plate fixations under axial compression, bending and torsional loads. The strength of fixation systems was in favor of DC plating with exception of the TF-HP fixation group under compression loads and torsional moments. The transvers fracture (TF) stability was found to be higher than that found in oblique fracture (OF) fixed by helical plates (HP). However, under torsional testing, compared to conventional plating, the helical plate fixations provided a higher torsional resistance and strength. The maximum stiffness at axial compression loading and maximum torsional strength was achieved in torsional testing for the TF-HP fixations. From in vitro biomechanical analysis, fracture type and plate fixation system groups showed different responses under different loadings. Consequently, current biomechanical analyses may encourage the usage of helical HP fixations in near future during clinical practice for transverse bone fractures.

Effective Solar Indices for Ionospheric Modeling: A Review and a Proposal for a Real-Time Regional IRI

NASA Astrophysics Data System (ADS)

Pignalberi, A.; Pezzopane, M.; Rizzi, R.; Galkin, I.

2018-01-01

The first part of this paper reviews methods using effective solar indices to update a background ionospheric model focusing on those employing the Kriging method to perform the spatial interpolation. Then, it proposes a method to update the International Reference Ionosphere (IRI) model through the assimilation of data collected by a European ionosonde network. The method, called International Reference Ionosphere UPdate (IRI UP), that can potentially operate in real time, is mathematically described and validated for the period 9-25 March 2015 (a time window including the well-known St. Patrick storm occurred on 17 March), using IRI and IRI Real Time Assimilative Model (IRTAM) models as the reference. It relies on foF2 and M(3000)F2 ionospheric characteristics, recorded routinely by a network of 12 European ionosonde stations, which are used to calculate for each station effective values of IRI indices IG_{12} and R_{12} (identified as IG_{{12{eff}}} and R_{{12{eff}}}); then, starting from this discrete dataset of values, two-dimensional (2D) maps of IG_{{12{eff}}} and R_{{12{eff}}} are generated through the universal Kriging method. Five variogram models are proposed and tested statistically to select the best performer for each effective index. Then, computed maps of IG_{{12{eff}}} and R_{{12{eff}}} are used in the IRI model to synthesize updated values of foF2 and hmF2. To evaluate the ability of the proposed method to reproduce rapid local changes that are common under disturbed conditions, quality metrics are calculated for two test stations whose measurements were not assimilated in IRI UP, Fairford (51.7°N, 1.5°W) and San Vito (40.6°N, 17.8°E), for IRI, IRI UP, and IRTAM models. The proposed method turns out to be very effective under highly disturbed conditions, with significant improvements of the foF2 representation and noticeable improvements of the hmF2 one. Important improvements have been verified also for quiet and moderately disturbed conditions. A visual analysis of foF2 and hmF2 maps highlights the ability of the IRI UP method to catch small-scale changes occurring under disturbed conditions which are not seen by IRI.

[Total flavones derived from Lagotis brevituba maxim reduce the levels of inflammatory cytokines in cerebral cortex and hippocampus of Alzheimer's disease mice].

PubMed

Yang, Bailing; Hou, Qian; Hu, Feng; Zhang, Fan

2016-07-01

Objective To investigate the mechanism behind the treatment of Alzheimer's disease (AD) with total flavones derived from Lagotis brevituba maxim (TF-LBM). Methods Fifty SAMP8 mice (aged 8 months) were randomly divided into 5 groups, (150, 300, 600) mg/kg TF-LBM groups, 0.65 g/kg donepezil HCl group and AD model group; 10 SAMR1 mice (aged 8 months) were used as a control group of normal aging. The AD model group and the normal aging control group were given the same volume of distilled water as TF-LBM groups. Eight weeks after intragastric administration, Morris water maze experiment was conducted to calculate the latency of place navigation. After the behavioral experiment, the brain cortical tissue and hippocampus (CA1 region) of the mice from various groups were taken to observe the morphological changes of the cortical tissue and hippocampus and test IL-1β, IL-6, TNF-α content. Results Compared with the model group, the escape latency of the normal aging group, the high-dose TF-LBM group and the donepezil HCl group were evidently shortened; compared with the normal aging group, IL-1β, IL-6, TNF-αof the model group increased significantly; compared with the model group, IL-1β content of the low-dose TF-LBM group had no obvious difference, while IL-1β content of the median-dose and high-dose TF-LBM groups and the donepezil HCl group decreased significantly; IL-6 content decreased in all TF-LBM groups and the donepezil HCl group; TNF-α level in the low-dose and median-dose TF-LBM groups had no evident difference, while it was reduced significantly in the high-dose TF-LBM group and the donepezil HCl group. Compared with the normal aging group, IL-1β, IL-6 and TNF-α content of the model group increased significantly; compared with the model group, IL-1β, IL-6 and TNF-α content of all TF-LBM groups and the donepezil HCl group decreased. Conclusion TF-LBM can improve the behavior change of SAMP8 mice with AD. TF-LBM can reduce the content of IL-6, IL-1β and TNF-α in cerebral cortex and hippocampus CA1.

EFF Voice. Volume 1, Number 1, Fall-Winter 1999

ERIC Educational Resources Information Center

National Institute for Literacy, 1999

1999-01-01

This premier issue of "The Equipped for the Future (EFF) Voice" has been put together to give everyone a snapshot of EFF-related activities across the country. It includes reports on the 12 states that have been participating in the EFF field development process since 1998, and on the many other programs and states that have begun…

EFF/NRS Data Collection Project, 2000-2001: An Interim Report on the Development of the EFF Assessment Framework.

ERIC Educational Resources Information Center

SRI International, Arlington, VA.

The Equipped for the Future (EFF) framework describes adult performance along these four dimensions: structure of the knowledge-base; fluency of performance; independence of performance; and range of conditions for performance. When completed it will include a developmental sequence of descriptions of learner performance for each EFF standard;…

On the measurement of the crack tip stress field as a means of determining Delta K(sub eff) under conditions of fatigue crack closure

NASA Technical Reports Server (NTRS)

Wallhead, Ian R.; Edwards, Lyndon; Poole, Peter

1994-01-01

The optical method of caustics has been successfully extended to enable stress intensity factors as low as 1MPa square root of m to be determined accurately for central fatigue cracks in 2024-T3 aluminium alloy test panels. The feasibility of using this technique to study crack closure, and to determine the effective stress intensity factor range, Delta K(sub eff), has been investigated. Comparisons have been made between the measured values of stress intensity factor, K(sub caus), and corresponding theoretical values, K(sub theo), for a range of fatigue cracks grown under different loading conditions. The values of K(sub caus) and K(sub theo) were in good agreement at maximum stress, where the cracks are fully open, while K(sub caus) exceeded K(sub theo) at minimum stress, due to crack closure. However, the levels of crack closure and values of Delta K(sub eff) obtained could not account for the variations of crack growth rate with loading conditions. It is concluded that the values of Delta K(sub eff), based on caustic measurements in a 1/square root of r stress field well outside the plastic zone, do not fully reflect local conditions which control crack tip behavior.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry

PubMed Central

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671

Cyclic fatigue resistance of 3 different nickel-titanium reciprocating instruments in artificial canals.

PubMed

Higuera, Oscar; Plotino, Gianluca; Tocci, Luigi; Carrillo, Gabriela; Gambarini, Gianluca; Jaramillo, David E

2015-06-01

The purpose of this study was to evaluate the cyclic fatigue resistance of 3 different nickel-titanium reciprocating instruments. A total of 45 nickel-titanium instruments were tested and divided into 3 experimental groups (n = 15): group 1, WaveOne Primary instruments; group 2, Reciproc R25 instruments; and group 3, Twisted File (TF) Adaptive M-L1 instruments. The instruments were then subjected to cyclic fatigue test on a static model consisting of a metal block with a simulated canal with 60° angle of curvature and a 5-mm radius of curvature. WaveOne Primary, Reciproc R25, and TF Adaptive instruments were activated by using their proprietary movements, WaveOne ALL, Reciproc ALL, and TF Adaptive, respectively. All instruments were activated until fracture occurred, and the time to fracture was recorded visually for each file with a 1/100-second chronometer. Mean number of cycles to failure and standard deviations were calculated for each group, and data were statistically analyzed (P < .05). Instruments were also observed through scanning electron microscopy to evaluate type of fracture. Cyclic fatigue resistance of Reciproc R25 and TF Adaptive M-L1 was significantly higher than that of WaveOne Primary (P = .009 and P = .002, respectively). The results showed no statistically significant difference between TF Adaptive M-L1 and Reciproc R25 (P = .686). Analysis of the fractured portion under scanning electron microscopy indicated that all instruments showed morphologic characteristics of ductile fracture that were due to accumulation of metal fatigue. No statistically significant differences were found between the instruments tested except for WaveOne Primary, which showed the lowest resistance to cyclic fatigue. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Cyclic fatigue resistance of R-Pilot, WaveOne Gold Glider, and ProGlider glide path instruments.

PubMed

Keskin, Cangül; İnan, Uğur; Demiral, Murat; Keleş, Ali

2018-02-17

The aim of the present study was to compare the cyclic fatigue resistance of R-Pilot (VDW; Munich, Germany) with ProGlider (Denstply Sirona; Ballaigues, Switzerland) and WaveOne Gold Glider (Denstply Sirona; Ballaigues, Switzerland) glide path instruments. R-Pilot, ProGlider, and WaveOne Gold Glider instruments were collected (n = 15) and tested in a dynamic cyclic fatigue test device, which has an artificial canal with 60° angle of curvature and a 5-mm radius of curvature. All instruments were operated until fracture occurred, and both time to fracture (TF) and the lengths of the fractured fragments were recorded. Mean and standard deviations of TF and fragment length were calculated for each reciprocating system. TF data and fractured fragment length data were subjected to one-way ANOVA and post-hoc Tukey tests (P < 0.05). Also a Weibull analysis was performed on TF data. The cyclic fatigue resistance values of the WaveOne Gold Glider and R-Pilot were significantly higher than those of the ProGlider (P < 0.05), with no significant difference between them (P > 0.05). Weibull analysis revealed that WaveOne Gold Glider showed the highest predicted TF value for 99% survival rate, which was followed by R-Pilot and ProGlider. Regarding the length of the fractured tips, there were no significant differences among the instruments (P > 0.05). The reciprocating WaveOne Gold Glider and R-Pilot instruments had significantly higher cyclic fatigue resistance than rotary ProGlider instruments. This study reported that novel reciprocating glide path instruments exhibited higher cyclic fatigue resistance than rotating glide path instrument.

Evaluation of the root canal shaping ability of two rotary nickel-titanium systems.

PubMed

Al-Manei, K K; Al-Hadlaq, S M S

2014-10-01

The aim was to investigate the canal shaping abilities of the twisted file (TF) and GT series X file (GTX) systems. Sixty mesial root canals of mandibular molars with curvatures of 15-50° were divided randomly into two groups of 30 canals each. The teeth were sectioned horizontally at 3, 6 and 9 mm from the apex. Root canals were prepared with TF and GTX files, respectively, and the shaping abilities of the systems were evaluated at three levels (coronal, middle and apical) based on the comparison of pre- and post-instrumentation photographs using AutoCAD software. Preparation time was also assessed. Data from the two groups were compared statistically using the Student's t-test. There was no significant difference between the rotary systems in terms of change in root canal cross-sectional area, root canal transportation, centring ability or minimum dentine thickness. Remaining dentine thickness at the coronal and middle levels was similar in the TF and GTX groups, but GTX instruments left significantly less dentine than TF instruments on the mesial aspects of root canals at the apical level. Root canal preparation with TF instruments required significantly less time than with GTX instruments. The TF and GTX NiTi rotary instruments showed similar shaping abilities, but root canal preparation was more rapid with the TF than with the GTX system. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Inhibition effects of total flavonoids from Scutellaria barbata D. Don on human breast carcinoma bone metastasis via downregulating PTHrP pathway

PubMed Central

Liu, Huihui; Guo, Shanyu

2018-01-01

It is abundantly clear that tumor-derived parathyroid hormone-related protein (PTHrP), receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are central contributors in promoting osteolytic process of breast carcinoma bone metastasis. Forcusing on this molecular basis, the study was undertaken to explore the inhibition effects of total flavonoids from Scutellaria barbata D. Don (TF-SB) on human breast carcinoma bone metastasis. MDA-MB-231 cells and nude mouse models of breast cancer bone metastasis were given TF-SB in different concentrations. The proliferation, migration and invasion potentials of MDA-MB-231 cells were respectively tested. The effects of TF-SB on tumor weights and bone destruction were investigated. The mRNA and protein expression of PTHrP, OPG and RANKL were assessed by qPCR and western blot analysis. In vitro, TF-SB inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose-dependent manner. In vivo, TF-SB prevented bone metastasis of breast cancer by decreasing the number of osteoclast cells per field in a dose-dependent manner, but not affecting tumor growth or mouse survival. Molecular analysis revealed that TF-SB controled the secretion of osteolysis-related factors PTHrP and its downstream RANKL/OPG. Together, by controlling the expression of PTHrP and its downstream OPG/RANKL, TF-SB has significant inhibition effects on breast cancer bone metastasis, which indicates a new therapeutic method. PMID:29512770

Intakes of apple juice, fruit drinks and soda are associated with prevalent asthma in US children aged 2-9 years.

PubMed

DeChristopher, Luanne Robalo; Uribarri, Jaime; Tucker, Katherine L

2016-01-01

High soft drink consumption has been linked with asthma. Anecdotal evidence links high-fructose corn syrup with asthma. The receptor of advanced glycation end products (RAGE) has emerged as a mediator of asthma. The objectives of the present study were to: (i) assess the correlation between intake of beverages containing excess free fructose (EFF beverages) and asthma in children; and (ii) epidemiologically test the mechanistic hypothesis that intake of high EFF beverages, such as apple juice or beverages sweetened with high-fructose corn syrup, is associated with increased risk of asthma. This hypothesis is based on the possible effect of increases in the in situ intestinal formation of advanced glycation end products (enFruAGE) with EFF, which may be absorbed and play a role in RAGE-mediated asthma. We examined cross-sectional associations between beverage intake and self-reported current or history of asthma. Exposure variables were EFF beverages, including apple juice (AJ), non-diet soft drinks (ndSD) and fruit drinks (FD). Orange juice (OJ), not an EFF beverage, was included as a comparison. Rao-Scott χ(2) analysis was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race/ethnicity, BMI and total energy intake. Data are from the National Health and Nutrition Examination Survey 2003-2006, a nationally representative survey. US children (n 1961) aged 2-9 years with complete responses on the dietary frequency questionnaire. Intakes of EFF beverages were significantly associated with asthma in 2-9-year-olds. Adjusted odds of asthma in children consuming EFF beverages ≥5 times/week was more than five times that in children consuming these beverages ≤1 time/month (OR=5·29, P=0·012). Children consuming AJ ≥5 times/week v. ≤1 time/month, adjusted for the other beverages, were more than twice as likely to have asthma (OR=2·43, P=0·035). In contrast, there was a tendency for OJ to be protective. These results support the hypothesis that intake of high EFF beverages, including AJ and beverages sweetened with high-fructose corn syrup, is associated with asthma in children aged 2-9 years. Results support the mechanistic hypothesis that enFruAGE may be an overlooked contributor to asthma in children. Longitudinal studies are needed to provide evidence of causal association.

EFF Voice. Volume 3, Number 1, Spring 2003

ERIC Educational Resources Information Center

National Institute for Literacy, 2003

2003-01-01

This issue of "EFF Voice" was assembled by the staff to share with their readers some of the ways their partners are using Equipped for the Future (EFF) to help adults build the skills they need to be successful in the workforce today. Readers will learn about how states like New Jersey are using EFF to craft a common vision and a common…

Benchmarks--Standards Comparisons. Math Competencies: EFF Benchmarks Comparison [and] Reading Competencies: EFF Benchmarks Comparison [and] Writing Competencies: EFF Benchmarks Comparison.

ERIC Educational Resources Information Center

Kent State Univ., OH. Ohio Literacy Resource Center.

This document is intended to show the relationship between Ohio's Standards and Competencies, Equipped for the Future's (EFF's) Standards and Components of Performance, and Ohio's Revised Benchmarks. The document is divided into three parts, with Part 1 covering mathematics instruction, Part 2 covering reading instruction, and Part 3 covering…

Characterization of the interaction between diferric transferrin and transferrin receptor 2 by functional assays and atomic force microscopy*

PubMed Central

Ikuta, Katsuya; Yersin, Alexandre; Ikai, Atsushi; Aisen, Philip; Kohgo, Yutaka

2010-01-01

Transferrin receptor (TfR2), a homologue of classical transferrin receptor 1 (TfR1), is found in two isoforms, α and β. Like TfR1, TfR2α is a type II membrane protein, but the β form lacks transmembrane portions and therefore is likely to be an intracellular protein. To investigate the functional properties of TfR2α we expressed the protein with FLAG-tagging in transferrin receptor-deficient Chinese hamster ovary cells. The association constant for binding of diferric transferrin (Tf) to TfR2α is 5.6 × 106 M−1, which is about 50 times lower than that of TfR1, with correspondingly reduced rates of iron uptake. Evidence for Tf internalization and recycling via TfR2α without degradation, as in the TfR1 pathway, was also found. The interaction of TfR2α with Tf was further investigated using atomic force microscopy (AFM), a powerful tool for investigation of the interaction between ligand and receptor at the single molecule level on the living cell surface. Dynamic force microscopy reveals a difference in the interactions of Tf with TfR2α and TfR1, with Tf-TfR1 unbinding characterized by 2 energy barriers, while only one is present for Tf-TfR2. We speculate that this difference may reflect Tf binding to TfR2α by a single lobe, whereas two lobes of Tf participate in binding to TfR1. The difference in the binding properties of Tf to TfR1 and TfR2α may help account for the different physiological roles of the two receptors. PMID:20096706

Systematic Analysis of Zn2Cys6 Transcription Factors Required for Development and Pathogenicity by High-Throughput Gene Knockout in the Rice Blast Fungus

PubMed Central

Huang, Pengyun; Lin, Fucheng

2014-01-01

Because of great challenges and workload in deleting genes on a large scale, the functions of most genes in pathogenic fungi are still unclear. In this study, we developed a high-throughput gene knockout system using a novel yeast-Escherichia-Agrobacterium shuttle vector, pKO1B, in the rice blast fungus Magnaporthe oryzae. Using this method, we deleted 104 fungal-specific Zn2Cys6 transcription factor (TF) genes in M. oryzae. We then analyzed the phenotypes of these mutants with regard to growth, asexual and infection-related development, pathogenesis, and 9 abiotic stresses. The resulting data provide new insights into how this rice pathogen of global significance regulates important traits in the infection cycle through Zn2Cys6TF genes. A large variation in biological functions of Zn2Cys6TF genes was observed under the conditions tested. Sixty-one of 104 Zn2Cys6 TF genes were found to be required for fungal development. In-depth analysis of TF genes revealed that TF genes involved in pathogenicity frequently tend to function in multiple development stages, and disclosed many highly conserved but unidentified functional TF genes of importance in the fungal kingdom. We further found that the virulence-required TF genes GPF1 and CNF2 have similar regulation mechanisms in the gene expression involved in pathogenicity. These experimental validations clearly demonstrated the value of a high-throughput gene knockout system in understanding the biological functions of genes on a genome scale in fungi, and provided a solid foundation for elucidating the gene expression network that regulates the development and pathogenicity of M. oryzae. PMID:25299517

The Novel Endocrine Disruptor Tolylfluanid Impairs Insulin Signaling in Primary Rodent and Human Adipocytes through a Reduction in Insulin Receptor Substrate-1 Levels

PubMed Central

Sargis, Robert M.; Neel, Brian A.; Brock, Clifton O.; Lin, Yuxi; Hickey, Allison T.; Carlton, Daniel A.; Brady, Matthew J.

2012-01-01

Emerging data suggest that environmental endocrine disrupting chemicals (EDCs) may contribute to the pathophysiology of obesity and diabetes. In prior work, the phenylsulfamide fungicide tolylfluanid (TF) was shown to augment adipocyte differentiation, yet its effects on mature adipocyte metabolism remain unknown. Because of the central role of adipose tissue in global energy regulation, the present study tested the hypothesis that TF modulates insulin action in primary rodent and human adipocytes. Alterations in insulin signaling in primary mammalian adipocytes were determined by the phosphorylation of Akt, a critical insulin signaling intermediate. Treatment of primary murine adipose tissue in vitro with 100 nM TF for 48 h markedly attenuated acute insulin-stimulated Akt phosphorylation in a strain- and species-independent fashion. Perigonadal, perirenal, and mesenteric fat were all sensitive to TF-induced insulin resistance. A similar TF-induced reduction in insulin-stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue. TF-treatment led to a potent and specific reduction in insulin receptor substrate-1 (IRS-1) mRNA and protein levels, a key upstream mediator of insulin’s diverse metabolic effects. In contrast, insulin receptor-β, phosphatidylinositol 3-kinase, and Akt expression were unchanged, indicating a specific abrogation of insulin signaling. Additionally, TF-treated adipocytes exhibited altered endocrine function with a reduction in both basal and insulin-stimulated leptin secretion. These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes. PMID:22387882

EMISSION TEST REPORT, OMSS FIELD TEST ON CARBON INJECTION FOR MERCURY CONTROL

EPA Science Inventory

The report discusses results of a parametric evaluation of powdered activated carbon for control of mercury (Hg) emission from a municipal waste cornbustor (MWC) equipped with a lime spray dryer absorber/fabric filter (SD/FF). The primary test objectives were to evaluate the effe...

FXIa and platelet polyphosphate as therapeutic targets during human blood clotting on collagen/tissue factor surfaces under flow.

PubMed

Zhu, Shu; Travers, Richard J; Morrissey, James H; Diamond, Scott L

2015-09-17

Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas platelet-derived polyphosphate (polyP) may potentiate contact or thrombin-feedback pathways. The significance of these mediators in human blood under thrombotic flow conditions on tissue factor (TF) -bearing surfaces remains inadequately resolved. Human blood (corn trypsin inhibitor treated [4 μg/mL]) was tested by microfluidic assay for clotting on collagen/TF at TF surface concentration ([TF]wall) from ∼0.1 to 2 molecules per μm(2). Anti-FXI antibodies (14E11 and O1A6) or polyP-binding protein (PPXbd) were used to block FXIIa-dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet-derived polyP, respectively. Fibrin formation was sensitive to 14E11 at 0 to 0.1 molecules per µm(2) and sensitive to O1A6 at 0 to 0.2 molecules per µm(2). However, neither antibody reduced fibrin generation at ∼2 molecules per µm(2) when the extrinsic pathway became dominant. Interestingly, PPXbd reduced fibrin generation at low [TF]wall (0.1 molecules per µm(2)) but not at zero or high [TF]wall, suggesting a role for polyP distinct from FXIIa activation and requiring low extrinsic pathway participation. Regardless of [TF]wall, PPXbd enhanced fibrin sensitivity to tissue plasminogen activator and promoted clot retraction during fibrinolysis concomitant with an observed PPXbd-mediated reduction of fibrin fiber diameter. This is the first detection of endogenous polyP function in human blood under thrombotic flow conditions. When triggered by low [TF]wall, thrombosis may be druggable by contact pathway inhibition, although thrombolytic susceptibility may benefit from polyP antagonism regardless of [TF]wall. © 2015 by The American Society of Hematology.

Hypoxia and PGE2 Regulate MiTF-CX During Cervical Ripening

PubMed Central

Hari Kishore, Annavarapu; Li, Xiang-Hong

2012-01-01

The mechanisms by which the cervix remains closed during the massive uterine expansion of pregnancy are unknown. IL-8 is important for recruitment of immune cells into the cervical stroma, matrix remodeling, and dilation of the cervix during labor. Previously, we have shown that several cytokine genes transcriptionally repressed in the cervix during gestation are activated during cervical ripening and dilation. IL-8 gene expression is repressed in cervical stromal cells during pregnancy by the transcription factor microphthalmia-associated transcription factor (MiTF-CX). Here, we tested the hypothesis that hypoxia and the transcription factor hypoxia inducible factor-1α (HIF-1α) may regulate MiTF-CX and cervical ripening. Using tissues from women during pregnancy before and after cervical ripening, we show that, during cervical ripening, HIF-1α was stabilized and relocalized to the nucleus. Further, we found that hypoxia and two hypoxia mimetics that stabilize HIF-1α activated the transcriptional repressor differentiated embryo chondrocyte-expressed gene 1, which bound to sites in the MiTF-CX promoter crucial for its positive autoregulation. Ectopic overexpression of MiTF-CX abrogated hypoxia-induced up-regulation of IL-8 gene expression. We also show that activation of HIF-1α induced cyclooxygenase-2 and that prostaglandin E2 repressed MiTF-CX. We conclude that hypoxia and stabilization of the transcription factor HIF-1α result in up-regulation of differentiated embryo chondrocyte-expressed gene 1, loss of MiTF, and absence of MiTF binding to the IL-8 promoter, which in turn leads to up-regulation of IL-8 gene expression. Hypoxia also up-regulated cyclooxygenase-2, leading to prostaglandin E2-mediated loss of MiTF in cervical stromal cells. The results support a pivotal role for hypoxia and HIF-1α in the cervical ripening process during pregnancy. PMID:23144021

Prostaglandin E2 Regulates Its Own Inactivating Enzyme, 15-PGDH, by EP2 Receptor-Mediated Cervical Cell-Specific Mechanisms

PubMed Central

Kishore, A. Hari; Owens, David

2014-01-01

Context: Prostaglandins play important roles in parturition and have been used to induce cervical ripening and labor. Prior to cervical ripening at term, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is highly expressed in the cervix and metabolizes cyclooxygenase-2-mediated increases in active prostaglandin E2 (PGE2) to inactive 15-keto PGE2. At term, 15-PGDH gene expression decreases and PGE2 accumulates, leading to cervical ripening and labor. Previously, we found that the cervical isoform of microphthalmia-associated transcription factor (MiTF-CX) serves as a progestational transcription factor that represses IL-8 and hypoxia-mediated increases in cyclooxygenase-2. Objective: We tested the hypothesis that PGE2 regulates its own inactivation through MiTF-CX. Design: We used human cervical stromal cells to investigate the regulation of 15-PGDH. Setting: This was a laboratory-based study using cells from clinical tissue samples. Main Outcome Measures: We evaluated the mechanisms by which PGE2 regulates 15-PGDH in human cervical stromal cells. Results: PGE2 repressed MiTF-CX and 15-PGDH, whereas ectopic overexpression of MiTF-CX induced 15-PGDH expression levels. Stabilization of HIF-1α by deferoxamine resulted in concomitant down-regulation of MiTF-CX and 15-PGDH. Ectopic overexpression of MiTF-CX abrogated PGE2- and deferoxamine-mediated loss of MiTF-CX and 15-PGDH. PGE2-induced loss of MiTF-CX and 15-PGDH was mediated through prostaglandin E2 receptor (EP2) receptors (PTGER2), but not cAMP. Conclusions: The 15-PGDH gene is a MiTF-CX target gene in cervical stromal cells and is down-regulated by PGE2 through EP2 receptors. The findings suggest that EP2 receptor-specific antagonists may be used as an adjunct to present clinical management for the prevention of preterm cervical ripening and preterm labor. PMID:24471568

Fluorescent adduct formation with terbium: a novel strategy for transferrin glycoform identification in human body fluids and carbohydrate-deficient transferrin HPLC method validation.

PubMed

Sorio, Daniela; De Palo, Elio Franco; Bertaso, Anna; Bortolotti, Federica; Tagliaro, Franco

2017-02-01

This paper puts forward a new method for the transferrin (Tf) glycoform analysis in body fluids that involves the formation of a transferrin-terbium fluorescent adduct (TfFluo). The key idea is to validate the analytical procedure for carbohydrate-deficient transferrin (CDT), a traditional biochemical serum marker to identify chronic alcohol abuse. Terbium added to a human body-fluid sample produced TfFluo. Anion exchange HPLC technique, with fluorescence detection (λ exc 298 nm and λ em 550 nm), permitted clear separation and identification of Tf glycoform peaks without any interfering signals, allowing selective Tf sialoforms analysis in human serum and body fluids (cadaveric blood, cerebrospinal fluid, and dried blood spots) hampered for routine test. Serum samples (n = 78) were analyzed by both traditional absorbance (Abs) and fluorescence (Fl) HPLC methods and CDT% levels demonstrated a significant correlation (p < 0.001 Pearson). Intra- and inter-runs CV% was 3.1 and 4.6%, respectively. The cut-off of 1.9 CDT%, related to the HPLC Abs proposed as the reference method, by interpolation in the correlation curve with the present method demonstrated a 1.3 CDT% cut-off. Method comparison by Passing-Bablok and Bland-Altman tests demonstrated Fl versus Abs agreement. In conclusion, the novel method is a reliable test for CDT% analysis and provides a substantial analytical improvement offering important advantages in terms of types of body fluid analysis. Its sensitivity and absence of interferences extend clinical applications being reliable for CDT assay on body fluids usually not suitable for routine test. Graphical Abstract The formation of a transferrin-terbium fluorescent adduct can be used to analyze the transferrin glycoforms. The HPLC method for carbohydrate-deficient transferrin (CDT%) measurement was validated and employed to determine the levels in different body fluids.

Comparing the dynamic performance of wastewater treatment systems: A metafrontier Malmquist productivity index approach.

PubMed

Molinos-Senante, María; Hernández-Sancho, Francesc; Sala-Garrido, Ramón

2015-09-15

The assessment of productivity change of wastewater treatment plants (WWTPs) is essential to improve the performance over time of the facilities evaluated. This study assessed and compared the productivity growth of WWTPs operating with non-homogeneous technologies. The metafrontier Malmquist productivity index (MMPI) was computed for a sample of 99 WWTPs encompassing 4 alternative technologies: activated sludge (AS), aerated lagoon (AL), trickling filter (TF) and rotating biological contactor (BD). The results indicated that, on average, WWTPs with AS and BD exhibited better performance over time than WWTPs with AL and TF. The MMPI indicates that, over the period 2007-2009, the productivity rose by 0.9% and 0.3% for AS and BD technologies, respectively, whilst for the AL and TF processes, the productivity decreased by 0.5% and 2.2%, respectively. The decomposition of the MMPI into efficiency change (EC) and technical change (TC) illustrated that EC was a positive driver of productivity change for WWTPs that use AS, whilst TC contributed positively to the productivity growth of WWTPs using AL and BD. Several policy implications to help managers make informed decisions were drawn from our empirical analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implementation of non-condensable gases condensation suppression model into the WCOBRA/TRAC-TF2 LOCA safety evaluation code

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

Liao, J.; Cao, L.; Ohkawa, K.

2012-07-01

The non-condensable gases condensation suppression model is important for a realistic LOCA safety analysis code. A condensation suppression model for direct contact condensation was previously developed by Westinghouse using first principles. The model is believed to be an accurate description of the direct contact condensation process in the presence of non-condensable gases. The Westinghouse condensation suppression model is further revised by applying a more physical model. The revised condensation suppression model is thus implemented into the WCOBRA/TRAC-TF2 LOCA safety evaluation code for both 3-D module (COBRA-TF) and 1-D module (TRAC-PF1). Parametric study using the revised Westinghouse condensation suppression model ismore » conducted. Additionally, the performance of non-condensable gases condensation suppression model is examined in the ACHILLES (ISP-25) separate effects test and LOFT L2-5 (ISP-13) integral effects test. (authors)« less

Assessment of Electrical Safety in Afghanistan

DTIC Science & Technology

2009-07-24

effectiveness of command efforts to ensure the electrical safety of Department of Defense occupied and constructed facilities in Afghanistan. We...March 31, 2009, we announced the Assessment of Electrical Safety in Afghanistan. The objective of this assessment was to review the effectiveness of...used contractors to review and identify electrical deficiencies to include life, health , and safety issues at FOBs. According to TF POWER

Sound speed and viscosity of semi-relativistic relic neutrinos

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

Krauss, Lawrence; Long, Andrew J., E-mail: krauss@asu.edu, E-mail: andrewjlong@kicp.uchicago.edu

2016-07-01

Generalized fluid equations, using sound speed c {sub eff}{sup 2} and viscosity c {sub vis}{sup 2} as effective parameters, provide a convenient phenomenological formalism for testing the relic neutrino 'null hypothesis,' i.e. that that neutrinos are relativistic and free-streaming prior to recombination. In this work, we relax the relativistic assumption and ask 'to what extent can the generalized fluid equations accommodate finite neutrino mass?' We consider both the mass of active neutrinos, which are largely still relativistic at recombination m {sup 2} / T {sup 2} ∼ 0.2, and the effect of a semi-relativistic sterile component. While there is nomore » one-to-one mapping between mass/mixing parameters and c {sub eff}{sup 2} and c {sub vis}{sup 2}, we demonstrate that the existence of a neutrino mass could induce a bias to measurements of c {sub eff}{sup 2} and c {sub vis}{sup 2} at the level of 0.01 m {sup 2} / T {sup 2} ∼ 10{sup -3}.« less

Analysis of distortion data from TF30-P-3 mixed compression inlet test

NASA Technical Reports Server (NTRS)

King, R. W.; Schuerman, J. A.; Muller, R. G.

1976-01-01

A program was conducted to reduce and analyze inlet and engine data obtained during testing of a TF30-P-3 engine operating behind a mixed compression inlet. Previously developed distortion analysis techniques were applied to the data to assist in the development of a new distortion methodology. Instantaneous distortion techniques were refined as part of the distortion methodology development. A technique for estimating maximum levels of instantaneous distortion from steady state and average turbulence data was also developed as part of the program.

Equipment and Tracking Test Results for the NRL Ship-to- Ship DF Laser Transmission Experiment.

DTIC Science & Technology

1982-04-05

combined with the 2" collimated HeNe laser beam at dichoric beam splitter TBSI. TF2, TF1 , and TPFI direct the beam onto the f/6 parabola Pl. From...following work was done on the pumping system: 1. Install new valves , springs, and seats. 2. Install a new drive shaft, with new bearings and seals. 3...Install a new needle valve in the oil regulator. 4. Steam clean the inside pump surface. The new components were tested first with F2 fuel, then with NF 3

Accuracy of the raw-data-based effective atomic numbers and monochromatic CT numbers for contrast medium with a dual-energy CT technique.

PubMed

Kawahara, Daisuke; Ozawa, Shuichi; Yokomachi, Kazushi; Tanaka, Sodai; Higaki, Toru; Fujioka, Chikako; Suzuki, Tatsuhiko; Tsuneda, Masato; Nakashima, Takeo; Ohno, Yoshimi; Nagata, Yasushi

2018-02-01

To evaluate the accuracy of raw-data-based effective atomic number (Z eff ) values and monochromatic CT numbers for contrast material of varying iodine concentrations, obtained using dual-energy CT. We used a tissue characterization phantom and varying concentrations of iodinated contrast medium. A comparison between the theoretical values of Z eff and that provided by the manufacturer was performed. The measured and theoretical monochromatic CT numbers at 40-130 keV were compared. The average difference between the Z eff values of lung (inhale) inserts in the tissue characterization phantom was 81.3% and the average Z eff difference was within 8.4%. The average difference between the Z eff values of the varying concentrations of iodinated contrast medium was within 11.2%. For the varying concentrations of iodinated contrast medium, the differences between the measured and theoretical monochromatic CT values increased with decreasing monochromatic energy. The Z eff and monochromatic CT numbers in the tissue characterization phantom were reasonably accurate. The accuracy of the raw-data-based Z eff values was higher than that of image-based Z eff values in the tissue-equivalent phantom. The accuracy of Z eff values in the contrast medium was in good agreement within the maximum SD found in the iodine concentration range of clinical dynamic CT imaging. Moreover, the optimum monochromatic energy for human tissue and iodinated contrast medium was found to be 70 keV. Advances in knowledge: The accuracy of the Z eff values and monochromatic CT numbers of the contrast medium created by raw-data-based, dual-energy CT could be sufficient in clinical conditions.

A study of effective atomic numbers and electron densities of some vitamins for electron, H, He and C ion interactions

NASA Astrophysics Data System (ADS)

Büyükyıldız, M.

2017-09-01

The radiological properties of some vitamins such as Retinol, Beta-carotene, Riboflavin, Niacin, Niacinamide, Pantothenic acid, Pyridoxine, Pyridoxamine, Pyridoxal, Biotin, Folic acid, Ascorbic acid, Cholecalciferol, Alpha-tocopherol, Gamma-tocopherol, Phylloquinone have been investigated with respect to total electron interaction and some heavy charged particle interaction as means of effective atomic numbers (Z_{eff}) and electron densities (N_{eff}) for the first time. Calculations were performed for total electron interaction and heavy ions such as H, He and C ion interactions in the energy region 10keV-10MeV by using a logarithmic interpolation method. Variations in Z_{eff}'s and N_{eff}'s of given vitamins have been studied according to the energy of electron or heavy charged particles, and significant variations have been observed for all types of interaction in the given energy region. The maximum values of Z_{eff} have been found in the different energy regions for different interactions remarkably and variations in N_{eff} seem approximately to be the same with variation in Z_{eff} for the given vitamins as expected. Z_{eff} values of some vitamins were plotted together and compared with each other for electron, H, He and C interactions and the ratios of Z_{eff}/ < A > have been changed in the range of 0.25-0.36, 0.20-0.36, 0.22-0.35 and 0.20-0.35 for electron, H, He and C interactions, respectively.

Sanitation and water supply coverage thresholds associated with active trachoma: Modeling cross-sectional data from 13 countries

PubMed Central

Boisson, Sophie; Willis, Rebecca; Bakhtiari, Ana; al-Khatib, Tawfik; Amer, Khaled; Batcho, Wilfrid; Courtright, Paul; Dejene, Michael; Goepogui, Andre; Kalua, Khumbo; Kebede, Biruck; Macleod, Colin K.; Madeleine, Kouakou IIunga Marie; Mbofana, Mariamo Saide Abdala; Mpyet, Caleb; Ndjemba, Jean; Olobio, Nicholas; Pavluck, Alexandre L.; Sokana, Oliver; Southisombath, Khamphoua; Taleo, Fasihah

2018-01-01

Background Facial cleanliness and sanitation are postulated to reduce trachoma transmission, but there are no previous data on community-level herd protection thresholds. We characterize associations between active trachoma, access to improved sanitation facilities, and access to improved water sources for the purpose of face washing, with the aim of estimating community-level or herd protection thresholds. Methods and findings We used cluster-sampled Global Trachoma Mapping Project data on 884,850 children aged 1–9 years from 354,990 households in 13 countries. We employed multivariable mixed-effects modified Poisson regression models to assess the relationships between water and sanitation coverage and trachomatous inflammation—follicular (TF). We observed lower TF prevalence among those with household-level access to improved sanitation (prevalence ratio, PR = 0.87; 95%CI: 0.83–0.91), and household-level access to an improved washing water source in the residence/yard (PR = 0.81; 95%CI: 0.75–0.88). Controlling for household-level water and latrine access, we found evidence of community-level protection against TF for children living in communities with high sanitation coverage (PR80–90% = 0.87; 95%CI: 0.73–1.02; PR90–100% = 0.76; 95%CI: 0.67–0.85). Community sanitation coverage levels greater than 80% were associated with herd protection against TF (PR = 0.77; 95%CI: 0.62–0.97)—that is, lower TF in individuals whose households lacked individual sanitation but who lived in communities with high sanitation coverage. For community-level water coverage, there was no apparent threshold, although we observed lower TF among several of the higher deciles of community-level water coverage. Conclusions Our study provides insights into the community water and sanitation coverage levels that might be required to best control trachoma. Our results suggest access to adequate water and sanitation can be important components in working towards the 2020 target of eliminating trachoma as a public health problem. PMID:29357365

Adult perceptions of dental fluorosis and select dental conditions-an Asian perspective.

PubMed

Nair, Rahul; Chuang, Janice Cheah Ping; Lee, Pauline Shih Jia; Leo, Song Jie; Yang, Naomi QiYue; Yee, Robert; Tong, Huei Jinn

2016-04-01

To compare lay people's perceptions with regard to various levels of dental fluorosis and select dental defects versus normal dentition. Adults rated digitally created photographs made showing lips (without retraction) and teeth depicting the following conditions: no apparent aesthetic defects (normal, Thylstrup- Fejerskov score 0 - TF0), 6 levels of fluorosis (TF1-6), carious lesions (two cavitated and one noncavitated), malocclusions (Class II, Class III, anterior open bite and greater spacing), extrinsic staining and an incisal chip. The photographs were displayed on colour-calibrated iPads(™) . Participants used a self-administered questionnaire to rate their perceptions on (Item 1) how normal teeth were, (Item 2) how attractive the teeth were, (Item 3) need to seek correction of teeth, (Item 4) how well the person took care of their teeth and (Item 5) whether the person was born like this. Data from Item 5 were excluded due to low reliability. Ratings for Item 1 showed that TF1-4 was similar or significantly better than TF0. For Item 2, TF1 and TF4 were significantly better than TF0, with TF2 and TF3 being similar. For Item 3, there was significantly lower need to seek correction with TF2 and TF4 versus TF0, whereas TF1 and TF3 were similar to TF0. TF5 and TF6 were rated significantly lower than TF0 for Item 1 and Item 2, and significantly higher rating for Item 3 (need to seek correction). Ratings for Item 4 were similar, with TF1, TF2 and TF4 being rated significantly higher than TF0, and TF5 and TF6 being rated lower. Cavitated caries and staining were generally perceived as being significantly less favourable than TF6, with higher need to seek correction as well. Noncavitated carious lesion and incisal chip were rated similar to TF0. Cavitated carious lesions were rated aesthetically similar or significantly worse than TF0 and TF6. Severe fluorosis (TF5 and 6) was perceived to be less aesthetically pleasing and received higher ratings for need to seek correction than normal teeth. Mild-to-moderate fluorosis (TF1-4) showed similar or better aesthetic perceptions and similar or lower need to seek correction, when compared to normal teeth (TF0). Easily visible cavitated dental caries was rated worse than teeth with severe fluorosis (TF6) and normal teeth (TF0). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circumferential distortion modeling of the TF30-P-3 compression system

NASA Technical Reports Server (NTRS)

Mazzawy, R. S.; Banks, G. A.

1977-01-01

Circumferential inlet pressure and temperature distortion testing of the TF30 P-3 turbofan engine was conducted. The compressor system at the test conditions run was modelled according to a multiple segment parallel compressor model. Aspects of engine operation and distortion configuration modelled include the effects of compressor bleeds, relative pressure-temperature distortion alignment and circumferential distortion extent. Model predictions for limiting distortion amplitudes and flow distributions within the compression system were compared with test results in order to evaluate predicted trends. Relatively good agreement was obtained. The model also identified the low pressure compressor as the stall-initiating component, which was in agreement with the data.

Radical-scavenging abilities and antioxidant properties of theaflavins and their gallate esters in H2O2-mediated oxidative damage system in the HPF-1 cells.

PubMed

Yang, Ziyin; Jie, Guoliang; Dong, Fang; Xu, Yi; Watanabe, Naoharu; Tu, Youying

2008-08-01

The antioxidant properties of theaflavins and their gallate esters, namely theaflavin (TF1), theaflavin-3(3')-gallate (TF2) and theaflavin-3,3'-digallate (TF3) were investigated by comparing with epigallocatechin gallate (EGCG). The order of hydroxyl radicals-scavenging ability was TF3>TF2>TF1>EGCG. The order of 2,2-diphenyl-1-picrylhydrazyl scavenging ability was TF3>TF2>EGCG>TF1. TF1, TF2, and TF3 showed more effective effects than EGCG in protection against H2O2-mediated damage in HPF-1 cells. TF2 was the most potent accelerant of HPF-1 cell proliferation. TF1, TF2 and TF3 suppressed the accumulation of intracellular reactive species in H2O2-mediated damage HPF-1 cells. Pre-treated for 2h and eliminated from the cells, TF1 and TF3 still showed protective effects against H2O2-mediated damage in HPF-1 cells. This suggests that the protective effects of TF1 and TF3 on oxidative damage HPF-1 cells may be responsible for other mechanisms, rather than only scavenging the already formed reactive species. It remains to be determined whether TF1 and TF3 improved the normal HPF-1 cell resistive abilities toward radical-damage in pre-treatment. Further studies of the effects of theaflavins on some enzymes or signal transduction in the normal HPF-1 cells are underway.

Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development

PubMed Central

Kazemian, Majid; Pham, Hannah; Wolfe, Scot A.; Brodsky, Michael H.; Sinha, Saurabh

2013-01-01

Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein–protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action. PMID:23847101

Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development.

PubMed

Kazemian, Majid; Pham, Hannah; Wolfe, Scot A; Brodsky, Michael H; Sinha, Saurabh

2013-09-01

Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein-protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action.

Modulation of transferrin receptor mRNA by transferrin-gallium in human myeloid HL60 and lymphoid CCRF-CEM leukaemic cells.

PubMed Central

Ul-Haq, R; Chitambar, C R

1993-01-01

Gallium binds to the iron transport protein transferrin (Tf), is incorporated into cells through transferrin receptors (TfR) and inhibits iron-dependent DNA synthesis. Since cellular TfR expression is tightly regulated by the availability of iron, we investigated the effects of transferrin-gallium (Tf-Ga) on TfR mRNA levels in myeloid HL60 and lymphoid CCRF-CEM cells. In HL60 cells, Tf-Ga increased TfR mRNA levels in a dose-dependent fashion. This increase in TfR mRNA was blocked by Tf-Fe and by cycloheximide. Analysis of the rate of mRNA decay in the presence of actinomycin D revealed that the half-life of TfR mRNA was increased in HL60 cells incubated with Tf-Ga. The rate of transcription of TfR mRNA was not increased by Tf-Ga. In contrast with HL60 cells, CCRF-CEM cells displayed a decrease in the level of TfR mRNA after incubation with Tf-Ga. Tf-Ga inhibited iron uptake in both HL60 and CCRF-CEM cells but increased the level of TfR mRNA only in HL60 cells, suggesting that the Tf-Ga induction of TfR mRNA was not solely due to inhibition of cellular iron uptake. At growth-inhibitory concentrations, Tf-Ga increased the TfR mRNA level in HL60 cells but decreased it in CCRF-CEM cells. Our studies suggest that in HL60 cells, gallium regulates TfR expression at the post-transcriptional level by mechanisms which require de novo protein synthesis and involve interaction with iron. The divergent effects of Tf-Ga on TfR mRNA in myeloid HL60 and lymphoid CCRF-CEM cells suggest that differences exist in the regulation of TfR expression between these two cell types. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8379943

Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ.

PubMed

Kim, Jinah; Taube, Janis M; McCalmont, Timothy H; Glusac, Earl J

2011-10-01

It is often challenging to reliably assess the number of lesional melanocytes in intraepidermal melanocytic proliferations involving sun-damaged skin. Therefore, dermatopathologists routinely use immunostains to help differentiate melanocytes from surrounding keratinocytes. Forty-three cases of solar lentigo or melanoma in situ (of the lentigo maligna type) were retrospectively chosen (20 melanomas in situ and 23 solar lentigo). Microphthalmia transcription factor (MiTF), HMB-45, Melan-A and Mel-5 immunostains were performed with an Azure blue counterstain, and the mean melanocyte counts were calculated within a 1-mm segment of epidermis. In solar lentigines, the mean melanocyte counts were 27 (MiTF), 23 (HMB-45 and Mel-5) and 41 (Melan-A), as compared to hematoxylin and eosin (H&E) (25). In melanoma in situ, the mean melanocyte counts were 112 (MiTF), 149 (Melan-A), 111 (HMB-45) and 80 (Mel-5), as compared to H&E (109). These results show that Melan-A significantly overestimates the density of melanocytes within dermatoheliotic skin. Compared to other tested stains, nuclear staining MiTF allowed greater distinction of melanocytes from keratinocytes with melanized cytoplasm. These findings indicate that MiTF is a superior marker for quantification of melanocytes in the evaluation of subtle intraepidermal melanocytic proliferations and in the differential diagnosis of solar lentigo. Copyright © 2011 John Wiley & Sons A/S.

Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol.

PubMed

Kaur, Gurjeet; Roberti, Marinella; Raul, Francis; Pendurthi, Usha R

2007-01-01

Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction.

Estimation of Theaflavins (TF) and Thearubigins (TR) Ratio in Black Tea Liquor Using Electronic Vision System

NASA Astrophysics Data System (ADS)

Akuli, Amitava; Pal, Abhra; Ghosh, Arunangshu; Bhattacharyya, Nabarun; Bandhopadhyya, Rajib; Tamuly, Pradip; Gogoi, Nagen

2011-09-01

Quality of black tea is generally assessed using organoleptic tests by professional tea tasters. They determine the quality of black tea based on its appearance (in dry condition and during liquor formation), aroma and taste. Variation in the above parameters is actually contributed by a number of chemical compounds like, Theaflavins (TF), Thearubigins (TR), Caffeine, Linalool, Geraniol etc. Among the above, TF and TR are the most important chemical compounds, which actually contribute to the formation of taste, colour and brightness in tea liquor. Estimation of TF and TR in black tea is generally done using a spectrophotometer instrument. But, the analysis technique undergoes a rigorous and time consuming effort for sample preparation; also the operation of costly spectrophotometer requires expert manpower. To overcome above problems an Electronic Vision System based on digital image processing technique has been developed. The system is faster, low cost, repeatable and can estimate the amount of TF and TR ratio for black tea liquor with accuracy. The data analysis is done using Principal Component Analysis (PCA), Multiple Linear Regression (MLR) and Multiple Discriminate Analysis (MDA). A correlation has been established between colour of tea liquor images and TF, TR ratio. This paper describes the newly developed E-Vision system, experimental methods, data analysis algorithms and finally, the performance of the E-Vision System as compared to the results of traditional spectrophotometer.

Kinetics of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 ATPase.

PubMed

Rögner, M; Gräber, P

1986-09-01

The rate of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 was measured as a function of the ATP concentration in the presence of inhibitors [ADP, Pi and 3'-O-(1-naphthoyl)ATP]. ATP hydrolysis can be described by Michaelis-Menten kinetics with Km(TF1) = 390 microM and Km (TF0F1) = 180 microM. The inhibition constants are for ADP Ki(TF1) = 20 microM and Ki(TF0F1) = 100 microM, for 3'-O-(1-naphthoyl)ATP Ki(TF1) = 150 microM and Ki(TF0F1) = 3 microM, and for Pi Ki(TF1) = 60 mM. From these results it is concluded that upon binding of TF0 to TF1 the mechanism of ATP hydrolysis catalyzed by TF1 is not changed qualitatively; however, the kinetic constants differ quantitatively.

Carbohydrates and activity of natural and recombinant tissue factor.

PubMed

Krudysz-Amblo, Jolanta; Jennings, Mark E; Mann, Kenneth G; Butenas, Saulius

2010-01-29

The effect of glycosylation on tissue factor (TF) activity was evaluated, and site-specific glycosylation of full-length recombinant TF (rTF) and that of natural TF from human placenta (pTF) were studied by liquid chromatography-tandem mass spectrometry. The amidolytic activity of the TF.factor VIIa (FVIIa) complex toward a fluorogenic substrate showed that the catalytic efficiency (V(max)) of the complex increased in the order rTF(1-243) (Escherichia coli) < rTF(1-263) (Sf9 insect cells) < pTF for the glycosylated and deglycosylated forms. Substrate hydrolysis was unaltered by deglycosylation. In FXase, the K(m) of FX for rTF(1-263)-FVIIa remained unchanged after deglycosylation, whereas the k(cat) decreased slightly. A pronounced decrease, 4-fold, in k(cat) was observed for pTF.FVIIa upon deglycosylation, whereas the K(m) was minimally altered. The parameters of FX activation by both rTF(1-263D)-FVIIa and pTF(D)-FVIIa were identical and similar to those for rTF(1-243)-FVIIa. In conclusion, carbohydrates significantly influence the activity of TF proteins. Carbohydrate analysis revealed glycosylation on asparagines 11, 124, and 137 in both rTF(1-263) and pTF. The carbohydrates of rTF(1-263) contain high mannose, hybrid, and fucosylated glycans. Natural pTF contains no high mannose glycans but is modified with hybrid, highly fucosylated, and sialylated sugars.

Evidence for two transferrin loci in the Salmo trutta genome.

PubMed

Rozman, T; Dovc, P; Marić, S; Kokalj-Vokac, N; Erjavec-Skerget, A; Rab, P; Snoj, A

2008-12-01

To determine the organization of transferrin (TF) locus in the Salmo trutta genome, partial DNA and cDNA sequencing, fluorescent in situ hybridization (FISH) and Salmo salar BAC analysis were performed. TF expression levels and copy number prediction were assessed using real-time PCR. In addition to two previously reported DNA TF variant sequences of S. trutta and Salmo marmoratus (TF1), two novel variant sequences (TF2) were revealed in both species. Variant-specific sequence tags, characterizing two variants for each TF type (TF1 and TF2), were identified in genomic clones from each of the F1 hybrids between S. trutta and S. marmoratus. These clearly documented double heterozygote status at the TF loci. The real-time PCR data showed that each of the two TF types (TF1 and TF2) existed in one copy only and that the transcription of TF2 was considerably lower compared with TF1. Using FISH, hybridization signals were observed on two medium-sized acrocentric chromosomes of S. trutta karyotype. A TF type-specific PCR followed by a restriction analysis revealed the presence of two TF loci in the majority of analysed BAC clones. It was concluded that the TF gene is duplicated in the genome of S. trutta, and that the two TF loci are located adjacent to one another on the same chromosome. The differing transcription levels of TF1 and TF2 appear to depend on the corresponding promoter activity, which at least for TF2 seems to vary between different Salmo congeners.

Comparison of canal transportation and centering ability of twisted files, Pathfile-ProTaper system, and stainless steel hand K-files by using computed tomography.

PubMed

Gergi, Richard; Rjeily, Joe Abou; Sader, Joseph; Naaman, Alfred

2010-05-01

The purpose of this study was to compare canal transportation and centering ability of 2 rotary nickel-titanium (NiTi) systems (Twisted Files [TF] and Pathfile-ProTaper [PP]) with conventional stainless steel K-files. Ninety root canals with severe curvature and short radius were selected. Canals were divided randomly into 3 groups of 30 each. After preparation with TF, PP, and stainless steel files, the amount of transportation that occurred was assessed by using computed tomography. Three sections from apical, mid-root, and coronal levels of the canal were recorded. Amount of transportation and centering ability were assessed. The 3 groups were statistically compared with analysis of variance and Tukey honestly significant difference test. Less transportation and better centering ability occurred with TF rotary instruments (P < .0001). K-files showed the highest transportation followed by PP system. PP system showed significant transportation when compared with TF (P < .0001). The TF system was found to be the best for all variables measured in this study. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

PubMed

Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

2016-06-24

Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

Signatures of a hidden cosmic microwave background.

PubMed

Jaeckel, Joerg; Redondo, Javier; Ringwald, Andreas

2008-09-26

If there is a light Abelian gauge boson gamma' in the hidden sector its kinetic mixing with the photon can produce a hidden cosmic microwave background (HCMB). For meV masses, resonant oscillations gamma<-->gamma' happen after big bang nucleosynthesis (BBN) but before CMB decoupling, increasing the effective number of neutrinos Nnu(eff) and the baryon to photon ratio, and distorting the CMB blackbody spectrum. The agreement between BBN and CMB data provides new constraints. However, including Lyman-alpha data, Nnu(eff) > 3 is preferred. It is tempting to attribute this effect to the HCMB. The interesting parameter range will be tested in upcoming laboratory experiments.

Study of impurity effects on CFETR steady-state scenario by self-consistent integrated modeling

NASA Astrophysics Data System (ADS)

Shi, Nan; Chan, Vincent S.; Jian, Xiang; Li, Guoqiang; Chen, Jiale; Gao, Xiang; Shi, Shengyu; Kong, Defeng; Liu, Xiaoju; Mao, Shifeng; Xu, Guoliang

2017-12-01

Impurity effects on fusion performance of China fusion engineering test reactor (CFETR) due to extrinsic seeding are investigated. An integrated 1.5D modeling workflow evolves plasma equilibrium and all transport channels to steady state. The one modeling framework for integrated tasks framework is used to couple the transport solver, MHD equilibrium solver, and source and sink calculations. A self-consistent impurity profile constructed using a steady-state background plasma, which satisfies quasi-neutrality and true steady state, is presented for the first time. Studies are performed based on an optimized fully non-inductive scenario with varying concentrations of Argon (Ar) seeding. It is found that fusion performance improves before dropping off with increasing {{Z}\\text{eff}} , while the confinement remains at high level. Further analysis of transport for these plasmas shows that low-k ion temperature gradient modes dominate the turbulence. The decrease in linear growth rate and resultant fluxes of all channels with increasing {{Z}\\text{eff}} can be traced to impurity profile change by transport. The improvement in confinement levels off at higher {{Z}\\text{eff}} . Over the regime of study there is a competition between the suppressed transport and increasing radiation that leads to a peak in the fusion performance at {{Z}\\text{eff}} (~2.78 for CFETR). Extrinsic impurity seeding to control divertor heat load will need to be optimized around this value for best fusion performance.

European Scientific Notes. Volume 39, Number 2.

DTIC Science & Technology

1985-02-01

activated guinea pig perito- laboratory facilities are excellent, as neal macrophages and of normal alveolar are the research scientists in Thoenen’s...macrophages of the guinea pig , TF department. There is close collaboration isolated from human lymphocytes seems to with the Max Planck Institute of Bio...representative of the use in production of prototype software. Commerce Department for industrial Included are cross-reference tools, assessment in

The Model Analyst’s Toolkit: Scientific Model Development, Analysis, and Validation

DTIC Science & Technology

2013-11-20

Granger causality F-test validation 3.1.2. Dynamic time warping for uneven temporal relationships Many causal relationships are imperfectly...mapping for dynamic feedback models Granger causality and DTW can identify causal relationships and consider complex temporal factors. However, many ...variant of the tf-idf algorithm (Manning, Raghavan, Schutze et al., 2008), typically used in search engines, to “score” features. The (-log tf) in

Cacao seeds are a "Super Fruit": A comparative analysis of various fruit powders and products

PubMed Central

2011-01-01

Background Numerous popular media sources have developed lists of "Super Foods" and, more recently, "Super Fruits". Such distinctions often are based on the antioxidant capacity and content of naturally occurring compounds such as polyphenols within those whole fruits or juices of the fruit which may be linked to potential health benefits. Cocoa powder and chocolate are made from an extract of the seeds of the fruit of the Theobroma cacao tree. In this study, we compared cocoa powder and cocoa products to powders and juices derived from fruits commonly considered "Super Fruits". Results Various fruit powders and retail fruit products were obtained and analyzed for antioxidant capacity (ORAC (μM TE/g)), total polyphenol content (TP (mg/g)), and total flavanol content (TF (mg/g)). Among the various powders that were tested, cocoa powder was the most concentrated source of ORAC and TF. Similarly, dark chocolate was a significantly more concentrated source of ORAC and TF than the fruit juices. Conclusions Cocoa powder and dark chocolate had equivalent or significantly greater ORAC, TP, and TF values compared to the other fruit powders and juices tested, respectively. Cacao seeds thus provide nutritive value beyond that derived from their macronutrient composition and appear to meet the popular media's definition of a "Super Fruit". PMID:21299842

Associations of TF Gene Polymorphisms with the Risk of Ischemic Stroke.

PubMed

Cai, Yi; Wu, Shaofang; Zeng, Chaosheng; Su, Qingjie; Zhou, Jingxia; Li, Pengxiang; Dai, Mingming; Wang, Desheng; Long, Faqing

2018-06-23

Ischemic stroke (IS) is the main cause of mortality and disability in China; thus, this study aimed to examine the association between six variants and their haplotypes within the transferrin (TF) gene and the risk of IS in the Southern Chinese Han population. Genotyping was performed using the Sequenom MassARRAY platform for 249 IS patients and 249 age- and sex-matched controls. The association between polymorphisms and IS risk was tested by Chi squared test and haplotype and stratification analysis. Odds ratios (ORs) and confidence intervals (CIs) were estimated by unconditional logistic regression analysis. The results of genetic model analyses indicated that the two SNPs (rs1880669 and rs2692695) were associated with decreased IS risk under the co-dominant, dominant, and additive models. Additionally, rs4525863 was also associated with decreased IS risk both under the dominant and additive models in males. Moreover, the CG haplotype of TF (rs1880669 and rs2692695) was significantly associated with a decreased risk of IS in the total population and males. Our findings suggested that polymorphisms (rs4525863, rs1880669, and rs2692695) of the TF gene might be a protective factor for IS in Southern Chinese Han population. Further large prospective studies are required to confirm these findings.

Cacao seeds are a "Super Fruit": A comparative analysis of various fruit powders and products.

PubMed

Crozier, Stephen J; Preston, Amy G; Hurst, Jeffrey W; Payne, Mark J; Mann, Julie; Hainly, Larry; Miller, Debra L

2011-02-07

Numerous popular media sources have developed lists of "Super Foods" and, more recently, "Super Fruits". Such distinctions often are based on the antioxidant capacity and content of naturally occurring compounds such as polyphenols within those whole fruits or juices of the fruit which may be linked to potential health benefits. Cocoa powder and chocolate are made from an extract of the seeds of the fruit of the Theobroma cacao tree. In this study, we compared cocoa powder and cocoa products to powders and juices derived from fruits commonly considered "Super Fruits". Various fruit powders and retail fruit products were obtained and analyzed for antioxidant capacity (ORAC (μM TE/g)), total polyphenol content (TP (mg/g)), and total flavanol content (TF (mg/g)). Among the various powders that were tested, cocoa powder was the most concentrated source of ORAC and TF. Similarly, dark chocolate was a significantly more concentrated source of ORAC and TF than the fruit juices. Cocoa powder and dark chocolate had equivalent or significantly greater ORAC, TP, and TF values compared to the other fruit powders and juices tested, respectively. Cacao seeds thus provide nutritive value beyond that derived from their macronutrient composition and appear to meet the popular media's definition of a "Super Fruit".

Fabrication of transferrin functionalized gold nanoclusters/graphene oxide nanocomposite for turn-on near-infrared fluorescent bioimaging of cancer cells and small animals.

PubMed

Wang, Yong; Chen, Jia-Tong; Yan, Xiu-Ping

2013-02-19

Transferrin (Tf)-functionalized gold nanoclusters (Tf-AuNCs)/graphene oxide (GO) nanocomposite (Tf-AuNCs/GO) was fabricated as a turn-on near-infrared (NIR) fluorescent probe for bioimaging cancer cells and small animals. A one-step approach was developed to prepare Tf-AuNCs via a biomineralization process with Tf as the template. Tf acted not only as a stabilizer and a reducer but also as a functional ligand for targeting the transferrin receptor (TfR). The prepared Tf-AuNCs gave intense NIR fluorescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The assembly of Tf-AuNCs and GO gave the Tf-AuNCs/GO nanocomposite, a turn-on NIR fluorescent probe with negligible background fluorescence due to the super fluorescence quenching property of GO. The NIR fluorescence of the Tf-AuNCs/GO nanocomposite was effectively restored in the presence of TfR, due to the specific interaction between Tf and TfR and the competition of TfR with the GO for the Tf in Tf-AuNCs/GO composite. The developed turn-on NIR fluorescence probe offered excellent water solubility, stability, and biocompatibility, and exhibited high specificity to TfR with negligible cytotoxicity. The probe was successfully applied for turn-on fluorescent bioimaging of cancer cells and small animals.

The growth temperature and measurement temperature dependences of soft magnetic properties and effective damping parameter of (FeCo)-Al alloy thin films

NASA Astrophysics Data System (ADS)

Ariake, Yusuke; Wu, Shuang; Kanada, Isao; Mewes, Tim; Tanaka, Yoshitomo; Mankey, Gary; Mewes, Claudia; Suzuki, Takao

2018-05-01

The soft magnetic properties and effective damping parameters of Fe73Co25Al2 alloy thin films are discussed. The effective damping parameter αeff measured by ferromagnetic resonance for the 10 nm-thick sample is nearly constant (≈0.004 ± 0.0008) for a growth temperature Ts from ambient to 200 °C, and then tends to decrease for higher temperatures and αeff is 0.002 ± 0.0004 at Ts = 300 °C. For the 80 nm-thick sample, the αeff seems to increase with Ts from αeff = 0.001 ± 0.0002 at Ts = ambient to αeff = 0.002 ± 0.0004. The αeff is found nearly constant (αeff = 0.004 ± 0.0008) over a temperature range from 10 to 300 K for the 10 nm films with the different Ts (ambient, 100 and 200 °C). Together with an increasing non-linearity of the frequency dependence of the linewidth at low Ts, extrinsic contributions such as two-magnon scattering dominate the observed temperature dependence of effective damping and linewidth.

Direct experimental observation of the molecular J eff=3/2 ground state in the lacunar spinel GaTa 4Se 8

DOE PAGES

Jeong, Min Yong; Chang, Seo Hyoung; Kim, Beom Hyun; ...

2017-10-04

Strong spin-orbit coupling lifts the degeneracy of t 2g orbitals in 5d transition-metal systems, leaving a Kramers doublet and quartet with effective angular momentum of J eff = 1/2 and 3/2, respectively. These spin-orbit entangled states can host exotic quantum phases such as topological Mott state, unconventional superconductivity, and quantum spin liquid. The lacunar spinel GaTa 4Se 8 was theoretically predicted to form the molecular J eff = 3/2 ground state. Experimental verification of its existence is an important first step to exploring the consequences of the J eff = 3/2 state. Here, we report direct experimental evidence of themore » J eff = 3/2 state in GaTa 4Se 8 by means of excitation spectra of resonant inelastic x-rays scattering at the Ta L 3 and L 2 edges. In conclusion, we found that the excitations involving the J eff = 1/2 molecular orbital were absent only at the Ta L 2 edge, manifesting the realization of the molecular J eff = 3/2 ground state in GaTa 4Se 8.« less

Direct experimental observation of the molecular J eff=3/2 ground state in the lacunar spinel GaTa 4Se 8

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

Jeong, Min Yong; Chang, Seo Hyoung; Kim, Beom Hyun

Strong spin-orbit coupling lifts the degeneracy of t 2g orbitals in 5d transition-metal systems, leaving a Kramers doublet and quartet with effective angular momentum of J eff = 1/2 and 3/2, respectively. These spin-orbit entangled states can host exotic quantum phases such as topological Mott state, unconventional superconductivity, and quantum spin liquid. The lacunar spinel GaTa 4Se 8 was theoretically predicted to form the molecular J eff = 3/2 ground state. Experimental verification of its existence is an important first step to exploring the consequences of the J eff = 3/2 state. Here, we report direct experimental evidence of themore » J eff = 3/2 state in GaTa 4Se 8 by means of excitation spectra of resonant inelastic x-rays scattering at the Ta L 3 and L 2 edges. In conclusion, we found that the excitations involving the J eff = 1/2 molecular orbital were absent only at the Ta L 2 edge, manifesting the realization of the molecular J eff = 3/2 ground state in GaTa 4Se 8.« less

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

Margaret A. Marshall; John D. Bess; Yevgeniy Rozhikhin

In the early 1970s Dr. John T. Mihalczo (team leader), J.J. Lynn, and J.R. Taylor performed experiments at the Oak Ridge Critical Experiments Facility (ORCEF) with highly enriched uranium (HEU) metal (called Oak Ridge Alloy or ORALLOY) in an attempt to recreate GODIVA I results with greater accuracy than those performed at Los Alamos National Laboratory in the 1950s (HEU-MET-FAST-001). The purpose of the Oak Ridge ORALLOY Sphere (ORSphere) experiments was to estimate the unreflected and unmoderated critical mass of an idealized sphere of uranium metal corrected to a density, purity, and enrichment such that it could be compared withmore » the GODIVA I experiments[1]. Part of the experimental series was the measurement of the delayed neutron fraction, ßeff, using time correlation measurements and using the central void reactivity measurement. The time correlations measurements were rejected by the experimenter. The measurements using the central void reactivity measurement yielded a ßeff value of 0.00657, which agrees well with the value measured with GODIVA I (0.0066). This measurement is evaluated, found to be acceptable, and discussed in extensive detail in “ORSphere: Physics Measurements for Bare, HEU(93.2) Metal Sphere”[2]. In order to determine the delayed neutron fraction using the central void reactivity delayed neutron parameters must be used. The experimenter utilized the delayed neutron parameters set forth by Keepin, Wimment, and Zeigler[3]. If the derivation of the ßeff is repeated with different delayed neutron parameters from various modern nuclear data sets the resulting values vary greatly from the expected results.« less

Fatigue Lives of Specimens Representing Critical Locations in Mirage III Spars under Australian and Swiss Test Spectra,

DTIC Science & Technology

1985-02-01

TF16 103 TFI 1 143 TV21 183 TFI I 24 FI-7 64 T-21 104 THI7 144 TF4 184 TFI7 25 T1I 65 T122 105 T-18 145 TFI5 185 TF24 26 TF13 66 Tt-I9 106 T1:5 [ 146...4.990 9GB I)H 2 2 4 6 7.990 161E-2 DH -2 I S.046 N.910 0.079 131) PH 2.2 4 6 10.990 126 I)lf 20 II 12.564 7EB D H 1.8 4-6 12.643 9BB DH I x 4-6 2.703...13.990 0-075 IOJA DH IŜ 46 6 7,064 7F D H 1-4 4.6 29,185 12 D DH 1-4 4.6 52.292 43,230 0148 I IJB DH i 4 4.6 52.953 Swiss sequeLce 19E SH 2Ŗ 9.3

Identification and expression of the WRKY transcription factors of Carica papaya in response to abiotic and biotic stresses.

PubMed

Pan, Lin-Jie; Jiang, Ling

2014-03-01

The WRKY transcription factor (TF) plays a very important role in the response of plants to various abiotic and biotic stresses. A local papaya database was built according to the GenBank expressed sequence tag database using the BioEdit software. Fifty-two coding sequences of Carica papaya WRKY TFs were predicted using the tBLASTn tool. The phylogenetic tree of the WRKY proteins was classified. The expression profiles of 13 selected C. papaya WRKY TF genes under stress induction were constructed by quantitative real-time polymerase chain reaction. The expression levels of these WRKY genes in response to 3 abiotic and 2 biotic stresses were evaluated. TF807.3 and TF72.14 are upregulated by low temperature; TF807.3, TF43.76, TF12.199 and TF12.62 are involved in the response to drought stress; TF9.35, TF18.51, TF72.14 and TF12.199 is involved in response to wound; TF12.199, TF807.3, TF21.156 and TF18.51 was induced by PRSV pathogen; TF72.14 and TF43.76 are upregulated by SA. The regulated expression levels of above eight genes normalized against housekeeping gene actin were significant at probability of 0.01 levels. These WRKY TFs could be related to corresponding stress resistance and selected as the candidate genes, especially, the two genes TF807.3 and TF12.199, which were regulated notably by four stresses respectively. This study may provide useful information and candidate genes for the development of transgenic stress tolerant papaya varieties.

Macrophyte species distribution, indices of biotic integrity and sampling intensity in isolated Florida marshes

EPA Science Inventory

This study tested macrophyte condition metrics calculated after decreasing the effort and area of sampling by 33% to 66%, as tested in 74 emergent isolated wetlands. Four belted transects from wetland edge to center were established and rooted macrophytes were identified. The eff...

Modeling the near-ultraviolet band of GK stars. III. Dependence on abundance pattern

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

Short, C. Ian; Campbell, Eamonn A., E-mail: ishort@ap.smu.ca

2013-06-01

We extend the grid of non-LTE (NLTE) models presented in Paper II to explore variations in abundance pattern in two ways: (1) the adoption of the Asplund et al. (GASS10) abundances, (2) for stars of metallicity, [M/H], of –0.5, the adoption of a non-solar enhancement of α-elements by +0.3 dex. Moreover, our grid of synthetic spectral energy distributions (SEDs) is interpolated to a finer numerical resolution in both T {sub eff} (ΔT {sub eff} = 25 K) and log g (Δlog g = 0.25). We compare the values of T {sub eff} and log g inferred from fitting LTE andmore » NLTE SEDs to observed SEDs throughout the entire visible band, and in an ad hoc 'blue' band. We compare our spectrophotometrically derived T {sub eff} values to a variety of T {sub eff} calibrations, including more empirical ones, drawn from the literature. For stars of solar metallicity, we find that the adoption of the GASS10 abundances lowers the inferred T {sub eff} value by 25-50 K for late-type giants, and NLTE models computed with the GASS10 abundances give T {sub eff} results that are marginally in better agreement with other T {sub eff} calibrations. For stars of [M/H] = –0.5 there is marginal evidence that adoption of α-enhancement further lowers the derived T {sub eff} value by 50 K. Stellar parameters inferred from fitting NLTE models to SEDs are more dependent than LTE models on the wavelength region being fitted, and we find that the effect depends on how heavily line blanketed the fitting region is, whether the fitting region is to the blue of the Wien peak of the star's SED, or both.« less

Variation in fluorosis and caries experience among Lithuanian 12 year olds exposed to more than 1 ppm F in tap water.

PubMed

Narbutaitė, Julija; Virtanen, Jorma I; Vehkalahti, Miira M

2016-05-01

The aim of the present study was to analyze caries experience in relation to the occurrence of fluorosis in 12 year olds in a natural fluoride area. This cross-sectional study was conducted among 12-year-old lifetime residents (n = 301) of Klaipeda, Lithuania, where the natural fluoride content is 1.7-2.2 ppm F. Data collection included a clinical dental examination and an inquiry about toothbrushing habits. Dental caries was diagnosed according to the World Health Organization criteria and described in terms of decayed, missing, and filled teeth (DMFT)/decayed, missing and filled surfaces (DMFS) indices and decayed, filled surfaces (DFS) on selected proximal surfaces. Dental fluorosis was diagnosed according to the Thylstrup-Fejerskov (TF) index and categorized as none (TF = 0), mild (TF = 1-2), moderate (TF = 3-7), or severe (TF = 8-9). The χ(2)-, Kruskal-Wallis, and Mann-Whitney tests, Pearson's correlation, and linear regression served for statistical analyses. A total of 34% of the 12 year olds studied had no signs of fluorosis, while the rest had mild (42%) or moderate (24%) fluorosis. Caries experience was negatively related to the presence of fluorosis. When present (TF > 0), the mean DMFT was 1.8 (standard deviation [SD]: 1.7) versus 2.6 (SD: 2.3) in the absence of fluorosis (TF = 0, P = 0.008). The corresponding mean DMFS values were 2.6 (SD: 3.1) versus 3.8 (SD: 4.3, P = 0.014). The presence of fluorosis associates with lesser caries experience in 12-year-old lifetime residents of an area with moderately-elevated natural fluoride. © 2014 Wiley Publishing Asia Pty Ltd.

Enhanced Delivery of Galanin Conjugates to the Brain through Bioengineering of the Anti-Transferrin Receptor Antibody OX26.

PubMed

Thom, George; Burrell, Matthew; Haqqani, Arsalan S; Yogi, Alvaro; Lessard, Etienne; Brunette, Eric; Delaney, Christie; Baumann, Ewa; Callaghan, Deborah; Rodrigo, Natalia; Webster, Carl I; Stanimirovic, Danica B

2018-04-02

The blood-brain barrier (BBB) is a formidable obstacle for brain delivery of therapeutic antibodies. However, antibodies against the transferrin receptor (TfR), enriched in brain endothelial cells, have been developed as delivery carriers of therapeutic cargoes into the brain via a receptor-mediated transcytosis pathway. In vitro and in vivo studies demonstrated that either a low-affinity or monovalent binding of these antibodies to the TfR improves their release on the abluminal side of the BBB and target engagement in brain parenchyma. However, these studies have been performed with mouse-selective TfR antibodies that recognize different TfR epitopes and have varied binding characteristics. In this study, we evaluated serum pharmacokinetics and brain and CSF exposure of the rat TfR-binding antibody OX26 affinity variants, having K D s of 5 nM, 76 nM, 108 nM, and 174 nM, all binding the same epitope in bivalent format. Pharmacodynamic responses were tested in the Hargreaves chronic pain model after conjugation of OX26 affinity variants with the analgesic and antiepileptic peptide, galanin. OX26 variants with affinities of 76 nM and 108 nM showed enhanced brain and cerebrospinal fluid (CSF) exposure and higher potency in the Hargreaves model, compared to a 5 nM affinity variant; lowering affinity to 174 nM resulted in prolonged serum pharmacokinetics, but reduced brain and CSF exposure. The study demonstrates that binding affinity optimization of TfR-binding antibodies could improve their brain and CSF exposure even in the absence of monovalent TfR engagement.

Detection of eQTL modules mediated by activity levels of transcription factors.

PubMed

Sun, Wei; Yu, Tianwei; Li, Ker-Chau

2007-09-01

Studies of gene expression quantitative trait loci (eQTL) in different organisms have shown the existence of eQTL hot spots: each being a small segment of DNA sequence that harbors the eQTL of a large number of genes. Two questions of great interest about eQTL hot spots arise: (1) which gene within the hot spot is responsible for the linkages, i.e. which gene is the quantitative trait gene (QTG)? (2) How does a QTG affect the expression levels of many genes linked to it? Answers to the first question can be offered by available biological evidence or by statistical methods. The second question is harder to address. One simple situation is that the QTG encodes a transcription factor (TF), which regulates the expression of genes linked to it. However, previous results have shown that TFs are not overrepresented in the eQTL hot spots. In this article, we consider the scenario that the propagation of genetic perturbation from a QTG to other linked genes is mediated by the TF activity. We develop a procedure to detect the eQTL modules (eQTL hot spots together with linked genes) that are compatible with this scenario. We first detect 27 eQTL modules from a yeast eQTL data, and estimate TF activity profiles using the method of Yu and Li (2005). Then likelihood ratio tests (LRTs) are conducted to find 760 relationships supporting the scenario of TF activity mediation: (DNA polymorphism --> cis-linked gene --> TF activity --> downstream linked gene). They are organized into 4 eQTL modules: an amino acid synthesis module featuring a cis-linked gene LEU2 and the mediating TF Leu3; a pheromone response module featuring a cis-linked gene GPA1 and the mediating TF Ste12; an energy-source control module featuring two cis-linked genes, GSY2 and HAP1, and the mediating TF Hap1; a mitotic exit module featuring four cis-linked genes, AMN1, CSH1, DEM1 and TOS1, and the mediating TF complex Ace2/Swi5. Gene Ontology is utilized to reveal interesting functional groups of the downstream genes in each module. Our methods are implemented in an R package: eqtl.TF, which includes source codes and relevant data. It can be freely downloaded at http://www.stat.ucla.edu/~sunwei/software.htm. http://www.stat.ucla.edu/~sunwei/yeast_eQTL_TF/supplementary.pdf.

Lawrence Transfer Factor: Transference of Specific Immune Memory by Dialyzable Leukocyte Extract from a CD8+ T Cell Line.

PubMed

Wang, Jason F; Park, Andrew J; Rendini, Tina; Levis, William R

2017-12-01

Lawrence transfer factor (TF) is defined as dialyzable leukocyte extract (DLE) that can transfer antigen-specific cell-mediated immunity from a person testing positive for the antigen in a delayed type hypersensitivity skin test manner to a person negative for the same antigen. A recent article by Myles et al1 has identified a DLE isolated from an established CD8+ T cell line capable of transferring antigen-specific immunity. The DLE contains a portion of the beta chain of the T cell receptor and additional nucleotide and protein factors that are being subjected to further modern biochemical analysis. After months of study that included interviews of TF physician-scientists, we conclude that an antigen-specific TF exists for most, if not all, antigens. By working from a CD8+ T cell line with modern biochemical technology, it should be possible to identify and patent products capable of treating infectious diseases, antigen-responsive cancers, and autoimmune disorders.

The effects of small interfering RNA–targeting tissue factor on an in vitro model of neovascularization

PubMed Central

Peng, Wenyan; Yu, Ying; Li, Tiejun; Zhu, Yuanyuan

2013-01-01

Purpose Tissue factor (TF) plays an important role in neovascularization (NV). This study aimed to determine whether small interfering RNA–targeting TF (TF-siRNA) could knock down TF expression and inhibit cell proliferation, cell migration, and tube formation in an in vitro model of NV. Methods Lipopolysaccharide (LPS) was used to stimulate human umbilical vein endothelial cell (HUVEC) lines to express TF and mimic certain phenotypes of NV in vitro. HUVECs were transfected with TF-siRNAs and control siRNAs using LipofectamineTM 2000. The inhibitory effect of the siRNAs on the expression of TF mRNA and protein was evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and western blot analysis. The effects on the cell viability, migration, and tube formation of siRNA-treated cells were examined by MTT assay, wound-healing assay, and Matrigel-induced capillary tube formation. Results Lipopolysaccharide treatment increased the expression of TF. TF-siRNAs effectively knocked down TF expression, with the most efficient TF-siRNA reducing 78.9% of TF expression. TF protein was also notably curtailed by TF-siRNA. The MTT and wound-healing assays showed that the TF-siRNA substantially inhibited the proliferation and migration of HUVECs. Tube formation was decreased by 47.4% and 59.4% in cells treated with the TF-siRNA and vascular endothelial growth factor–siRNA, respectively, compared with the blank control. Conclusions TF-siRNA can knockdown TF expression and inhibit cell proliferation, migration, and tube formation in vitro. TF-siRNA may provide a novel therapeutic candidate for NV-related diseases. PMID:23805036

Tissue Factor promotes breast cancer stem cell activity in vitro.

PubMed

Shaker, Hudhaifah; Harrison, Hannah; Clarke, Robert; Landberg, Goran; Bundred, Nigel J; Versteeg, Henri H; Kirwan, Cliona C

2017-04-18

Cancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.

Using digital multimedia to improve parents' and children's understanding of clinical trials.

PubMed

Tait, Alan R; Voepel-Lewis, Terri; Levine, Robert

2015-06-01

Data show that many research subjects have difficulty understanding study information using traditional paper consent documents. This study, therefore, was designed to evaluate the effect of an interactive multimedia program on improving parents' and children's understanding of clinical trial concepts and participation. Parents (n=148) and children (n=135) were each randomised to receive information regarding clinical trials using either a traditional paper format (TF) or an interactive iPad program (IP) with inline exercises. Participants' understanding of the information was assessed using semistructured interviews prior to (pretest) and after (post-test) receiving the information. Participants also completed a short survey to assess their perceptions of information delivery and satisfaction with the process. Regardless of the mode of information delivery, all participants demonstrated improved pretest to post-test understanding. While there were no statistical differences in parents' post-test understanding between the TF and IP groups, children in the IP group had significantly greater post-test understanding compared with children in the TF group (11.65 (4.1) vs 8.85 (4.1) (2.8, 1.4, 4.2) 0-18 scale where 18=complete understanding). Furthermore, the IP was found to be significantly 'easier to follow' and 'more effective' in presenting information compared with the TF. Results demonstrated the importance of providing information regarding clinical trial concepts to parents and children. Importantly, the ability of interactive multimedia to improve understanding of clinical trial concepts and satisfaction with information delivery, particularly among children, supports this approach as a novel and effective vehicle for enhancing the informed consent process. 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.

High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development

PubMed Central

Shirotani, Keiro; Futakawa, Satoshi; Nara, Kiyomitsu; Hoshi, Kyoka; Saito, Toshie; Tohyama, Yuriko; Kitazume, Shinobu; Yuasa, Tatsuhiko; Miyajima, Masakazu; Arai, Hajime; Kuno, Atsushi; Narimatsu, Hisashi; Hashimoto, Yasuhiro

2011-01-01

We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin) bound an unique N-acetylglucosamine-terminated N-glycans on “CSF-type” Tf whereas SSA (Sambucus sieboldiana agglutinin) bound α2,6-N-acetylneuraminic acid-terminated N-glycans on “serum-type” Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected “CSF-type” Tf but not “serum-type” Tf whereas SSA-TfAb ELISA detected “serum-type” Tf but not “CSF-type” Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases. PMID:21876827

High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development.

PubMed

Shirotani, Keiro; Futakawa, Satoshi; Nara, Kiyomitsu; Hoshi, Kyoka; Saito, Toshie; Tohyama, Yuriko; Kitazume, Shinobu; Yuasa, Tatsuhiko; Miyajima, Masakazu; Arai, Hajime; Kuno, Atsushi; Narimatsu, Hisashi; Hashimoto, Yasuhiro

2011-01-01

We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin) bound an unique N-acetylglucosamine-terminated N-glycans on "CSF-type" Tf whereas SSA (Sambucus sieboldiana agglutinin) bound α2,6-N-acetylneuraminic acid-terminated N-glycans on "serum-type" Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected "CSF-type" Tf but not "serum-type" Tf whereas SSA-TfAb ELISA detected "serum-type" Tf but not "CSF-type" Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases.

Measurement of pulmonary capillary blood flow in infants by plethysmography.

PubMed Central

Stocks, J; Costeloe, K; Winlove, C P; Godfrey, S

1977-01-01

An accurate method for measuring effective pulmonary capillary blood flow (Qc eff) in infants has been developed with an adaptation of the plethysmographic technique. Measurements were made on 19 preterm. 14 small-for-dates, and 7 fullterm normal infants with a constant volume whole body plethysmograph in which the infant rebreathed nitrous oxide. There was a highly significant correlation between Qc eff and body weight, and this relationship was unaffected by premature delivery or intrauterine growth retardation. Mean Qc eff in preterm, small-for dates, and fullterm infants was 203, 208 and 197 ml min-1 kg-1, respectively, with no significant differences between the groups. A significant negative correlation existed between Qc eff and haematocrit in the preterm infants. There was no relationship between weight standardized Qc eff and postnatal age in any of the groups. With this technique, it was possible to readily recognise the presence of rapid recirculation (indicative of shunting) in several of the infants, suggesting that rebreathing methods for the assessment of Qc eff should not be applied indiscriminately during the neonatal period. By taking care to overcome the potential sources of technical error, it was possible to obtain highly reproducible results of Qc eff in infants over a wider age range than has been previously reported. PMID:838861

Conceptual design of new polychromator on Thomson scattering system to measure Zeff.

PubMed

Lee, Jongha; Oh, Seungtae; Wi, Hanmin; Oh, Youngkook; Yamada, I; Narihara, K; Kawahata, K; Jeon, Jongsu

2012-10-01

To measure the Z(eff) with electron temperature (T(e)) and electron density (n(e)) profiles at the same time and the same position in the KSTAR tokamak, we design a new polychromator for Thomson scattering system that has additional function. The additional function is measuring bremsstrahlung intensity to calculate Z(eff) independent of Thomson signals. For this new polychromator, we design and fabricate a collimation lens set, and interference filter that has center wavelength of 523 nm and 2 nm FWHM. Finally, we change the lenses, detector diodes, and add the bremsstrahlung filter on the KSTAR edge Thomson scattering polychromator. Then this new polychromator was tested by Tungsten light and monochromator.

Isomeric organic semiconductors containing fused-thiophene cores: molecular packing and charge transport.

PubMed

Dang, Dongfeng; Zhou, Pei; Wu, Yong; Xu, Yanzi; Zhi, Ying; Zhu, Weiguo

2018-05-16

Isomeric TF1 and TF2 with highly fused thiophene cores were designed and synthesized here, in which a highly planar molecular structure was obtained for TF1 with the face-to-face sulfur atoms in the lateral region and a twisted molecular backbone was observed for TF2 with the back-to-back sulfur atoms. It is worth noting that different intermolecular interactions dominated in TF1 and TF2 caused by their isomeric thiophene cores, in which strong π-π stacking was achieved for TF1, whereas sulphur-involved nonbonding intermolecular interactions dominated in TF2, leading to the different fluorescence behaviors and also the altered liquid crystalline phases. Finally, typical P-type charge transport behaviors were achieved in both TF1- and TF2-based solution-processed OFETs. Also owing to the much ordered molecular packing in TF1, a higher charge carrier mobility of 3.7 × 10-3 cm2 V-1 s-1 was achieved for TF1-based OFETs compared to TF2-based OFETs.

Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor

PubMed Central

Tang, Haiwang; Ivanciu, Lacramioara; Popescu, Narcis; Peer, Glenn; Hack, Erik; Lupu, Cristina; Taylor, Fletcher B.; Lupu, Florea

2007-01-01

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis. PMID:17640967

Summary of the effects of engine throttle response on airplane formation-flying qualities

NASA Technical Reports Server (NTRS)

Walsh, Kevin R.

1992-01-01

A flight evaluation as conducted to determine the effect of engine throttle response characteristics on precision formation-flying qualities. A variable electronic throttle control system was developed and flight-tested on a TF-104G airplane with a J79-11B engine at the NASA Dryden Flight Research Facility. Ten research flights were flown to evaluate the effects of throttle gain, time delay, and fuel control rate limiting on engine handling qualities during a demanding precision wing formation task. Handling quality effects of lag filters and lead compensation time delays were also evaluated. Data from pilot ratings and comments indicate that throttle control system time delays and rate limits cause significant degradations in handling qualities. Threshold values for satisfactory (level 1) and adequate (level 2) handling qualities of these key variables are presented.

Spectroscopic studies of the interaction mechanisms between mono-caffeoylquinic acids and transferrin

NASA Astrophysics Data System (ADS)

Guan, Yanqing; Dong, Jing; Chen, Shizhong; Liu, Meixian; Wang, Daidong; Zhang, Xiaotian; Wang, Hong; Lin, Zongtao

2017-06-01

Transferrin (Tf) is an important protein responsible for circulating and transporting iron into cytoplasm. Tf can be taken into cells through endocytosis mediated by Tf receptor, which usually overexpresses in cancer cells. The Tf-Tf receptor pathway opens a possible avenue for novel targeted cancer therapy by utilizing Tf-binding active compounds. Among which, anti-cancer active caffeoylquinic acids (CQAs) were recently found to be promising Tf-binders by our group. For better understanding the anti-cancer activities of CQAs, it is important to unveil the binding mechanisms between CQAs and Tf. In this study, the fluorescence quenching, surface plasmon resonance (SPR), circular dichroism (CD) and molecular docking were used to investigate the interactions between CQA and Tf. The results showed that the calculated apparent association constants of interactions between 1-, 3-, 4- and 5-CQA and Tf at 298 K were 7.97 × 105 M- 1, 4.36 × 107 M- 1, 6.58 × 105 M- 1 and 4.42 × 106 M- 1, respectively. The thermodynamic parameters indicated that the interaction between 1-, 3-, 5-CQA and Tf is due to H-bonding, and electrostatic interactions were likely involved in the binding of 4-CQA and Tf. The CD results indicated that bindings of 1-CQA, 4-CQA and 5-CQA with Tf resulted in more stretched β-turn and random coil translated from β-sheet. In contrast, 3-CQA led to more stable a-helix conformation. Molecular docking studies of CQAs with Tf further displayed that CQAs were able to interact with residues near Fe3 + binding site. The spectroscopic studies revealed the action mechanisms, thermodynamics and interacting forces between CQAs and Tf, and thus are helpful for future design and discovery of Tf-binders for targeted cancer therapy applying Tf-Tf receptor pathway.

Soluble tissue factor has unique angiogenic activities that selectively promote migration and differentiation but not proliferation of endothelial cells

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

He Yingbo; Chang Guodong; Zhan Shunli

2008-06-06

The level of circulating tissue factor (TF) is up-regulated in human angiogenesis-related malignancies. However, whether circulating TF has angiogenic activities has not been determined. Soluble TF (sTF) is the main domain of circulating TF. Here, using cell migration, wound healing, and tubule formation assays, human recombinant sTF was found to significantly promote the migration and differentiation of endothelial cells. The stress fiber formation and rearrangement induced by sTF observed through immunofluorescence microscope may be responsible for the stimulatory migration effect of sTF. Nevertheless, sTF had no effects on endothelial cell proliferation. Interestingly, sTF can be internalized by endothelial cells, whichmore » implies a novel mechanism for sTF in angiogenesis. These results suggest that sTF has unique angiogenic activities and may serve as a potential therapeutic target to treat diseases associated with angiogenesis such as cancer and rheumatoid arthritis.« less

Dynamic and Transient Performance of Turbofan/Turboshaft Convertible Engine With Variable Inlet Guide Vanes

NASA Technical Reports Server (NTRS)

McArdle, Jack G.; Barth, Richard L.; Wenzel, Leon M.; Biesiadny, Thomas J.

1996-01-01

A convertible engine called the CEST TF34, using the variable inlet guide vane method of power change, was tested on an outdoor stand at the NASA Lewis Research Center with a waterbrake dynamometer for the shaft load. A new digital electronic system, in conjunction with a modified standard TF34 hydromechanical fuel control, kept engine operation stable and safely within limits. All planned testing was completed successfully. Steady-state performance and acoustic characteristics were reported previously and are referenced. This report presents results of transient and dynamic tests. The transient tests measured engine response to several rapid changes in thrust and torque commands at constant fan (shaft) speed. Limited results from dynamic tests using the pseudorandom binary noise technique are also presented. Performance of the waterbrake dynamometer is discussed in an appendix.

A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

PubMed

Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

2018-05-10

The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

ENDF/B-VII.0 Data Testing Using 1,172 Critical Assemblies

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

Plechaty, E F; Cullen, D E

2007-10-01

In order to test the ENDF/B-VII.0 neutron data library [1], 1,172 critical assemblies from [2] have been calculated using the Monte Carlo transport code TART [3]. TART's 'best' physics was used for all of these calculations; this included continuous energy cross sections, delayed neutrons in their spectrum that is slower than prompt neutrons, unresolved resonance region self-shielding, the thermal scattering (free atom for all materials plus thermal scattering law data S({alpha},{beta}) when available). In this first pass through the assemblies the objective was to 'quickly' test the validity of the ENDF/B-VII.0 data [1], the assembly models as defined in [2]more » and coded for use with TART, and TART's physics treatment [3] of these assemblies. With TART we have the option of running criticality problems until K-eff has been calculated to an acceptable input accuracy. In order to 'quickly' calculate all of these assemblies K-eff was calculated in each case to +/- 0.002. For these calculations the assemblies were divided into ten types based on fuel (mixed, Pu239, U233, U235) and median fission energy (Fast, Midi, Slow). A table is provided that shows a summary of these results. This is followed be details for every assembly, and statistical information about the distribution of K-eff for each type of assembly. After a review of these results to eliminate any obvious errors in ENDF/B data, assembly models, or TART physics, all assemblies will be run again to a higher precision. Only after this second run is finished will we have highly precise results. Until then the results presently here should only be interpreted as approximate values of K-eff with a standard deviation of +/- 0.002; for such a large number of assemblies we expected the results to be approximately normal, with a spread out to several times the standard deviation; see the calculated statistical distributions and their comparisons to a normal distribution.« less

Validation of a new technique to detect Cryptosporidium spp. oocysts in bovine feces.

PubMed

Inácio, Sandra Valéria; Gomes, Jancarlo Ferreira; Oliveira, Bruno César Miranda; Falcão, Alexandre Xavier; Suzuki, Celso Tetsuo Nagase; Dos Santos, Bianca Martins; de Aquino, Monally Conceição Costa; de Paula Ribeiro, Rafaela Silva; de Assunção, Danilla Mendes; Casemiro, Pamella Almeida Freire; Meireles, Marcelo Vasconcelos; Bresciani, Katia Denise Saraiva

2016-11-01

Due to its important zoonotic potential, cryptosporidiosis arouses strong interest in the scientific community, because, it was initially considered a rare and opportunistic disease. The parasitological diagnosis of the causative agent of this disease, the protozoan Cryptosporidium spp., requires the use of specific techniques of concentration and permanent staining, which are laborious and costly, and are difficult to use in routine laboratory tests. In view of the above, we conducted the feasibility, development, evaluation and intralaboratory validation of a new parasitological technique for analysis in optical microscopy of Cryptosporidium spp. oocysts, called TF-Test Coccidia, using fecal samples from calves from the city of Araçatuba, São Paulo. To confirm the aforementioned parasite and prove the diagnostic efficiency of the new technique, we used two established methodologies in the scientific literature: parasite concentration by centrifugal sedimentation and negative staining with malachite green (CSN-Malachite) and Nested-PCR. We observed good effectiveness of the TF-Test Coccidia technique, being statistically equivalent to CSN-Malachite. Thus, we verified the effectiveness of the TF-Test Coccidia parasitological technique for the detection of Cryptosporidium spp. oocysts and observed good concentration and morphology of the parasite, with a low amount of debris in the fecal smear. Copyright © 2016 Elsevier B.V. All rights reserved.

Time-varying spectral analysis for comparison of HRV and PPG variability during tilt table test.

PubMed

Gil, Eduardo; Orini, Michele; Bailon, Raquel; Vergara, Jose Maria; Mainardi, Luca; Laguna, Pablo

2010-01-01

In this work we assessed the possibility of using the pulse rate variability (PRV) extracted from photoplethysmography signal as an alternative measurement of the HRV signal in non-stationary conditions. The study is based on the analysis of the changes observed during tilt table test in the heart rate modulation of 17 young subjects. Time-varying spectral properties of both signals were compared by time-frequency (TF) and TF coherence analysis. In addition, the effect of replacing PRV with HRV in the assessment of the changes of the autonomic modulation of the heart rate was considered. Time-frequency analysis revealed that: the TF spectra of both signals were highly correlated (0.99 ± 0.01); the difference between the instantaneous power, in LF and HF bands, obtained from HRV and PRV was small (, 10(-3) s(-2)) and their temporal patterns were highly correlated (0.98 ± 0.04 and 0.95 ± 0.06 in LF and HF bands respectively); TF coherence in LF and HF bands was high (0.97 ± 0.04 and 0.89 ± 0.08, respectively). Finally, the instantaneous power in LF band was observed to significantly increase during head-up tilt by both HRV and PRV analysis. These results suggest that, although some small differences in the time-varying spectral indices extracted from HRV and PRV exist, mainly in the HF band associated with respiration, PRV could be used as an acceptable surrogate of HRV during non-stationary conditions, at least during tilt table test.

Formation and emission of nitrogen oxide in gas turbine engines: plume effluent characteristics of TF3O-P111+ and TF33-P9 engines. Final technical report, 1 November-17 December 1993

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

Dill, J.W.; Sowa, W.A.; Samuelsen, G.S.

1996-06-30

Phase I of this project focused on the creation of a spatial emissions map of the plume effluent in the exhaust stream directly behind the engine in a jet engine test cell (JETC). Both afterburning TF30-P111+ and non-after-burning TF33-P9 engines were tested. Measurements were taken in conjunction with actual engine tests for validity of the data. Temperature, oxides of nitrogen (NOx), carbon monoxide (CO) concentration, and velocity were among the characteristics measured radially and axially in the plume for each engine type. The main focus of this study was on NOx, consisting of nitric oxide (NO) and nitrogen dioxide (NO2).more » Measurements in the P111+ plume reveal levels of NOx above 300 ppm along the centerline of the effluent. A dip in the NOx emissions at afterburner shows signs of a reburning and/or dilution effect by the atmospheric combustion in the effluent. Significant amounts of NO2 are present in the effluent over the entire power range. Temperatures at military power reach 1100 deg F along the centerline, and CO values are below 80 ppm. Carbon monoxide concentrations decrease from idle to military power (full power, no afterburner), then rise sharply in afterburner. The CO peaks shift outward from centerline as do the temperatures due to the radial geometry of the afterburner combustion (over 10 percent CO at 2850 deg F).« less

Effects of core type, placement, and width on the estimated interstrand coupling properties of QXF-type Nb 3Sn Rutherford cables

DOE PAGES

Collings, E. W.; Sumption, M. D.; Majoros, M.; ...

2015-01-12

The coupling magnetization of a Rutherford cable is inversely proportional to an effective interstrand contact resistance R eff , a function of the crossing-strand resistance R c, and the adjacent strand resistance R a. In cored cables, R eff continuously varies with W, the core width expressed as percent interstrand cover. For a series of un-heat-treated stabrite-coated NbTi LHC-inner cables with stainless-steel (SS, insulating) cores, R eff (W) decreased smoothly as W decreased from 100%, whereas for a set of research-wound SS-cored Nb 3Sn cables, R eff plummeted abruptly and remained low over most of the range. The difference ismore » due to the controlling influence of R c - 2.5 μΩ for the stabrite/NbTi and 0.26 μΩ for Nb 3Sn. The experimental behavior was replicated in the R eff (W)’s calculated by the program CUDI, which (using the basic parameters of the QXF cable) went on to show in terms of decreasing W that: 1) in QXF-type Nb 3Sn cables (R c = 0.26 μΩ), R eff dropped even more suddenly when the SS core, instead of being centered, was offset to one edge of the cable; 2) R eff decreased more gradually in cables with higher R c’s; and 3) a suitable R eff for a Nb 3Sn cable can be achieved by inserting a suitably resistive core rather than an insulating (SS) one.« less

Modeling and analysis of the TF30-P-3 compressor system with inlet pressure distortion

NASA Technical Reports Server (NTRS)

Mazzawy, R. S.; Banks, G. A.

1976-01-01

Circumferential inlet distortion testing of a TF30-P-3 afterburning turbofan engine was conducted at NASA-Lewis Research Center. Pratt and Whitney Aircraft analyzed the data using its multiple segment parallel compressor model and classical compressor theory. Distortion attenuation analysis resulted in a detailed flow field calculation with good agreement between multiple segment model predictions and the test data. Sensitivity of the engine stall line to circumferential inlet distortion was calculated on the basis of parallel compressor theory to be more severe than indicated by the data. However, the calculated stall site location was in agreement with high response instrumentation measurements.

Cyclic fatigue analysis of twisted file rotary NiTi instruments used in reciprocating motion.

PubMed

Gambarini, G; Gergi, R; Naaman, A; Osta, N; Al Sudani, D

2012-09-01

To evaluate the cyclic fatigue fracture resistance of engine-driven twisted file (TF) instruments under reciprocating movement. A sample of 30 size 25, 0.08 taper NiTi TF instruments was tested in a simulated canal with 60˚ angle of curvature and a 3 mm radius. During mechanical testing, different movement kinematics were used at a constant speed, which resulted in three experimental groups (each group n = 10). The instruments from the first group (G1) were rotated until fracture occurred. The instruments in the second (G2) and third group (G3) were driven under reciprocating movement with different angles of reciprocation. The time of fracture for each instrument was measured, and statistical analysis was performed using one-way analysis of variance followed by Tukey's Honestly Significant Different test. Reciprocating movement resulted in a significantly longer cyclic fatigue life (P < 0.0001) when compared with continuous rotation. No difference was found between reciprocation 150° clockwise/30° counterclockwise (CW/CCW) and 30° CW/150° CCW. The reciprocating movement was associated with an extended cyclic fatigue life of the TF size 0.25, 0.08 taper instruments in comparison with conventional rotation. © 2012 International Endodontic Journal.

Structural modulation of factor VIIa by full-length tissue factor (TF1-263): implication of novel interactions between EGF2 domain and TF.

PubMed

Prasad, Ramesh; Sen, Prosenjit

2018-02-01

Tissue factor (TF)-mediated factor VII (FVII) activation and a subsequent proteolytic TF-FVIIa binary complex formation is the key step initiating the coagulation cascade, with implications in various homeostatic and pathologic scenarios. TF binding allosterically modifies zymogen-like free FVIIa to its highly catalytically active form. As a result of unresolved crystal structure of the full-length TF 1-263 -FVIIa binary complex and free FVIIa, allosteric alterations in FVIIa following its binding to full-length TF and the consequences of these on function are not entirely clear. The present study aims to map and identify structural alterations in FVIIa and TF resulting from full-length TF binding to FVIIa and the key events responsible for enhanced FVIIa activity in coagulation. We constructed the full-length TF 1-263 -FVIIa membrane bound complex using computational modeling and subjected it to molecular dynamics (MD) simulations. MD simulations showed that TF alters the structure of each domain of FVIIa and these combined alterations contribute to enhanced TF-FVIIa activity. Detailed, domain-wise investigation revealed several new non-covalent interactions between TF and FVIIa that were not found in the truncated soluble TF-FVIIa crystal structure. The structural modulation of each FVIIa domain imparted by TF indicated that both inter and intra-domain communication is crucial for allosteric modulation of FVIIa. Our results suggest that these newly formed interactions can provide additional stability to the protease domain and regulate its activity profile by governing catalytic triad (CT) orientation and localization. The unexplored newly formed interactions between EGF2 and TF provides a possible explanation for TF-induced allosteric activation of FVIIa.

Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

PubMed

Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

2017-03-07

The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole-cell kinetic models can be useful in cancer therapeutic design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preliminary Kalman Filter Design to Improve Air Combat Maneuvering Target Estimation for the F-4E/G Fire Control System.

DTIC Science & Technology

1985-12-01

ADDED TN~*************************** COMMON/AIR/RATE,PHI ,PHIDIT,PP-HI ,PITCH,PITCHD,PPITCHTRATE, 1 TURN,TURND,FPTURNTR1 ,TR2,TR3,TR4, TF1 ,TF2...READ(2,*)ALPHAE’ETA *C READ(2,*)TR1, TF1 !FORWARD ROLL START,STOP TIMES READ(2,*)TR1 , TF1 C READ(2,*)TR2,TF2 !REVERSE ROLL START,STOP TIMES READ(2... TF1 ,TR2, 1 TF2,TR3,TF3,TR4,TF4,HORT1 ,1ORT2,HORTGEIELTA C C INITIALIZE AIRCRAFT MODEL C IA IR=0 CALL AIR C C INITIALIZE RADAR MODEL -- C I RADAR=O CALL

LIN-39/Hox triggers cell division and represses EFF-1/fusogen-dependent vulval cell fusion

PubMed Central

Shemer, Gidi; Podbilewicz, Benjamin

2002-01-01

General mechanisms by which Hox genes establish cell fates are known. However, a few Hox effectors mediating cell behaviors have been identified. Here we found the first effector of LIN-39/HoxD4/Dfd in Caenorhabditis elegans. In specific vulval precursor cells (VPCs), LIN-39 represses early and late expression of EFF-1, a membrane protein essential for cell fusion. Repression of eff-1 is also achieved by the activity of CEH-20/Exd/Pbx, a known cofactor of Hox proteins. Unfused VPCs in lin-39(−);eff-1(−) double mutants fail to divide but migrate, executing vulval fates. Thus, lin-39 is essential for inhibition of EFF-1-dependent cell fusion and stimulation of cell proliferation during vulva formation. Supplemental material is available at http://www.genesdev.org. PMID:12502736

Schizosaccharomyces pombe Retrotransposon Tf2 Mobilizes Primarily through Homologous cDNA Recombination

PubMed Central

Hoff, Eleanor F.; Levin, Henry L.; Boeke, Jef D.

1998-01-01

The Tf2 retrotransposon, found in the fission yeast Schizosaccharomyces pombe, is nearly identical to its sister element, Tf1, in its reverse transcriptase-RNase H and integrase domains but is very divergent in the gag domain, the protease, the 5′ untranslated region, and the U3 domain of the long terminal repeats. It has now been demonstrated that a neo-marked copy of Tf2 overexpressed from a heterologous promoter can mobilize into the S. pombe genome and produce true transposition events. However, the Tf2-neo mobilization frequency is 10- to 20-fold lower than that of Tf1-neo, and 70% of the Tf2-neo events are homologous recombination events generated independently of a functional Tf2 integrase. Thus, the Tf2 element is primarily dependent on homologous recombination with preexisting copies of Tf2 for its propagation. Finally, production of Tf2-neo proteins and cDNA was also analyzed; surprisingly, Tf2 was found to produce its reverse transcriptase as a single species in which it is fused to protease, unlike all other retroviruses and retrotransposons. PMID:9774697

The role of the non-magnetic material in spin pumping and magnetization dynamics in NiFe and CoFeB multilayer systems

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

Ruiz-Calaforra, A., E-mail: ruiz@physik.uni-kl.de; Brächer, T.; Lauer, V.

2015-04-28

We present a study of the effective magnetization M{sub eff} and the effective damping parameter α{sub eff} by means of ferromagnetic resonance spectroscopy on the ferromagnetic (FM) materials Ni{sub 81}Fe{sub 19} (NiFe) and Co{sub 40}Fe{sub 40}B{sub 20} (CoFeB) in FM/Pt, FM/NM, and FM/NM/Pt systems with the non-magnetic (NM) materials Ru, Cr, Al, and MgO. Moreover, for NiFe layer systems, the influence of interface effects is studied by way of thickness dependent measurements of M{sub eff} and α{sub eff}. Additionally, spin pumping in NiFe/NM/Pt is investigated by means of inverse spin Hall effect (ISHE) measurements. We observe a large dependence ofmore » M{sub eff} and α{sub eff} of the NiFe films on the adjacent NM layer. While Cr and Al do not induce a large change in the magnetic properties, Ru, Pt, and MgO affect M{sub eff} and α{sub eff} in different degrees. In particular, NiFe/Ru and NiFe/Ru/Pt systems show a large perpendicular surface anisotropy and a significant enhancement of the damping. In contrast, the magnetic properties of CoFeB films do not have a large influence of the NM adjacent material and only CoFeB/Pt systems present an enhancement of α{sub eff}. However, this enhancement is much more pronounced in NiFe/Pt. By the introduction of the NM spacer material, this enhancement is reduced. Furthermore, a difference in symmetry between NiFe/NM/Pt and NiFe/NM systems in the output voltage signal from the ISHE measurements reveals the presence of spin pumping into the Pt layer in all-metallic NiFe/NM/Pt and NiFe/Pt systems.« less

Short Diffusion Time Diffusion-Weighted Imaging With Oscillating Gradient Preparation as an Early Magnetic Resonance Imaging Biomarker for Radiation Therapy Response Monitoring in Glioblastoma: A Preclinical Feasibility Study.

PubMed

Bongers, Andre; Hau, Eric; Shen, Han

2018-01-04

To investigate a novel alternative diffusion-weighted imaging (DWI) approach using oscillating gradients preparation (OGSE) to obtain much shorter effective diffusion times (Δ eff ) for tumor response monitoring by apparent diffusion coefficient (ADC) mapping in a glioblastoma mouse model. Twenty-four BALB/c nude mice inoculated with U87 glioblastoma cells were randomized into a control group and an irradiation group, which underwent a 15-day fractioned radiation therapy (RT) course with 2 Gy/d. Therapy response was assessed by mapping of ADCs at 6 time points using an in-house implementation of a cos-OGSE DWI sequence with Δ eff  = 1.25 ms and compared with a standard pulsed gradient DWI protocol (PGSE) with typical clinical diffusion time Δ eff  = 18 ms. Longitudinal ADC changes in tumor and contralateral white matter (WM) were statistically assessed using repeated-measures analysis of variance and post hoc (Sidak) testing. On short Δ eff OGSE maps tumor ADC was generally 30%-50% higher than in surrounding WM. Areas correlated well with histology. Tumor identification was generally more difficult on PGSE maps owing to nonsignificant WM/tumor contrast. During RT, OGSE maps also showed significant tumor ADC increase (approximately 15%) in response to radiation, consistently seen after 14-Gy RT dose. The clinical reference (PGSE) showed lower sensitivity to radiation changes, and no significant response across the radiation group and time course could be detected. Our short Δ eff DWI method using OGSE better reflected histologically defined tumor areas and enabled more consistent and earlier detection of microstructural radiation changes than conventional methods. Oscillating gradients preparation offers significant potential as a robust microstructural RT response biomarker, potentially helping to shift important therapy decisions to earlier stages in the RT time course. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of Martian meteorites with earth composition: Study of effective atomic numbers in the energy range 1 keV-100 GeV

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

Ün, Adem, E-mail: ademun25@yahoo.com; Han, İbrahim, E-mail: ibrahimhan25@hotmail.com; Ün, Mümine, E-mail: mun@agri.edu.tr

2016-04-18

Effective atomic (Z{sub eff}) and electron numbers (N{sub eff}) for 24 Martian meteorites have been determined in the energy range from 1 keV to 100 GeV and also for sixteen significant energies of commonly used radioactive sources. The values of Z{sub eff} and N{sub eff} for all sample were obtained from the DirectZeff program. The obtained results for Martian meteorites have been compared with the results for Earth composition and similarities or differences also evaluated.

Hemoglobin enhances tissue factor expression on human malignant cells.

PubMed

Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

2001-04-01

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

Nifedipine Increases Iron Content in WKPT-0293 Cl.2 Cells via Up-Regulating Iron Influx Proteins

PubMed Central

Yu, Shuang-Shuang; Jiang, Li-Rong; Ling, Yan; Qian, Zhong-Ming; Zhou, Yu-Fu; Li, Juan; Ke, Ya

2017-01-01

Nifedipine was reported to enhance urinary iron excretion in iron overloaded mice. However, it remains unknown how nifedipine stimulates urinary iron excretion in the kidney. We speculated that nifedipine might inhibit the TfR1/ DMT1 (transferrin receptor 1/divalent metal transporter1)-mediated iron uptake by proximal tubule cells in addition to blocking L-type Ca2+ channels, leading to an increase in iron in lumen-fluid and then urinary iron excretion. To test this hypothesis, we investigated the effects of nifedipine on iron content and expression of TfR1, DMT1 and ferroportin1 (Fpn1) in WKPT-0293 Cl.2 cells of the S1 segment of the proximal tubule in rats, using a graphite furnace atomic absorption spectrophotometer and Western blot analysis, respectively. We demonstrated for the first time that nifedipine significantly enhanced iron content as well as TfR1 and DMT1 expression and had no effect on Fpn1 levels in the cells. We also found that ferric ammonium citrate decreased TfR1 levels, increased Fpn1 expression and had no effect on DMT1 content, while co-treatment with nifedipine and FAC increase TfR1 and DMT1 expression and also had no effect on Fpn1 levels. These findings suggest that the nifedipine-induced increase in cell iron may mainly be due to the corresponding increase in TfR1 and DMT1 expression and also imply that the effects of nifedipine on iron transport in proximal tubule cells can not explain the increase in urinary iron excretion. PMID:28243203

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

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

Schechter, Melissa E.; Andrade, Bruno B.; He, Tianyu

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidencemore » of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.« less

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

DOE PAGES

Schechter, Melissa E.; Andrade, Bruno B.; He, Tianyu; ...

2017-08-30

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidencemore » of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.« less

Electromagnetic Launching for Affordable Agile Access to Space

DTIC Science & Technology

2006-04-15

requirements are advantageous compared to other EM launch technologies. 14 I Pp TRI TF1 (P) TR2 TF2 (P) ... TRM TFM (P) TF1 TRI(n) TF2 TH .)񔰣 -n F- on 71...some integer M. The distance between the rear coil TRI and the corresponding front coil TF1 is MxPT. PP: distance between coils in the projectile, PT...TRI with TFI/p), TR2 with TF2(P) ..., and also TR/("),with TF1 , TR2(n)with TF2, etc. ). * For a slender projectile (i.e. length >> diameter), it is

Mutation in Torenia fournieri Lind. UFO homolog confers loss of TfLFY interaction and results in a petal to sepal transformation.

PubMed

Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro

2012-09-01

We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

An initial evaluation of a proof-of-concept 128-Hz electronic tuning fork in the detection of peripheral neuropathy.

PubMed

O'Brien, Todd; Karem, Joseph

2014-03-01

Diabetic peripheral neuropathy (DPN) is an essential precursor leading to diabetic limb loss. Neurologic screening tests, including the 128-Hz tuning fork (TF), have long been used to identify and track the progression of DPN, thereby guiding the implementation of preventive strategies. Although a sensitive indicator of neuropathy, shortcomings of TF testing include the lack of standardization and quantification of clinical findings. In an attempt to overcome these limitations, a novel 128-Hz electronic TF (ETF) prototype has been developed that is capable of performing accurate timed vibration tests (TVTs). This study was designed to assess the ability of the ETF to detect sensory impairment compared with three established neurologic screening methods: the Semmes-Weinstein monofilament test, the biothesiometer, and the sharp/dull discrimination test. Fifty-five test patients were recruited from the primary author's practice and enrolled according to an approved protocol. The 10-g Semmes-Weinstein monofilament test and the sharp/dull discrimination test were administered in standard fashion to the plantar aspects of digits 1 and 5 bilaterally. The ETF and the biothesiometer (25-V setting) were applied to the dorsal aspects of the distal phalanx of the hallux and fifth metatarsal head bilaterally. The sensitivity and specificity of neuropathy detection for the ETF were 0.953 and 0.761, respectively, using conventional tests as reference standards. Performance of TVTs with the ETF detected sensory impairment compared with three conventional neurologic screening methods. Given these findings, the ETF could facilitate the use of standardized TVTs as an indicator of DPN progression.

Phase boundaries, structural characteristics, and NMR spectra of ionic liquid-in-oil microemulsions containing double chain surface active ionic liquid: a comparative study.

PubMed

Rao, Vishal Govind; Mandal, Sarthak; Ghosh, Surajit; Banerjee, Chiranjib; Sarkar, Nilmoni

2013-02-07

A method developed for the first time, to create a huge number of ionic liquid (IL)-in-oil microemulsions has been discussed in our earlier publication (Rao, V. G.; Ghosh, S.; Ghatak, C.; Mandal, S.; Brahmachari, U.; Sarkar, N. J. Phys. Chem. B 2012, 116, 2850-2855). Here, we present facile methods to adjust the structural parameters of microemulsions using different ionic liquids (ILs) as additives (polar phase). We have characterized ILs/[C(4)mim][AOT]/benzene ternary system by performing a phase behavior study, dynamic light scattering (DLS) measurements, and (1)H NMR measurements. The IL loading capacity of microemulsions (area of single phase region) (i) increases with increase in alkyl chain length of cation of ILs and follows the trend [C(6)mim][TF(2)N] > [C(4)mim][TF(2)N] > [C(2)mim][TF(2)N], (ii) increases with decrease in cation anion interaction strength of added ILs and follows the trend [C(4)mim][TF(2)N] > [C(4)mim][PF(6)] > [C(4)mim][BF(4)]. So depending on the IL used, the amount of IL within the core of microemulsions can be easily manipulated to directly affect the size of aggregates in microemulsions. The size increase with increasing R value (R value is defined as the molar ratio of RTILs to [C(4)mim][AOT]) was found to be maximum in the case of [C(2)mim][TF(2)N]/[C(4)mim][AOT]/benzene microemulsions and follows the trend [C(2)mim][TF(2)N] > [C(4)mim][TF(2)N] > [C(6)mim][TF(2)N]. However, the size increase was almost the same with increase in R value in the case of ILs with different anions. The most promising fact about IL-in-oil microemulsions is their high thermal stability compared to that of aqueous microemulsions, so we investigated the effect of temperature on size of aggregates in microemulsions at R = 1.0. It is evident from dynamic light scattering measurements that the aggregates in microemulsions remain monodisperse in nature with increasing temperature, and in all the cases, the size of aggregates in microemulsions decreases with increasing temperature. The effect of water addition on IL-in-oil (IL/O) microemulsions was also studied in detail. By far, this is the first report where the effect of water addition on microemulsions containing hydrophobic ILs is being reported and compared with microemulsions containing hydrophilic ILs. We observed that the added water has a prominent effect on the microstructure of the microemulsions. In all the cases, (1)H NMR spectra provide more detailed information about intra/intermolecular interactions thus affording a clear picture of locations of (i) the RTILs in RTILs/[C(4)mim][AOT]/benzene microemulsions and (ii) the added water molecules in microemulsions.

Comparative Analysis of Ultrasonic Inspection Procedures for Kaman K747 Root End Fittings

DTIC Science & Technology

1989-04-01

I.CI- IA 4cz 4c-- a- LLJ 4A ccu I46 APPENDIX III. TRANSDUCER WEDGE ANGLE DATA RESULTS No Procedure, Gain = 70 dB 45.Degre Probe REF# TF1 TF2 TF3 TAl...Degree Probe REF # TF1 TF2 TF3 TAl TA2 TA3 BF1 BF2 BF3 BAl BA2 BA3 B5328 35 33 -. . . 31 - - - - - 38 38 B5102 38 - 31 .. - - 31 - - - B5298 40 42...50 No Procedure, Gain = 70 dB 50-Degree Probe REF # TF1 TF2 TF3 TAl TA2 TA3 BF1 BF2 BF3 BAl BA2 BA3 B5328 - . . . . 32 - 40 B5102 34 .- 30

Optimum Design Methods for Structural Sandwich Panels

DTIC Science & Technology

1989-02-01

B)*ROS TF1 -STRE?4*SS**2/(Cl(CONFI)*AFA*(ROCl/ROS)**(2*A/3. )*TCI) Wlm(2* TF1 *WS*SS*ROF+TCi*WS*SS*ROCI)/1728000. IF (W1.LT.WEIGHT) THEN TF- TF1 TC-TC1...B)*ROS W1-(2* TF1 *WS*SS*ROF+TC1*WS*SS*RoC1)/172800O. IF (WI.LT.WEIGHT) THEN TF- TF1 TC-TC1 ROC-ROC1 WEIGHT-Wi FAIL-3 END IF END IF WRITE(*, 260)TC,TF...8217THE PROGRAM IS RUNNING. PL.EASE WAIT!’ DO 273 1-1,999 * TCl-P*SS/(C1 lrONFI)*YF*WS*TFI) COEFF-C5 (CONFI )*EF*P*SS* TF1 *TC1/ (CG*C6 (CONFI ) *E) COEFF

EFF HOT Topics. Volume 1, Number 1, Spring 2001

ERIC Educational Resources Information Center

National Institute for Literacy, 2001

2001-01-01

HOT Topics is a new quarterly publication from the Equipped for the Future (EFF) National Center. HOT stands for Highlights On Teaching, and this publication is committed to providing teachers and tutors with tools and ideas for teaching using the EFF Framework and Standards. This first issue of HOT Topics focuses on strategies that use the EFF…

The Long Terminal Repeat Retrotransposons Tf1 and Tf2 of Schizosaccharomyces pombe.

PubMed

Esnault, Caroline; Levin, Henry L

2015-08-01

The long terminal repeat (LTR) retrotransposons Tf1 and Tf2 of Schizosaccharomyces pombe are active mobile elements of the Ty3/gypsy family. The mobilization of these retrotransposons depends on particle formation, reverse transcription and integration, processes typical of other LTR retrotransposons. However, Tf1 and Tf2 are distinct from other LTR elements in that they assemble virus-like particles from a single primary translation product, initiate reverse transcription with an unusual self-priming mechanism, and, in the case of Tf1, integrate with a pattern that favors specific promoters of RNA pol II-transcribed genes. To avoid the chromosome instability and genome damage that results from increased copy number, S. pombe applies a variety of defense mechanisms that restrict Tf1 and Tf2 activity. The mRNA of the Tf elements is eliminated by an exosome-based pathway when cells are in favorable conditions whereas nutrient deprivation triggers an RNA interference-dependent pathway that results in the heterochromatization of the elements. Interestingly, Tf1 integrates into the promoters of stress-induced genes and these insertions are capable of increasing the expression of adjacent genes. These properties of Tf1 transposition raise the possibility that Tf1 benefits cells with specific insertions by providing resistance to environmental stress.

Flaw Growth of 6Al-4V Titanium in a Freon TF Environment

NASA Technical Reports Server (NTRS)

Tiffany, C. F.; Masters, J. N.; Bixler, W. D.

1969-01-01

The plane strain threshold stress intensity and sustained stress flaw growth rates were experimentally determined for 6AI-4V S.T.A. titanium forging and weldments in environments of Freon TF at room temperature. Sustained load tests of surface flawed specimens were conducted with the experimental approach based on linear elastic fracture mechanics. It was concluded that sustained stress flaw growth rates, in conjunction with threshold stress intensities, can be used in assessing the service life of pressure vessels.

Distributed Combustion in Solid Propellants

DTIC Science & Technology

1993-03-01

SENTRY. During that year three full scale development motors were test fired. All three motors experienced an unacceptabiy high level of combustion...CO. Thermochemical Implications," Journal of Physical Chemistry , 1986, Vol. 90, pp. 1688-1691. Rundinger, G., "Effect of Velocity Slip on the...resulting equation is found to be M (r, l = Lelnf 1 F (T-f- T’) I F(Tf- Ts) -J (B.20) where (p is given by P = (MvQ1 + McQ + H) Mil and F is the ratio of

Improved Therapy by Pretargeted Radioimmunotherapy of Non-Hodgkin Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody

PubMed Central

Sharkey, Robert M.; Karacay, Habibe; Litwin, Samuel; Rossi, Edmund A.; McBride, William J.; Chang, Chein-Hsing; Goldenberg, David M.

2008-01-01

We examined whether a pretargeting method using a new, recombinant anti-CD20 bispecific antibody (bsMAb) followed by 90Y-DOTA-peptide could reduce hematological toxicity yet improve therapeutic responses, compared to conventional 90Y-anti-CD20 IgG and a chemically-conjugated bsMAb. TF4, a humanized, tri-Fab, bsMAb with 2 Fabs binding CD20 and 1 Fab binding HSG (histamine-succinyl-glycine), developed by the Dock-and-Lock (DNL) method, was tested in nude mice with Ramos B-cell lymphomas. Optimal pretargeting required a 29-h interval between TF4 and 90Y-DOTA-HSG, and 20-fold more moles of TF4. TF4 cleared more rapidly from the blood than anti-CD20 IgG, with early processing in the liver, spleen and kidneys. At 24 h, TF4 improved tumor uptake of 111In-HSG-peptide 2.6-fold (13% vs 5% injected-dose/g) and enhanced tumor/blood ratios more than 45-fold (770 vs 17), compared to an anti-CD20 Fab x anti-HSG Fab chemical conjugate, and by 1.6-fold (9.0% vs 5.6% injected-dose/g) and 1600-fold (522 vs 0.32), respectively, compared to radiolabeled anti-CD20 IgG. A severe (≥90%) and prolonged reduction of white blood cells was observed at the maximum dose of 90Y-anti-CD20 IgG, whereas pretargeting resulted in a ≤60% transient drop. TF4-pretargeting resulted in highly significant improvement in survival, curing 33-90% of the animals, even at relatively low doses, while most tumors progressed quickly without cures with 90Y-anti-CD20 IgG. These results indicate an improved therapeutic index with pretargeting radioimmunotherapy using a DNL-constructed tri-Fab, bsMAb, as compared to conventional therapy with directly-radiolabeled antibody or with a chemically-conjugated bsMAb. These encouraging results prompt testing of these constructs for pretargeting radioimmunotherapy in patients. PMID:18593929

Skin extracts from 2 Italian table grapes (Italia and Palieri) inhibit tissue factor expression by human blood mononuclear cells.

PubMed

Milella, Rosa Anna; Antonacci, Donato; Crupi, Pasquale; Incampo, Francesca; Carrieri, Cosimo; Semeraro, Nicola; Colucci, Mario

2012-08-01

Grape and its products such as red wine and grape juice have well-known antithrombotic properties, which have been attributed to their high content in polyphenolic compounds. Most studies on the mechanisms underlying these beneficial effects, among which the suppression of tissue factor (TF) synthesis in blood mononuclear cells (MNC) and vascular endothelium is a prominent one, have been performed with purified polyphenols, while little is known about the effect of fresh grapes which contain a multitude of phytochemicals whose interaction may lead to different cell responses. In this study, we investigated the effect of grape skin extracts (GSEs) on TF expression in isolated blood MNC and in whole blood. Alcoholic extracts from skins of 2 grape varieties (Palieri and Italia) inhibited TF expression in lipopolysaccharide (LPS)-stimulated MNC in a concentration-dependent manner with ≥90% inhibition of TF activity and antigen at 6 μg/mL of gallic acid equivalents. Noteworthy, GSEs were also able to inhibit the appearance of TF in whole blood challenged with LPS. The 2 grape varieties displayed a fairly similar TF-inhibiting capacity despite marked differences in phenolic profile. When selected purified polyphenols were tested, their ability to inhibit TF expression was markedly lower as compared to grape extracts, whereas a mixture of some representative polyphenols was much more efficient, supporting the occurrence of a synergistic effect. Given the key role of cell TF in thrombotic diseases, the inhibition of MNC-mediated clotting activation, if confirmed by in vivo studies, might represent an important antithrombotic mechanism. Our data indicate that the combination of different polyphenols, as in grape extracts, is much more efficient than the single constituents, a finding that might be useful as starting point for the development of new antithrombotic nutraceutics. In addition, our study validated a simple, inexpensive, and physiologically relevant in vitro method on whole blood that allows the evaluation of one of the most important antithrombotic activities of food and food-derived products. The simplicity of the method makes it suitable also for screening purposes in large-scale studies. © 2012 Institute of Food Technologists®

Evaluation of standing noise barriers.

DOT National Transportation Integrated Search

1978-01-01

A series of tests have been carried out at six sites for the evaluation of noise barriers to determine their relative effectiveness. Two barriers were metal, two were wooden, and one was concrete. One site, used for reference, had no barrier. The eff...

Image Quality and Diagnostic Performance of a Digital PET Prototype in Patients with Oncologic Diseases: Initial Experience and Comparison with Analog PET.

PubMed

Nguyen, Nghi C; Vercher-Conejero, Jose L; Sattar, Abdus; Miller, Michael A; Maniawski, Piotr J; Jordan, David W; Muzic, Raymond F; Su, Kuan-Hao; O'Donnell, James K; Faulhaber, Peter F

2015-09-01

We report our initial clinical experience for image quality and diagnostic performance of a digital PET prototype scanner with time-of-flight (DigitalTF), compared with an analog PET scanner with time-of-flight (GeminiTF PET/CT). Twenty-one oncologic patients, mean age 58 y, first underwent clinical (18)F-FDG PET/CT on the GeminiTF. The scanner table was then withdrawn while the patient remained on the table, and the DigitalTF was inserted between the GeminiTF PET and CT scanner. The patients were scanned for a second time using the same PET field of view with CT from the GeminiTF for attenuation correction. Two interpreters reviewed the 2 sets of PET/CT images for overall image quality, lesion conspicuity, and sharpness. They counted the number of suggestive (18)F-FDG-avid lesions and provided the TNM staging for the 5 patients referred for initial staging. Standardized uptake values (SUVs) and SUV gradients as a measure of lesion sharpness were obtained. The DigitalTF showed better image quality than the GeminiTF. In a side-by-side comparison using a 5-point scale, lesion conspicuity (4.3 ± 0.6), lesion sharpness (4.3 ± 0.6), and diagnostic confidence (3.4 ± 0.7) were better with DigitalTF than with GeminiTF (P < 0.01). In 52 representative lesions, the lesion maximum SUV was 36% higher with DigitalTF than with GeminiTF, lesion-to-blood-pool SUV ratio was 59% higher, and SUV gradient was 51% higher, with good correlation between the 2 scanners. Lesions less than 1.5 cm showed a greater increase in SUV from GeminiTF to DigitalTF than those lesions 1.5 cm or greater. In 5 of 21 patients, DigitalTF showed an additional 8 suggestive lesions that were not seen using GeminiTF. In the 15 restaging patients, the true-negative rate was 100% and true-positive rate was 78% for both scanners. In the 5 patients for initial staging, DigitalTF led to upstaging in 2 patients and showed the same staging in the other 3 patients, compared with GeminiTF. DigitalTF provides better image quality, diagnostic confidence, and accuracy than GeminiTF. DigitalTF may be the most beneficial in detecting small tumor lesions and disease staging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

STAT1:DNA sequence-dependent binding modulation by phosphorylation, protein:protein interactions and small-molecule inhibition

PubMed Central

Bonham, Andrew J.; Wenta, Nikola; Osslund, Leah M.; Prussin, Aaron J.; Vinkemeier, Uwe; Reich, Norbert O.

2013-01-01

The DNA-binding specificity and affinity of the dimeric human transcription factor (TF) STAT1, were assessed by total internal reflectance fluorescence protein-binding microarrays (TIRF-PBM) to evaluate the effects of protein phosphorylation, higher-order polymerization and small-molecule inhibition. Active, phosphorylated STAT1 showed binding preferences consistent with prior characterization, whereas unphosphorylated STAT1 showed a weak-binding preference for one-half of the GAS consensus site, consistent with recent models of STAT1 structure and function in response to phosphorylation. This altered-binding preference was further tested by use of the inhibitor LLL3, which we show to disrupt STAT1 binding in a sequence-dependent fashion. To determine if this sequence-dependence is specific to STAT1 and not a general feature of human TF biology, the TF Myc/Max was analysed and tested with the inhibitor Mycro3. Myc/Max inhibition by Mycro3 is sequence independent, suggesting that the sequence-dependent inhibition of STAT1 may be specific to this system and a useful target for future inhibitor design. PMID:23180800

A Long Terminal Repeat-Containing Retrotransposon of Schizosaccharomyces pombe Expresses a Gag-Like Protein That Assembles into Virus-Like Particles Which Mediate Reverse Transcription

PubMed Central

Teysset, Laure; Dang, Van-Dinh; Kim, Min Kyung; Levin, Henry L.

2003-01-01

The Tf1 element of Schizosaccharomyces pombe is a long terminal repeat-containing retrotransposon that encodes functional protease, reverse transcriptase, and integrase proteins. Although these proteins are known to be necessary for protein processing, reverse transcription, and integration, respectively, the function of the protein thought to be Gag has not been determined. We present here the first electron microscopy of Tf1 particles. We tested whether the putative Gag of Tf1 was required for particle formation, packaging of RNA, and reverse transcription. We generated deletions of 10 amino acids in each of the four hydrophilic domains of the protein and found that all four mutations reduced transposition activity. The N-terminal deletion removed a nuclear localization signal and inhibited nuclear import of the transposon. The two mutations in the center of Gag destabilized the protein and resulted in no virus-like particles. The C-terminal deletion caused a defect in RNA packaging and, as a result, low levels of cDNA. The electron microscopy of cells expressing a truncated Tf1 showed that Gag alone was sufficient for the formation of virus-like particles. Taken together, these results indicate that Tf1 encodes a Gag protein that is a functional equivalent of the Gag proteins of retroviruses. PMID:12692246

[Comparative analysis of 6 kinds of bacteria in the subgingival plaque in different types of patients with periodontal diseases].

PubMed

Ma, Ying-ying; Zhang, Tao-wen; Jiang, Yu-xi; Liu, Shu-tai

2015-10-01

To detect the existence of Aa,Pg,Tf,Cr,Ec and Pn in the subgingival plaque, and determine their relationships among different types of periodontal diseases. Dental plaques from 120 subjects were sampled, including 40 volunteers with health periodontal status(Group A) , forty patients with dental plaque-induced gingival diseases(Group B) and 40 patients with moderate or severe chronic periodontitis (Group C) . These samples were detected based on bacterial composition using the terminal restriction fragment length polymorphism of 16S rRNA genes by multiple-polymerase chain reaction. The data was analysed with SPSS 13.0 software package for Chi-square test. The detection rate of Pn, Cr and Pg had significant differences between group A and B. The detection rate of Ec, Cr, Pg, Aa and Tf had significant differences between group C and B. The detection rate of Ec, Pn, Cr, Pg, Aa and Tf had significant differences between group A and C. The rate of Ec, Pn, Cr, Pg and Tf detected in moderate or patients with moderate or severe chronic periodontitis are significantly higher than that in healthy subjects, indicating that these bacteria have certain correlation with chronic periodontitis. The rate of Ec, Cr, Pg and Tf detected in severe chronic periodontitis are significantly higher than that in dental-induced gingivitis, suggesting their close relationship with the progress of periodontal disease.

USF-related transcription factor, HIV-TF1, stimulates transcription of human immunodeficiency virus-1.

PubMed

Maekawa, T; Sudo, T; Kurimoto, M; Ishii, S

1991-09-11

The transcription factor HIV-TF1, which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 (HIV-1), was purified from human B cells. HIV-TF1 had a molecular weight of 39,000. Binding of HIV-TF1 to the HIV long terminal repeat (LTR) activated transcription from the HIV promoter in vitro. The HIV-TF1-binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor (USF) in the adenovirus major late promoter. DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF. Interestingly, treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity, suggesting that phosphorylation of HIV-TF1 was essential for DNA binding. The disruption of HIV-TF1-binding site induced a 60% decrease in the level of transcription from the HIV promoter in vivo. These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1.

Antigen targeting to antigen-presenting cells enhances presentation to class II-restricted T lymphocytes.

PubMed Central

Scardino, A; Paroli, M; De Petrillo, G; Michel, M L; Barnaba, V

1994-01-01

Receptor-mediated uptake increases by several orders of magnitude the efficiency of APC to internalize Ag, and is stringently required for the Ag-presenting function of T lymphocytes due to their inability to take up Ag non-specifically. We have previously reported that hepatitis B envelope antigen (HBenvAg) can be internalized by T cells via transferrin receptor (TfR). To evaluate if Ag targeting to receptors expressed on APC could be an effective tool for promoting Ag uptake and presentation, we tested the capacity of activated T cells not expressing TfR to induce HBenvAg-specific T-cell responses when pulsed with a hybrid particle containing HBenvAg coupled to gp120 of human immunodeficiency virus (HIV), exploiting the ability of gp120 to bind to CD4 receptor. We found that CD4+/TfR- T cells pulsed either with the hybrid particle or peptide (S193-207) but not with S, L Ag, a recombinant form of HBenvAg, induced a specific proliferative response of a T-cell clone recognizing peptide (S193-207) of HBenvAg. The finding that the addition of anti-CD4 monoclonal antibody (mAb) before the pulsing of CD4+/TfR- T cells with the hybrid particle drastically blocked the specific T-cell response, together with the finding that CD8+/TfR- T cells were unable to serve as APC even if pulsed with this molecule, demonstrated that CD4 receptor was crucial for the HBenvAg internalization. On the other hand, HBenvAg presentation by CD4+/TfR+ T cells pulsed with the hybrid particle was inhibited only when both anti-CD4 and anti-TfR were added before the pulsing. These results suggest that Ag targeting to APC receptors may be usefully exploited to improve Ag-presentation efficiency in potential immunotherapeutic approaches. PMID:7907575

Change in Parental Depressive Symptoms in Trauma-Focused Cognitive-Behavioral Therapy: Results from a Randomized Controlled Trial.

PubMed

Tutus, Dunja; Keller, Ferdinand; Sachser, Cedric; Pfeiffer, Elisa; Goldbeck, Lutz

2017-03-01

Depressive symptoms are frequently described in parents whose children have been exposed to traumatic events. Hence, including nonoffending parents in trauma-focused cognitive-behavioral therapy (TF-CBT) for children and adolescents may help both children and their parents to cope with the trauma. Up to now, three randomized controlled trials have investigated parental depressive symptoms after TF-CBT. Given the ambiguous results, further effectiveness trials are needed to investigate parental benefit from TF-CBT. The aim of this study is to determine whether TF-CBT is superior to waitlist (WL) regarding change in parental depressive symptoms. Parents, N = 84, whose children (age 6-17 years) were randomly assigned to either 12 sessions of TF-CBT (n = 40) or to WL condition (n = 44) completed the Beck Depression Inventory-Second Edition (BDI-II) for pre-post comparison. The group difference was tested through repeated-measures analyses of variance (ANOVA). The change in parental depressive symptoms was additionally categorized using the reliable change index. Repeated-measures ANOVA indicated a significant time effect F(1, 82) = 2.55, p = 0.02, and no significant time-group interaction F(1, 82) = 1.09, p = 0.30, suggesting a similar reduction in parental depressive symptoms in both groups. Across both conditions, most of the parents remained unchanged (n = 62), some of them improved (n = 17), and a few deteriorated (n = 5). There was no significant difference between the conditions (χ 2 (2) = 1.74; p = 0.42). Contrary to findings of several previous studies, our results suggest no superiority of TF-CBT in comparison with WL regarding change in depressive symptoms in parents. This might be due to different types of the child's trauma. Parental benefit from TF-CBT was found in samples of sexually abused, but not in children and adolescents exposed to diverse trauma types.

POGO ground simulation test of H-I launch vehicle's second stage

NASA Astrophysics Data System (ADS)

Ono, Yoshio; Kohsetsu, Yuji; Shibukawa, Kiwao

This paper describes a POGO ground simulation test of the Japanese new second stage for the H-I launch vehicle. It was the final prelaunch verification test of a POGO prevention of the H-I. This test was planned to examine POGO stability and was conducted in a Captive Firing Test (CFT) by mounting a flight-type second stage by a soft suspension system on the CFT test stand which gave the vehicle a pseudo inflight boundary condition of free-free in terms of the vehicle's structural dynamics. There was no indication that implied POGO from the data measured during the CFT. Consequently, this test suggested that the new second stage of the H-I was POGO free. Therefore, it was decided that the first test flight (TF no. 1) of the H-I would be made without a POGO Suppression Device. TF no. 1 was launched successfully on August 13, 1986, and its telemetry data showed no evidence of POGO phenomenon.

Characterization of iron uptake from transferrin by murine endothelial cells.

PubMed

Hallmann, R; Savigni, D L; Morgan, E H; Baker, E

2000-01-01

Iron is required by the brain for normal function, however, the mechanisms by which it crosses the blood-brain barrier (BBB) are poorly understood. The uptake and efflux of transferrin (Tf) and Fe by murine brain-derived (bEND3) and lymph node-derived (m1END1) endothelial cell lines was compared. The effects of iron chelators, metabolic inhibitors and the cellular activators, lipopolysaccharide (LPS) and tumour necrosis factor-alpha (TNF-alpha), on Tf and Fe uptake were investigated. Cells were incubated with 59Fe-125I-Tf; Fe uptake was shown to increase linearly over time for both cell lines, while Tf uptake reached a plateau within 2 h. Both Tf and Fe uptake were saturable. bEND3 cells were shown to have half as many Tf receptors as m1END1 cells, but the mean cycling times of a Tf molecule were the same. Tf and Fe efflux from the cells were measured over time, revealing that after 2 h only 25% of the Tf but 80% of the Fe remained associated with the cells. Of 7 iron chelators, only deferriprone (L1) markedly decreased Tf uptake. However, Fe uptake was reduced by more than 50% by L1, pyridoxal isonicotinoyl hydrazone (PIH) and desferrithiocin (DFT). The cellular activators TNF-alpha or LPS had little effect on Tf turnover, but they accelerated Fe uptake in both endothelial cell types. Phenylarsenoxide (PhAsO) and N-ethyl maleimide (NEM), inhibitors of Tf endocytosis, reduced both Tf and Fe uptake in both cell lines, while bafilomycin A1, an inhibitor of endosomal acidification, reduced Fe uptake but did not affect Tf uptake. The results suggest that Tf and Fe uptake by both bEND3 and m1END1 is via receptor-mediated endocytosis with release of Fe from Tf within the cell and recycling of apo-Tf. On the basis of Tf- and Fe-metabolism both cell lines are similar and therefore well suited for use in in vitro models for Fe transport across the BBB.

Demasculinization of male fish by wastewater treatment plant effluent

USGS Publications Warehouse

Vajda, A.M.; Barber, L.B.; Gray, J.L.; Lopez, E.M.; Bolden, A.M.; Schoenfuss, H.L.; Norris, D.O.

2011-01-01

Adult male fathead minnows (Pimephales promelas) were exposed to effluent from the City of Boulder, Colorado wastewater treatment plant (WWTP) under controlled conditions in the field to determine if the effluent induced reproductive disruption in fish. Gonadal intersex and other evidence of reproductive disruption were previously identified in white suckers (Catostomus commersoni) in Boulder Creek downstream from this WWTP effluent outfall. Fish were exposed within a mobile flow-through exposure laboratory in July 2005 and August 2006 to WWTP effluent (EFF), Boulder Creek water (REF), or mixtures of EFF and REF for up to 28 days. Primary (sperm abundance) and secondary (nuptial tubercles and dorsal fat pads) sex characteristics were demasculinized within 14 days of exposure to 50% and 100% EFF. Vitellogenin was maximally elevated in both 50% and 100% EFF treatments within 7 days and significantly elevated by 25% EFF within 14 days. The steroidal estrogens 17??-estradiol, estrone, estriol, and 17??-ethynylestradiol, as well as estrogenic alkylphenols and bisphenol A were identified within the EFF treatments and not in the REF treatment. These results support the hypothesis that the reproductive disruption observed in this watershed is due to endocrine-active chemicals in the WWTP effluent. ?? 2011 Elsevier B.V.

Ionic residues of human serum transferrin affect binding to the transferrin receptor and iron release.

PubMed

Steere, Ashley N; Miller, Brendan F; Roberts, Samantha E; Byrne, Shaina L; Chasteen, N Dennis; Smith, Valerie C; MacGillivray, Ross T A; Mason, Anne B

2012-01-17

Efficient delivery of iron is critically dependent on the binding of diferric human serum transferrin (hTF) to its specific receptor (TFR) on the surface of actively dividing cells. Internalization of the complex into an endosome precedes iron removal. The return of hTF to the blood to continue the iron delivery cycle relies on the maintenance of the interaction between apohTF and the TFR after exposure to endosomal pH (≤6.0). Identification of the specific residues accounting for the pH-sensitive nanomolar affinity with which hTF binds to TFR throughout the cycle is important to fully understand the iron delivery process. Alanine substitution of 11 charged hTF residues identified by available structures and modeling studies allowed evaluation of the role of each in (1) binding of hTF to the TFR and (2) TFR-mediated iron release. Six hTF mutants (R50A, R352A, D356A, E357A, E367A, and K511A) competed poorly with biotinylated diferric hTF for binding to TFR. In particular, we show that Asp356 in the C-lobe of hTF is essential to the formation of a stable hTF-TFR complex: mutation of Asp356 in the monoferric C-lobe hTF background prevented the formation of the stoichiometric 2:2 (hTF:TFR monomer) complex. Moreover, mutation of three residues (Asp356, Glu367, and Lys511), whether in the diferric or monoferric C-lobe hTF, significantly affected iron release when in complex with the TFR. Thus, mutagenesis of charged hTF residues has allowed identification of a number of residues that are critical to formation of and release of iron from the hTF-TFR complex.

Radiation hardness of lead glasses TF1 and TF101

NASA Astrophysics Data System (ADS)

Kobayashi, Masaaki; Prokoshkin, Yuri; Singovsky, Alexandre; Takamatsu, Kunio

1994-06-01

We have measured the radiation hardness of two types of lead glasses, TF1 and TF101, for low energy γ-rays from 60Co. TF101 containing cerium is a few tens times radiation harder than TF1 which contains no cerium. The radiation hardness, or the tolerable accumulated dose, of TF101 is 2 × 10 3 rad when the degradation of the transmittance is required to be less than 1% for the unit radiation length X0 = 2.8 cm. When the present result is compared with the work of Inyakin et al., the radiation hardness of TF101 glass should be similar for both γ-rays and for high energy hadrons.

Stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1.

PubMed

Schneider, G J; Geiduschek, E P

1990-06-25

The stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1 has been determined. 3H-Labeled TF1 was allowed to bind to a 32P-labeled DNA fragment containing a TF1 binding site. Multiple TF1-DNA complexes were resolved from each other and from unbound DNA by native gel electrophoresis. DNA-protein complexes were cut from polyacrylamide gels, and the amounts of 3H and 32P contained in each slice were measured. A ratio of 1.12 +/- 0.06 TF1 dimer/DNA molecule was calculated for the fastest-migrating TF1-DNA complex. We conclude that TF1 has a DNA-binding unit of one dimer. More slowly migrating complexes are apparently formed by serial addition of single TF1 dimers.

Identifying sensitive areas of adaptive observations for prediction of the Kuroshio large meander using a shallow-water model

NASA Astrophysics Data System (ADS)

Zou, Guang'an; Wang, Qiang; Mu, Mu

2016-09-01

Sensitive areas for prediction of the Kuroshio large meander using a 1.5-layer, shallow-water ocean model were investigated using the conditional nonlinear optimal perturbation (CNOP) and first singular vector (FSV) methods. A series of sensitivity experiments were designed to test the sensitivity of sensitive areas within the numerical model. The following results were obtained: (1) the eff ect of initial CNOP and FSV patterns in their sensitive areas is greater than that of the same patterns in randomly selected areas, with the eff ect of the initial CNOP patterns in CNOP sensitive areas being the greatest; (2) both CNOP- and FSV-type initial errors grow more quickly than random errors; (3) the eff ect of random errors superimposed on the sensitive areas is greater than that of random errors introduced into randomly selected areas, and initial errors in the CNOP sensitive areas have greater eff ects on final forecasts. These results reveal that the sensitive areas determined using the CNOP are more sensitive than those of FSV and other randomly selected areas. In addition, ideal hindcasting experiments were conducted to examine the validity of the sensitive areas. The results indicate that reduction (or elimination) of CNOP-type errors in CNOP sensitive areas at the initial time has a greater forecast benefit than the reduction (or elimination) of FSV-type errors in FSV sensitive areas. These results suggest that the CNOP method is suitable for determining sensitive areas in the prediction of the Kuroshio large-meander path.

Additional nuclear criticality safety calculations for small-diameter containers

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

Hone, M.J.

This report documents additional criticality safety analysis calculations for small diameter containers, which were originally documented in Reference 1. The results in Reference 1 indicated that some of the small diameter containers did not meet the criteria established for criticality safety at the Portsmouth facility (K{sub eff} +2{sigma}<.95) when modeled under various contingency assumptions of reflection and moderation. The calculations performed in this report reexamine those cases which did not meet the criticality safety criteria. In some cases, unnecessary conservatism is removed, and in other cases mass or assay limits are established for use with the respective containers.

Determination of enoxaparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent.

PubMed

Schaden, Eva; Schober, Andreas; Hacker, Stefan; Spiss, Christian; Chiari, Astrid; Kozek-Langenecker, Sibylle

2010-04-01

Drug monitoring of low molecular weight heparin is generally not recommended, but could be reasonable in critically ill patients, whose risk for bleeding or thrombosis shows a high interpatient variability. Anti-Xa assays are not available around the clock even in central hospitals, whereas rotational thrombelastometry (ROTEM) becomes increasingly used at the bedside. Prothrombinase-induced clotting time (PiCT) reagent allows determination of factor Xa-inhibition in plasma. The aim of our study was to evaluate enoxaparin determination in whole blood with the ROTEM using specific test modifications, including PiCT. After ethics committee's approval, citrated whole blood obtained from overall 16 healthy volunteers was incubated with enoxaparin at 16 different anti-Xa concentrations. Main endpoint was the clotting time (CT) in ROTEM representing initial activation of clot formation. CT was determined in the new PiCT-ROTEM test, in a low-tissue factor-activated modification (LowTF-ROTEM) as well as in the commercially available heparin-sensitive ROTEM assays (HEPTEM and INTEM). In the absence of enoxaparin, CT values were 168.6 +/- 6.1 s (PiCT-ROTEM), 247.3 +/- 18.6 s (LowTF-ROTEM), and -6.2 +/- 7.9 s (INTEM-HEPTEM). A linear dependency (P < 0.01) between anti-Xa concentration and CT was found for PiCT-ROTEM, LowTF-ROTEM, and for INTEM-HEPTEM with correlation coefficients of 0.93 for PiCT-ROTEM, 0.94 for LowTF-ROTEM, and 0.81 for INTEM-HEPTEM. This in-vitro experiment demonstrates a strong correlation between enoxaparin anti-Xa concentrations and specific ROTEM tests. These promising assays should be further evaluated for monitoring anticoagulation in high-risk patients in clinical studies.

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes

PubMed Central

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak

2017-01-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements. PMID:29232693

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

PubMed

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

2017-12-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Development of a high hertz-stress contact for conventional batch production using a unique scribing technology

NASA Astrophysics Data System (ADS)

Bhuiyan, M. M. I.; Alamgir, T.; Bhuiyan, M.; Kajihara, M.

2013-12-01

Gradually the electronic devices are getting more compact dimension with respect to the width and thickness. As a result, the contacts are becoming thinner and which leads the contact to be loose and unstable contact. In comercial stamping methode, connector tip diameter should be more than 300μm due to its size limitation. Consequently, the connector contact resistance is becoming higher due to weak contact force. To overcome this problem there were few more basic research using MEMS and Electro Fine Forming (EFF) technology to make high Hertz-Stress Contact (5μm) due to the limitation in the commercial stamping process and the result was in satisfactory level. However, since the MEMS and EFF fabrication is costly therefore, a new method is introduced in this paper using the commercial Phosphor Bronze stamping method to reduce the production cost. Moreover, scribing method is used to make tip on the contact. Accordingly, more compact fine pitch contact is successfully fabricated and tested with 5μm High Hertz Stress without using the MEMS and EFF technology. Hence the manufactured contact resistance becomes less than 20mΩ ±5mΩ.

Volcanic Signatures in Estimates of Stratospheric Aerosol Size, Distribution Width, Surface Area, and Volume Deduced from Global Satellite-Based Observations

NASA Technical Reports Server (NTRS)

Bauman, J. J.; Russell, P. B.

2000-01-01

Volcanic signatures in the stratospheric aerosol layer are revealed by two independent techniques which retrieve aerosol information from global satellite-based observations of particulate extinction. Both techniques combine the 4-wavelength Stratospheric Aerosol and Gas Experiment (SAGE) II extinction measurements (0.385 <= lambda <= 1.02 microns) with the 7.96 micron and 12.82 micron extinction measurements from the Cryogenic Limb Array Etalon Spectrometer (CLAES) instrument. The algorithms use the SAGE II/CLAES composite extinction spectra in month-latitude-altitude bins to retrieve values and uncertainties of particle effective radius R(sub eff), surface area S, volume V and size distribution width sigma(sub R). The first technique is a multi-wavelength Look-Up-Table (LUT) algorithm which retrieves values and uncertainties of R(sub eff) by comparing ratios of extinctions from SAGE II and CLAES (e.g., E(sub lambda)/E(sub 1.02) to pre-computed extinction ratios which are based on a range of unimodal lognormal size distributions. The pre-computed ratios are presented as a function of R(sub eff) for a given sigma(sub g); thus the comparisons establish the range of R(sub eff) consistent with the measured spectra for that sigma(sub g). The fact that no solutions are found for certain sigma(sub g) values provides information on the acceptable range of sigma(sub g), which is found to evolve in response to volcanic injections and removal periods. Analogous comparisons using absolute extinction spectra and error bars establish the range of S and V. The second technique is a Parameter Search Technique (PST) which estimates R(sub eff) and sigma(sub g) within a month-latitude-altitude bin by minimizing the chi-squared values obtained by comparing the SAGE II/CLAES extinction spectra and error bars with spectra calculated by varying the lognormal fitting parameters: R(sub eff), sigma(sub g), and the total number of particles N(sub 0). For both techniques, possible biases in retrieved-parameters caused by assuming a unimodal functional form are removed using correction factors computed from representative in situ measurements of bimodal size distributions. Some interesting features revealed by the LUT and PST retrievals include: (1) Increases in S and V (but not R(sub eff)) after the Ruiz and Kelut injections, (2) Increases in S, V, R(sub eff) after Pinatubo, (3) Post-Pinatubo increases in S, V, and R(sub eff) that are more rapid in the tropics than elsewhere, (4) Mid-latitude post-Pinatubo increases in R(sub eff) that lag increases in S and V, (5) S and V returning to pre-Pinatubo values sooner than R(sub eff) does, (6) Sharp increases in sigma(sub g), after Pinatubo and slight increases in sigma(sub g) after Ruiz, Etna, Kelut, Spurr and Rabaul, and (7) Gradual declines in the heights at which R(sub eff), S and V peak after Pinatubo.

Immunological and biochemical analysis of glycosylated surface antigens and lipophosphoglycan of Tritrichomonas foetus.

PubMed

Singh, B N; BonDurant, R H; Campero, C M; Corbeil, L B

2001-08-01

Immunoaffinity-purified TF1.17 adhesin antigen was compared biochemically and antigenically to Tritrichomonas foetus (TF) lipophosphoglycan (LPG) and a soluble glycosylated antigen (SGA) released from T. foetus and implicated in pathogenesis and immunity. The monoclonal antibodies (Mabs TF1.15 and TF1.17) specific for a glycosylated TF1.17 antigen were previously shown to prevent adhesion of the T. foetus parasites to bovine vaginal epithelial cells and to mediate killing by bovine complement. SGA was isolated from T. foetus-conditioned buffer and purified by octyl-Sepharose hydrophobic column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of SGA showed a major SGA1 component (approximately 190 kDa) and a minor SGA2 component (50-70 kDa), which migrated close to TF-LPG and TF1.17. The carbohydrate and lipid compositional analyses of affinity-purified TF1.17 and SGA2 by high-performance liquid chromatography (HPLC) and gas-liquid chromatography revealed the presence of monosaccharides and fatty acids as found in TF-LPG. All antigens contained terminal fucose as determined by alpha-fucosidase digestion followed by HPLC. ELISA and western blots were used to further characterize these glycosylated antigens and to analyze their relationships. The Mabs TF1.15 and TF1.17 reacted very strongly to TF-LPG and SGA2. as well as TF1.17 antigen, indicating that these molecules share common epitopes. These Mabs did not react with the SGA1 component either in ELISA and western blot analyses. Also, the monosaccharide composition of SGA1 was very different from the other three antigen, suggesting SGA1 was different from LPG, SGA2 and TF1.17. Although LPG reacted with Mabs to native TF1.17 antigen, LPG did not induce an immune response in cattle with the same route and adjuvant used to produce strong antibody responses to the native antigen. The latter response suggests that the tightly bound peptide present in the immunoaffinity-purified antigen is necessary for induction of a response to (an) epitope(s) in TF-LPG and TF1.17. Furthermore, vaginal fluid from T. foetus-infected heifers and serum from a cow with a T. foetus-associated pyometra recognized both TF1.17 and TF-LPG in western blots. These results suggest that T. foetus LPG and SGA2 are related to TF1.17 antigen, which was previously shown to play an important role in the pathogenesis and host response in bovine trichomoniasis.

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis.

PubMed

Babaliaros, Vasilis; Devireddy, Chandan; Lerakis, Stamatios; Leonardi, Robert; Iturra, Sebastian A; Mavromatis, Kreton; Leshnower, Bradley G; Guyton, Robert A; Kanitkar, Mihir; Keegan, Patricia; Simone, Amy; Stewart, James P; Ghasemzadeh, Nima; Block, Peter; Thourani, Vinod H

2014-08-01

The aim of this study was to compare transfemoral transcatheter aortic valve replacement (TF TAVR) performed in a catheterization laboratory (minimalist approach [MA]) with TF TAVR performed in a hybrid operating room (standard approach [SA]). A MA-TF TAVR can be performed without general anesthesia, transesophageal echocardiography, or a surgical hybrid room. The outcomes and cost of MA-TF TAVR compared with those of the SA have not been described. Patients who underwent elective, percutaneous TF TAVR using the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) were studied. Baseline characteristics, outcomes, and hospital costs of MA-TF TAVR and SA-TF TAVR were compared. A total of 142 patients were studied (MA-TF TAVR, n = 70 and SA-TF TAVR, n = 72). There were no differences in baseline comorbidities (Society of Thoracic Surgeons score, 10.6 ± 4.3 vs. 11.4 ± 5.8; p = 0.35). All procedures in the MA-TF TAVR group were successful; 1 patient was intubated. Three patients in the SA-TF TAVR group had procedure-related death. Procedure room time (150 ± 48 min vs. 218 ± 56 min, p < 0.001), total intensive care unit time (22 h vs. 28 h, p < 0.001), length of stay from procedure to discharge (3 days vs. 5 days, p < 0.001), and cost ($45,485 ± 14,397 vs. $55,377 ± 22,587, p < 0.001) were significantly less in the MA-TF TAVR group. Mortality at 30 days was not significantly different in the MA-TF TAVR group (0 vs. 6%, p = 0.12) and 30-day stroke/transient ischemic attack was similar (4.3% vs. 1.4%, p = 0.35). Moderate or severe paravalvular leak and device success were similar in the MA-TF TAVR and SA-TF TAVR groups (3% vs. 5.8%, p = 0.4 and 90% vs. 88%, p = 0.79, respectively) at 30 days. At a median follow-up of 435 days, there was no significant difference in survival (MA-TF TAVR, 83% vs. SA-TF TAVR, 82%; p = 0.639). MA-TF TAVR can be performed with minimal morbidity and mortality and equivalent effectiveness compared with SA-TF TAVR. The shorter length of stay and lower resource use with MA-TF TAVR significantly lowers hospital costs. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Educating Idaho Teenage Drivers of the Dangers of Distracted Driving

DOT National Transportation Integrated Search

2017-08-01

The objective of this research project efforts are: 1) to develop an interactive driver-distracted presentation that can be used at different high schools in Idaho to educate teenage drivers about the danger of distracted driving, 2) to test the effe...

Performance evaluation of Arizona's LTPP SPS-6 project : strategic study of rehabilitation techniques.

DOT National Transportation Integrated Search

2013-10-01

As part of the Long Term Pavement Performance (LTPP) Program, the Arizona Department of Transportation (ADOT) : constructed 19 Specific Pavement Studies 6 (SPS6) test sections on Interstate 40 near Flagstaff. The SPS6 project : studied the effe...

Optical Rotation Curves and Linewidths for Tully-Fisher Applications

NASA Astrophysics Data System (ADS)

Courteau, Stephane

1997-12-01

We present optical long-slit rotation curves for 304 northern Sb-Sc UGC galaxies from a sample designed for Tully-Fisher (TF) applications. Matching r-band photometry exists for each galaxy. We describe the procedures of rotation curve (RC) extraction and construction of optical profiles analogous to 21 cm integrated linewidths. More than 20% of the galaxies were observed twice or more, allowing for a proper determination of systematic errors. Various measures of maximum rotational velocity to be used as input in the TF relation are tested on the basis of their repeatability, minimization of TF scatter, and match with 21 cm linewidths. The best measure of TF velocity, V2.2 is given at the location of peak rotational velocity of a pure exponential disk. An alternative measure to V2.2 which makes no assumption about the luminosity profile or shape of the rotation curve is Vhist, the 20% width of the velocity histogram, though the match with 21 cm linewidths is not as good. We show that optical TF calibrations yield internal scatter comparable to, if not smaller than, the best calibrations based on single-dish 21 cm radio linewidths. Even though resolved H I RCs are more extended than their optical counterpart, a tight match between optical and radio linewidths exists since the bulk of the H I surface density is enclosed within the optical radius. We model the 304 RCs presented here plus a sample of 958 curves from Mathewson et al. (1992, APJS, 81, 413) with various fitting functions. An arctan function provides an adequate simple fit (not accounting for non-circular motions and spiral arms). More elaborate, empirical models may yield a better match at the expense of strong covariances. We caution against physical or "universal" parametrizations for TF applications.

Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

PubMed

Büyükkaragöz, Bahar; Akgun, Necat A; Bulus, Ayse D; Durmus Aydogdu, Sultan; Bal, Cengiz

2017-04-01

To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p <0.001). Ferritin and C-reactive protein (CRP) were significantly higher in MA group (p <0.05 ferritin, p 0.01 for CRP). Mean sTfR was similar in both MA and A groups (p >0.05) and significantly higher than controls (p <0.001). Following iron treatment, sTfR decreased in both MA and A groups (p <0.001) to similar values as controls. sTfR was negatively correlated to Hb throughout the study (for MA group, r= -0.350, p <0.05; for A group, r= -0.683, p <0.01). As sTfR values in both MA and A groups decreased following iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

A Combination of Extreme Environmental Conditions Favor the Prevalence of Endospore-Forming Firmicutes

PubMed Central

Filippidou, Sevasti; Wunderlin, Tina; Junier, Thomas; Jeanneret, Nicole; Dorador, Cristina; Molina, Veronica; Johnson, David R.; Junier, Pilar

2016-01-01

Environmental conditions unsuitable for microbial growth are the rule rather than the exception in most habitats. In response to this, microorganisms have developed various strategies to withstand environmental conditions that limit active growth. Endospore-forming Firmicutes (EFF) deploy a myriad of survival strategies in order to resist adverse conditions. Like many bacterial groups, they can form biofilms and detect nutrient scarcity through chemotaxis. Moreover, within this paraphyletic group of Firmicutes, ecophysiological optima are diverse. Nonetheless, a response to adversity that delimits this group is the formation of wet-heat resistant spores. These strategies are energetically demanding and therefore might affect the biological success of EFF. Therefore, we hypothesize that abundance and diversity of EFF should be maximized in those environments in which the benefits of these survival strategies offsets the energetic cost. In order to address this hypothesis, geothermal and mineral springs and drillings were selected because in these environments of steep physicochemical gradients, diversified survival strategies may become a successful strategy.We collected 71 samples from geothermal and mineral environments characterized by none (null), single or multiple limiting environmental factors (temperature, pH, UV radiation, and specific mineral composition). To measure success, we quantified EFF gene copy numbers (GCN; spo0A gene) in relation to total bacterial GCN (16S rRNA gene), as well as the contribution of EFF to community composition. The quantification showed that relative GCN for EFF reached up to 20% at sites characterized by multiple limiting environmental factors, whereas it corresponded to less than 1% at sites with one or no limiting environmental factor. Pyrosequencing of the 16S rRNA gene supports a higher contribution of EFF at sites with multiple limiting factors. Community composition suggested a combination of phylotypes for which active growth could be expected, and phylotypes that are most likely in the state of endospores, in all the sites. In summary, our results suggest that diversified survival strategies, including sporulation and metabolic adaptations, explain the biological success of EFF in geothermal and natural springs, and that multiple extreme environmental factors favor the prevalence of EFF. PMID:27857706

A Combination of Extreme Environmental Conditions Favor the Prevalence of Endospore-Forming Firmicutes.

PubMed

Filippidou, Sevasti; Wunderlin, Tina; Junier, Thomas; Jeanneret, Nicole; Dorador, Cristina; Molina, Veronica; Johnson, David R; Junier, Pilar

2016-01-01

Environmental conditions unsuitable for microbial growth are the rule rather than the exception in most habitats. In response to this, microorganisms have developed various strategies to withstand environmental conditions that limit active growth. Endospore-forming Firmicutes (EFF) deploy a myriad of survival strategies in order to resist adverse conditions. Like many bacterial groups, they can form biofilms and detect nutrient scarcity through chemotaxis. Moreover, within this paraphyletic group of Firmicutes, ecophysiological optima are diverse. Nonetheless, a response to adversity that delimits this group is the formation of wet-heat resistant spores. These strategies are energetically demanding and therefore might affect the biological success of EFF. Therefore, we hypothesize that abundance and diversity of EFF should be maximized in those environments in which the benefits of these survival strategies offsets the energetic cost. In order to address this hypothesis, geothermal and mineral springs and drillings were selected because in these environments of steep physicochemical gradients, diversified survival strategies may become a successful strategy.We collected 71 samples from geothermal and mineral environments characterized by none (null), single or multiple limiting environmental factors (temperature, pH, UV radiation, and specific mineral composition). To measure success, we quantified EFF gene copy numbers (GCN; spo0A gene) in relation to total bacterial GCN (16S rRNA gene), as well as the contribution of EFF to community composition. The quantification showed that relative GCN for EFF reached up to 20% at sites characterized by multiple limiting environmental factors, whereas it corresponded to less than 1% at sites with one or no limiting environmental factor. Pyrosequencing of the 16S rRNA gene supports a higher contribution of EFF at sites with multiple limiting factors. Community composition suggested a combination of phylotypes for which active growth could be expected, and phylotypes that are most likely in the state of endospores, in all the sites. In summary, our results suggest that diversified survival strategies, including sporulation and metabolic adaptations, explain the biological success of EFF in geothermal and natural springs, and that multiple extreme environmental factors favor the prevalence of EFF.

Binding affinity of aluminium to human serum transferrin and effects of carbohydrate chain modification as studied by HPLC/high-resolution ICP-MS--speciation of aluminium in human serum.

PubMed

Nagaoka, Megumi Hamano; Maitani, Tamio

2005-09-01

Aluminium (Al) in the blood is bound to transferrin (Tf), a glycoprotein of about 80kDa that is characterized by its need for a synergistic anion. In this focused review, the binding affinity of Al to Tf is surveyed in the context of our recent studies using on-line high-performance liquid chromatography/high-resolution inductively coupled plasma mass spectrometry (HPLC/HR-ICP-MS). Al in human serum without any in vitro Al-spikes was present in a form bound to the N-lobe site of Tf. The influences of sialic acid in the carbohydrate chain of human serum Tf (hTf) were studied using asialo-hTf, obtained by treatment with sialidase. The binding affinity of Fe was similar between asialo-hTf and native-hTf, while that of Al for asialo-hTf was larger than that for native-hTf, especially in the presence of oxalate, a synergistic anion. The above findings are discussed in relation to diseases in which the serum concentrations of carbohydrate-deficient Tf and oxalate are augmented.

Advising the Command: Best Practices from the Special Operations Advisory Experience in Afghanistan

DTIC Science & Technology

2015-01-01

in their spare time. They looked for opportunities to have lunch with Afghans and reportedly extended offers for dinner .18 The SMW ETT cultivated...extremely close relationships with their counterparts, in part by routinely eating with colleagues in the Afghan dining facility. They initiated the...October 21 and November 21, 2013. The practice is very much akin to that of Task Force (TF) 51, where Norwegian SOF operators eat daily meals with

Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.

PubMed

Antoniak, S; Tatsumi, K; Hisada, Y; Milner, J J; Neidich, S D; Shaver, C M; Pawlinski, R; Beck, M A; Bastarache, J A; Mackman, N

2016-06-01

Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection. © 2016 International Society on Thrombosis and Haemostasis.

p53 determines prognostic significance of the carbohydrate stem cell marker TF1 (CD176) in ovarian cancer.

PubMed

Heublein, Sabine; Page, Sabina K; Mayr, Doris; Ditsch, Nina; Jeschke, Udo

2016-06-01

The oncofoetal Thomsen-Friedenreich (TF1, CD176) epitope is a carbohydrate cancer stem cell (CSC) antigen, and TF1-mediated cancer progression can be widely reversed by anti-TF1 antibodies. Particularly, CSC-like cells are regarded to be tumorigenic and chemoresistant. Aberrant p53 is probably the factor most closely associated with chemoresistance and tumour aggressiveness in ovarian tumours. We thus questioned whether TF1 in combination with p53 or as a single marker may be related to clinico-pathological features and survival of ovarian cancer patients. Both markers were quantified in ovarian cancer tissue (n = 151) by immunohistochemistry. p53 staining was subdivided into three subgroups [n (completely negative) = 57, n (moderately stained) = 28, n (overexpressing) = 66]. TF1 was scored as positive (n = 30) versus negative (n = 121). Only in those cancers classified with moderate p53 staining-and thus most likely displaying with wild-type TP53-TF1 positivity turned out to be a predictor for shortened overall survival (univariate: p < 0.001, multivariate: p = 0.001). By screening 17 different protein markers for correlation with TF1, only mucin-1 emerged as a potential TF1 carrier protein. It is hypothesized that TF1 may confer tumour-promoting features, especially in a TP53 wild-type genetic background. In addition, TF1 is an attractive immunotherapeutic target. Whether those cases classified as TF1 positive and at the same time as moderately stained for p53 might particularly benefit from a future anti-TF1 antibody treatment or from TF1 vaccination therapy remains to be determined.

The removal of RNA primers from DNA synthesized by the reverse transcriptase of the retrotransposon Tf1 is stimulated by Tf1 integrase.

PubMed

Herzig, Eytan; Voronin, Nickolay; Hizi, Amnon

2012-06-01

The Tf1 retrotransposon represents a group of long terminal repeat retroelements that use an RNA self-primer for initiating reverse transcription while synthesizing the minus-sense DNA strand. Tf1 reverse transcriptase (RT) was found earlier to generate the self-primer in vitro. Here, we show that this RT can remove from the synthesized cDNA the entire self-primer as well as the complete polypurine tract (PPT) sequence (serving as a second primer for cDNA synthesis). However, these primer removals, mediated by the RNase H activity of Tf1 RT, are quite inefficient. Interestingly, the integrase of Tf1 stimulated the specific Tf1 RT-directed cleavage of both the self-primer and PPT, although there was no general enhancement of the RT's RNase H activity (and the integrase by itself is devoid of any primer cleavage). The RTs of two prototype retroviruses, murine leukemia virus and human immunodeficiency virus, showed only a partial and nonspecific cleavage of both Tf1-associated primers with no stimulation by Tf1 integrase. Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity. Nonetheless, a double mutant integrase that has lost its integration functions can still stimulate the RT's activity, though heat-inactivated integrase cannot enhance primer removals. These findings suggest that the enzymatic activity of Tf1 integrase is not essential for stimulating the RT-mediated primer removal, while the proper folding of this protein is obligatory for this function. These results highlight possible new functions of Tf1 integrase in the retrotransposon's reverse transcription process.

The Removal of RNA Primers from DNA Synthesized by the Reverse Transcriptase of the Retrotransposon Tf1 Is Stimulated by Tf1 Integrase

PubMed Central

Herzig, Eytan; Voronin, Nickolay

2012-01-01

The Tf1 retrotransposon represents a group of long terminal repeat retroelements that use an RNA self-primer for initiating reverse transcription while synthesizing the minus-sense DNA strand. Tf1 reverse transcriptase (RT) was found earlier to generate the self-primer in vitro. Here, we show that this RT can remove from the synthesized cDNA the entire self-primer as well as the complete polypurine tract (PPT) sequence (serving as a second primer for cDNA synthesis). However, these primer removals, mediated by the RNase H activity of Tf1 RT, are quite inefficient. Interestingly, the integrase of Tf1 stimulated the specific Tf1 RT-directed cleavage of both the self-primer and PPT, although there was no general enhancement of the RT's RNase H activity (and the integrase by itself is devoid of any primer cleavage). The RTs of two prototype retroviruses, murine leukemia virus and human immunodeficiency virus, showed only a partial and nonspecific cleavage of both Tf1-associated primers with no stimulation by Tf1 integrase. Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity. Nonetheless, a double mutant integrase that has lost its integration functions can still stimulate the RT's activity, though heat-inactivated integrase cannot enhance primer removals. These findings suggest that the enzymatic activity of Tf1 integrase is not essential for stimulating the RT-mediated primer removal, while the proper folding of this protein is obligatory for this function. These results highlight possible new functions of Tf1 integrase in the retrotransposon's reverse transcription process. PMID:22491446

The Microbiota Is Essential for the Generation of Black Tea Theaflavins-Derived Metabolites

PubMed Central

Chen, Huadong; Hayek, Saeed; Rivera Guzman, Javier; Gillitt, Nicholas D.; Ibrahim, Salam A.; Jobin, Christian; Sang, Shengmin

2012-01-01

Background Theaflavins including theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3′-gallate (TF3′G), and theaflavin-3,3′-digallate (TFDG), are the most important bioactive polyphenols in black tea. Because of their poor systemic bioavailability, it is still unclear how these compounds can exert their biological functions. The objective of this study is to identify the microbial metabolites of theaflavins in mice and in humans. Methods and Findings In the present study, we gavaged specific pathogen free (SPF) mice and germ free (GF) mice with 200 mg/kg TFDG and identified TF, TF3G, TF3′G, and gallic acid as the major fecal metabolites of TFDG in SPF mice. These metabolites were absent in TFDG- gavaged GF mice. The microbial bioconversion of TFDG, TF3G, and TF3′G was also investigated in vitro using fecal slurries collected from three healthy human subjects. Our results indicate that TFDG is metabolized to TF, TF3G, TF3′G, gallic acid, and pyrogallol by human microbiota. Moreover, both TF3G and TF3′G are metabolized to TF, gallic acid, and pyrogallol by human microbiota. Importantly, we observed interindividual differences on the metabolism rate of gallic acid to pyrogallol among the three human subjects. In addition, we demonstrated that Lactobacillus plantarum 299v and Bacillus subtilis have the capacity to metabolize TFDG. Conclusions The microbiota is important for the metabolism of theaflavins in both mice and humans. The in vivo functional impact of microbiota-generated theaflavins-derived metabolites is worthwhile of further study. PMID:23227227

Differential effects of somatostatin on circulating tissue factor procoagulant activity and protein.

PubMed

Boden, Guenther; Vaidyula, Vijender; Homko, Carol; Mozzoli, Maria; Rao, A Koneti

2007-05-01

The tissue factor (TF) pathway is the primary mechanism for initiation of blood coagulation. Circulating blood contains TF, which originates mainly from monocytes and is thrombogenic. The presence of somatostatin (SMS) receptors on monocytes suggests the possibility that SMS may regulate TF synthesis and/or release. Circulating TF procoagulant activity (TF-PCA), factor VIIa activity (FVIIa; clotting assays), TF antigen (TF-Ag; ELISA), prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complexes (ELISAs), CD40 ligand expression on platelets, and monocyte-platelet aggregates (flow cytometry) were determined in blood from normal volunteers undergoing 24 h of basal glucose/basal insulin (BG/BI) clamps and high-glucose/high-insulin (HG/HI) clamps with and without SMS. Infusions of SMS under basal conditions (BG/BI) raised TF-PCA 1.8-fold (P < 0.03), TF-Ag 2.3-fold (P < 0.001), and TF expression on monocytes by 36% (P < 0.001) and decreased plasma levels of FVIIa by 30% (P < 0.001). Infusion of SMS reduced the 8.6-fold HG/HI-induced increase in TF-Ag by 26% and the 8.6-fold increase in TF-PCA by 100%. SMS also prevented the 60% increase in TF expression on monocytes, the 2.2-fold increase in F1.2, the 40% increase in CD40L expression on platelets, and the 17% increase in monocyte-platelet aggregates seen during HG/HI. We conclude that SMS completely prevented HG/HI-induced TF activation in normal volunteers and may be of use to reduce the procoagulant state and acute vascular events in hyperinsulinemic insulin-resistant patients with type 2 diabetes.

The Intracellular Trafficking Pathway of Transferrin

PubMed Central

Mayle, Kristine M.; Le, Alexander M.; Kamei, Daniel T.

2011-01-01

Background Transferrin (Tf) is an iron-binding protein that facilitates iron-uptake in cells. Iron-loaded Tf first binds to the Tf receptor (TfR) and enters the cell through clathrin-mediated endocytosis. Inside the cell, Tf is trafficked to early endosomes, delivers iron, and then is subsequently directed to recycling endosomes to be taken back to the cell surface. Scope of Review We aim to review the various methods and techniques that researchers have employed for elucidating the Tf trafficking pathway and the cell-machinery components involved. These experimental methods can be categorized as microscopy, radioactivity, and surface plasmon resonance (SPR). Major Conclusions Qualitative experiments, such as total internal reflectance fluorescence (TIRF), electron, laser-scanning confocal, and spinning-disk confocal microscopy, have been utilized to determine the roles of key components in the Tf trafficking pathway. These techniques allow temporal resolution and are useful for imaging Tf endocytosis and recycling, which occur on the order of seconds to minutes. Additionally, radiolabeling and SPR methods, when combined with mathematical modeling, have enabled researchers to estimate quantitative kinetic parameters and equilibrium constants associated with Tf binding and trafficking. General Significance Both qualitative and quantitative data can be used to analyze the Tf trafficking pathway. The valuable information that is obtained about the Tf trafficking pathway can then be combined with mathematical models to identify design criteria to improve the ability of Tf to deliver anticancer drugs. PMID:21968002

Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome.

PubMed

Killisch, I; Steinlein, P; Römisch, K; Hollinshead, R; Beug, H; Griffiths, G

1992-09-01

We describe a detailed morphological characterization of the endocytic pathway in differentiating chicken erythroblasts transformed by a temperature-sensitive mutant of avian erythroblastosis virus (AEV). These cells express high levels of transferrin receptors (TfR) when induced to differentiate at 42 degrees C. Biochemical analysis showed that most (approximately 90%) of the internalized 125I-Tf recycled within approximately 30 min while a smaller fraction of 125I-Tf required up to 2 h for recycling. By immunocytochemistry, the bulk of Tf and TfR was localized at the plasma membrane and in tubuloreticular early endosomes. This structure contained coated buds that labelled with an antibody specific for the clathrin light chain. Decreasing amounts of both Tf and TfR were detected in two distal compartments, spherical endosome vesicles resembling multivesicular bodies and the prelysosomal compartment (PLC) enriched in cation-independent mannose 6-phosphate receptor. As shown by fluorescent (FITC-Tf) labelling of living cells, the movement of Tf/TfR complex into these late structures was accompanied by a significant drop in pH from about 6, the value displayed by early endosomes, to values below pH 5.0. Since no detectable 125I-Tf degradation was observed during a 4 h period we believe that the Tf/TfR detected in these late endocytic structures avoids degradation and recycles back to the cell surface. The addition of an anti-TfR monoclonal antibody to the culture medium of these cells blocks their differentiation. Under this condition the antibody-TfR complex was trapped in an early endosome compartment that enlarged to more than twice its normal size. However, this condition did not affect the transport kinetics of horseradish peroxidase from the medium to the PLC.

Sensitivity-Uncertainty Techniques for Nuclear Criticality Safety

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

Brown, Forrest B.; Rising, Michael Evan; Alwin, Jennifer Louise

2017-08-07

The sensitivity and uncertainty analysis course will introduce students to k eff sensitivity data, cross-section uncertainty data, how k eff sensitivity data and k eff uncertainty data are generated and how they can be used. Discussion will include how sensitivity/uncertainty data can be used to select applicable critical experiments, to quantify a defensible margin to cover validation gaps and weaknesses, and in development of upper subcritical limits.

Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

PubMed

Clark, Andrew J; Davis, Mark E

2015-10-06

Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

Directed Energy Beam Jitter Mitigation Using the Line-of-Sight Reference Frame

DTIC Science & Technology

2011-05-10

tg,’Connected’); C4 = ’Yes’ TF1 =strcmp(C1, C2);TF2=strcmp(C3, C4); if ~ TF1 ; unload(tg); load(tg,’FFD_9’); tg=xpctarget.xpc; end if...C1 = (get(tg,’Application’));C2=’FFD_9’C3 = get(tg,’Connected’); C4 = ’Yes’ TF1 =strcmp(C1, C2);TF2=strcmp(C3, C4); if ~ TF1 ; unload(tg

On the Design of VLSI Circuits for the Winograd Fourier Transform Algorithm

DTIC Science & Technology

1991-12-01

3-:3 T’able 8: Twiddle factors in TF1 (real side) ... .. .. .. .. .... ... .. .. ...- 4 T;l1)a1e 9: Twiddle factors I n... TF1 (imaginary side) .. .. .. .. ... ... .... .. 13-5 ’fable 10: Twiddle factors in TF2 (r’eal side) ... .. .. .. .. .... ... .... .. 13-6 ’Table 11...reads its twiddle factor from Y. The four other possibilities (TFO, TF1 , TF2, and TF3) correspond to the fixed values that are necessary for computing 20

Direct experimental observation of the molecular J eff = 3/2 ground state in the lacunar spinel GaTa4Se8.

PubMed

Jeong, Min Yong; Chang, Seo Hyoung; Kim, Beom Hyun; Sim, Jae-Hoon; Said, Ayman; Casa, Diego; Gog, Thomas; Janod, Etienne; Cario, Laurent; Yunoki, Seiji; Han, Myung Joon; Kim, Jungho

2017-10-04

Strong spin-orbit coupling lifts the degeneracy of t 2g orbitals in 5d transition-metal systems, leaving a Kramers doublet and quartet with effective angular momentum of J eff  = 1/2 and 3/2, respectively. These spin-orbit entangled states can host exotic quantum phases such as topological Mott state, unconventional superconductivity, and quantum spin liquid. The lacunar spinel GaTa 4 Se 8 was theoretically predicted to form the molecular J eff  = 3/2 ground state. Experimental verification of its existence is an important first step to exploring the consequences of the J eff  = 3/2 state. Here, we report direct experimental evidence of the J eff  = 3/2 state in GaTa 4 Se 8 by means of excitation spectra of resonant inelastic X-ray scattering at the Ta L 3 and L 2 edges. We find that the excitations involving the J eff  = 1/2 molecular orbital are absent only at the Ta L 2 edge, manifesting the realization of the molecular J eff  = 3/2 ground state in GaTa 4 Se 8 .The strong interaction between electron spin and orbital degrees of freedom in 5d oxides can lead to exotic electronic ground states. Here the authors use resonant inelastic X-ray scattering to demonstrate that the theoretically proposed J eff  = 3/2 state is realised in GaTa 4 Se 8 .

Water ice cloud property retrievals at Mars with OMEGA:Spatial distribution and column mass

NASA Astrophysics Data System (ADS)

Olsen, Kevin S.; Madeleine, Jean-Baptiste; Szantai, Andre; Audouard, Joachim; Geminale, Anna; Altieri, Francesca; Bellucci, Giancarlo; Montabone, Luca; Wolff, Michael J.; Forget, Francois

2017-04-01

Spectral images of Mars recorded by OMEGA (Observatoire pour la Minéralogie, l'Eau, les Glaces et l'Activité) on Mars Express can be used to deduce the mean effective radius (r_eff) and optical depth (τ_i) of water ice particles in clouds. Using new data sets for a priori surface temperature, vertical profiles of atmospheric temperature, dust opacity, and multi-spectral surface albedo, we have analyzed over 40 OMEGA image cubes over the Tharsis, Arabia, and Syrtis Major quadrangles, and mapped the spatial distribution of r_eff, τ_i, and water ice column mass. We also explored the parameter space of r_eff and τ_i, which are inversely proportional, and the ice cloud index (ICI), which is the ratio of the reflectance at 3.4 and 3.52 μm, and indicates the thickness of water ice clouds. We found that the ICI, trivial to calculate for OMEGA image cubes, can be a proxy for column mass, which is very expensive to compute, requiring accurate retrievals of surface albedo, r_eff, and τ_i. Observing the spatial distribution, we find that within each cloud system, r_eff varies about a mean of 2.1 μm, that τi is closely related to r_eff, and that the values allowed for τ_i, given r_eff, are related to the ICI. We also observe areas where our retrieval detects very thin clouds made of very large particles (mean of 12.5 μm), which are still under investigation.

Site-Specific 64Cu Labeling of the Serine Protease, Active Site Inhibited Factor Seven Azide (FVIIai-N3), Using Copper Free Click Chemistry.

PubMed

Jeppesen, Troels E; Kristensen, Lotte K; Nielsen, Carsten H; Petersen, Lars C; Kristensen, Jesper B; Behrens, Carsten; Madsen, Jacob; Kjaer, Andreas

2018-01-17

A method for site-specific radiolabeling of the serine protease active site inhibited factor seven (FVIIai) with 64 Cu has been applied using a biorthogonal click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein involved in hemostasis, angiogenesis, proliferation, cell migration, and survival of cancer cells. First a single azide moiety was introduced in the active site of this 50 kDa protease. Then a NOTA moiety was introduced via a strain promoted azide-alkyne reaction and the corresponding conjugate was labeled with 64 Cu. Binding to TF and the stability was evaluated in vitro. TF targeting capability of the radiolabeled conjugate was tested in vivo by positron emission tomography (PET) imaging in pancreatic human xenograft cancer mouse models with various TF expressions. The conjugate showed good stability (>91% at 16 h), an immunoreactivity of 93.5%, and a mean tumor uptake of 2.1 ± 0.2%ID/g at 15 h post injection. In conclusion, FVIIai was radiolabeled with 64 Cu in single well-defined position of the protein. This method can be utilized to prepare conjugates from serine proteases with the label at a specific position.

Transcriptomics hit the target: Monitoring of ligand-activated and stress response pathways for chemical testing.

PubMed

Limonciel, Alice; Moenks, Konrad; Stanzel, Sven; Truisi, Germaine L; Parmentier, Céline; Aschauer, Lydia; Wilmes, Anja; Richert, Lysiane; Hewitt, Philip; Mueller, Stefan O; Lukas, Arno; Kopp-Schneider, Annette; Leonard, Martin O; Jennings, Paul

2015-12-25

High content omic methods provide a deep insight into cellular events occurring upon chemical exposure of a cell population or tissue. However, this improvement in analytic precision is not yet matched by a thorough understanding of molecular mechanisms that would allow an optimal interpretation of these biological changes. For transcriptomics (TCX), one type of molecular effects that can be assessed already is the modulation of the transcriptional activity of a transcription factor (TF). As more ChIP-seq datasets reporting genes specifically bound by a TF become publicly available for mining, the generation of target gene lists of TFs of toxicological relevance becomes possible, based on actual protein-DNA interaction and modulation of gene expression. In this study, we generated target gene signatures for Nrf2, ATF4, XBP1, p53, HIF1a, AhR and PPAR gamma and tracked TF modulation in a large collection of in vitro TCX datasets from renal and hepatic cell models exposed to clinical nephro- and hepato-toxins. The result is a global monitoring of TF modulation with great promise as a mechanistically based tool for chemical hazard identification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver.

PubMed

Adrian, G S; Rivera, E V; Adrian, E K; Lu, Y; Buchanan, J; Herbert, D C; Weaker, F J; Walter, C A; Bowman, B H

1993-01-01

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.

Influence of Hamstring Tightness in Pelvic, Lumbar and Trunk Range of Motion in Low Back Pain and Asymptomatic Volunteers during Forward Bending

PubMed Central

Macedo, Adriana Ribeiro

2015-01-01

Study Design Cross-sectional study. Purpose To verify the association of hamstring tightness and range of motion in anterior pelvic tilt (PT), lumbar motion (LM), and trunk flexion (TF) during forward bending. Overview of Literature Increased hamstring stiffness could be a possible contributing factor to low back injuries. Clinical observations have suggested that hamstring tightness influences lumbar pelvic rhythm. Movement restrictions or postural asymmetry likely lead to compensatory movement patterns of the lumbar spine, and subsequently to increased stress on the spinal soft tissues and an increased risk of low back pain (LBP). Methods Hamstring muscle tightness was measured using the self-monitored active knee extension (AKE) test. A bubble inclinometer was used to determine the range of motion of PT, LM, and TF during forward bending. Statistical analysis included descriptive statistics, comparisons between groups and a correlation between hamstring tightness (AKE) and anterior PT, TF, and regional LM with p≤0.05. Results The LBP group was composed of 36 participants, and the asymptomatic group consisted of 32 participants. The mean for PT in the control group was 66.7°, 64.5° for LM and 104.6° for TF. Respective values in the symptomatic group were 57.0°, 79.8°, and 82.2°. Conclusions Participants with LBP showed restriction in the pelvis and TF range of motion, but had higher amplitudes in the lumbar spine during forward bending. PMID:26240711

Influence of Hamstring Tightness in Pelvic, Lumbar and Trunk Range of Motion in Low Back Pain and Asymptomatic Volunteers during Forward Bending.

PubMed

Jandre Reis, Felipe Jose; Macedo, Adriana Ribeiro

2015-08-01

Cross-sectional study. To verify the association of hamstring tightness and range of motion in anterior pelvic tilt (PT), lumbar motion (LM), and trunk flexion (TF) during forward bending. Increased hamstring stiffness could be a possible contributing factor to low back injuries. Clinical observations have suggested that hamstring tightness influences lumbar pelvic rhythm. Movement restrictions or postural asymmetry likely lead to compensatory movement patterns of the lumbar spine, and subsequently to increased stress on the spinal soft tissues and an increased risk of low back pain (LBP). Hamstring muscle tightness was measured using the self-monitored active knee extension (AKE) test. A bubble inclinometer was used to determine the range of motion of PT, LM, and TF during forward bending. Statistical analysis included descriptive statistics, comparisons between groups and a correlation between hamstring tightness (AKE) and anterior PT, TF, and regional LM with p≤0.05. The LBP group was composed of 36 participants, and the asymptomatic group consisted of 32 participants. The mean for PT in the control group was 66.7°, 64.5° for LM and 104.6° for TF. Respective values in the symptomatic group were 57.0°, 79.8°, and 82.2°. Participants with LBP showed restriction in the pelvis and TF range of motion, but had higher amplitudes in the lumbar spine during forward bending.

Role of androgen-mediated enhancement of erythropoiesis in the increased body iron stores of patients with polycystic ovary syndrome.

PubMed

Escobar-Morreale, Héctor F; Luque-Ramírez, Manuel

2011-04-01

To determine whether androgen excess contributes to the increased body iron stores of polycystic ovary syndrome (PCOS) by stimulating erythropoietic activity, by measuring serum soluble transferrin receptor (sTfR) concentrations and its ratio to ferritin levels in patients with PCOS, as surrogate markers of erythropoietic activity and of the appropriateness of cellular iron demands for the total body iron contents, respectively. Case-control study. Academic hospital. One hundred-four patients with PCOS and 100 controls without androgen excess. Blood sampling and oral glucose tolerance test. Serum sTfR and ferritin concentrations, as well as indexes of androgen excess, inflammation, obesity, and insulin and glucose metabolism. Serum ferritin levels increased in women presenting with PCOS, obesity, and/or abnormal glucose tolerance, but these disorders did not influence sTfR concentrations. The sTfR/ferritin ratio decreased with obesity and abnormal glucose tolerance, and its logarithm correlated inversely with body mass index, free T, and C-reactive protein levels and directly with the insulin sensitivity and disposition indexes. A stepwise multiple regression analysis indicated that the changes in the insulin sensitivity index explained 7% of the variability of the logarithm of sTfR/ferritin ratio. Increased serum ferritin levels in patients with PCOS are associated with a reduction in insulin sensitivity but do not result from a putative enhancement of erythropoiesis by androgen excess. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Spectroscopic studies of the interaction between alprazolam and apo-human serum transferrin as a drug carrier protein.

PubMed

Karimian Amroabadi, Marzieh; Taheri-Kafrani, Asghar; Heidarpoor Saremi, Leily; Rastegari, Ali Asghar

2018-03-01

The interaction between apo-human serum transferrin (Apo-hTf) and alprazolam was investigated using various spectroscopic techniques. The drug quenched the fluorescence intensity of Apo-hTf and the mechanism behind the quenching was static. The thermodynamic parameters (ΔG, ΔH, and ΔS) that obtained from tryptophan fluorescence study revealed that the interactions between alprazolam and Apo-hTf were spontaneous. Collectively, hydrophobic interactions and hydrogen bonding most likely played major roles in Apo-hTf/alprazolam interactions. Also, the absorption spectra of Apo-hTf increased in the presence of increasing concentration of alprazolam, reflecting Apo-hTf structural alteration after drug's binding. The CD results demonstrated that the Apo-hTf/alprazolam interaction does not affect the protein secondary and tertiary structure significantly until the molar ratios (alprazolam/Apo-hTf) of 10, but the conformational changes become visible at higher molar ratios. The DSC results suggested that alprazolam stabilized the Apo-hTf at alprazolam/Apo-hTf molar ratio of 20. Based on the achieved results, this potentially therapeutic agent can significantly bind to Apo-hTf which also further confirmed by molecular docking study. This study on the interaction of the drug with Apo-hTf should be helpful for understanding the transportation and distribution of drugs in vivo, as well as the action mechanism and dynamics of a drug at the molecular level. Copyright © 2017 Elsevier B.V. All rights reserved.

Stepped care versus standard trauma-focused cognitive behavioral therapy for young children

PubMed Central

Salloum, Alison; Wang, Wei; Robst, John; Murphy, Tanya K.; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2015-01-01

Background Compare the effectiveness and cost of stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT), a new service delivery method designed to address treatment barriers, to standard TF-CBT among young children who were experiencing posttraumatic stress symptoms (PTSS). Methods A total of 53 children (ages 3-7 years) who were experiencing PTSS were randomly assigned (2:1) to receive SC-TF-CBT or TF-CBT. Assessments by a blinded evaluator occurred at screening/baseline, after Step One for SC-TF-CBT, post-treatment, and 3-month follow-up. Trial registration: ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01603563 Results There were comparable improvements over time in PTSS and secondary outcomes in both conditions. Non-inferiority of SC-TF-CBT compared to TF-CBT was supported for the primary outcome of PTSS, and the secondary outcomes of severity and internalizing symptoms, but not for externalizing symptoms. There were no statistical differences in comparisons of changes over time from pre- to post-treatment and pre- to 3 month follow-up for PTSD diagnostic status, treatment response or remission. Parent satisfaction was high for both conditions. Costs were 51.3% lower for children in SC-TF-CBT compared to TF-CBT. Conclusions Although future research is needed, preliminary evidence suggests that SC-TF-CBT is comparable to TF-CBT, and delivery costs are significantly less than standard care. SC-TF-CBT may be a viable service delivery system to address treatment barriers. PMID:26443493

A proximity-based graph clustering method for the identification and application of transcription factor clusters.

PubMed

Spadafore, Maxwell; Najarian, Kayvan; Boyle, Alan P

2017-11-29

Transcription factors (TFs) form a complex regulatory network within the cell that is crucial to cell functioning and human health. While methods to establish where a TF binds to DNA are well established, these methods provide no information describing how TFs interact with one another when they do bind. TFs tend to bind the genome in clusters, and current methods to identify these clusters are either limited in scope, unable to detect relationships beyond motif similarity, or not applied to TF-TF interactions. Here, we present a proximity-based graph clustering approach to identify TF clusters using either ChIP-seq or motif search data. We use TF co-occurrence to construct a filtered, normalized adjacency matrix and use the Markov Clustering Algorithm to partition the graph while maintaining TF-cluster and cluster-cluster interactions. We then apply our graph structure beyond clustering, using it to increase the accuracy of motif-based TFBS searching for an example TF. We show that our method produces small, manageable clusters that encapsulate many known, experimentally validated transcription factor interactions and that our method is capable of capturing interactions that motif similarity methods might miss. Our graph structure is able to significantly increase the accuracy of motif TFBS searching, demonstrating that the TF-TF connections within the graph correlate with biological TF-TF interactions. The interactions identified by our method correspond to biological reality and allow for fast exploration of TF clustering and regulatory dynamics.

Attenuation of epsilon(sub eff) of coplanar waveguide transmission lines on silicon substrates

NASA Technical Reports Server (NTRS)

Taub, Susan R.; Young, Paul G.

1993-01-01

Attenuation and epsilon(sub eff) of Coplanar Waveguide (CPW) transmission lines were measured on Silicon substrates with resistivities ranging from 400 to greater than 30,000 ohm-cm, that have a 1000 angstrom coating of SiO2. Both attenuation and epsilon(sub eff) are given over the frequency range 5 to 40 GHz for various strip and slot widths. These measured values are also compared to the theoretical values.

Stepped and Standard Care for Childhood Trauma: A Pilot Randomized Clinical Trial

ERIC Educational Resources Information Center

Salloum, Alison; Small, Brent J.; Robst, John; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2017-01-01

Objective: This study explored the feasibility of stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT) relative to TF-CBT with children (aged 8--12). Method: Children (N = 33) with post-traumatic stress symptoms (PTSS) were randomly assigned (2:1) to SC-TF-CBT or TF-CBT. SC-TF-CBT consisted of Step 1, parent-led therapist-assisted…

Reduction in Brain Heparan Sulfate with Systemic Administration of an IgG Trojan Horse-Sulfamidase Fusion Protein in the Mucopolysaccharidosis Type IIIA Mouse.

PubMed

Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric Ka-Wai; Pardridge, William M

2018-02-05

Mucopolysaccharidosis Type IIIA (MPSIIIA), also known as Sanfilippo A syndrome, is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase (SGSH), also known as sulfamidase. Mutations in the SGSH enzyme, the only mammalian heparan N-sulfatase, cause accumulation of lysosomal inclusion bodies in brain cells comprising heparan sulfate (HS) glycosaminoglycans (GAGs). Treatment of MPSIIIA with intravenous recombinant SGSH is not possible because this large molecule does not cross the blood-brain barrier (BBB). BBB penetration by SGSH was enabled in the present study by re-engineering this enzyme as an IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), designated the cTfRMAb. The IgG domain of the fusion protein acts as a molecular Trojan horse to deliver the enzyme into brain via transport on the endogenous BBB TfR. The cTfRMAb-SGSH fusion protein bound to the mouse TfR with high affinity, ED 50 = 0.74 ± 0.07 nM, and retained high SGSH enzyme activity, 10 043 ± 1003 units/mg protein, which is comparable to recombinant human SGSH. Male and female MPSIIIA mice, null for the SGSH enzyme, were treated for 6 weeks with thrice-weekly intraperitoneal injections of vehicle, 5 mg/kg of the cTfRMAb alone, or 5 mg/kg of the cTfRMAb-SGSH fusion protein, starting at the age of 2 weeks, and were euthanized 1 week after the last injection. Brain and liver HS, as determined by liquid chromatography-mass spectrometry, were elevated 30-fold and 36-fold, respectively, in the MPSIIIA mouse. Treatment of the mice with the cTfRMAb-SGSH fusion protein caused a 70% and 85% reduction in brain and liver HS, respectively. The reduction in brain HS was associated with a 28% increase in latency on the rotarod test of motor activity in male mice. The mice exhibited no injection related reactions, and only a low titer end of study antidrug antibody response was observed. In conclusion, substantial reductions in brain pathologic GAGs in a murine model of MPSIIIA are produced by chronic systemic administration of an IgG-SGSH fusion protein engineered to penetrate the BBB via receptor-mediated transport.

Design, synthesis, nuclear localization, and biological activity of a fluorescent duocarmycin analog, HxTfA.

PubMed

Kiakos, Konstantinos; Englinger, Bernhard; Yanow, Stephanie K; Wernitznig, Debora; Jakupec, Michael A; Berger, Walter; Keppler, Bernhard K; Hartley, John A; Lee, Moses; Patil, Pravin C

2018-05-01

HxTfA 4 is a fluorescent analog of a potent cytotoxic and antimalarial agent, TfA 3, which is currently being investigated for the development of an antimalarial vaccine, PlasProtect®. HxTfA contains a p-anisylbenzimidazole or Hx moiety, which is endowed with a blue emission upon excitation at 318 nm; thus enabling it to be used as a surrogate for probing the cellular fate of TfA using confocal microscopy, and addressing the question of nuclear localization. HxTfA exhibits similar selectivity to TfA for A-tract sequences of DNA, alkylating adenine-N3, albeit at 10-fold higher concentrations. It also possesses in vitro cytotoxicity against A549 human lung carcinoma cells and Plasmodium falciparum. Confocal microscopy studies showed for the first time that HxTfA, and by inference TfA, entered A549 cells and localized in the nucleus to exert its biological activity. At biologically relevant concentrations, HxTfA elicits DNA damage response as evidenced by a marked increase in the levels of γH2AX observed by confocal microscopy and immunoblotting studies, and ultimately induces apoptosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody.

PubMed

Pardridge, William M

2015-02-01

Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG-neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG-avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials.

A river-scale Lagrangian experiment examining controls on phytoplankton dynamics in the presence and absence of treated wastewater effluent high in ammonium

USGS Publications Warehouse

Kraus, Tamara; Carpenter, Kurt; Bergamaschi, Brian; Parker, Alexander; Stumpner, Elizabeth; Downing, Bryan D.; Travis, Nicole; Wilkerson, Frances; Kendall, Carol; Mussen, Timothy

2017-01-01

Phytoplankton are critical component of the food web in most large rivers and estuaries, and thus identifying dominant controls on phytoplankton abundance and species composition is important to scientists, managers, and policymakers. Recent studies from a variety of systems indicate that ammonium ( NH+4) in treated wastewater effluent decreases primary production and alters phytoplankton species composition. However, these findings are based mainly on laboratory and enclosure studies, which may not adequately represent natural systems. To test effects of effluent high in ammonium on phytoplankton at the ecosystem scale, we conducted whole-river–scale experiments by halting discharges to the Sacramento River from the regional wastewater treatment plant (WWTP), and used a Lagrangian approach to compare changes in phytoplankton abundance and species composition in the presence (+EFF) and absence (−EFF) of effluent. Over 5 d of downstream travel from 20 km above to 50 km below the WWTP, chlorophyll concentrations declined from 15–25 to ∼2.5 μg L−1, irrespective of effluent addition. Benthic diatoms were dominant in most samples. We found no significant difference in phytoplankton abundance or species composition between +EFF and −EFF conditions. Moreover, greatest declines in chlorophyll occurred upstream of the WWTP where NH+4 concentrations were low. Grazing by clams and zooplankton could not account for observed losses, suggesting other factors such as hydrodynamics and light limitation were responsible for phytoplankton declines. These results highlight the advantages of conducting ecosystem-scale, Lagrangian-based experiments to understand the dynamic and complex interplay between physical, chemical, and biological factors that control phytoplankton populations.

Hydrologic characterization of desert soils with varying degrees of pedogenesis: 2. Inverse modeling for eff ective properties

USGS Publications Warehouse

Mirus, B.B.; Perkins, K.S.; Nimmo, J.R.; Singha, K.

2009-01-01

To understand their relation to pedogenic development, soil hydraulic properties in the Mojave Desert were investi- gated for three deposit types: (i) recently deposited sediments in an active wash, (ii) a soil of early Holocene age, and (iii) a highly developed soil of late Pleistocene age. Eff ective parameter values were estimated for a simplifi ed model based on Richards' equation using a fl ow simulator (VS2D), an inverse algorithm (UCODE-2005), and matric pressure and water content data from three ponded infi ltration experiments. The inverse problem framework was designed to account for the eff ects of subsurface lateral spreading of infi ltrated water. Although none of the inverse problems converged on a unique, best-fi t parameter set, a minimum standard error of regression was reached for each deposit type. Parameter sets from the numerous inversions that reached the minimum error were used to develop probability distribu tions for each parameter and deposit type. Electrical resistance imaging obtained for two of the three infi ltration experiments was used to independently test fl ow model performance. Simulations for the active wash and Holocene soil successfully depicted the lateral and vertical fl uxes. Simulations of the more pedogenically developed Pleistocene soil did not adequately replicate the observed fl ow processes, which would require a more complex conceptual model to include smaller scale heterogeneities. The inverse-modeling results, however, indicate that with increasing age, the steep slope of the soil water retention curve shitis toward more negative matric pressures. Assigning eff ective soil hydraulic properties based on soil age provides a promising framework for future development of regional-scale models of soil moisture dynamics in arid environments for land-management applications. ?? Soil Science Society of America.

Novel gene expression mechanism in a fission yeast retroelement: Tf1 proteins are derived from a single primary translation product.

PubMed

Levin, H L; Weaver, D C; Boeke, J D

1993-12-01

In sharp contrast to the single ORF of the Schizosaccharomyces pombe retrotransposon Tf1, retroviruses and most retrotransposons employ two different ORFs to separately encode the Gag and Pol proteins. The different ORFs are thought to allow for overexpression of the Gag protein relative to Pol protein presumed necessary for the assembly of functional retrovirus particles and virus-like particles (VLPs). The results of in vivo experiments designed to detect the transposition of Tf1 show that Tf1 is indeed active and can insert itself into the host genome via a true retrotransposition process. Thus, a paradox emerged between the lack of any obvious means of overexpressing Tf1 Gag protein and the demonstrated functionality of the element. Epitope tagging experiments described here confirm that the Tf1 large ORF is intact and that there is no translational or transcriptional mechanism used to overexpress the Tf1 Gag protein. In addition, we used sucrose gradients and antisera specific for Tf1 capsid (CA) and integrase (IN) to show that the Tf1 proteins do assemble into uniform populations of macromolecular particles that also cosediment with Tf1 reverse transcription products. This evidence suggests that Tf1 proteins form VLPs without using the previously described mechanisms that retroviruses and retrotransposons require to overexpress Gag proteins.

Does taking endurance into account improve the prediction of weaning outcome in mechanically ventilated children?

PubMed Central

Noizet, Odile; Leclerc, Francis; Sadik, Ahmed; Grandbastien, Bruno; Riou, Yvon; Dorkenoo, Aimée; Fourier, Catherine; Cremer, Robin; Leteurtre, Stephane

2005-01-01

Introduction We conducted the present study to determine whether a combination of the mechanical ventilation weaning predictors proposed by the collective Task Force of the American College of Chest Physicians (TF) and weaning endurance indices enhance prediction of weaning success. Method Conducted in a tertiary paediatric intensive care unit at a university hospital, this prospective study included 54 children receiving mechanical ventilation (≥6 hours) who underwent 57 episodes of weaning. We calculated the indices proposed by the TF (spontaneous respiratory rate, paediatric rapid shallow breathing, rapid shallow breathing occlusion pressure [ROP] and maximal inspiratory pressure during an occlusion test [Pimax]) and weaning endurance indices (pressure-time index, tension-time index obtained from P0.1 [TTI1] and from airway pressure [TTI2]) during spontaneous breathing. Performances of each TF index and combinations of them were calculated, and the best single index and combination were identified. Weaning endurance parameters (TTI1 and TTI2) were calculated and the best index was determined using a logistic regression model. Regression coefficients were estimated using the maximum likelihood ratio (LR) method. Hosmer–Lemeshow test was used to estimate goodness-of-fit of the model. An equation was constructed to predict weaning success. Finally, we calculated the performances of combinations of best TF indices and best endurance index. Results The best single TF index was ROP, the best TF combination was represented by the expression (0.66 × ROP) + (0.34 × Pimax), and the best endurance index was the TTI2, although their performance was poor. The best model resulting from the combination of these indices was defined by the following expression: (0.6 × ROP) – (0.1 × Pimax) + (0.5 × TTI2). This integrated index was a good weaning predictor (P < 0.01), with a LR+ of 6.4 and LR+/LR- ratio of 12.5. However, at a threshold value <1.3 it was only predictive of weaning success (LR- = 0.5). Conclusion The proposed combined index, incorporating endurance, was of modest value in predicting weaning outcome. This is the first report of the value of endurance parameters in predicting weaning success in children. Currently, clinical judgement associated with spontaneous breathing trials apparently remain superior. PMID:16356229

Comparative Evaluation of Physical Surface Changes and Incidence of Separation in Rotary Nickel-Titanium Instruments: An in Vitro SEM Study

PubMed Central

Kaul, Rudra; Farooq, Riyaz; Kaul, Vibhuti; Khateeb, Shafayat Ullah; Purra, Aamir Rashid; Mahajan, Roopali

2014-01-01

Introduction: The aim of the present study was to comparatively evaluate the physical surface changes and incidence of separation in rotary nickel-titanium (NiTi) instruments using scanning electron microscope (SEM). Methods and Materials: A total number of 210 freshly extracted human maxillary and mandibular first molars were selected and distributed between three groups. Three different systems of rotary NiTi instruments, namely ProFile (PF), RaCe (RC) and Twisted File (TF), were used to prepare the canals using crown-down technique. All instruments were evaluated by means of SEM with 500× and 1500× magnifications, at four different stages; before use, after preparation of 7 and 14 canals and after instrument separation. Photomicrographs were also taken. The data was analyzed using the Kruskal-Wallis test and the level of significance was set at 0.001. It was found that H (HAT matrix) was 15.316 with 2 degrees of freedom. Moreover the various groups were compared using the Student-Newman-Keuls test with P<0.05 and it was found that all groups were significantly different. Results: RC showed the maximum wear of the surface followed by TF (P<0.05). PF showed the minimum wear except for its tip. There was no correlation between electropolishing and file fracture. Insignificant difference was observed in the mean number of canals shaped by PF and TF before their separation. Conclusion: Clinically, TF performance was superior, followed by PF then RC. RC fracture rate was the greatest after preparing the least number of canals. PMID:25031595

Bis(tri-n-hexylsilyl oxide) silicon phthalocyanine: a unique additive in ternary bulk heterojunction organic photovoltaic devices.

PubMed

Lessard, Benoît H; Dang, Jeremy D; Grant, Trevor M; Gao, Dong; Seferos, Dwight S; Bender, Timothy P

2014-09-10

Previous studies have shown that the use of bis(tri-n-hexylsilyl oxide) silicon phthalocyanine ((3HS)2-SiPc) as an additive in a P3HT:PC61BM cascade ternary bulk heterojunction organic photovoltaic (BHJ OPV) device results in an increase in the short circuit current (J(SC)) and efficiency (η(eff)) of up to 25% and 20%, respectively. The previous studies have attributed the increase in performance to the presence of (3HS)2-SiPc at the BHJ interface. In this study, we explored the molecular characteristics of (3HS)2-SiPc which makes it so effective in increasing the OPV device J(SC) and η(eff. Initially, we synthesized phthalocyanine-based additives using different core elements such as germanium and boron instead of silicon, each having similar frontier orbital energies compared to (3HS)2-SiPc and tested their effect on BHJ OPV device performance. We observed that addition of bis(tri-n-hexylsilyl oxide) germanium phthalocyanine ((3HS)2-GePc) or tri-n-hexylsilyl oxide boron subphthalocyanine (3HS-BsubPc) resulted in a nonstatistically significant increase in JSC and η(eff). Secondly, we kept the silicon phthalocyanine core and substituted the tri-n-hexylsilyl solubilizing groups with pentadecyl phenoxy groups and tested the resulting dye in a BHJ OPV. While an increase in JSC and η(eff) was observed at low (PDP)2-SiPc loadings, the increase was not as significant as (3HS)2-SiPc; therefore, (3HS)2-SiPc is a unique additive. During our study, we observed that (3HS)2-SiPc had an extraordinary tendency to crystallize compared to the other compounds in this study and our general experience. On the basis of this observation, we have offered a hypothesis that when (3HS)2-SiPc migrates to the P3HT:PC61BM interface the reason for its unique performance is not solely due to its frontier orbital energies but also might be due to a high driving force for crystallization.

Expansion of effective wet bulb globe temperature for vapor impermeable protective clothing.

PubMed

Sakoi, Tomonori; Mochida, Tohru; Kurazumi, Yoshihito; Sawada, Shin-Ichi; Horiba, Yosuke; Kuwabara, Kohei

2018-01-01

The wet bulb globe temperature (WBGT) is an effective measure for risk screening to prevent heat dISOrders. However, a heat risk evaluation by WBGT requires adjustments depending on the clothing. In this study, we proposed a new effective WBGT (WBGT eff * ) for general vapor permeable clothing ensembles and vapor impermeable protective clothing that is applicable to occupants engaged in moderate intensity work with a metabolic heat production value of around 174W/m 2 . WBGT eff * enables the conversion of heat stress into the scale experienced by the occupant dressed in the basic clothing ensemble (work clothes) based on the heat balances for a human body. We confirmed that WBGT eff * was effective for expressing the critical thermal environments for the prescriptive zones for occupants wearing vapor impermeable protective clothing. Based on WBGT eff * , we succeeded in clarifying how the weights for natural wet bulb, globe, and air temperatures and the intercept changed depending on clothing properties and the surrounding environmental factors when heat stress is expressed by the weighted sum of natural wet bulb, globe, and air temperatures and the intercept. The weight of environmental temperatures (globe and air temperatures) for WBGT eff * for vapor impermeable protective clothing increased compared with that for general vapor permeable clothing, whereas that of the natural wet bulb temperature decreased. For WBGT eff * in outdoor conditions with a solar load, the weighting ratio of globe temperature increased and that of air temperature decreased with air velocity. Approximation equations of WBGT eff * were proposed for both general vapor permeable clothing ensembles and for vapor impermeable protective clothing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression of the Thomsen-Friedenreich (TF) tumor antigen in human abort placentas.

PubMed

Richter, D U; Jeschke, U; Bergemann, C; Makovitzky, J; Lüthen, F; Karsten, U; Briese, V

2005-01-01

The Thomsen-Friedenreich antigen (TF), or more precisely epitope, has been known as a pancarcinoma antigen. It consists of galactose-beta1-3-N-acetylgalactose. We have already described the expression of TF in the normal placenta. TF is expressed by the syncytium and by extravillous trophoblast cells. In this study, we investigated the expression of TF in the abort placenta. Frozen samples of human abort placentas (12 placentas), obtained from the first and second trimesters of pregnancy and, for comparison, samples of normal placentas (17 placentas) from the first, second and third trimesters of pregnancy, were used. Expression of TF was investigated by immunohistochemical methods. For identification of TF-positive cells in abort placentas, immunofluorescence methods were used. Evaluation of simple and double immunofluorescence was performed on a laser scanning microscope. Furthermore, we isolated trophoblast cells from first and third trimester placentas and evaluated cytokeratin 7 and Muc1 expression by immunofluorescence methods. We observed expression of TF antigen in the syncytiotrophoblasts layer of the placenta in all three trimesters of pregnancy in normal and abort placentas evaluated by immunohistochemical methods. There was no expression of TF antigen in the decidua of abort placentas. Immunofluorescence double staining of TF antigen and cytokeratin 7 showed reduced expression of both antigens in the abort decidua and co-expression of both antigens in the syncytiotrophoblast layer of normal and abort placentas. TF expression in the syncytiotrophoblast was reduced in abort placentas. In the isolated trophoblast cells, no TF expression was found, however, Muc1 expression was visualized. Expression of TF antigen was reduced in the first and second trimester abort decidua compared to the normal decidua during the same time of pregnancy. TF antigen was restricted to the syncytiotrophoblast and extravillous trophoblast cells in the decidua. Abort placentas expressed TF antigen on the syncytiotrophoblast layer, but with lower intensity compared to normal placentas. We found a significantly reduced co-expression of TF antigen and cytokeratin 7 in the decidua of abort placentas. These data suggested a reduction of extravillous trophoblast cells in the decidua of abort placentas. In addition, we found higher numbers of CD45-positive cells in the abort decidua compared to normal placentas.

Transfer factor - hypotheses for its structure and function.

PubMed

Shifrine, M; Scibienski, R

1975-01-01

Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses

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

Abraham, Jonathan; Corbett, Kevin D.; Farzan, Michael

New World hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1-TfR1 interface clarify the importance of TfR1 residues implicated in New World arenavirus host specificity. Analysis of sequence variation among New World arenavirus GP1s and their host-species receptors, in light of the molecular structure, indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip ofmore » the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular New World arenaviruses. We propose that New World arenaviruses that are pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.« less

Ion transport with charge-protected and non-charge-protected cations using the compensated Arrhenius formalism. Part 2. Relationship between ionic conductivity and diffusion.

PubMed

Petrowsky, Matt; Fleshman, Allison; Bopege, Dharshani N; Frech, Roger

2012-08-09

Temperature-dependent ionic conductivities and cation/anion self-diffusion coefficients are measured for four electrolyte families: TbaTf-linear primary alcohols, LiTf-linear primary alcohols, TbaTf-n-alkyl acetates, and LiTf-n-alkyl acetates. The Nernst-Einstein equation does not adequately describe the data. Instead, the compensated Arrhenius formalism is applied to both conductivity and diffusion data. General trends based on temperature and alkyl chain length are observed when conductivity is plotted against cation or anion diffusion coefficient, but there is no clear pattern to the data. However, plotting conductivity exponential prefactors against those for diffusion results in four distinct curves, one each for the alcohol and acetate families described above. Furthermore, the TbaTf-alcohol and TbaTf-acetate data are "in line" with each other. The conductivity prefactors for the LiTf-alcohol data are smaller than those for the TbaTf data. The LiTf-acetate data have the lowest conductivity prefactors. This trend in prefactors mirrors the observed trend in degree of ionic association for these electrolytes.

"Hit-and-Run" leaves its mark: catalyst transcription factors and chromatin modification.

PubMed

Varala, Kranthi; Li, Ying; Marshall-Colón, Amy; Para, Alessia; Coruzzi, Gloria M

2015-08-01

Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome-wide evidence for a "Hit-and-Run" model of transcription. In this model, a master TF "hits" a target promoter to initiate a rapid response to a signal. As the "hit" is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the "run", the master TF "hits" other targets to propagate the response genome-wide. As such, a TF may act as a "catalyst" to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long-term adaptive behavior in the whole organism. This "Hit-and-Run" model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF-regulated and TF-bound genes, implicating transient TF-target binding. Here, we explore this "Hit-and-Run" model to suggest molecular mechanisms and its biological relevance. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

Specificity of the weak binding between the phage SPO1 transcription-inhibitory protein, TF1, and SPO1 DNA.

PubMed

Johnson, G G; Geiduschek, E P

1977-04-05

The interaction of the phage SPO1 protein transcription factor 1 (TF1), with DNA has been analyzed by membrane filter binding and by sedimentation methods. Substantially specific binding of TF1 to helical SPO1 DNA can be demonstrated by nitrocellulose filter-binding assays at relatively low ionic strength (0.08). However, TF1-DNA complexes dissociate and reequilibrate relatively rapidly and this makes filter-binding assays unsuitable for quantitative measurements of binding equilibra. Accordingly, the sedimentation properties of TF1-DNA complexes have been explored and a short-column centrifugation assay has been elaborated for quantitative measurements. Preferential binding of TF1 to the hydroxymethyluracil-containing SPO1 DNA has also been demonstrated by short-column centrifugation. TF1 binds relatively weakly and somewhat cooperatively to SPO1 DNA at many sites; TF1-DNA complexes dissociate and reequilibrate rapidly. At 20 degrees C in 0.01 M phosphate, pH 7.5, 0.15 KC1, one molecule of TF1 can bind to approximately every 60 nucleotide pairs of SPO1 DNA.

Segregation of Impurities in Directionally Solidified Silicon

NASA Technical Reports Server (NTRS)

Ravishankar, P. S.; Younghouse, L. B.

1984-01-01

Hall measurements and four-point probe resistivity measurements are used to determine the concentration profile of boron and iron in doped semi-conductor silicon ingots grown by the Bridgman technique. The concentration profiles are fitted to the normal segregation equation and the effective segregation coefficient, K sub eff, is calculated. The average value of K sub eff, is 0.803 for boron. For iron, K sub eff, is concentration dependent and is in the range 0.00008 to 0.00012.

Measurements of Z{sub EFF} spatial profiles from bremsstrahlung emission in the visible and near infrared spectral region

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

Orsitto, F.; Belforte, M.R.; Borra, M.

1997-01-01

Measurement of plasma radiation (i.e., breusstrahlung) in the infrared (IR) range ({lambda}=933, 978 nm), at six lines of sight from z={minus}20 cm to z=8 cm above the equatorial plane, using the detection system of the Frascati Tokamak Upgrade (FTU) Thomson scattering system (TSS) are reported. The agreement of IR with visible ({lambda}=540 nm) bremsstrahlung intensity {ital S}, [S=photons/(m{sup 2}srnms)] measurements is within 20{percent}{endash}30{percent} and depends upon the absolute calibration of both systems. The intensity is equal S(z)={l_angle}Z{sub eff}Gn{sup 2}/T{sub e}{sup 1/2}{r_angle}, where {l_angle}{center_dot}{r_angle} means average on a line of sight. For determining the Z{sub eff} the Gaunt factor(G) is needed,more » and analysis the Born{endash}Elwert formula is used. The Z{sub eff} spatial profiles (i.e., Z{sub eff}(r)), are determined using the plasma temperature (T{sub e}) and density (n{sub e}) measured by the TSS and the Abel inverted intensity profiles, determined using the plasma radiation S(z) measured from six horizontal chords. Z{sub eff}(r) behavior in a variety of FTU discharges is presented. {copyright} {ital 1997 American Institute of Physics.}« less

[Multiple analysis of the difference in intestinal absorption between the main components and the extract of Glycyrrhiza uralensis].

PubMed

Wu, Qing-Qing; Chen, Yan; Xin, Ran; Wang, Jin-Yan; Zhou, Lei; Yuan, Ling; Jia, Xiao-Bin

2012-05-01

The aim of this study is to investigate the rat intestinal absorption behavior of two main active components, liquiritin, glycyrrhizin and the extract of Glycyrrhiza uralensis. The rat intestinal perfusion model was employed. Concentrations of the compounds of the interest in the intestinal perfusate, bile and plasma samples were determined by HPLC and UPLC. At the same time, the intestinal enzymes incubation test and the partition coefficient determination, the absorption of liquiritin and glycyrrhizin alone and the extract were multiple analyzed. The results showed that the P(eff) (effective permeability) of liquiritin or glycyrrhizin alone or the extract was less than 0.3, which suggested their poor absorption in the intestine. The P(eff) of the two main active components or the extract was not significantly different in duodenum, jejunum, colon and ileum segment. The P(eff) of the glycyrrhizin in the extract had no significant difference in the four intestinal segments compared with the glycyrrhizin alone. The absorption of the liquiritin displayed significant difference (P < 0.05) at ileum segment compared with the liquiritin alone, while it had no markedly change in the other three segments. This phenomenon indicated that some ingredients in the extract might improve the absorption of liquiritin. Moreover, no parent compounds and their metabolites were found in the intestinal perfusate, bile and the plasma samples. The results demonstrated that the influence of the other ingredients in the extract on the two components might not increase the amount of liquiritin and glycyrrhizin in the bile and plasma within the duration of the test.

Accurate prediction of bacterial type IV secreted effectors using amino acid composition and PSSM profiles.

PubMed

Zou, Lingyun; Nan, Chonghan; Hu, Fuquan

2013-12-15

Various human pathogens secret effector proteins into hosts cells via the type IV secretion system (T4SS). These proteins play important roles in the interaction between bacteria and hosts. Computational methods for T4SS effector prediction have been developed for screening experimental targets in several isolated bacterial species; however, widely applicable prediction approaches are still unavailable In this work, four types of distinctive features, namely, amino acid composition, dipeptide composition, .position-specific scoring matrix composition and auto covariance transformation of position-specific scoring matrix, were calculated from primary sequences. A classifier, T4EffPred, was developed using the support vector machine with these features and their different combinations for effector prediction. Various theoretical tests were performed in a newly established dataset, and the results were measured with four indexes. We demonstrated that T4EffPred can discriminate IVA and IVB effectors in benchmark datasets with positive rates of 76.7% and 89.7%, respectively. The overall accuracy of 95.9% shows that the present method is accurate for distinguishing the T4SS effector in unidentified sequences. A classifier ensemble was designed to synthesize all single classifiers. Notable performance improvement was observed using this ensemble system in benchmark tests. To demonstrate the model's application, a genome-scale prediction of effectors was performed in Bartonella henselae, an important zoonotic pathogen. A number of putative candidates were distinguished. A web server implementing the prediction method and the source code are both available at http://bioinfo.tmmu.edu.cn/T4EffPred.

Evaluation of attenuated PSM photomask blanks with TF11 chrome and FEP-171 resist on a 248 nm DUV laser pattern generator

NASA Astrophysics Data System (ADS)

Xing, Kezhao; Björnborg, Charles; Karlsson, Henrik; Paulsson, Adisa; Rosendahl, Anna; Beiming, Peter; Vedenpää, Jukka; Walford, Jonathan; Newman, Tom

2007-10-01

Tighter requirements on mask resolution, CD and image positioning accuracy at and beyond the 45 nm technology node push the development of improved photomask blanks. One such blank for attenuated phase-shift masks (att-PSM) provides a thinner chrome film, named TF11, with higher chrome etch rate compared to the previous generation Att- PSM blank (NTAR5 chrome film) from the same supplier. Reduced stress in the chrome film also results in less image placement error induced by the material. FEP-171 is the positive chemically amplified resist (PCAR) that is most commonly used in advanced mask manufacturing with both 50 keV variable shaped e-beam (VSB) and DUV laser pattern generators. TF11 allows an FEP-171 resist film down to about 2000 Å thickness with sufficient etch resistance, while the standard resist thickness for NTAR5 is around 3000 Å. This work has experimentally evaluated the use of TF11 chrome and FEP-171 resist together with a 248 nm DUV laser pattern generator, the Sigma7500. First, patterning performance in resist with thicknesses from 2000 Å to 2600 Å, in steps of 100 Å, was tested with respect to swing curve and basic lithographic parameters including resolution, CD linearity, CD iso-dense bias and dose sensitivity. Patterning results on mask showed a swing minimum at around 2200 Å and a swing maximum at around 2500 Å, which correspond to reflectivity measurements for 248 nm wavelength performed by the blank supplier. It was concluded that the overall patterning performance was best close to the swing maximum. Thereafter the patterning performance using TF11 at two resist thicknesses, 2000 Å and 2550 Å, was studied in more detail and compared to performance using NTAR5 with 3200 Å resist. The evaluation showed that the Sigma7500-II offers good compatibility with TF11, especially using the optimized FEP-171 resist thickness of 2550 Å. It also showed that the patterning capability of the Sigma7500-II using TF11 and 2550 Å resist is improved compared to using NTAR5 and 3200 Å resist.

40 CFR 63.849 - Test methods and procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Test methods and procedures. 63.849... Test methods and procedures. (a) The owner or operator shall use the following reference methods to determine compliance with the applicable emission limits for TF and POM emissions: (1) Method 1 in appendix...

Incorporation of Interfacial Intermetallic Morphology in Fracture Mechanism Map for Sn-Ag-Cu Solder Joints

NASA Astrophysics Data System (ADS)

Huang, Z.; Kumar, P.; Dutta, I.; Sidhu, R.; Renavikar, M.; Mahajan, R.

2014-01-01

A fracture mechanism map (FMM) is a powerful tool which correlates the fracture behavior of a material to its microstructural characteristics in an explicit and convenient way. In the FMM for solder joints, an effective thickness of the interfacial intermetallic compound (IMC) layer ( t eff) and the solder yield strength ( σ ys,eff) are used as abscissa and ordinate axes, respectively, as these two predominantly affect the fracture behavior of solder joints. Earlier, a definition of t eff, based on the uniform thickness of IMC ( t u) and the average height of the IMC scallops ( t s), was proposed and shown to aptly explain the fracture behavior of solder joints on Cu. This paper presents a more general definition of t eff that is more widely applicable to a range of metallizations, including Cu and electroless nickel immersion gold (ENIG). Using this new definition of t eff, mode I FMM for SAC387/Cu joints has been updated and its validity was confirmed. A preliminary FMM for SAC387/Cu joints with ENIG metallization is also presented.

The fungicide Pristine® inhibits mitochondrial function in vitro but not flight metabolic rates in honey bees

USDA-ARS?s Scientific Manuscript database

Honey bees and other pollinators are exposed to fungicides that act by inhibiting mitochondrial function. Here we test whether a common fungicide (Pristine®) inhibits the function of mitochondria of honeybees, and whether consumption of ecologically-realistic concentrations can cause negative eff...

Performance evaluation of Arizona's LTPP SPS-9 Project : strategic study of flexible pavement mix design factors.

DOT National Transportation Integrated Search

2016-01-01

As part of the Long Term Pavement Performance (LTPP) Program, the Arizona Department of Transportation (ADOT) constructed five Specific Pavement Studies 9 (SPS9) test sections on U.S. Route 93 near Kingman. This project, SPS9B, studied the effe...

Electronic fitness function for screening semiconductors as thermoelectric materials

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

Xing, Guangzong; Sun, Jifeng; Li, Yuwei

Here, we introduce a simple but efficient electronic fitness function (EFF) that describes the electronic aspect of the thermoelectric performance. This EFF finds materials that overcome the inverse relationship between σ and S based on the complexity of the electronic structures regardless of specific origin (e.g., isosurface corrugation, valley degeneracy, heavy-light bands mixture, valley anisotropy or reduced dimensionality). This function is well suited for application in high throughput screening. We applied this function to 75 different thermoelectric and potential thermoelectric materials including full- and half-Heuslers, binary semiconductors, and Zintl phases. We find an efficient screening using this transport function. Themore » EFF identifies known high-performance p- and n-type Zintl phases and half-Heuslers. In addition, we find some previously unstudied phases with superior EFF.« less

Using atomic layer deposited tungsten to increase thermal conductivity of a packed bed

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

Van Norman, Staci A.; Falconer, John L.; Weimer, Alan W., E-mail: alan.weimer@colorado.edu

2015-04-13

This study investigated the effective thermal conductivity (k{sub eff}) of packed-beds that contained porous particles with nanoscale tungsten (W) films of different thicknesses formed by atomic layer deposition (ALD). A continuous film on the particles is vital towards increasing k{sub eff} of the packed beds. For example, the k{sub eff} of an alumina packed bed was increased by three times after an ∼8-nm continuous W film with 20 cycles of W ALD, whereas k{sub eff} was decreased on a polymer packed bed with discontinuous, evenly dispersed W-islands due to nanoparticle scattering of phonons. For catalysts, understanding the thermal properties ofmore » these packed beds is essential for developing thermally conductive supports as alternatives to structured supports.« less

Electronic fitness function for screening semiconductors as thermoelectric materials

DOE PAGES

Xing, Guangzong; Sun, Jifeng; Li, Yuwei; ...

2017-11-17

Here, we introduce a simple but efficient electronic fitness function (EFF) that describes the electronic aspect of the thermoelectric performance. This EFF finds materials that overcome the inverse relationship between σ and S based on the complexity of the electronic structures regardless of specific origin (e.g., isosurface corrugation, valley degeneracy, heavy-light bands mixture, valley anisotropy or reduced dimensionality). This function is well suited for application in high throughput screening. We applied this function to 75 different thermoelectric and potential thermoelectric materials including full- and half-Heuslers, binary semiconductors, and Zintl phases. We find an efficient screening using this transport function. Themore » EFF identifies known high-performance p- and n-type Zintl phases and half-Heuslers. In addition, we find some previously unstudied phases with superior EFF.« less

Development of therapeutic Au-methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells.

PubMed

Yu, Jiashing; Hsu, Che-Hao; Huang, Chih-Chia; Chang, Po-Yang

2015-01-14

Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development.

Fluid pressure and fault strength: insights from load-controlled experiments on carbonate-bearing rocks

NASA Astrophysics Data System (ADS)

Spagnuolo, E.; Violay, M.; Nielsen, S. B.; Di Toro, G.

2013-12-01

Fluid pressure Pf has been indicated as a major factor controlling natural (e.g., L'Aquila, Italy, 2009 Mw 6.3) and induced seismicity (e.g., Wilzetta, Oklahoma, 2011 Mw 5.7). The Terzaghi's principle states that the effective normal stress σeff= σn (1- α Pf ), with α the Biot coefficient and σn the normal stress, is reduced in proportion to Pf. A value of α=1 is often used by default; however, within a complex fault core of inhomogeneous permeability, α may vary in a yet poorly understood way. To shed light on this problem, we conducted experiments on carbonate-bearing rock samples (Carrara marble) in room humidity conditions and in the presence of pore fluids (drained conditions), where a pre-cut fault is loaded by shear stress τ in a rotary apparatus (SHIVA) under constant σn=15 MPa. Two types of tests were performed with fluids: (1) the fluid pressure was kept constant at Pf=5 MPa (close to hydrostatic conditions at a depth of 0.5 km) and the fault was driven to failure instability by gradually increasing τ; (2) the fluid pressure was kept at Pf=5 MPa and τ was increased until close to instability (τ = 7 MPa): at this point Pf was raised of 0.5 MPa every 10 s up to Pf =10 MPa to induce a main (failure) instability. Assuming α=1 and an effective peak strength (τp)eff=μp σeff at failure, the experiments reveal that: 1) (τp)eff is sensitive to the shear loading rate: fast loading rates (0.5 MPa every 20 s) induce higher peak shear-stress values than slow loading rates (0.5 MPa every 40 s). Such effect is not observed (minor or inexistent) in the absence of pore fluids. 2) Under fast loading rates the (τp)eff may surpass that measured in the absence of pore fluids under identical effective normal stress σeff. 3) An increase of Pf does not necessarily induce the main instability (within the time intervals studied here, i.e. up to ~10 s) even if the effective strength threshold is largely surpassed (e.g., (τp)eff=1.3 μp σeff). We interpret these results in terms of limited permeability of the fault slip zone which reduces α. Indeed result (3) may indicate that a Pf increase did not rapidly penetrate the slip zone because a seal (thin layer of wet ultrafine calcite gouge) formed during the slip preceding the main instability. On the other hand, shearing of the slip zone probably induces dilation (not measured because below resolution) in the slip zone and results in a decrease in pore pressure. Again, due to limited permeability, the drop in pore pressure within the slip zone does not have time to re-equilibrate with the imposed Pf, provided that the hold time is short (20 s) with respect to the diffusion time, but it may re-equilibrate under longer hold times (40 s). As a consequence the Biot coefficient depends on the time interval of observation, with α~0 at short time periods and α~1 at long time periods. This yields an approximate hydraulic diffusivity κ~10-8 m2 s-1 using κ=l2/td with the half length of the contact surface l=5 mm and td=30 s. Such diffusivity is compatible, for example, with a low porosity shale.

Trauma-focused cognitive behavioral therapy a clinical trial to increase self-efficacy in abused the primary school children.

PubMed

Farina, Vahid; Salemi, Safora; Tatari, Faezeh; Abdoli, Nasrin; Jouybari, Touraj Ahmadi; Alikhani, Mostafa; Basanj, Behrad; Zakiei, Ali

2018-01-01

Child abuse and violence toward children has become a complex phenomenon in nowadays societies leaving hurt children with numerous complications such as lowered self-efficacy. Hence, this study was conducted to assess the effect of trauma-focused cognitive behavioral therapy (TF-CBT) in physically abused children self-efficacy. This study was a randomized clinical trial. From this statistical population of all abused children aged 9-12 in Kermanshah in 2016-2017, 40 were divided into intervention and control groups randomly. Tools used in this study were Maurice self-efficacy questionnaire and child abuse questionnaire. Data analysis was done using Chi-square test, paired t -test, and independent t -test. It was revealed that the mean difference between two groups was not meaningful before intervention. After TF-CBT in intervention group, self-efficacy mean scores of social (17.95 vs. 24.20) and emotional (15.05 vs. 19.05) domains showed meaningful differences, whereas academic self-efficacy mean score did not change significantly (14.10 vs. 14.65) ( P < 0.086). In control group, social (16.20 vs. 15.55), emotional (13.90 vs. 14.35), and academic (13.40 vs. 13.90) mean self-efficacy scores were not of significant difference ( P > 0.001). TF-CBT can be used as an appropriate therapy intervention to improve social and emotional self-efficacy in abused children.

Cutting efficiency of instruments with different movements: a comparative study.

PubMed

Tocci, Luigi; Plotino, Gianluca; Al-Sudani, Dina; Rubini, Alessio Giansiracusa; Sannino, Gianpaolo; Piasecki, Lucila; Putortì, Ermanno; Testarelli, Luca; Gambarini, Gianluca

2015-01-01

The aim of the present study was to evaluate the cutting efficiency of two new reciprocating instruments, Twisted File Adaptive and WaveOne Primary. 10 new Twisted File Adaptive (TF Adaptive) (SybronEndo, Glendora, CA, USA) and 10 new WaveOne Primary files (Dentsply Maillefer, Ballaigues, Switzerland) were activated using a torque-controlled motor, respectively TFA motor (SybronEndo, Glendora, CA, USA) and Silver motor (VDW, Munich, Germany). The device used for the cutting test consisted on a mainframe to which a mobile plastic support for the hand-piece is connected and a stainless-steel block containing a Plexiglas block against which the cutting efficiency of the instruments was tested. The length of the block cut in 1 minute was measured in a computerized program with a precision of 0.1 mm. Mean and standard deviations of each group were calculated and data were statistically analyzed with one-way ANOVA and Bonferroni t test (P < 0.05). TF Adaptive displayed significantly greater maximum penetration depth than WaveOne Primary (P < 0.05). In fact, TF Adaptive instruments (Group 1) cut the Plexiglas block to a mean depth of 8.7 (SD 0.5) mm, while WaveOne Primary instruments cut the Plexiglas block to a mean depth of 6.4 (SD 0.3) mm. Twisted File Adaptive instruments demonstrated statistically higher cutting efficiency than WaveOne instruments.

Cutting Efficiency of Instruments with Different Movements: a Comparative Study

PubMed Central

Plotino, Gianluca; Al-Sudani, Dina; Rubini, Alessio Giansiracusa; Sannino, Gianpaolo; Piasecki, Lucila; Putortì, Ermanno; Testarelli, Luca; Gambarini, Gianluca

2015-01-01

ABSTRACT Objectives The aim of the present study was to evaluate the cutting efficiency of two new reciprocating instruments, Twisted File Adaptive and WaveOne Primary. Material and Methods 10 new Twisted File Adaptive (TF Adaptive) (SybronEndo, Glendora, CA, USA) and 10 new WaveOne Primary files (Dentsply Maillefer, Ballaigues, Switzerland) were activated using a torque-controlled motor, respectively TFA motor (SybronEndo, Glendora, CA, USA) and Silver motor (VDW, Munich, Germany). The device used for the cutting test consisted on a mainframe to which a mobile plastic support for the hand-piece is connected and a stainless-steel block containing a Plexiglas block against which the cutting efficiency of the instruments was tested. The length of the block cut in 1 minute was measured in a computerized program with a precision of 0.1 mm. Mean and standard deviations of each group were calculated and data were statistically analyzed with one-way ANOVA and Bonferroni t test (P < 0.05). Results TF Adaptive displayed significantly greater maximum penetration depth than WaveOne Primary (P < 0.05). In fact, TF Adaptive instruments (Group 1) cut the Plexiglas block to a mean depth of 8.7 (SD 0.5) mm, while WaveOne Primary instruments cut the Plexiglas block to a mean depth of 6.4 (SD 0.3) mm. Conclusions Twisted File Adaptive instruments demonstrated statistically higher cutting efficiency than WaveOne instruments. PMID:25937877

Dissolution of fine particle fraction from truncated Anderson cascade impactor with an enhancer cell.

PubMed

Tay, Justin Yong Soon; Liew, Celine Valeria; Heng, Paul Wan Sia

2018-04-22

Dissolution testing for inhalers were previously conducted either on unfractionated drug-carrier powders or drug of specific aerodynamic particle size. In this study, the collection of the full fine particle fraction (FPF) was attempted on a single stage. Capsules containing 30 mg of 2% salbutamol sulfate (SS) was tested to have a FPF of 9 ± 1% using the full set of Andersen cascade impactor (ACI) and a modified Rotahaler® capable of achieving 4.0 kPa pressure drop at 60 L/min air flow rate. A truncated ACI comprising the USP throat, pre-separator, stage 0, stage 4, stage F, polytetrafluoroethylene funnel (TF) and small collection plate (sCP) was found to be capable of achieving a FPF of 9% collected on TF and sCP. An adhesive tape was used to collect the FPF from the TF and sCP and held in place by an enhancer cell in a 200 mL round bottom vessel containing 50 mL Gamble's solution with 0.2 v/v, % Tween 80. Dissolution testing of SS and Seretide® showed burst release of SS and salmeterol while sustained release of fluticasone. This study demonstrated a reproducible method which may be used for evaluation of the full FPF of orally inhaled products. Copyright © 2018 Elsevier B.V. All rights reserved.

Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

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

Jeong, Seung Min, E-mail: smjeong@catholic.ac.kr; Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701; Hwang, Sunsook

2016-03-11

The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derivedmore » ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.« less

Increased circulating procoagulant and anticoagulant factors as TF and TFPI according to severity or infecting serotypes in human dengue infection.

PubMed

Leal de Azeredo, Elzinandes; Solórzano, Victor Edgar Fiestas; de Oliveira, Débora Batista; Marinho, Cintia Ferreira; de Souza, Luiz José; da Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de-Oliveira-Pinto, Luzia Maria

2017-01-01

Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Endothelial connexin 32 regulates tissue factor expression induced by inflammatory stimulation and direct cell-cell interaction with activated cells.

PubMed

Okamoto, Takayuki; Akita, Nobuyuki; Hayashi, Tatsuya; Shimaoka, Motomu; Suzuki, Koji

2014-10-01

Endothelial cell (EC) interacts with adjacent EC through gap junction, and abnormal expression or function of Cxs is associated with cardiovascular diseases. In patients with endothelial dysfunction, the up-regulation of tissue factor (TF) expression promotes the pathogenic activation of blood coagulation, however the relationship between gap junctions and TF expression in ECs remains uncharacterized. ECs express the gap junction (GJ) proteins connexin32 (Cx32), Cx37, Cx40 and Cx43. We investigated the role of endothelial gap junctions, particularly Cx32, in modulating TF expression during vascular inflammation. Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor-α (TNF-α) and TF activity was assessed in the presence of GJ blockers and an inhibitory anti-Cx32 monoclonal antibody. Treatment with GJ blockers and anti-Cx32 monoclonal antibody enhanced the TNF-α-induced TF activity and mRNA expression in HUVECs. TNF-α-activated effector HUVECs or mouse MS-1 cells were co-cultured with non-stimulated acceptor HUVECs and TF expression in acceptor HUVECs was detected. Effector EC induced TF expression in adjacent acceptor HUVECs through direct cell-cell interaction. Cell-cell interaction induced TF expression was reduced by anti-intercellular adhesion molecule-1 (ICAM1) monoclonal antibody. Soluble ICAM1-Fc fusion protein promotes TF expression. GJ blockers and anti-Cx32 monoclonal antibody enhanced TF expression induced by cell-cell interaction and ICAM1-Fc treatment. Blockade of endothelial Cx32 increased TF expression induced by TNF-α stimulation and cell-cell interaction which was at least partly dependent upon ICAM1. These results suggest that direct Cx32-mediated interaction modulates TF expression in ECs during vascular inflammation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Transcriptome-wide profiling and expression analysis of transcription factor families in a liverwort, Marchantia polymorpha

PubMed Central

2013-01-01

Background Transcription factors (TFs) are vital elements that regulate transcription and the spatio-temporal expression of genes, thereby ensuring the accurate development and functioning of an organism. The identification of TF-encoding genes in a liverwort, Marchantia polymorpha, offers insights into TF organization in the members of the most basal lineages of land plants (embryophytes). Therefore, a comparison of Marchantia TF genes with other land plants (monocots, dicots, bryophytes) and algae (chlorophytes, rhodophytes) provides the most comprehensive view of the rates of expansion or contraction of TF genes in plant evolution. Results In this study, we report the identification of TF-encoding transcripts in M. polymorpha for the first time, as evidenced by deep RNA sequencing data. In total, 3,471 putative TF encoding transcripts, distributed in 80 families, were identified, representing 7.4% of the generated Marchantia gametophytic transcriptome dataset. Overall, TF basic functions and distribution across families appear to be conserved when compared to other plant species. However, it is of interest to observe the genesis of novel sequences in 24 TF families and the apparent termination of 2 TF families with the emergence of Marchantia. Out of 24 TF families, 6 are known to be associated with plant reproductive development processes. We also examined the expression pattern of these TF-encoding transcripts in six male and female developmental stages in vegetative and reproductive gametophytic tissues of Marchantia. Conclusions The analysis highlighted the importance of Marchantia, a model plant system, in an evolutionary context. The dataset generated here provides a scientific resource for TF gene discovery and other comparative evolutionary studies of land plants. PMID:24365221

Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy.

PubMed

Jacobsen, Christine; Oechsle, Karin; Hauschild, Jessica; Steinemann, Gustav; Spath, Brigitte; Bokemeyer, Carsten; Ruf, Wolfram; Honecker, Friedemann; Langer, Florian

2015-09-01

Patients with germ cell tumors (GCTs) receiving cisplatin-based chemotherapy are at increased risk of thrombosis, but the underlying cellular and molecular mechanisms remain obscure. To study baseline tissue factor (TF) expression by GCT cell lines and its modulation by cisplatin treatment. TF expression was assessed by single-stage clotting and thrombin generation assay, flow cytometry, ELISA, and Western blot analysis. Cell cycle analysis and detection of phosphatidylserine (PS) membrane exposure were carried out by flow cytometry. TF mRNA was analyzed by quantitative RT-PCR. Significant expression of TF-specific procoagulant activity (PCA) was detected on three non-seminoma (NT2, 2102Ep, NCCIT) and one seminoma cell line (TCam-2). Treatment with 0.4μM cisplatin (corresponding to the IC50) for 48hrs increased TF PCA on NT2 cells 3-fold, an effect that was largely independent of PS exposure and that could not be explained by translocation of active TF from intracellular storage pools. Cisplatin-induced TF PCA expression in NT2 cells did not occur before 12hrs, but was steady thereafter and accompanied by a 2-fold increase in total and surface-located TF antigen. Importantly, increased TF gene transcription or production and release of an intermediate factor were not involved in this process. Cell cycle analysis suggested that cisplatin-induced G2/M arrest resulted in an accumulation of procoagulant TF on the membrane surface of NT2 cells. In addition to induction of apoptosis/necrosis with PS-mediated activation of preformed TF, cisplatin may alter the procoagulant phenotype of GCT cells through an increase in total cellular TF antigen. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Almus, F.E.; Rao, L.V.; Fleck, R.A.

An umbilical vein model was designed in which washed vein segments are filled with a reaction mixture containing factor VIIa, Ca(+)+, and a substrate, either 3H-factor IX or 3H-factor X. The vein wall provides the tissue factor (TF) for factor VIIa/TF complexes that activate the substrates as measured by activation peptide release. The model was developed to study TF induced on venous endothelium in situ. However, unlike previous studies with TF expressed on cultured umbilical vein endothelial cells, factors IX and X were activated without first having to expose the vein wall to a perturbing stimulus. Histologic studies revealed thatmore » washing the vein and mixing the reaction mixture before subsampling had disrupted the endothelium. Immunostaining with anti-TF antibodies revealed no staining of endothelium but intense staining in extensions of Wharton's jelly penetrating fenestrations of the muscularis media of the vein. Thus, the model provided data on factor VIIa/TF formed, not on endothelium, but within the mucoid connective tissue of Wharton's jelly. It is known that factor VIIa/TF formed with TF in suspension or with TF expressed on the surface of cultured cells activates factor X more rapidly than factor IX. In contrast, in the umbilical vein model, when each substrate was present in an 88 nmol/L concentration, factors IX and X were activated at equivalent rates (mean activation rate for factor IX, 18.8 +/- 3.6 nmol/L/h; for factor X, 17.8 +/- 2.9 nmol/L/h; n = 9 paired vein segments). These data strengthen the evidence that factor VIIa/TF activation of factor IX represents a key initial reaction of coagulation in tissues. These results also show that data obtained with factor VIIa/TF complexes formed on the surface of cultured cells need not hold for factor VIIa/TF complexes formed in extracellular matrix.« less

Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

PubMed Central

Collier, Mary E. W.; Ettelaie, Camille

2011-01-01

The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

Significance testing testate amoeba water table reconstructions

NASA Astrophysics Data System (ADS)

Payne, Richard J.; Babeshko, Kirill V.; van Bellen, Simon; Blackford, Jeffrey J.; Booth, Robert K.; Charman, Dan J.; Ellershaw, Megan R.; Gilbert, Daniel; Hughes, Paul D. M.; Jassey, Vincent E. J.; Lamentowicz, Łukasz; Lamentowicz, Mariusz; Malysheva, Elena A.; Mauquoy, Dmitri; Mazei, Yuri; Mitchell, Edward A. D.; Swindles, Graeme T.; Tsyganov, Andrey N.; Turner, T. Edward; Telford, Richard J.

2016-04-01

Transfer functions are valuable tools in palaeoecology, but their output may not always be meaningful. A recently-developed statistical test ('randomTF') offers the potential to distinguish among reconstructions which are more likely to be useful, and those less so. We applied this test to a large number of reconstructions of peatland water table depth based on testate amoebae. Contrary to our expectations, a substantial majority (25 of 30) of these reconstructions gave non-significant results (P > 0.05). The underlying reasons for this outcome are unclear. We found no significant correlation between randomTF P-value and transfer function performance, the properties of the training set and reconstruction, or measures of transfer function fit. These results give cause for concern but we believe it would be extremely premature to discount the results of non-significant reconstructions. We stress the need for more critical assessment of transfer function output, replication of results and ecologically-informed interpretation of palaeoecological data.

Membrane triangles with corner drilling freedoms. I - The EFF element

NASA Technical Reports Server (NTRS)

Alvin, Ken; De La Fuente, Horacio M.; Haugen, Bjorn; Felippa, Carlos A.

1992-01-01

The formulation of 3-node 9-DOF membrane elements with normal-to-element-plane rotations (drilling freedoms) is examined in the context of parametrized variational principles. In particular, attention is given to the application of the extended free formulation (EFF) to the construction of a triangular membrane element with drilling freedoms that initially has complete quadratic polynomial expansions in each displacement component. The main advantage of the EFF over the free formulation triangle is that an explicit form is obtained for the higher-order stiffness.

DNA-bending properties of TF1.

PubMed

Schneider, G J; Sayre, M H; Geiduschek, E P

1991-10-05

Transcription factor 1 (TF1) is the Bacillus subtilis phage SPO1-encoded member of the family of DNA-binding proteins that includes Escherichia coli HU and integration host factor, IHF. A gel electrophoretic retardation method has been used to show that a TF1 dimer binding to one of its preferred sites in (5-hydroxymethyl)uracil (hmUra)-containing DNA sharply bends the latter. In fact, the DNA-bending properties of TF1 and E. coli IHF are indistinguishable. Substitutions at amino acid 61 in the DNA-binding "arm" of TF1 are known to affect DNA-binding affinity and site selectivity. Experiments described here show that these substitutions also affect DNA bending. The selectivity of TF1 binding is very greatly diminished and the affinity is reduced when hmUra is replaced in DNA by thymine (T). An extension of the gel retardation method that permits an analysis of DNA bending by non-specifically bound TF1 is proposed. Under the assumptions of this analysis, the reduced affinity of TF1 for T-containing DNA is shown to be associated with bending that is still sharp. The analysis of the TF1-DNA interaction has also been extended by hydroxyl radical (.OH) and methylation interference footprinting at two DNA sites. At each of these sites, and on each strand, TF1 strongly protects three segments of DNA from attack by OH. Patches of protected DNA are centered approximately ten base-pairs apart and fall on one side of the B-helix. Methylation in either the major or minor groove in the central ten base-pairs of the two TF1 binding sites quantitatively diminishes, but does not abolish, TF1 binding. We propose that multiple protein contacts allow DNA to wrap around the relatively small TF1 dimer, considerably deforming the DNA B-helix in the process.

Quantitative analysis of collagens and fibronectin expression in human right ventricular hypertrophy.

PubMed

Peters, T H; Sharma, H S; Yilmaz, E; Bogers, A J

1999-06-30

One of the main features in human tetralogy of Fallot (TF) is right ventricular hypertrophy (RVH) due to pressure (sub-pulmonary stenosis) and volume overload (ventricular septal defect). Currently, primary correction at a young age is the treatment of choice. To unravel the role of extracellular matrix in RVH, we examined myocardial expression of collagens and fibronectin in TF patients with primary correction (TF1, age 0.7 +/- 0.2 yr.), secondary surgery (TF2, age 36.9 +/- 4.6 yr), and in age-matched control patients. Sirius red staining quantified by video imaging showed significantly increased interstitial staining for collagens in both TF1 and TF2 groups as compared to respective controls. Fibronectin was expressed in extracellular spaces, perivascular regions, and in some cardiomyocytes. Quantitative analysis of fibronectin revealed increased expression in only TF1 group as compared to respective control. Our results indicate an increased amount of myocardial extracellular matrix deposition as a sign of fibrosis during RVH in patients with TF.

Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo

PubMed Central

Wen, Jiexia; Pan, Sumin; Liang, Shuang; Zhong, Zhenyu; He, Ying; Lin, Hongyu; Li, Wenyan; Wang, Liyue; Li, Xiujin; Zhong, Fei

2013-01-01

Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo. PMID:24089666

The clinical value of tissue factor assays.

PubMed

Francis, J L; Carvalho, M; Francis, D A

1995-06-01

Tissue factor (TF) is now considered to be the primary physiologic activator of the blood coagulation system. Coupled with recent advances in our understanding of the biochemistry of TF this has heightened interest in measuring aspects of TF activity in disease states. Expression of TF by blood monocytes in various diseases is an established trigger for intravascular coagulation and there is now a considerable body of experience with its measurement. This has considerable clinical potential although more widespread application awaits a consensus on the most appropriate methodologic approach to its measurement. TF can be detected in urine and may reflect the activation state of renal macrophages. Urinary TF is increased in cancer and could have diagnostic and prognostic value in a variety of malignant diseases. Finally, it is now possible to measure soluble TF in plasma. One such assay is commercially available and is technically simple to perform. The clinical value of such assays, however, must await better understanding of the source and function of soluble TF in plasma.

Toward the Reliability of Fault Representation Methods in Finite Difference Schemes for Simulation of Shear Rupture Propagation

NASA Astrophysics Data System (ADS)

Dalguer, L. A.; Day, S. M.

2006-12-01

Accuracy in finite difference (FD) solutions to spontaneous rupture problems is controlled principally by the scheme used to represent the fault discontinuity, and not by the grid geometry used to represent the continuum. We have numerically tested three fault representation methods, the Thick Fault (TF) proposed by Madariaga et al (1998), the Stress Glut (SG) described by Andrews (1999), and the Staggered-Grid Split-Node (SGSN) methods proposed by Dalguer and Day (2006), each implemented in a the fourth-order velocity-stress staggered-grid (VSSG) FD scheme. The TF and the SG methods approximate the discontinuity through inelastic increments to stress components ("inelastic-zone" schemes) at a set of stress grid points taken to lie on the fault plane. With this type of scheme, the fault surface is indistinguishable from an inelastic zone with a thickness given by a spatial step dx for the SG, and 2dx for the TF model. The SGSN method uses the traction-at-split-node (TSN) approach adapted to the VSSG FD. This method represents the fault discontinuity by explicitly incorporating discontinuity terms at velocity nodes in the grid, with interactions between the "split nodes" occurring exclusively through the tractions (frictional resistance) acting between them. These tractions in turn are controlled by the jump conditions and a friction law. Our 3D tests problem solutions show that the inelastic-zone TF and SG methods show much poorer performance than does the SGSN formulation. The SG inelastic-zone method achieved solutions that are qualitatively meaningful and quantitatively reliable to within a few percent. The TF inelastic-zone method did not achieve qualitatively agreement with the reference solutions to the 3D test problem, and proved to be sufficiently computationally inefficient that it was not feasible to explore convergence quantitatively. The SGSN method gives very accurate solutions, and is also very efficient. Reliable solution of the rupture time is reached with a median resolution of the cohesive zone of only ~2 grid points, and efficiency is competitive with the Boundary Integral (BI) method. The results presented here demonstrate that appropriate fault representation in a numerical scheme is crucial to reduce uncertainties in numerical simulations of earthquake source dynamics and ground motion, and therefore important to improving our understanding of earthquake physics in general.

LAMOST DR1: Stellar Parameters and Chemical Abundances with SP_Ace

NASA Astrophysics Data System (ADS)

Boeche, C.; Smith, M. C.; Grebel, E. K.; Zhong, J.; Hou, J. L.; Chen, L.; Stello, D.

2018-04-01

We present a new analysis of the LAMOST DR1 survey spectral database performed with the code SP_Ace, which provides the derived stellar parameters {T}{{eff}}, {log}g, [Fe/H], and [α/H] for 1,097,231 stellar objects. We tested the reliability of our results by comparing them to reference results from high spectral resolution surveys. The expected errors can be summarized as ∼120 K in {T}{{eff}}, ∼0.2 in {log}g, ∼0.15 dex in [Fe/H], and ∼0.1 dex in [α/Fe] for spectra with S/N > 40, with some differences between dwarf and giant stars. SP_Ace provides error estimations consistent with the discrepancies observed between derived and reference parameters. Some systematic errors are identified and discussed. The resulting catalog is publicly available at the LAMOST and CDS websites.

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load.

PubMed

Galizzi, Nadia; Galli, Laura; Poli, Andrea; Gianotti, Nicola; Carini, Elisabetta; Bigoloni, Alba; Tambussi, Giuseppe; Nozza, Silvia; Lazzarin, Adriano; Castagna, Antonella; Mancusi, Daniela; Termini, Roberta

2018-01-01

A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015. The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters. In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient's decision, 1 due to enrolment in a study protocol]. In this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.

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

Novales-Sanchez, H.; Toscano, J. J.; Rosado, A.

In this paper, we review the search of possible physics effects beyond the standard model on the electromagnetic charge and anapole form factors, f{sub Q}(q{sup 2}) and f{sub A}(q{sup 2}), for a no massive Dirac neutrino, when these quantities are calculated in the frame of an effective electroweak Yang-Mills theory, which induces the most general SU{sub L}(2)-invariant Lorentz tensor structure of nonrenormalizable type for the WW{gamma} vertex. We found that in this frame, besides the standard model contribution, the additional contribution to f{sub Q}(q{sup 2}) and f{sub A}(q{sup 2}) (f{sub Q}{sup O{sub W}}(q{sup 2}) and f{sub A}{sup O{sub W}}(q{sup 2}),more » respectively) are gauge independent and finite functions of q{sup 2} after adopting a renormalization scheme. These form factors, f{sub Q}{sup O{sub W}}(q{sup 2}) and f{sub A}{sup O{sub W}}(q{sup 2}), get contribution at the one loop level only from the proper neutrino electromagnetic vertex. Besides, the relation f{sub Q}{sup eff}(q{sup 2}) = q{sup 2}f{sub A}{sup eff}(q{sup 2})(f{sub Q}{sup eff}(q{sup 2}) = f{sub Q}{sup SM}(q{sup 2})+f{sub Q}{sup O{sub W}}(q{sup 2}),f{sub A}{sup eff}(q{sup 2}) = f{sub A}{sup SM}(q{sup 2})+f{sub A}{sup O{sub W}}(q{sup 2})) is still fulfilled and hence the relation a{sub v}{sup eff} = {sup eff}/6(a{sub v}{sup eff} = a{sub v}{sup SM}+a{sub v}{sup O{sub W}},{sup eff} = {sup SM}+{sup O{sub W}}) is obtained, just as in the SM. Using the experimental constraint on the anomalous WW{gamma} vertex, a value for the additional contribution to the charge radius of Double-Vertical-Line {sup O{sub W}} Double-Vertical-Line Less-Than-Or-Equivalent-To 10{sup -34} cm{sup 2} is gotten, which is one order of magnitude lower than the SM value.« less

"Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".

PubMed

Doidy, Joan; Li, Ying; Neymotin, Benjamin; Edwards, Molly B; Varala, Kranthi; Gresham, David; Coruzzi, Gloria M

2016-02-03

Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.

Tracing artificial trans fat in popular foods in Europe: a market basket investigation.

PubMed

Stender, Steen; Astrup, Arne; Dyerberg, Jørn

2014-05-20

To minimise the intake of industrial artificial trans fat (I-TF), nearly all European countries rely on food producers to voluntarily reduce the I-TF content in food. The objective of this study was to investigate the effect of this strategy on I-TF content in prepackaged biscuits/cakes/wafers in 2012-2013 in 20 European countries. The I-TF content was assessed in a market basket investigation. Three large supermarkets were visited in each capital, and in some countries, three additional ethnic shops were included. A total of 598 samples of biscuits/cakes/wafers with 'partially hydrogenated vegetable fat' or a similar term high on the list of ingredients were analysed, 312 products had more than 2% of fat as I-TF, exceeding the legislatively determined I-TF limit in Austria and Denmark; the mean (SD) was 19 (7)%. In seven countries, no I-TF was found, whereas nine predominantly Eastern European countries had products with very high I-TF content, and the remaining four countries had intermediate levels. Of the five countries that were examined using the same procedure as in 2006, three had unchanged I-TF levels in 2013, and two had lower levels. The 18 small ethnic shops examined in six Western European countries sold 83 products. The mean (SD) was 23 (12)% of the fat as I-TF, all imported from countries in Balkan. In Sweden, this type of food imported from Balkan was also available in large supermarkets. The findings suggest that subgroups of the population in many countries in Europe still consume I-TF in amounts that increase their risk of coronary heart disease. Under current European Union (EU) legislation, the sale of products containing I-TF is legal but conflicts with the WHO recommendation to minimise the intake of I-TF. An EU-legislative limit on I-TF content in foods is expected to be an effective strategy to achieve this goal. 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.

An analysis of subunit exchange in the dimeric DNA-binding and DNA-bending protein, TF1.

PubMed

Andera, L; Schneider, G J; Geiduschek, E P

1994-01-01

TF1 is the Bacillus subtilis bacteriophage-encoded dimeric type II DNA-binding protein. This relative of the eubacterial HU proteins and of the Escherichia coli integration host factor binds preferentially to 5-(hydroxymethyluracil)-containing DNA. We have examined the dynamics of exchange of monomer subunits between molecules of dimeric TF1. The analysis takes advantage of the fact that replacement of phenylalanine with arginine at amino acid 61 in the beta-loop 'arm' of TF1 alters DNA-bending and -binding properties, generating DNA complexes with distinctively different mobilities in gel electrophoresis. New species of DNA-protein complexes were formed by mixtures of wild type and mutant TF1, reflecting the formation of heterodimeric TF1, and making the dynamics of monomer exchange between TF1 dimers accessible to a simple gel retardation analysis. Exchange was rapid at high protein concentrations, even at 0 degrees C, and is proposed to be capable of proceeding through an interaction of molecules of TF1 dimer rather than exclusively through dissociation into monomer subunits. Evidence suggesting that DNA-bound TF1 dimers do not exchange subunits readily is also presented.

The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation.

PubMed Central

Lazennec, G; Kern, L; Valotaire, Y; Salbert, G

1997-01-01

The rainbow trout estrogen receptor (rtER) is a positively autoregulated gene in liver cells. In a previous report, we showed that upregulation is mediated by an estrogen response element (ERE) located in the proximal promoter of the gene and that a half binding site for nuclear receptors (5'-TGACCT-3') located 15 bp upstream of the ERE is involved in the magnitude of the estrogen response. We now report that the human orphan receptor COUP-TF and a COUP-TF-like protein from trout liver are able to bind to the consensus half-site. When cotransfected with the rtER gene proximal promoter, COUP-TF had no regulatory functions on its own. Interestingly, COUP-TF enhanced rtER transactivation properties in the presence of estradiol in a dose-dependent manner when cotransfected with the rtER gene promoter. Unliganded retinoid receptor heterodimers had the same helper function as COUP-TF in the presence of estradiol but were switched to repressors when the ligand all-trans-retinoic acid was added. Mutation of the consensus half-site only slightly reduced COUP-TF helper function, suggesting that it actually results from a complex mechanism that probably involves both DNA binding of COUP-TF to the promoter and protein-protein interaction with another transcription factor bound to the promoter. Nevertheless, a DNA-binding-defective mutant of COUP-TF was also defective in ER helper function. Competition footprinting analysis suggested that COUP-TF actually establishes contacts with the consensus upstream half-site and the downstream ERE half-site that would form a DR-24-like response element. Interaction of COUP-TF with the DR-24 element was confirmed in footprinting assays by using nuclear extracts from Saccharomyces cerevisiae expressing COUP-TF. Finally, interaction of COUP-TF with mutants of the rtER gene promoter showed that COUP-TF recognizes the ERE when the upstream half-site is mutated. These data show that COUP-TF may activate transcription through interaction with other nuclear receptors. This cross-talk between liganded nuclear receptors and orphan receptors is likely to modulate the spectrum of action of a particular ligand-receptor complex and may participate in the cell-type specificity of the ligand effect. PMID:9271383

Progressing in cable-in-conduit for fusion magnets: from ITER to low cost, high performance DEMO

NASA Astrophysics Data System (ADS)

Uglietti, D.; Sedlak, K.; Wesche, R.; Bruzzone, P.; Muzzi, L.; della Corte, A.

2018-05-01

The performance of ITER toroidal field (TF) conductors still have a significant margin for improvement because the effective strain between ‑0.62% and ‑0.95% limits the strands’ critical current between 15% and 45% of the maximum achievable. Prototype Nb3Sn cable-in-conduit conductors have been designed, manufactured and tested in the frame of the EUROfusion DEMO activities. In these conductors the effective strain has shown a clear improvement with respect to the ITER conductors, reaching values between ‑0.55% and ‑0.28%, resulting in a strand critical current which is two to three times higher than in ITER conductors. In terms of the amount of Nb3Sn strand required for the construction of the DEMO TF magnet system, such improvement may lead to a reduction of at least a factor of two with respect to a similar magnet built with ITER type conductors; a further saving of Nb3Sn is possible if graded conductors/windings are employed. In the best case the DEMO TF magnet could require fewer Nb3Sn strands than the ITER one, despite the larger size of DEMO. Moreover high performance conductors could be operated at higher fields than ITER TF conductors, enabling the construction of low cost, compact, high field tokamaks.

A comparison of apical transportation between FlexMaster and Twisted Files rotary instruments.

PubMed

Duran-Sindreu, Fernando; García, Marc; Olivieri, Juan Gonzalo; Mercadé, Montse; Morelló, Sergio; Roig, Miguel

2012-07-01

The aim of this study was to evaluate apical transportation in root canals after the use of Twisted Files (TF; SybronEndo, Orange, CA) and FlexMaster (VDW, Munich, Germany) #40/04 rotary files. A double-digital radiographic technique was used to compare apical transportation between the TF and FlexMaster systems. Each rotary system was used to instrument mesial canals from 80 extracted mandibular molars. The central axes of the file imaged before instrumentation (#15 K-file) and the master apical rotary file (#40/04) were superimposed digitally. AutoCAD 2008 (Autodesk Inc, San Rafael, CA) was used to measure apical transportation at 0.5 mm from the working length (WL). The data were analyzed using the Student's t test, and significance was set at P < .05. The mean amount of apical transportation at 0.5 mm from the WL was 0.17 ± 0.09 mm for the FlexMaster group and 0.19 ± 0.12 mm for the TF group. No statistically significant differences in apical transportation were found between the 2 groups. Under the conditions of the study, no statistically significant differences in apical transportation were observed between FlexMaster and TF rotary files. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Infection of Monkeys by Simian-human Immunodeficiency Viruses with Transmitted/ founder Clade C HIV-1 Envelopes

PubMed Central

Asmal, Mohammed; Luedemann, Corinne; Lavine, Christy L.; Mach, Linh V.; Balachandran, Harikrishnan; Brinkley, Christie; Denny, Thomas N.; Lewis, Mark G.; Anderson, Hanne; Pal, Ranajit; Sok, Devin; Le, Khoa; Pauthner, Matthias; Hahn, Beatrice H.; Shaw, George M.; Seaman, Michael S.; Letvin, Norman L.; Burton, Dennis R.; Sodroski, Joseph G.; Haynes, Barton F.; Santra, Sampa

2014-01-01

Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed ten clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques. PMID:25462344

International Collaborations on Engineered Barrier Systems: Brief Overview of SKB-EBS Activities.

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

Jove-Colon, Carlos F.

2015-10-01

Research collaborations with international partners on the behavior and performance of engineered barrier systems (EBS) are an important aspect of the DOE-NE Used Fuel Disposition Campaign strategy in the evaluation of disposal design concepts. These international partnerships are a cost-effective way of engaging in key R&D activities with common goals resulting in effective scientific knowledge exchanges thus enhancing existing and future research programs in the USA. This report provides a brief description of the activities covered by the Swedish Nuclear Fuel and Waste Management Company (SKB) EBS Task Force (TF) (referred hereafter as SKB EBS TF) and potential future directionsmore » for engagement of the DOE-NE UFDC program in relevant R&D activities. Emphasis is given to SKB EBS TF activities that are still ongoing and aligned to the UFDC R&D program. This include utilization of data collected in the bentonite rock interaction experiment (BRIE) and data sets from benchmark experiments produced by the chemistry or “C” part of the SKB EBS TF. Potential applications of information generated by this program include comparisons/tests between model and data (e.g., reactive diffusion), development and implementation of coupled-process models (e.g., HM), and code/model benchmarking.« less

Exploring lateral genetic transfer among microbial genomes using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Ragan, Mark A

2016-07-25

Many microbes can acquire genetic material from their environment and incorporate it into their genome, a process known as lateral genetic transfer (LGT). Computational approaches have been developed to detect genomic regions of lateral origin, but typically lack sensitivity, ability to distinguish donor from recipient, and scalability to very large datasets. To address these issues we have introduced an alignment-free method based on ideas from document analysis, term frequency-inverse document frequency (TF-IDF). Here we examine the performance of TF-IDF on three empirical datasets: 27 genomes of Escherichia coli and Shigella, 110 genomes of enteric bacteria, and 143 genomes across 12 bacterial and three archaeal phyla. We investigate the effect of k-mer size, gap size and delineation of groups on the inference of genomic regions of lateral origin, finding an interplay among these parameters and sequence divergence. Because TF-IDF identifies donor groups and delineates regions of lateral origin within recipient genomes, aggregating these regions by gene enables us to explore, for the first time, the mosaic nature of lateral genes including the multiplicity of biological sources, ancestry of transfer and over-writing by subsequent transfers. We carry out Gene Ontology enrichment tests to investigate which biological processes are potentially affected by LGT.

Incremental Drag due to Grooves and Threads for KE (Kinetic Energy) Projectiles

DTIC Science & Technology

1989-03-01

RFI • CTsB TF * - MF (3a) q L where TF1 is the Thread Factor defined as: TF 0.84 + 0.117 P - o (3b) where p is the groove pitch in inches, MF1 is...g2) MF RF CD (4) where TF11 and TF1 2 are the thread factors for the threads of pitch p, and P2, respectively. 5 One can notice the large

Heparanase procoagulant activity as a predictor of wound necrosis following diabetic foot amputation.

PubMed

Peled, Eli; Melamed, Eyal; Portal, Tali Banker; Axelman, Elena; Norman, Doron; Brenner, Benjamin; Nadir, Yona

2016-03-01

Trans-metatarsal operation to diabetic foot necrosis is a common procedure although only half of the patients do not need a second amputation due to surgery wound ischemia. No current tools are available for early prediction of surgery success and the clinical decision for a second operation may take weeks. Heparanase protein is involved in inflammation, angiogenesis and coagulation activation. The aim of the study was to evaluate heparanase level and procoagulant activity as an early predictor for success or failure of diabetic foot trans-metatarsal surgery. The study group included 40 patients with diabetic foot necrosis requiring trans-metatarsal surgical intervention. Eighteen patients designated as necrotic group, developed post-surgery necrosis at the surgery wound within the first month, requiring a second more proximal amputation. Skin biopsies from the proximal surgery edge were stained for heparanase, tissue factor (TF), TF pathway inhibitor (TFPI) and by hematoxylin and eosin. Plasma samples were drawn pre-surgery and at 1h, 1week and 1month post-surgery. Samples were tested for heparanase levels by ELISA and TF+heparanase activity, TF activity and heparanase procoagulant activity. Skin biopsy staining did not predict subsequent necrosis. In the non-necrotic group a significant rise in TF+heparanase activity, heparanase activity and heparanase levels were observed 1h and 1week post-surgery. The most significant increase was in heparanase procoagulant activity at the time point of 1h post-surgery (P<0.0001). Pre-surgery TF activity was significantly lower in the non-necrotic group compared to the necrotic group (P<0.05). Measuring heparanase procoagulant activity pre-surgery and 1h post-surgery could potentially serve as an early tool to predict the procedure success. The present results broaden our understanding regarding early involvement of heparanase in the wound healing process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of ELISAs for diagnosis of acute typhoid fever in Nigerian children

PubMed Central

Felgner, Jiin; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskas, Algis; Gotuzzo, Eduardo; Vinetz, Joseph M.; Miyajima, Fabio; Pirmohamed, Munir; Hassan-Hanga, Fatimah; Umoru, Dominic; Jibir, Binta Wudil; Gambo, Safiya; Olateju, Kudirat; Felgner, Philip L.

2017-01-01

Improved serodiagnostic tests for typhoid fever (TF) are needed for surveillance, to facilitate patient management, curb antibiotic resistance, and inform public health programs. To address this need, IgA, IgM and IgG ELISAs using Salmonella enterica serovar Typhi (S. Typhi) lipopolysaccharide (LPS) and hemolysin E (t1477) protein were conducted on 86 Nigerian pediatric TF and 29 non-typhoidal Salmonella (NTS) cases, 178 culture-negative febrile cases, 28 “other” (i.e., non-Salmonella) pediatric infections, and 48 healthy Nigerian children. The best discrimination was achieved between TF and healthy children. LPS-specific IgA and IgM provided receiver operator characteristic areas under the curve (ROC AUC) values of 0.963 and 0.968, respectively, and 0.978 for IgA+M combined. Similar performance was achieved with t1477-specific IgA and IgM (0.968 and 0.968, respectively; 0.976 combined). IgG against LPS and t1477 was less accurate for discriminating these groups, possibly as a consequence of previous exposure, although ROC AUC values were still high (0.928 and 0.932, respectively). Importantly, discrimination between TF and children with other infections was maintained by LPS-specific IgA and IgM (AUC = 0.903 and 0.934, respectively; 0.938 combined), and slightly reduced for IgG (0.909), while t1477-specific IgG performed best (0.914). A similar pattern was seen when comparing TF with other infections from outside Nigeria. The t1477 may be recognized by cross-reactive antibodies from other acute infections, although a robust IgG response may provide some diagnostic utility in populations where incidence of other infections is low, such as in children. The data are consistent with IgA and IgM against S. Typhi LPS being specific markers of acute TF. PMID:28640809

Dynamic Transcription Factor Networks in Epithelial-Mesenchymal Transition in Breast Cancer Models

PubMed Central

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J.; Shin, Seungjin; Jeruss, Jacqueline S.; Shea, Lonnie D.

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy. PMID:23593114

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

PubMed

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

A complex structure in the mRNA of Tf1 is recognized and cleaved to generate the primer of reverse transcription.

PubMed

Lin, J H; Levin, H L

1997-01-15

All retroviruses and LTR-containing retrotransposons are thought to require specific tRNA molecules to serve as primers of reverse transcription. An exception is the LTR-containing retrotransposon Tf1, isolated from Schizosaccharomyces pombe. Instead of requiring a tRNA, the reverse transcriptase of Tf1 uses the first 11 bases of the Tf1 transcript as the primer for reverse transcription. The primer is generated by a cleavage that occurs between bases 11 and 12 of the Tf1 mRNA. Sequence analysis of the 5' untranslated region of the Tf1 mRNA resulted in the identification of a region with the potential to form an RNA structure of 89 bases that included the primer binding site and the first 11 bases of the Tf1 mRNA. Systematic mutagenesis of this region revealed 34 single-point mutants in the structure that resulted in reduced transposition activity. The defects in transposition correlated with reduced level of Tf1 reverse transcripts as determined by DNA blot analysis. Evidence that the RNA structure did form in vivo included the result that strains with second site mutations that restored complementarity resulted in increased levels of reverse transcripts and Tf1 transposition. The majority of the mutants defective for reverse transcription were unable to cleave the Tf1 mRNA between bases 11 and 12. These data indicate that formation of an extensive RNA structure was required for the cleavage reaction that generated the primer for Tf1 reverse transcription.

Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic approach.

PubMed

Shamsi, Anas; Ahmed, Azaj; Khan, Mohd Shahnawaz; Husain, Fohad Mabood; Amani, Samreen; Bano, Bilqees

2018-05-16

In our present study, binding between an important anti renal cancer drug temsirolimus and human transferrin (hTF) was investigated employing spectroscopic and molecular docking approach. In the presence of temsirolimus, hyper chromaticity is observed in hTF in UV spectroscopy suggestive of complex formation between hTF and temsirolimus. Fluorescence spectroscopy revealed the occurrence of quenching in hTF in the presence of temsirolimus implying complex formation taking place between hTF and temsirolimus. Further, the mode of interaction between hTF and temsirolimus was revealed to be static by fluorescence quenching analysis at 3 different temperatures. Binding constant values obtained employing fluorescence spectroscopy depicts strong interaction between hTF and temsirolimus; temsirolimus binds to hTF at 298 K with a binding constant of .32 × 10 4  M -1 implying the strength of this interaction. The negative Gibbs free energy obtained through quenching experiments is evident of the fact that the binding is spontaneous. CD spectra of hTF also showed a downward shift in the presence of temsirolimus as compared with free hTF implying complex formation between hTF and temsirolimus. Molecular docking was performed with a view to find out which residues are key players in this interaction. The importance of our study stems from the fact it will provide an insight into binding pattern of commonly administered renal cancer drug with an important protein that plays a pivotal role in many physiological processes. Copyright © 2018 John Wiley & Sons, Ltd.

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

Zhang Peng; Department of Physics, Renmin University of China, Beijing 100872; Naidon, Pascal

Most of the current theories on the p-wave superfluid in cold atomic gases are based on the effective-range theory for the two-body scattering, where the low-energy p-wave scattering amplitude f{sub 1}(k) is given by f{sub 1}(k)=-1/[ik+1/(Vk{sup 2})+1/R]. Here k is the incident momentum, V and R are the k-independent scattering volume and effective range, respectively. However, due to the long-range nature of the van der Waals interaction between two colliding ultracold atoms, the p-wave scattering amplitude of the two atoms is not described by the effective-range theory [J. Math. Phys. 4, 54 (1963); Phys. Rev. A 58, 4222 (1998)]. Inmore » this paper we provide an explicit calculation for the p-wave scattering of two ultracold atoms near the p-wave magnetic Feshbach resonance. We show that in this case the low-energy p-wave scattering amplitude f{sub 1}(k)=-1/[ik+1/(V{sup eff}k{sup 2})+1/(S{sup eff}k)+1/R{sup eff}] where V{sup eff}, S{sup eff}, and R{sup eff} are k-dependent parameters. Based on this result, we identify sufficient conditions for the effective-range theory to be a good approximation of the exact scattering amplitude. Using these conditions we show that the effective-range theory is a good approximation for the p-wave scattering in the ultracold gases of {sup 6}Li and {sup 40}K when the scattering volume is enhanced by the resonance.« less

Contribution of relativistic quantum chemistry to electron’s electric dipole moment for CP violation

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

Abe, M., E-mail: minoria@tmu.ac.jp; Gopakumar, G., E-mail: gopakumargeetha@gmail.com; Hada, M., E-mail: hada@tmu.ac.jp

The search for the electric dipole moment of the electron (eEDM) is important because it is a probe of Charge Conjugation-Parity (CP) violation. It can also shed light on new physics beyond the standard model. It is not possible to measure the eEDM directly. However, the interaction energy involving the effective electric field (E{sub eff}) acting on an electron in a molecule and the eEDM can be measured. This quantity can be combined with E{sub eff}, which is calculated by relativistic molecular orbital theory to determine eEDM. Previous calculations of E{sub eff} were not sufficiently accurate in the treatment ofmore » relativistic or electron correlation effects. We therefore developed a new method to calculate E{sub eff} based on a four-component relativistic coupled-cluster theory. We demonstrated our method for YbF molecule, one of the promising candidates for the eEDM search. Using very large basis set and without freezing any core orbitals, we obtain a value of 23.1 GV/cm for E{sub eff} in YbF with an estimated error of less than 10%. The error is assessed by comparison of our calculations and experiments for two properties relevant for E{sub eff}, permanent dipole moment and hyperfine coupling constant. Our method paves the way to calculate properties of various kinds of molecules which can be described by a single-reference wave function.« less

Damage Detection and Impact Testing on Laminated and Sandwich Composite Panels

NASA Technical Reports Server (NTRS)

Hughes, Derke R.; Craft, William J.; Schulz, Mark J.; Naser, Ahmad S.; Martin, William N.

1998-01-01

This research investigates health monitoring of sandwich shell composites to determine if the Transmittance Functions (TF) are effective in determining the present of damage. The health monitoring test was conducted on the sandwich plates before and after low velocity impacts using the health monitoring technique given in TFs are a NDE (Nondestructive Evaluation) technique that utilizes the ratios of cross-spectrums to auto-spectrums between two response points on the sandwich composites. The test for transmittance was conducted on the same density foam core throughout the experiment. The test specimens were 17.8 cm by 25.4 cm in dimension. The external sheets (face sheets) were created from graphite/epoxy laminate with dimension of 1.58 mm thick. The polymethacrylide (Rohacell) foam core was 12.7 mm thick. These samples experienced a transformation in the TF that was considered the low velocity impact damage. The low velocity damage was observed in the TFs for the sandwich composites.

TSI test

MedlinePlus

... JE, ed. Guyton and Hall Textbook of Medical Physiology . 13th ed. Philadelphia, PA: Elsevier; 2016:chap 77. ... TF, Schlumberger MJ, Hay ID, Larsen PR. Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. ...

Fast Fourier Tranformation Algorithms: Experiments with Microcomputers.

DTIC Science & Technology

1986-07-01

is, functions a with a known, discrete Fourier transform A Such functions are given fn [I]. The functions, TF1 , TF2, and TF3, were used and are...the IBM PC, all with TF1 (Eq. 1). ’The compilers provided options to improve performance, as noted, for which a penalty in compiling time has to be...BASIC only. Series I In this series the procedures were as follows: (i) Calculate the input values for TF1 of ar and the modulus Iar (which is

Generation of a Multivariate Distribution for Specified Univariate Marginals and Covariance Structure.

DTIC Science & Technology

1981-05-28

x2-+,(y) . F7. y1 (-i! Tf1 ’ 2) 2 f. 2;X (3 1(2 X T= t I (Y) F= I (yI) .(-l I f ill ; X ( 2 ) Combining the one-to-one property of Tf, with (B-4...transformation of probability, dT; (y) g(Y) - f( Tf1 (Y)). ldet ( dY )I = f(TfI (Y))/f(Tf (Y)) =1 Remarks m 1. It immediately follows that Y is uniformly

A new tissue segmentation method to calculate 3D dose in small animal radiation therapy.

PubMed

Noblet, C; Delpon, G; Supiot, S; Potiron, V; Paris, F; Chiavassa, S

2018-02-26

In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Z eff ) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Z eff ) in small animal dose calculation. The method is based on the relationship found between CBCT number and ρ*Z eff product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZ eff variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZ eff method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations. The study of the impact of ρZ eff variation over the range of materials, from ρZ eff  = 2 g.cm - 3 (lung) to 27 g.cm - 3 (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZ eff method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose area with 4% and 0.3 mm criteria in dose and distance. Our new tissue segmentation method was developed for 40kVp CBCT images. Both density and elemental composition are assigned to each voxel by using a relationship between HU and the product ρZ eff . The method, validated by comparing measurements and calculations, enables more accurate small animal dose distribution calculated on low energy CBCT images.

[Effect of Leonurus Heterophyllus Sweet on tissue factor transcription and expression in human umbilical vein endothelial cells in vitro].

PubMed

Zheng, Lian; Fang, Chi-hua

2007-06-01

To investigate the effect of Leonurus Heterophyllus Sweet, (LHS) on tissue factor (TF) transcription and expression induced by thrombin in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with different concentrations of LHS and the TF mRNA expression was detected by reverse transcript-polymerase chain reaction (RT-PCR). LHS treatment of HUVECs at different concentrations and for different times resulted in significant differences in TF expression (Plt;0.01). The transcription of TF in LHS-treated cells was significantly different from that of the blank control group (Plt;0.01). LHS can decrease the expression of TF and intervene with TF transcription in HUVECs in vitro.

Overview of the IFMIF/EVEDA project

NASA Astrophysics Data System (ADS)

Knaster, J.; Garin, P.; Matsumoto, H.; Okumura, Y.; Sugimoto, M.; Arbeiter, F.; Cara, P.; Chel, S.; Facco, A.; Favuzza, P.; Furukawa, T.; Heidinger, R.; Ibarra, A.; Kanemura, T.; Kasugai, A.; Kondo, H.; Massaut, V.; Molla, J.; Micciche, G.; O'hira, S.; Sakamoto, K.; Yokomine, T.; Wakai, E.; the IFMIF/EVEDA Integrated Project Team

2017-10-01

IFMIF, the International Fusion Materials Irradiation Facility, is presently in its engineering validation and engineering design activities (EVEDA) phase under the Broader Approach Agreement. The engineering design activity (EDA) phase was successfully accomplished within the allocated time. The engineering validation activity (EVA) phase has focused on validating the Accelerator Facility (AF), the Target Facility and the Test Facility (TF) by constructing prototypes. The ELTL at JAEAc, Oarai successfully demonstrated the long-term stability of a Li flow under the IFMIF’s nominal operational conditions keeping the specified free-surface fluctuations below  ±1 mm in a continuous manner for 25 d. A full-scale prototype of the high flux test module (HFTM) was successfully tested in the HELOKA loop (KIT, Karlsruhe), where it was demonstrated that the irradiation temperature can be set individually and kept uniform. LIPAc, designed and constructed in European labs under the coordination of F4E, presently under installation and commissioning in the Rokkasho Fusion Institute, aims at validating the concept of IFMIF accelerators with a D+ beam of 125 mA continuous wave (CW) and 9 MeV. The commissioning phases of the H+/D+ beams at 100 keV are progressing and should be concluded in 2017; in turn, the commissioning of the 5 MeV beam is due to start during 2017. The D+ beam through the superconducting cavities is expected to be achieved within the Broader Approach Agreement time frame with the superconducting cryomodule being assembled in Rokkasho. The realisation of a fusion-relevant neutron source is a necessary step for the successful development of fusion. The ongoing success of the IFMIF/EVEDA involves ruling out concerns about potential technical showstoppers which were raised in the past. Thus, a situation has emerged where soon steps towards constructing a Li(d,xn) fusion-relevant neutron source could be taken, which is also justified in the light of costs which are marginal to those of a fusion plant. In Memoriam Yoshikazu Okumura who passed away on 6 March 2017.

Electron mobility in the inversion layers of fully depleted SOI films

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

Zaitseva, E. G., E-mail: ZaytsevaElza@yandex.ru; Naumova, O. V.; Fomin, B. I.

The dependences of the electron mobility μ{sub eff} in the inversion layers of fully depleted double–gate silicon-on-insulator (SOI) metal–oxide–semiconductor (MOS) transistors on the density N{sub e} of induced charge carriers and temperature T are investigated at different states of the SOI film (inversion–accumulation) from the side of one of the gates. It is shown that at a high density of induced charge carriers of N{sub e} > 6 × 10{sup 12} cm{sup –2} the μeff(T) dependences allow the components of mobility μ{sub eff} that are related to scattering at surface phonons and from the film/insulator surface roughness to be distinguished.more » The μ{sub eff}(N{sub e}) dependences can be approximated by the power functions μ{sub eff}(N{sub e}) ∝ N{sub e}{sup −n}. The exponents n in the dependences and the dominant mechanisms of scattering of electrons induced near the interface between the SOI film and buried oxide are determined for different N{sub e} ranges and film states from the surface side.« less

CD13 as target for tissue factor induced tumor vascular infarction in small cell lung cancer.

PubMed

Schmidt, Lars Henning; Stucke-Ring, Janine; Brand, Caroline; Schliemann, Christoph; Harrach, Saliha; Muley, Thomas; Herpel, Esther; Kessler, Torsten; Mohr, Michael; Görlich, Dennis; Kreuter, Michael; Lenz, Georg; Wardelmann, Eva; Thomas, Michael; Berdel, Wolfgang E; Schwöppe, Christian; Hartmann, Wolfgang

2017-11-01

Zinc-binding protease aminopeptidase N (CD13) is expressed on tumor vascular cells and tumor cells. It represents a potential candidate for molecular targeted therapy, e.g. employing truncated tissue factor (tTF)-NGR, which can bind CD13 and thereby induce tumor vascular infarction. We performed a comprehensive analysis of CD13 expression in a clinically well characterized cohort of patients with small cell lung cancer (SCLC) to evaluate its potential use for targeted therapies in this disease. CD13 expression was analyzed immunohistochemically in 27 SCLC patients and correlated with clinical course and outcome. In CD-1 nude mice bearing human HTB119 SCLC xenotransplants, the systemic effects of the CD13-targeting fusion protein tTF-NGR on tumor growth were tested. In 52% of the investigated SCLC tissue samples, CD13 was expressed in tumor stroma cells, while the tumor cells were negative for CD13. No prognostic effect was found in the investigated SCLC study collective with regard to overall survival (p>0.05). In CD-1 nude mice, xenografts of CD13 negative HTB119 SCLC cells showed CD13 expression in the intratumoral vascular and perivascular cells, and the systemic application of CD13-targeted tissue factor tTF-NGR led to a significant reduction of tumor growth. We here present first data on the expression of CD13 in SCLC tumor samples. Our results strongly recommend the further investigation of tTF-NGR and other molecules targeted by NGR-peptides in SCLC patients. Considering the differential expression of CD13 in SCLC samples pre-therapeutic CD13 analysis is proposed for testing as investigational predictive biomarker for patient selection. Copyright © 2017 Elsevier B.V. All rights reserved.

Analyzing machupo virus-receptor binding by molecular dynamics simulations.

PubMed

Meyer, Austin G; Sawyer, Sara L; Ellington, Andrew D; Wilke, Claus O

2014-01-01

In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein-protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host-virus protein-protein interface. We use steered molecular dynamics (SMD) to computationally pull the machupo virus (MACV) spike glycoprotein (GP1) away from the human transferrin receptor (hTfR1). We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein-protein interactions.

Analyzing machupo virus-receptor binding by molecular dynamics simulations

PubMed Central

Sawyer, Sara L.; Ellington, Andrew D.; Wilke, Claus O.

2014-01-01

In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein–protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host–virus protein–protein interface. We use steered molecular dynamics (SMD) to computationally pull the machupo virus (MACV) spike glycoprotein (GP1) away from the human transferrin receptor (hTfR1). We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein–protein interactions. PMID:24624315

The Chromodomain of Tf1 Integrase Promotes Binding to cDNA and Mediates Target Site Selection▿ †

PubMed Central

Chatterjee, Atreyi Ghatak; Leem, Young Eun; Kelly, Felice D.; Levin, Henry L.

2009-01-01

The long terminal repeat (LTR) retrotransposon Tf1 of Schizosaccharomyces pombe integrates specifically into the promoters of pol II-transcribed genes. Its integrase (IN) contains a C-terminal chromodomain related to the chromodomains that bind to the N-terminal tail of histone H3. Although we have been unable to detect an interaction between histone tails and the chromodomain of Tf1 IN, it is possible that the chromodomain plays a role in directing IN to its target sites. To test this idea, we generated transposons with single amino acid substitutions in highly conserved residues of the chromodomain and created a chromodomain-deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDΔ, substantially reduced transposition activity in vivo. Blotting assays showed that there was little or no reduction in the levels of IN or cDNA. By measuring the homologous recombination between cDNA and the plasmid copy of Tf1, we found that two of the mutations did not reduce the import of cDNA into the nucleus, while another caused a 33% reduction. Chromatin immunoprecipitation assays revealed that CHDΔ caused an approximately threefold reduction in the binding of IN to the downstream LTR of the cDNA. These data indicate that the chromodomain contributed directly to integration. We therefore tested whether the chromodomain contributed to selecting insertion sites. Results of a target plasmid assay showed that the deletion of the chromodomain resulted in a drastic reduction in the preference for pol II promoters. Collectively, these data indicate that the chromodomain promotes binding of cDNA and plays a key role in efficient targeting. PMID:19109383

The chromodomain of Tf1 integrase promotes binding to cDNA and mediates target site selection.

PubMed

Chatterjee, Atreyi Ghatak; Leem, Young Eun; Kelly, Felice D; Levin, Henry L

2009-03-01

The long terminal repeat (LTR) retrotransposon Tf1 of Schizosaccharomyces pombe integrates specifically into the promoters of pol II-transcribed genes. Its integrase (IN) contains a C-terminal chromodomain related to the chromodomains that bind to the N-terminal tail of histone H3. Although we have been unable to detect an interaction between histone tails and the chromodomain of Tf1 IN, it is possible that the chromodomain plays a role in directing IN to its target sites. To test this idea, we generated transposons with single amino acid substitutions in highly conserved residues of the chromodomain and created a chromodomain-deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDDelta, substantially reduced transposition activity in vivo. Blotting assays showed that there was little or no reduction in the levels of IN or cDNA. By measuring the homologous recombination between cDNA and the plasmid copy of Tf1, we found that two of the mutations did not reduce the import of cDNA into the nucleus, while another caused a 33% reduction. Chromatin immunoprecipitation assays revealed that CHDDelta caused an approximately threefold reduction in the binding of IN to the downstream LTR of the cDNA. These data indicate that the chromodomain contributed directly to integration. We therefore tested whether the chromodomain contributed to selecting insertion sites. Results of a target plasmid assay showed that the deletion of the chromodomain resulted in a drastic reduction in the preference for pol II promoters. Collectively, these data indicate that the chromodomain promotes binding of cDNA and plays a key role in efficient targeting.

Vertical Load Induced with Twisted File Adaptive System during Canal Shaping.

PubMed

Jamleh, Ahmed; Alfouzan, Khalid

2016-12-01

To evaluate the vertical load induced with the Twisted File Adaptive (TFA; SybronEndo, Orange, CA) system during canal shaping of extracted teeth by comparing it with the Twisted File (TF, SybronEndo), ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland), and ProTaper Universal (PTU, Dentsply Maillefer) systems. Fifty-two root canals were shaped using the TFA, TF, PTN, or PTU systems (n = 13 for each system). They were shaped gently according to the manufacturers' instructions. During canal shaping, vertical loads were recorded and shown in 2 directions, apically and coronally directed loads. The vertical peak loads of 3 instrumentation stages were used for comparison. The effects of rotary systems on the mean positive and negative peak loads were analyzed statistically using the Kruskal-Wallis and Mann-Whitney tests at a confidence level of 95%. The overall pattern of the instantaneous loads appeared to increase with the use of successive instruments within the system. During canal shaping in all groups, the apically and coronally directed peak loads ranged from 0.84-7.55 N and 2.16-2.79 N, respectively. There were significant differences in both peak loads among the tested systems at each instrumentation stage. TFA had the lowest apically directed peak loads. In terms of coronally directed peak loads, the TFA and TF had a significantly lower amount of loads developed with their instruments than PTN and PTU. The choice of instrument system had an influence on the loads developed during canal shaping. TFA instruments were associated favorably with the lowest values of peak loads followed by TF, PTN, and PTU. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The unrecognized burden of typhoid fever.

PubMed

Obaro, Stephen K; Iroh Tam, Pui-Ying; Mintz, Eric Daniel

2017-03-01

Typhoid fever (TF), caused by Salmonella enterica serovar Typhi, is the most common cause of enteric fever, responsible for an estimated 129,000 deaths and more than 11 million cases annually. Although several reviews have provided global and regional TF disease burden estimates, major gaps in our understanding of TF epidemiology remain. Areas covered: We provide an overview of the gaps in current estimates of TF disease burden and offer suggestions for addressing them, so that affected communities can receive the full potential of disease prevention offered by vaccination and water, sanitation, and hygiene interventions. Expert commentary: Current disease burden estimates for TF do not capture cases from certain host populations, nor those with atypical presentations of TF, which may lead to substantial underestimation of TF cases and deaths. These knowledge gaps pose major obstacles to the informed use of current and new generation typhoid vaccines.

Time-Frequency Masking for Speech Separation and Its Potential for Hearing Aid Design

PubMed Central

Wang, DeLiang

2008-01-01

A new approach to the separation of speech from speech-in-noise mixtures is the use of time-frequency (T-F) masking. Originated in the field of computational auditory scene analysis, T-F masking performs separation in the time-frequency domain. This article introduces the T-F masking concept and reviews T-F masking algorithms that separate target speech from either monaural or binaural mixtures, as well as microphone-array recordings. The review emphasizes techniques that are promising for hearing aid design. This article also surveys recent studies that evaluate the perceptual effects of T-F masking techniques, particularly their effectiveness in improving human speech recognition in noise. An assessment is made of the potential benefits of T-F masking methods for the hearing impaired in light of the processing constraints of hearing aids. Finally, several issues pertinent to T-F masking are discussed. PMID:18974204

Rational Design of a Transferrin-Binding Peptide Sequence Tailored to Targeted Nanoparticle Internalization.

PubMed

Santi, Melissa; Maccari, Giuseppe; Mereghetti, Paolo; Voliani, Valerio; Rocchiccioli, Silvia; Ucciferri, Nadia; Luin, Stefano; Signore, Giovanni

2017-02-15

The transferrin receptor (TfR) is a promising target in cancer therapy owing to its overexpression in most solid tumors and on the blood-brain barrier. Nanostructures chemically derivatized with transferrin are employed in TfR targeting but often lose their functionality upon injection in the bloodstream. As an alternative strategy, we rationally designed a peptide coating able to bind transferrin on suitable pockets not involved in binding to TfR or iron by using an iterative multiscale-modeling approach coupled with quantitative structure-activity and relationship (QSAR) analysis and evolutionary algorithms. We tested that selected sequences have low aspecific protein adsorption and high binding energy toward transferrin, and one of them is efficiently internalized in cells with a transferrin-dependent pathway. Furthermore, it promotes transferrin-mediated endocytosis of gold nanoparticles by modifying their protein corona and promoting oriented adsorption of transferrin. This strategy leads to highly effective nanostructures, potentially useful in diagnostic and therapeutic applications, which exploit (and do not suffer) the protein solvation for achieving a better targeting.

Ideal gas solubilities and solubility selectivities in a binary mixture of room-temperature ionic liquids.

PubMed

Finotello, Alexia; Bara, Jason E; Narayan, Suguna; Camper, Dean; Noble, Richard D

2008-02-28

This study focuses on the solubility behaviors of CO2, CH4, and N2 gases in binary mixtures of imidazolium-based room-temperature ionic liquids (RTILs) using 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][Tf2N]) and 1-ethyl-3-methylimidazolium tetrafluoroborate ([C2mim][BF4]) at 40 degrees C and low pressures (approximately 1 atm). The mixtures tested were 0, 25, 50, 75, 90, 95, and 100 mol % [C2mim][BF4] in [C2mim][Tf2N]. Results show that regular solution theory (RST) can be used to describe the gas solubility and selectivity behaviors in RTIL mixtures using an average mixture solubility parameter or an average measured mixture molar volume. Interestingly, the solubility selectivity, defined as the ratio of gas mole fractions in the RTIL mixture, of CO2 with N2 or CH4 in pure [C2mim][BF4] can be enhanced by adding 5 mol % [C2mim][Tf2N].

Molecular mechanism and structure of Trigger Factor bound to the translating ribosome

PubMed Central

Merz, Frieder; Boehringer, Daniel; Schaffitzel, Christiane; Preissler, Steffen; Hoffmann, Anja; Maier, Timm; Rutkowska, Anna; Lozza, Jasmin; Ban, Nenad; Bukau, Bernd; Deuerling, Elke

2008-01-01

Ribosome-associated chaperone Trigger Factor (TF) initiates folding of newly synthesized proteins in bacteria. Here, we pinpoint by site-specific crosslinking the sequence of molecular interactions of Escherichia coli TF and nascent chains during translation. Furthermore, we provide the first full-length structure of TF associated with ribosome–nascent chain complexes by using cryo-electron microscopy. In its active state, TF arches over the ribosomal exit tunnel accepting nascent chains in a protective void. The growing nascent chain initially follows a predefined path through the entire interior of TF in an unfolded conformation, and even after folding into a domain it remains accommodated inside the protective cavity of ribosome-bound TF. The adaptability to accept nascent chains of different length and folding states may explain how TF is able to assist co-translational folding of all kinds of nascent polypeptides during ongoing synthesis. Moreover, we suggest a model of how TF's chaperoning function can be coordinated with the co-translational processing and membrane targeting of nascent polypeptides by other ribosome-associated factors. PMID:18497744

Demonstration of retrotransposition of the Tf1 element in fission yeast.

PubMed

Levin, H L; Boeke, J D

1992-03-01

Tf1, a retrotransposon from fission yeast, has LTRs and coding sequences resembling the protease, reverse transcriptase and integrase domains of retroviral pol genes. A unique aspect of Tf1 is that it contains a single open reading frame whereas other retroviruses and retrotransposons usually possess two or more open reading frames. To determine whether Tf1 can transpose, we overproduced Tf1 transcripts encoded by a plasmid copy of the element marked with a neo gene. Approximately 0.1-4.0% of the cell population acquired chromosomally inherited resistance to G418. DNA blot analysis demonstrated that such strains had acquired both Tf1 and neo specific sequences within a restriction fragment of the same size; the size of this restriction fragment varied between different isolates. Structural analysis of the cloned DNA flanking the Tf1-neo element of two transposition candidates with the same regions in the parent strain showed that the ability to grow on G418 was due to transposition of Tf1-neo and not other types of recombination events.

Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.

PubMed

Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

2016-02-01

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of Dental Fluorosis, Socioeconomic Status and Self-Perception in Adolescents Exposed to a High Level of Fluoride in Water.

PubMed

Molina-Frechero, Nelly; Nevarez-Rascón, Martina; Nevarez-Rascón, Alfredo; González-González, Rogelio; Irigoyen-Camacho, María Esther; Sánchez-Pérez, Leonor; López-Verdin, Sandra; Bologna-Molina, Ronell

2017-01-12

Objective : To identify adolescents' self-perception of dental fluorosis from two areas with different socioeconomic levels. Methods : A cross-sectional, descriptive study was conducted with 15-year-old youths by applying a questionnaire designed and validated to assess self-perceptions of dental fluorosis in two areas with different socioeconomic statuses (SESs). Fluorosis was clinically evaluated by applying the Thylstrup and Fejerkov (TF) index on the upper front teeth. Results : A total of 308 adolescents were included in the study. The medium-SES population, which was exposed to 2.5 ppm of fluoride in water, and the low-SES population, which was exposed to 5.1 ppm, presented the following levels of dental fluorosis: TF 2-3 (50%), TF 4-5 (45.6%) and TF 6-7 (4.4%) for medium SES and TF 2-3 (12.3%), TF 4-5 (67.1%) and TF 67 (20.6%) for low SES. A significant association was found between self-perception and dental fluorosis in those with medium and low SESs ( p < 0.05). The multiple regression model found differences between TF levels and self-perception, with a 6-7 TF level for concerns about color (OR = 1.6), smile (OR = 1.2) and appearance (OR = 3.36). Conclusions : Self-perceptions of dental fluorosis affect adolescents such that adolescents with a medium SES have more negative perceptions than those with a low SES. Such perceptions increase as the TF index increases.

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

PubMed

Ark, B; Gummere, G; Bennett, D; Artzt, K

1991-06-01

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative in vivo imaging of tissue factor expression in glioma using dynamic contrast-enhanced MRI derived parameters.

PubMed

Chen, Xiao; Xie, Tian; Fang, Jingqin; Xue, Wei; Tong, Haipeng; Kang, Houyi; Wang, Sumei; Yang, Yizeng; Xu, Minhui; Zhang, Weiguo

2017-08-01

Tissue Factor (TF) has been well established in angiogenesis, invasion, metastasis, and prognosis in glioma. A noninvasive assessment of TF expression status in glioma is therefore of obvious clinical relevance. Dynamic contrast-enhanced (DCE) MRI parameters have been used to evaluate microvascular characteristics and predict molecular expression status in tumors. Our aim is to investigate whether quantitative DCE-MRI parameters could assess TF expression in glioma. Thirty-two patients with histopathologically diagnosed supratentorial glioma who underwent DCE-MRI were retrospectively recruited. Extended Tofts linear model was used for DCE-MRI post-processing. Hot-spot, whole tumor cross-sectional approaches, and histogram were used for analysis of model based parameters. Four serial paraffin sections of each case were stained with TF, CD105, CD34 and α-Sooth Muscle Actin, respectively for evaluating the association of TF and microvascular properties. Pearson correlation was performed between percentage of TF expression area and DCE-MRI parameters, multiple microvascular indexes. Volume transfer constant (K trans ) hot-spot value best correlated with TF (r=0.886, p<0.001), followed by 90th percentile K trans value (r=0.801, p<0.001). Moreover, histogram analysis of K trans value demonstrated that weak TF expression was associated with less heterogeneous and positively skewed distribution. Finally, pathology analysis revealed TF was associated with glioma grade and significantly correlated with these two dynamic angiogenic indexes which could be used to explain the strong correlation between K trans and TF expression. Our results indicate that K trans may serve as a potential clinical imaging biomarker to predict TF expression status preoperatively in gliomas. Copyright © 2017 Elsevier B.V. All rights reserved.

Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

PubMed Central

Li, Huihui; Choesang, Tenzin; Bao, Weili; Chen, Huiyong; Feola, Maria; Garcia-Santos, Daniel; Li, Jie; Sun, Shuming; Follenzi, Antonia; Pham, Petra; Liu, Jing; Zhang, Jinghua; Ponka, Prem; An, Xiuli; Mohandas, Narla; Fleming, Robert E.; Rivella, Stefano; Li, Guiyuan

2017-01-01

Iron availability for erythropoiesis and its dysregulation in β-thalassemia are incompletely understood. We previously demonstrated that exogenous apotransferrin leads to more effective erythropoiesis, decreasing erythroferrone (ERFE) and derepressing hepcidin in β-thalassemic mice. Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. We hypothesize that apotransferrin’s effect is mediated via decreased TfR1 expression and evaluate TfR1 expression in β-thalassemic mice in vivo and in vitro with and without added apotransferrin. Our findings demonstrate that β-thalassemic erythroid precursors overexpress TfR1, an effect that can be reversed by the administration of exogenous apotransferrin. In vitro experiments demonstrate that apotransferrin inhibits TfR1 expression independent of erythropoietin- and iron-related signaling, decreases TfR1 partitioning to reticulocytes during enucleation, and enhances enucleation of defective β-thalassemic erythroid precursors. These findings strongly suggest that overexpressed TfR1 may play a regulatory role contributing to iron overload and anemia in β-thalassemic mice. To evaluate further, we crossed TfR1+/− mice, themselves exhibiting iron-restricted erythropoiesis with increased hepcidin, with β-thalassemic mice. Resultant double-heterozygote mice demonstrate long-term improvement in ineffective erythropoiesis, hepcidin derepression, and increased erythroid enucleation in relation to β-thalassemic mice. Our data demonstrate for the first time that TfR1+/− haploinsufficiency reverses iron overload specifically in β-thalassemic erythroid precursors. Taken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice. PMID:28151426

Auditory Time-Frequency Masking for Spectrally and Temporally Maximally-Compact Stimuli

PubMed Central

Laback, Bernhard; Savel, Sophie; Ystad, Sølvi; Balazs, Peter; Meunier, Sabine; Kronland-Martinet, Richard

2016-01-01

Many audio applications perform perception-based time-frequency (TF) analysis by decomposing sounds into a set of functions with good TF localization (i.e. with a small essential support in the TF domain) using TF transforms and applying psychoacoustic models of auditory masking to the transform coefficients. To accurately predict masking interactions between coefficients, the TF properties of the model should match those of the transform. This involves having masking data for stimuli with good TF localization. However, little is known about TF masking for mathematically well-localized signals. Most existing masking studies used stimuli that are broad in time and/or frequency and few studies involved TF conditions. Consequently, the present study had two goals. The first was to collect TF masking data for well-localized stimuli in humans. Masker and target were 10-ms Gaussian-shaped sinusoids with a bandwidth of approximately one critical band. The overall pattern of results is qualitatively similar to existing data for long maskers. To facilitate implementation in audio processing algorithms, a dataset provides the measured TF masking function. The second goal was to assess the potential effect of auditory efferents on TF masking using a modeling approach. The temporal window model of masking was used to predict present and existing data in two configurations: (1) with standard model parameters (i.e. without efferents), (2) with cochlear gain reduction to simulate the activation of efferents. The ability of the model to predict the present data was quite good with the standard configuration but highly degraded with gain reduction. Conversely, the ability of the model to predict existing data for long maskers was better with than without gain reduction. Overall, the model predictions suggest that TF masking can be affected by efferent (or other) effects that reduce cochlear gain. Such effects were avoided in the experiment of this study by using maximally-compact stimuli. PMID:27875575

Auditory Time-Frequency Masking for Spectrally and Temporally Maximally-Compact Stimuli.

PubMed

Necciari, Thibaud; Laback, Bernhard; Savel, Sophie; Ystad, Sølvi; Balazs, Peter; Meunier, Sabine; Kronland-Martinet, Richard

2016-01-01

Many audio applications perform perception-based time-frequency (TF) analysis by decomposing sounds into a set of functions with good TF localization (i.e. with a small essential support in the TF domain) using TF transforms and applying psychoacoustic models of auditory masking to the transform coefficients. To accurately predict masking interactions between coefficients, the TF properties of the model should match those of the transform. This involves having masking data for stimuli with good TF localization. However, little is known about TF masking for mathematically well-localized signals. Most existing masking studies used stimuli that are broad in time and/or frequency and few studies involved TF conditions. Consequently, the present study had two goals. The first was to collect TF masking data for well-localized stimuli in humans. Masker and target were 10-ms Gaussian-shaped sinusoids with a bandwidth of approximately one critical band. The overall pattern of results is qualitatively similar to existing data for long maskers. To facilitate implementation in audio processing algorithms, a dataset provides the measured TF masking function. The second goal was to assess the potential effect of auditory efferents on TF masking using a modeling approach. The temporal window model of masking was used to predict present and existing data in two configurations: (1) with standard model parameters (i.e. without efferents), (2) with cochlear gain reduction to simulate the activation of efferents. The ability of the model to predict the present data was quite good with the standard configuration but highly degraded with gain reduction. Conversely, the ability of the model to predict existing data for long maskers was better with than without gain reduction. Overall, the model predictions suggest that TF masking can be affected by efferent (or other) effects that reduce cochlear gain. Such effects were avoided in the experiment of this study by using maximally-compact stimuli.

Template-independent DNA synthesis activity associated with the reverse transcriptase of the long terminal repeat retrotransposon Tf1.

PubMed

Oz-Gleenberg, Iris; Herzig, Eytan; Hizi, Amnon

2012-01-01

Reverse transcriptases (RTs) possess a non-templated addition (NTA) activity while synthesizing DNA with blunt-ended DNA primer/templates. Interestingly, the RT of the long terminal repeat retrotransposon Tf1 has an NTA activity that is substantially higher than that of HIV-1 or murine leukemia virus RTs. By performing steady state kinetics, we found that the differences between the NTA activities of Tf1 and HIV-1 RTs can be explained by the substantially lower K(M) value for the incoming dNTP of Tf1 RT (while the differences between the apparent k(cat) values of these two RTs are relatively small). Furthermore, the K(M) values, calculated for both RTs with the same dNTP, are much lower for the template-dependent synthesis (TDS) than those of NTA. However, TDS of HIV-1 RT is higher than that of Tf1 RT. The overall relative order of the apparent k(cat)/K(M) values for dATP is: HIV-1 RT (TDS) > Tf1 RT (TDS) > Tf1 RT (NTA) > HIV-1 RT (NTA). Under the employed conditions, Tf1 RT can add up to seven nucleotides to the blunt-ended substrate, while the other RTs add mostly a single nucleotide. The NTA activity of Tf1 RT is restricted to DNA primers. Furthermore, the NTA activity of Tf1 and HIV-1 RTs is suppressed by ATP, as it competes with the incoming dATP (although ATP is not incorporated by the NTA activity of the RTs). The unusually high NTA activity of Tf1 RT can explain why, after completing cDNA synthesis, the in vivo generated Tf1 cDNA has relatively long extra sequences beyond the highly conserved CA at its 3'-ends. © 2011 The Authors Journal compilation © 2011 FEBS.

On the connection between inherent DNA flexure and preferred binding of hydroxymethyluracil-containing DNA by the type II DNA-binding protein TF1.

PubMed

Grove, A; Galeone, A; Mayol, L; Geiduschek, E P

1996-07-12

TF1 is a member of the family of type II DNA-binding proteins, which also includes the bacterial HU proteins and the Escherichia coli integration host factor (IHF). Distinctive to TF1, which is encoded by the Bacillus subtilis bacteriophage SPO1, is its preferential binding to DNA in which thymine is replaced by 5-hydroxymethyluracil (hmU), as it is in the phage genome. TF1 binds to preferred sites within the phage genome and generates pronounced DNA bending. The extent to which DNA flexibility contributes to the sequence-specific binding of TF1, and the connection between hmU preference and DNA flexibility has been examined. Model flexible sites, consisting of consecutive mismatches, increase the affinity of thymine-containing DNA for TF1. In particular, tandem mismatches separated by nine base-pairs generate an increase, by orders of magnitude, in the affinity of TF1 for T-containing DNA with the sequence of a preferred TF1 binding site, and fully match the affinity of TF1 for this cognate site in hmU-containing DNA (Kd approximately 3 nM). Other placements of loops generate suboptimal binding. This is consistent with a significant contribution of site-specific DNA flexibility to complex formation. Analysis of complexes with hmU-DNA of decreasing length shows that a major part of the binding affinity is generated within a central 19 bp segment (delta G0 = 41.7 kJ mol-1) with more-distal DNA contributing modestly to the affinity (delta delta G = -0.42 kJ mol-1 bp-1 on increasing duplex length to 37 bp). However, a previously characterised thermostable and more tightly binding mutant TF1, TF1(E15G/T32I), derives most of its extra affinity from interaction with flanking DNA. We propose that inherent but sequence-dependent deformability of hmU-containing DNA underlies the preferential binding of TF1 and that TF1-induced DNA bendings is a result of distortions at two distinct sites separated by 9 bp of duplex DNA.

PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII.

PubMed

Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K; Jensen, Mette M; El Ali, Henrik H; Madsen, Jacob; Wiinberg, Bo; Petersen, Lars C; Kjaer, Andreas

2016-07-01

Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF. The purpose of this study was to investigate the possibility of using active site-inhibited FVII (FVIIai) labeled with (64)Cu for PET imaging of TF expression. FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu ((64)Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of (64)Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with (64)Cu-NOTA-FVIIai was investigated in subcutaneous pancreatic tumor models with different levels of TF expression and in a competition experiment. In addition, imaging of orthotopic pancreatic tumors was performed using (64)Cu-NOTA-FVIIai and PET/MRI. In vivo imaging data were supported by ex vivo biodistribution, flow cytometry, and immunohistochemistry. Longitudinal PET imaging with (64)Cu-NOTA-FVIIai showed a tumor uptake of 2.3 ± 0.2, 3.7 ± 0.3, 3.4 ± 0.3, and 2.4 ± 0.3 percentage injected dose per gram at 1, 4, 15, and 36 h after injection, respectively. An increase in tumor-to-normal-tissue contrast was observed over the imaging time course. Competition with unlabeled FVIIai significantly (P < 0.001) reduced the tumor uptake. The tumor uptake observed in models with different TF expression levels was significantly different from each other (P < 0.001) and was in agreement with the TF level evaluated by TF immunohistochemistry staining. Orthotopic tumors were clearly visible on the PET/MR images, and the uptake of (64)Cu-NOTA-FVIIai was colocalized with viable tumor tissue. (64)Cu-NOTA-FVIIai is well suited for PET imaging of tumor TF expression, and imaging is capable of distinguishing the TF expression level of various pancreatic tumor models. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A novel alignment-free method for detection of lateral genetic transfer based on TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Ragan, Mark A

2016-07-25

Lateral genetic transfer (LGT) plays an important role in the evolution of microbes. Existing computational methods for detecting genomic regions of putative lateral origin scale poorly to large data. Here, we propose a novel method based on TF-IDF (Term Frequency-Inverse Document Frequency) statistics to detect not only regions of lateral origin, but also their origin and direction of transfer, in sets of hierarchically structured nucleotide or protein sequences. This approach is based on the frequency distributions of k-mers in the sequences. If a set of contiguous k-mers appears sufficiently more frequently in another phyletic group than in its own, we infer that they have been transferred from the first group to the second. We performed rigorous tests of TF-IDF using simulated and empirical datasets. With the simulated data, we tested our method under different parameter settings for sequence length, substitution rate between and within groups and post-LGT, deletion rate, length of transferred region and k size, and found that we can detect LGT events with high precision and recall. Our method performs better than an established method, ALFY, which has high recall but low precision. Our method is efficient, with runtime increasing approximately linearly with sequence length.

T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy.

PubMed

Sackstein, Robert; Schatton, Tobias; Barthel, Steven R

2017-06-01

Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (T eff ) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue. Thus, defects intrinsic to the multi-step T-cell homing cascade have become an obvious, though significantly underappreciated contributor to immunotherapy resistance. Conspicuous have been low intralesional frequencies of tumor-infiltrating T-lymphocytes (TILs) below clinically beneficial threshold levels, and peripheral rather than deep lesional TIL infiltration. Therefore, a T eff cell 'homing deficit' may arguably represent a dominant factor responsible for ineffective immunotherapeutic outcomes, as tumors resistant to immune-targeted killing thrive in such permissive, immune-vacuous microenvironments. Fortunately, emerging data is shedding light into the diverse mechanisms of immune escape by which tumors restrict T eff cell trafficking and lesional penetrance. In this review, we scrutinize evolving knowledge on the molecular determinants of T eff cell navigation into tumors. By integrating recently described, though sporadic information of pivotal adhesive and chemokine homing signatures within the tumor microenvironment with better established paradigms of T-cell trafficking under homeostatic or infectious disease scenarios, we seek to refine currently incomplete models of T eff cell entry into tumor tissue. We further summarize how cancers thwart homing to escape immune-mediated destruction and raise awareness of the potential impact of immune checkpoint blockers on T eff cell homing. Finally, we speculate on innovative therapeutic opportunities for augmenting T eff cell homing capabilities to improve immunotherapy-based tumor eradication in cancer patients, with special focus on malignant melanoma.

Daughters mimic sterile neutrinos (almost!) perfectly

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

Hasenkamp, Jasper, E-mail: Jasper.Hasenkamp@nyu.edu

Since only recently, cosmological observations are sensitive to hot dark matter (HDM) admixtures with sub-eV mass, m{sub hdm}{sup eff} < eV, that are not fully-thermalised, Δ N{sub eff} < 1. We argue that their almost automatic interpretation as a sterile neutrino species is neither from theoretical nor practical parsimony principles preferred over HDM formed by decay products (daughters) of an out-of-equilibrium particle decay. While daughters mimic sterile neutrinos in N{sub eff} and m{sub hdm}{sup eff}, there are opportunities to assess this possibility in likelihood analyses. Connecting cosmological parameters and moments of momentum distribution functions, we show that—also in the case of mass-degenerate daughters with indistinguishablemore » main physical effects—the mimicry breaks down when the next moment, the skewness, is considered. Predicted differences of order one in the root-mean-squares of absolute momenta are too small for current sensitivities.« less

Stellar Atmospheric Parameterization Based on Deep Learning

NASA Astrophysics Data System (ADS)

Pan, R. Y.; Li, X. R.

2016-07-01

Deep learning is a typical learning method widely studied in machine learning, pattern recognition, and artificial intelligence. This work investigates the stellar atmospheric parameterization problem by constructing a deep neural network with five layers. The proposed scheme is evaluated on both real spectra from Sloan Digital Sky Survey (SDSS) and the theoretic spectra computed with Kurucz's New Opacity Distribution Function (NEWODF) model. On the SDSS spectra, the mean absolute errors (MAEs) are 79.95 for the effective temperature (T_{eff}/K), 0.0058 for lg (T_{eff}/K), 0.1706 for surface gravity (lg (g/(cm\\cdot s^{-2}))), and 0.1294 dex for metallicity ([Fe/H]), respectively; On the theoretic spectra, the MAEs are 15.34 for T_{eff}/K, 0.0011 for lg (T_{eff}/K), 0.0214 for lg (g/(cm\\cdot s^{-2})), and 0.0121 dex for [Fe/H], respectively.

An exact solution for R2,eff in CPMG experiments in the case of two site chemical exchange

PubMed Central

Baldwin, Andrew J.

2014-01-01

The Carr–Purcell–Meiboom–Gill (CPMG) experiment is widely used to quantitatively analyse the effects of chemical exchange on NMR spectra. In a CPMG experiment, the effective transverse relaxation rate, R2,eff, is typically measured as a function of the pulse frequency, νCPMG. Here, an exact expression for how R2,eff varies with νCPMG is derived for the commonly encountered scenario of two-site chemical exchange of in-phase magnetisation. This result, summarised in Appendix A, generalises a frequently used equation derived by Carver and Richards, published in 1972. The expression enables more rapid analysis of CPMG data by both speeding up calculation of R2,eff over numerical methods by a factor of ca. 130, and yields exact derivatives for use in data analysis. Moreover, the derivation provides insight into the physical principles behind the experiment. PMID:24852115

The Sequential Implementation of Array Processors when there is Directional Uncertainty

DTIC Science & Technology

1975-08-01

University of Washington kindly supplied office space and ccputing facilities. -The author hat, benefited greatly from discussions with several other...if i Q- inverse of Q I L general observation space R general vector of observation _KR general observation vector of dimension K Exiv] "Tf -- ’ -"-T’T...7" i ’i ’:"’ - ’ ; ’ ’ ’ ’ ’ ’" ’"- Glossary of Symbols (continued) R. ith observation 1 Rm real vector space of dimension m R(T) autocorrelation

Regulation of LPS-induced tissue factor expression in human monocytic THP-1 cells by curcumin

USDA-ARS?s Scientific Manuscript database

Tissue factor (TF) is a transmembrane receptor, which initiates thrombotic episodes associated with various diseases. In addition to membrane-bound TF, we have discovered an alternatively spliced form of human TF mRNA. It was later confirmed that this form of TF mRNA expresses a soluble protein circ...

Workload, Performance, and Reliability of Digital Computing Systems.

DTIC Science & Technology

1980-12-01

maximized is then P()(tf, ...... , ad .[[. P(ts) h( tf1 ),) (0 42.33) Note that this problem is equivalent to minimazing the function En Jn ,l~~f,) (-X) 1...have been observed at times tf1 , after observing the system since tsl. Take, for instance, the case of the distribution obtained from the simplified...represented by a set of pairs [ts,, tf1 ] i 1 ...... n the maximum likelihood values of a,y,P are these values that maximize the function p(n)( tf1 -ts 1 . . ts

Multisensor Calibration Procedure for an All Weather Short Range Air Defense System Concept.

DTIC Science & Technology

1983-08-15

are then integrated over the rotation interval tF1 - to 1 - tR, to arrive at the following angular displacement mesasuremnts: tF 1 eAl -f WAldt - K~len...g&dt (73) tol to1 tFlAOR1 tj~ 6p’Idt "( 1 8 0 ° " l1 + 0 12 ) (74) tF1 AVAl f Aldt (75) to’ &VB1 tl(6 to1 In order to integrate Al and B1, Reneral...rotation. TFl, TF2 tF1 , tF2 Upper limit of integration during rotation. THTI2,TT13,TRT21 Elments of BCS to ACS transformation THT23,THT311,THT32 matrix

Fatigue life and crack growth prediction methodology

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.; Phillips, E. P.; Everett, R. A., Jr.

1993-01-01

The capabilities of a plasticity-induced crack-closure model and life-prediction code to predict fatigue crack growth and fatigue lives of metallic materials are reviewed. Crack-tip constraint factors, to account for three-dimensional effects, were selected to correlate large-crack growth rate data as a function of the effective-stress-intensity factor range (delta(K(sub eff))) under constant-amplitude loading. Some modifications to the delta(K(sub eff))-rate relations were needed in the near threshold regime to fit small-crack growth rate behavior and endurance limits. The model was then used to calculate small- and large-crack growth rates, and in some cases total fatigue lives, for several aluminum and titanium alloys under constant-amplitude, variable-amplitude, and spectrum loading. Fatigue lives were calculated using the crack growth relations and microstructural features like those that initiated cracks. Results from the tests and analyses agreed well.

MRI-based, wireless determination of the transfer function of a linear implant: Introduction of the transfer matrix.

PubMed

Tokaya, Janot P; Raaijmakers, Alexander J E; Luijten, Peter R; van den Berg, Cornelis A T

2018-04-24

We introduce the transfer matrix (TM) that makes MR-based wireless determination of transfer functions (TFs) possible. TFs are implant specific measures for RF-safety assessment of linear implants. The TF relates an incident tangential electric field on an implant to a scattered electric field at its tip that generally governs local heating. The TM extends this concept and relates an incident tangential electric field to a current distribution in the implant therewith characterizing the RF response along the entire implant. The TM is exploited to measure TFs with MRI without hardware alterations. A model of rightward and leftward propagating attenuated waves undergoing multiple reflections is used to derive an analytical expression for the TM. This allows parameterization of the TM of generic implants, e.g., (partially) insulated single wires, in a homogeneous medium in a few unknowns that simultaneously describe the TF. These unknowns can be determined with MRI making it possible to measure the TM and, therefore, also the TF. The TM is able to predict an induced current due to an incident electric field and can be accurately parameterized with a limited number of unknowns. Using this description the TF is determined accurately (with a Pearson correlation coefficient R ≥ 0.9 between measurements and simulations) from MRI acquisitions. The TM enables measuring of TFs with MRI of the tested generic implant models. The MR-based method does not need hardware alterations and is wireless hence making TF determination in more realistic scenarios conceivable. © 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

PubMed

Buzala, Mateusz; Ponczek, Michal Blazej; Slomka, Artur; Roslewska, Aleksandra; Janicki, Bogdan; Zekanowska, Ewa; Bednarczyk, Marek

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Current Status and Recommendations for the Future of Research, Teaching, and Testing in the Biological Sciences of Radiation Oncology: Report of the American Society for Radiation Oncology Cancer Biology/Radiation Biology Task Force, Executive Summary

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

Wallner, Paul E., E-mail: pwallner@theabr.org; Anscher, Mitchell S.; Barker, Christopher A.

In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective ofmore » relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report.« less

Modes of Large-Scale Brain Network Organization during Threat Processing and Posttraumatic Stress Disorder Symptom Reduction during TF-CBT among Adolescent Girls.

PubMed

Cisler, Josh M; Sigel, Benjamin A; Kramer, Teresa L; Smitherman, Sonet; Vanderzee, Karin; Pemberton, Joy; Kilts, Clinton D

2016-01-01

Posttraumatic stress disorder (PTSD) is often chronic and disabling across the lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and mediating neural mechanisms are not well understood. Here, we test whether PTSD symptom reduction during TF-CBT is associated with individual differences in large-scale brain network organization during emotion processing. Twenty adolescent girls, aged 11-16, with PTSD related to assaultive violence completed a 12-session protocol of TF-CBT. Participants completed an emotion processing task, in which neutral and fearful facial expressions were presented either overtly or covertly during 3T fMRI, before and after treatment. Analyses focused on characterizing network properties of modularity, assortativity, and global efficiency within an 824 region-of-interest brain parcellation separately during each of the task blocks using weighted functional connectivity matrices. We similarly analyzed an existing dataset of healthy adolescent girls undergoing an identical emotion processing task to characterize normative network organization. Pre-treatment individual differences in modularity, assortativity, and global efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction. Patients who responded better to treatment had greater network modularity and assortativity but lesser efficiency, a pattern that closely resembled the control participants. At a group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, but this was more pronounced among participants with less symptom improvement. The results support the hypothesis that modularized and resilient brain organization during emotion processing operate as mechanisms enabling symptom reduction during TF-CBT.

Preliminary LOCA analysis of the westinghouse small modular reactor using the WCOBRA/TRAC-TF2 thermal-hydraulics code

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

Liao, J.; Kucukboyaci, V. N.; Nguyen, L.

2012-07-01

The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (> 225 MWe) integral pressurized water reactor (iPWR) with all primary components, including the steam generator and the pressurizer located inside the reactor vessel. The reactor core is based on a partial-height 17x17 fuel assembly design used in the AP1000{sup R} reactor core. The Westinghouse SMR utilizes passive safety systems and proven components from the AP1000 plant design with a compact containment that houses the integral reactor vessel and the passive safety systems. A preliminary loss of coolant accident (LOCA) analysis of the Westinghouse SMR has been performed using themore » WCOBRA/TRAC-TF2 code, simulating a transient caused by a double ended guillotine (DEG) break in the direct vessel injection (DVI) line. WCOBRA/TRAC-TF2 is a new generation Westinghouse LOCA thermal-hydraulics code evolving from the US NRC licensed WCOBRA/TRAC code. It is designed to simulate PWR LOCA events from the smallest break size to the largest break size (DEG cold leg). A significant number of fluid dynamics models and heat transfer models were developed or improved in WCOBRA/TRAC-TF2. A large number of separate effects and integral effects tests were performed for a rigorous code assessment and validation. WCOBRA/TRAC-TF2 was introduced into the Westinghouse SMR design phase to assist a quick and robust passive cooling system design and to identify thermal-hydraulic phenomena for the development of the SMR Phenomena Identification Ranking Table (PIRT). The LOCA analysis of the Westinghouse SMR demonstrates that the DEG DVI break LOCA is mitigated by the injection and venting from the Westinghouse SMR passive safety systems without core heat up, achieving long term core cooling. (authors)« less

Current status and recommendations for the future of research, teaching, and testing in the biological sciences of radiation oncology: report of the American Society for Radiation Oncology Cancer Biology/Radiation Biology Task Force, executive summary.

PubMed

Wallner, Paul E; Anscher, Mitchell S; Barker, Christopher A; Bassetti, Michael; Bristow, Robert G; Cha, Yong I; Dicker, Adam P; Formenti, Silvia C; Graves, Edward E; Hahn, Stephen M; Hei, Tom K; Kimmelman, Alec C; Kirsch, David G; Kozak, Kevin R; Lawrence, Theodore S; Marples, Brian; McBride, William H; Mikkelsen, Ross B; Park, Catherine C; Weidhaas, Joanne B; Zietman, Anthony L; Steinberg, Michael

2014-01-01

In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective of relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential co-expression analysis of rheumatoid arthritis with microarray data.

PubMed

Wang, Kunpeng; Zhao, Liqiang; Liu, Xuefeng; Hao, Zhenyong; Zhou, Yong; Yang, Chuandong; Li, Hongqiang

2014-11-01

The aim of the present study was to investigate the underlying molecular mechanisms of rheumatoid arthritis (RA) using microarray expression profiles from osteoarthritis and RA patients, to improve diagnosis and treatment strategies for the condition. The gene expression profile of GSE27390 was downloaded from Gene Expression Omnibus, including 19 samples from patients with RA (n=9) or osteoarthritis (n=10). Firstly, the differentially expressed genes (DEGs) were obtained with the thresholds of |logFC|>1.0 and P<0.05, using the t‑test method in LIMMA package. Then, differentially co-expressed genes (DCGs) and differentially co-expressed links (DCLs) were screened with q<0.25 by the differential coexpression analysis and differential regulation analysis of gene expression microarray data package. Secondly, pathway enrichment analysis for DCGs was performed by the Database for Annotation, Visualization and Integrated Discovery and the DCLs associated with RA were selected by comparing the obtained DCLs with known transcription factor (TF)-targets in the TRANSFAC database. Finally, the obtained TFs were mapped to the known TF-targets to construct the network using cytoscape software. A total of 1755 DEGs, 457 DCGs and 101988 DCLs were achieved and there were 20 TFs in the obtained six TF-target relations (STAT3-TNF, PBX1‑PLAU, SOCS3-STAT3, GATA1-ETS2, ETS1-ICAM4 and CEBPE‑GATA1) and 457 DCGs. A number of TF-target relations in the constructed network were not within DCLs when the TF and target gene were DCGs. The identified TFs may have an important role in the pathogenesis of RA and have the potential to be used as biomarkers for the development of novel diagnostic and therapeutic strategies for RA.

Diaphragm assessment by two dimensional speckle tracking imaging in normal subjects.

PubMed

Orde, Sam R; Boon, Andrea J; Firth, Daniel G; Villarraga, Hector R; Sekiguchi, Hiroshi

2016-07-25

Conventionally, ultrasonographic assessment of diaphragm contractility has involved measuring respiratory changes in diaphragm thickness (thickening fraction) using B-mode or caudal displacement with M-mode. Two-dimensional speckle-tracking has been increasingly used to assess muscle deformation ('strain') in echocardiography. We sought to determine in a pilot study if this technology could be utilized to analyze diaphragmatic contraction. Fifty healthy adult volunteers with normal exercise capacity underwent ultrasound imaging. A linear array transducer was used for the assessment of diaphragm thickness, thickening fraction (TF), and strain in the right anterior axillary line at approximately the ninth intercostal space. A phased array transducer was applied subcostally for the assessment of diaphragm displacement on the right mid-clavicular line. Diaphragmatic images were recorded from the end of expiration through the end of inspiration at 60 % maximal inspiratory capacity. Diaphragm strain was analyzed off-line by speckle tracking imaging. Blinded inter- and intra-rater variability was tested in 10 cases. Mean right diaphragm thickness at end-expiration (±SD: standard deviation) was 0.24 cm (±0.1), with TF of 45.1 % (±12) at 60 % peak inspiratory effort. Mean right diaphragm caudal displacement was 4.9 cm (±1). Mean right diaphragm strain was -40.3 % (±9). A moderate correlation was seen between longitudinal strain and TF (R(2) 0.44, p < 0.0001). A weak correlation was seen between strain and caudal displacement (R(2) 0.14, p < 0.01), and an even weaker correlation was seen between caudal displacement and TF (R(2) 0.1, p = 0.04). Age, gender, and body mass index were not significantly associated with right diaphragm strain or TF. Although inter- and intra-rater variability was overall good for TF, caudal displacement, and strain (inter-rater R(2); 0.8, 0.9, and 0.7, respectively [p < 0.01], intra-rater R(2); 0.9, 0.7, and 0.9, respectively [p < 0.01]), strain values did have a slightly lower inter-rater repeatability. Diaphragmatic strain estimated by speckle tracking imaging was associated with conventional ultrasound measures of diaphragmatic function (TF and caudal displacement). Further clinical studies are warranted to investigate its clinical utility.

SUPERFUND TREATABILITY CLEARINGHOUSE: LABORATORY FEASIBILITY TESTING OF PROTOTYPE SOIL WASHING CONCEPTS

EPA Science Inventory

This draft document reports on laboratory testing of several washing solutions to decontaminate soils contaminated vith dioxins. The following extractants were evaluated; surfactant mixtures of 0.5% to 3% Adsee 799 and 0.5* to 3% Hyonic NP90 in distilled water, Freon TF with ...

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

Brown, D. J. A.; Collier Cameron, A.; Enoch, B.

We present measurements of the spin-orbit alignment angle, {lambda}, for the hot Jupiter systems WASP-32, WASP-38, and HAT-P-27/WASP-40, based on data obtained using the HARPS spectrograph. We analyze the Rossiter-McLaughlin effect for all three systems and also carry out Doppler tomography for WASP-32 and WASP-38. We find that WASP-32 (T {sub eff} = 6140{sup +90} {sub -100} K) is aligned, with an alignment angle of {lambda} = 10.{sup 0}5{sup +6.4} {sub -6.5} obtained through tomography, and that WASP-38 (T {sub eff} = 6180{sup +40} {sub -60} K) is also aligned, with tomographic analysis yielding {lambda} = 7.{sup 0}5{sup +4.7} {submore » -6.1}. The latter result provides an order-of-magnitude improvement in the uncertainty in {lambda} compared to the previous analysis of Simpson et al. We are only able to loosely constrain the angle for HAT-P-27/WASP-40 (T{sub eff} = 5190{sup +160} {sub -170} K) to {lambda} = 24.{sup 0}2{sup +76.0}{sub -44.5}, owing to the poor signal-to-noise ratio of our data. We consider this result a non-detection under a slightly updated version of the alignment test of Brown et al. We place our results in the context of the full sample of spin-orbit alignment measurements, finding that they provide further support for previously established trends.« less

Neutrino Physics from the Cosmic Microwave Background and Large Scale Structure

DOE PAGES

Abazajian, K. N.; Arnold, K.; Austermann, J.; ...

2014-03-15

This is a report on the status and prospects of the quantification of neutrino properties through the cosmological neutrino background for the Cosmic Frontier of the Division of Particles and Fields Community Summer Study long-term planning exercise. Experiments planned and underway are prepared to study the cosmological neutrino background in detail via its influence on distance-redshift relations and the growth of structure. The program for the next decade described in this document, including upcoming spectroscopic galaxy surveys eBOSS and DESI and a new Stage-IV CMB polarization experiment CMB-S4, will achieve σ (σ mv) = 16 meV and σ (Neff)(N eff)more » = 0.020. Such a mass measurement will produce a high significance detection of non-zero σmνσmν, whose lower bound derived from atmospheric and solar neutrino oscillation data is about 58 meV. If neutrinos have a minimal normal mass hierarchy, this measurement will definitively rule out the inverted neutrino mass hierarchy, shedding light on one of the most puzzling aspects of the Standard Model of particle physics — the origin of mass. This precise a measurement of N eff will allow for high sensitivity to any light and dark degrees of freedom produced in the big bang and a precision test of the standard cosmological model prediction that N eff = 3.046.« less

June 2017 Ancho Canyon RF Collects: Final Report

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

Junor, William; Layne, John Preston; Goglio, Joshua Henry

2017-09-21

We report the results from the June 8, 2017, Ancho Canyon RF collection. While bright, electromagnetic signals were seen close to the firing point, there were no detections of signals from the explosively-fired fuse (EFF) at a collection point about 600m distant on the East Mesa. The East Mesa site was unable to collect data because the uninterruptible power supply (UPS) was exhausted by the time of the shot. We did see signals from the EFF at the Bunker 57 antennas, about 123m distant from the Point 88 firing point. The strength of these signals is consistent with our limitedmore » knowledge of the collection antenna performance and the use of the standard model to predict the electric field strength. From our knowledge of the geometry of the EFF loop and the current in the loop in this test, and from measurements at the Bunker 57 site, we predict that we would have seen signals of about 50mV at 3.67MHz in a 100 kHz channel on the Rohde & Schwarz HE010 antennas at the East Mesa location. The noise oor there is about 0.113mV (based on the March 2017 collects). Thus we would have had an SNR of 53 dB from the collect, had the data collection system been running.« less

A simple formulation for deriving effective atomic numbers via electron density calibration from dual-energy CT data in the human body.

PubMed

Saito, Masatoshi; Sagara, Shota

2017-06-01

The main objective of this study is to propose a simple formulation (which we called DEEDZ) for deriving effective atomic numbers (Z eff ) via electron density (ρ e ) calibration from dual-energy (DE) CT data. We carried out numerical analysis of this DEEDZ method for a large variety of materials with known elemental compositions and mass densities using an available photon cross sections database. The new conversion approach was also applied to previously published experimental DECT data to validate its practical feasibility. We performed numerical analysis of the DEEDZ conversion method for tissue surrogates that have the same chemical compositions and mass densities as a commercial tissue-characterization phantom in order to determine the parameters necessary for the ρ e and Z eff calibrations in the DEEDZ conversion. These parameters were then applied to the human-body-equivalent tissues of ICRU Report 46 as objects of interest with unknown ρ e and Z eff . The attenuation coefficients of these materials were calculated using the XCOM photon cross sections database. We also applied the DEEDZ conversion to experimental DECT data available in the literature, which was measured for two commercial phantoms of different shapes and sizes using a dual-source CT scanner at 80 kV and 140 kV/Sn. The simulated Z eff 's were in excellent agreement with the reference values for almost all of the ICRU-46 human tissues over the Z eff range from 5.83 (gallstones-cholesterol) to 16.11 (bone mineral-hydroxyapatite). The relative deviations from the reference Z eff were within ± 0.3% for all materials, except for one outlier that presented a -3.1% deviation, namely, the thyroid. The reason for this discrepancy is that the thyroid contains a small amount of iodine, an element with a large atomic number (Z = 53). In the experimental case, we confirmed that the simple formulation with less fit parameters enable to calibrate Z eff as accurately as the existing calibration procedure. The DEEDZ conversion method based on the simple formulation proposed could facilitate the construction of ρ e and Z eff images from acquired DECT data. © 2017 American Association of Physicists in Medicine.

Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.

PubMed

Hisada, Yohei; Alexander, Wyeth; Kasthuri, Raj; Voorhees, Peter; Mobarrez, Fariborz; Taylor, Angela; McNamara, Coleen; Wallen, Hakan; Witkowski, Marco; Key, Nigel S; Rauch, Ursula; Mackman, Nigel

2016-03-01

Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Dental Fluorosis, Socioeconomic Status and Self-Perception in Adolescents Exposed to a High Level of Fluoride in Water

PubMed Central

Molina-Frechero, Nelly; Nevarez-Rascón, Martina; Nevarez-Rascón, Alfredo; González-González, Rogelio; Irigoyen-Camacho, María Esther; Sánchez-Pérez, Leonor; López-Verdin, Sandra; Bologna-Molina, Ronell

2017-01-01

Objective: To identify adolescents’ self-perception of dental fluorosis from two areas with different socioeconomic levels. Methods: A cross-sectional, descriptive study was conducted with 15-year-old youths by applying a questionnaire designed and validated to assess self-perceptions of dental fluorosis in two areas with different socioeconomic statuses (SESs). Fluorosis was clinically evaluated by applying the Thylstrup and Fejerkov (TF) index on the upper front teeth. Results: A total of 308 adolescents were included in the study. The medium-SES population, which was exposed to 2.5 ppm of fluoride in water, and the low-SES population, which was exposed to 5.1 ppm, presented the following levels of dental fluorosis: TF 2–3 (50%), TF 4–5 (45.6%) and TF 6–7 (4.4%) for medium SES and TF 2–3 (12.3%), TF 4–5 (67.1%) and TF 67 (20.6%) for low SES. A significant association was found between self-perception and dental fluorosis in those with medium and low SESs (p < 0.05). The multiple regression model found differences between TF levels and self-perception, with a 6–7 TF level for concerns about color (OR = 1.6), smile (OR = 1.2) and appearance (OR = 3.36). Conclusions: Self-perceptions of dental fluorosis affect adolescents such that adolescents with a medium SES have more negative perceptions than those with a low SES. Such perceptions increase as the TF index increases. PMID:28085102

Rapid screening of transferrin-binders in the flowers of Bauhinia blakeana Dunn by on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-transferrin-fluorescence detection system.

PubMed

Liu, Meixian; Dong, Jing; Lin, Zongtao; Niu, Yanyan; Zhang, Xiaotian; Jiang, Haixiu; Guo, Ning; Li, Wei; Wang, Hong; Chen, Shizhong

2016-06-10

Transferrin (Transferrin, TRF, TF) has drawn increasing attention in cancer therapy due to its potential applications in drug delivery. TF receptor, highly expressed in tumor cells, recognizes and transports Fe(3+)-TF into cells to release iron into cytoplasm. Thus, discovering TF-binding compounds has become an active research area and is of great importance for target therapy. In this study, an on-line analysis method was established for screening TF-binding compounds from the flowers of Bauhinia blakeana Dunn using a high-performance liquid chromatography-diode-array detector-multi-stage mass spectrometry-transferrin-fluorescence detector (HPLC-DAD-MS(n)-TF-FLD) method. As a result, 33 of 80 identified or tentatively characterized compounds in the sample were TF-binding active. Twenty-five flavonol glycosides and eight phenolic acids were identified as TF-binders. Twelve of these active compounds together with six standard compounds were used to study the dose-response effects and structure-activity relationships of flavonoids and phenolic acids. The method was validated by vitexin with a good linearity in the range of concentrations used in the study. The limit of detection for vitexin was 0.1596 nmol. Our study indicated that the established method is simple, rapid and sensitive for screening TF-binding active compounds in the extract of Bauhinia blakeana Dunn, and therefore is important for discovering potential anti-cancer ingredients from complex samples for TF related drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Theaflavin-3,3'-digallate, a component of black tea: an inducer of oxidative stress and apoptosis.

PubMed

Schuck, Alyssa G; Ausubel, Miriam B; Zuckerbraun, Harriet L; Babich, Harvey

2008-04-01

Treatment of human oral squamous carcinoma HSC-2 cells and normal GN46 fibroblasts with theaflavin-3,3'-digallate (TF-3), a polyphenol in black tea, showed a concentration and time dependent inhibition of growth, with the tumor cells more sensitive than the fibroblasts. In buffer and in cell culture medium, TF-3 generated reactive oxygen species, with lower levels detected in buffer amended with catalase and superoxide dismutase, indicating the generation of hydrogen peroxide and superoxide, respectively, and suggesting that TF-3 may be an inducer of oxidative stress. The toxicity of TF-3 was decreased in the presence of catalase, pyruvate, and divalent cobalt, all scavengers of reactive oxygen species, but was potentiated in the presence of diethyldithiocarbamate, an inhibitor of superoxide dismutase. The intracellular level of glutathione in HSC-2 cells was lessened after a 4-h exposure to 250 and 500 microM TF-3. However, for GN46 fibroblasts, a 4-h exposure to 250 microM TF-3 stimulated, but to 500 microM TF-3 lessened, intracellular glutathione. Treatment of the cells with the glutathione depleters, 1,3-bis(2-chloroethyl)-N-nitrosourea, 1-chloro-2,4-dinitrobenzene, and d,l-buthionine-[S,R]-sulfoximine potentiated the toxicity of TF-3. Induction of apoptotic cell death in HSC-2 cells treated with TF-3 was noted by apoptotic cell morphologies, by TUNEL staining, by PARP cleavage, and by elevated activity of caspase-3. Apoptosis was not noted in GN46 fibroblasts treated with TF-3.

Identification and expression of the tig gene coding for trigger factor from psychrophilic bacteria with no information of genome sequence available.

PubMed

Lee, Kyunghee; Choi, Hyojung; Im, Hana

2009-08-01

Trigger factor (TF) plays a key role as a molecular chaperone with a peptidyl-prolyl cis-trans isomerase (PPIase) activity by which cells promote folding of newly synthesized proteins coming out of ribosomes. Since psychrophilic bacteria grow at a quite low temperature, between 4 and 15 degrees C, TF from such bacteria was investigated and compared with that of mesophilic bacteria E. coli in order to offer an explanation of cold-adaptation at a molecular level. Using a combination of gradient PCRs with homologous primers and LA PCR in vitro cloning technology, the tig gene was fully identified from Psychromonas arctica, whose genome sequence is not yet available. The resulting amino acid sequence of the TF was compared with other homologous TFs using sequence alignments to search for common domains. In addition, we have developed a protein expression system, by which TF proteins from P. arctica (PaTF) were produced by IPTG induction upon cloning the tig gene on expression vectors, such as pAED4. We have further examined the role of expressed psychrophilic PaTF on survival against cold treatment at 4 degrees C. Finally, we have attempted the in vitro biochemical characterization of TF proteins with His-tags expressed in a pET system, such as the PPIase activity of PaTF protein. Our results demonstrate that the expressed PaTF proteins helped cells survive against cold environments in vivo and the purified PaTF in vitro display the functional PPIase activity in a concentration dependent manner.

Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation

PubMed Central

Kang, Seok Yong; Jung, Hyo Won; Nam, Joo Hyun; Kim, Woo Kyung; Kang, Jong-Seong; Kim, Young-Ho; Cho, Cheong-Weon; Cho, Chong Woon

2017-01-01

Ethnopharmacological Relevance In this study, we investigated the effects of Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone-induced atopic dermatitis in mice. Materials and Methods TF extract was prepared with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was applied to the back skin daily for 24 days. Results 1% TF extract with 0.1% HC improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract decreased β-hexosaminidase release in RBL-2H3 cells. Conclusions The present study demonstrates that the topical application of TF extract improves skin inflammation in AD mice, and the mechanism for this effect appears to be related to the modulation of calcium channels and mast cell activation. This outcome suggests that the combination of TF and steroids could be a more effective and safe approach for AD treatment. PMID:29348776

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

PubMed Central

Schmidt, Florian; Gasparoni, Nina; Gasparoni, Gilles; Gianmoena, Kathrin; Cadenas, Cristina; Polansky, Julia K.; Ebert, Peter; Nordström, Karl; Barann, Matthias; Sinha, Anupam; Fröhler, Sebastian; Xiong, Jieyi; Dehghani Amirabad, Azim; Behjati Ardakani, Fatemeh; Hutter, Barbara; Zipprich, Gideon; Felder, Bärbel; Eils, Jürgen; Brors, Benedikt; Chen, Wei; Hengstler, Jan G.; Hamann, Alf; Lengauer, Thomas; Rosenstiel, Philip; Walter, Jörn; Schulz, Marcel H.

2017-01-01

The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid costly TF ChIP-seq assays. Thus, it is important to develop computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices. TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq. Additionally, Histone-Marks (HMs) can be used to identify candidate TF binding sites. TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength. Using machine learning, we find low affinity binding sites to improve our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites. Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance. In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq data sets. Finally, these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively. PMID:27899623

Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid.

PubMed

Porru, Manuela; Zappavigna, Silvia; Salzano, Giuseppina; Luce, Amalia; Stoppacciaro, Antonella; Balestrieri, Maria Luisa; Artuso, Simona; Lusa, Sara; De Rosa, Giuseppe; Leonetti, Carlo; Caraglia, Michele

2014-11-15

Glioblastomas are highly aggressive adult brain tumors with poor clinical outcome. In the central nervous system (CNS) the blood-brain barrier (BBB) is the most important limiting factor for both development of new drugs and drug delivery. Here, we propose a new strategy to treat glioblastoma based on transferrin (Tf)-targeted self-assembled nanoparticles (NPs) incorporating zoledronic acid (ZOL) (NPs-ZOL-Tf). NPs-ZOL-Tf have been assessed on the glioblastoma cell line U373MG-LUC that showed a refractoriness in vitro to temozolomide (TMZ) and fotemustine (FTM). NPs-ZOL-Tf treatment resulted in higher in vitro cytotoxic activity than free ZOL. However, the potentiation of anti-proliferative activity of NPs-ZOL-Tf was superimposable to that one induced by NPs-ZOL (not armed with Tf). On the other hand, NPs-ZOL-Tf showed a higher antitumor efficacy if compared with that one caused by NPs-ZOL in immunosuppressed mice intramuscularly bearing U373MG-LUC xenografts, inducing a significant tumor weight inhibition (TWI). The experiments performed on mice with intracranial U373MG-LUC xenografts confirmed the efficacy of NPs-ZOL-Tf. These effects were paralleled by a higher intratumour localization of fluorescently-labeled-NPs-Tf both in intramuscular and intracranial xenografts. In conclusion, our results demonstrate that the encapsulation of ZOL increases the antitumor efficacy of this drug in glioblastoma through the acquisition of ability to cross the BBB.

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

PubMed

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

Phenology and spatial distribution of native and exotic Tetropium longhorned beetles (Coleoptera: Cerambycidae).

PubMed

Rhainds, Marc; Heard, Stephen B; Sweeney, Jon D; Silk, Peter; Flaherty, Leah

2010-12-01

The co-existence of two closely related Tetropium species in eastern Canada, invasive T. fuscum and native T. cinnamopterum (TF and TC, respectively), provides a model system to investigate seasonal and spatial demographic parameters of biological invasions at the interspecific level. In this study, we take advantage of the similar semiochemical communication of TF and TC to evaluate the abundance of adults of the two species concurrently using grids of traps baited with pheromone and host volatiles in stands of spruce. Adult TF emerged on average 2 wk before TC both in the field and under controlled laboratory conditions. This observation, combined with the early reproduction of emergent females, implies that the smaller (younger) larvae of native TC may be at increased risk of intra-guild predation by TF. The high spatial association between male and female TF in dense, aggregated populations suggests that the rate of mate encounter is depressed in sparse populations toward the edge of the invasive range. The higher level of spatial aggregation for TF than TC, particularly at high population density, suggests a higher propensity of adult TF to congregate at "landmarks." Considering the broader range of host conditions, earlier seasonal emergence, and presumably more effective mate encounter for TF than TC, the exotic TF may be a superior competitor with the potential to displace or reduce the abundance of TC. © 2010 Entomological Society of America

Indications, usage, and dosage of the transfer factor.

PubMed

Berrón-Pérez, Renato; Chávez-Sánchez, Raúl; Estrada-García, Iris; Espinosa-Padilla, Sara; Cortez-Gómez, Rudyard; Serrano-Miranda, Ernestina; Ondarza-Aguilera, Rodolfo; Pérez-Tapia, Mayra; Pineda Olvera, Benjamín; Jiménez-Martínez, María del Carmen; Portugués, Abraham; Rodríguez, Azucena; Cano, Laura; Pacheco, Pedro Urcino; Barrientos, Javier; Chacón, Rommel; Serafín, Jeannet; Mendez, Patricia; Monges, Abelardo; Cervantes, Edgar; Estrada-Parra, Sergio

2007-01-01

The transfer factor (TF) was described in 1955 by S. Lawrence. In 1992 Kirkpatrick characterized the specific TF at molecular level. The TF is constituted by a group of numerous molecules, of low molecular weight, from 1.0 to 6.0 kDa. The 5 kDa fraction corresponds to the TF specific to antigens. There are a number of publications about the clinical indications of the TF for diverse diseases, in particular those where the cellular immune response is compromised or in those where there is a deficient regulation of the immune response. In this article we present our clinical and basic experiences, especially regarding the indications, usage and dosage of the TF. Our group demonstrated that the TF increases the expression of IFN-gamma and RANTES, while decreases the expression of osteopontine. Using animal models we have worked with M. tuberculosis, and with a model of glioma with good therapeutic results. In the clinical setting we have worked with herpes zoster, herpes simplex type I, herpetic keratitis, atopic dermatitis, osteosarcoma, tuberculosis, asthma, post-herpetic neuritis, anergic coccidioidomycosis, leishmaniasis, toxoplasmosis, mucocutaneous candidiasis, pediatric infections produced by diverse pathogen germs, sinusitis, pharyngitis, and otits media. All of these diseases were studied through protocols which main goals were to study the therapeutic effects of the TF, and to establish in a systematic way diverse dosage schema and time for treatment to guide the prescription of the TF.

Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

PubMed

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid

PubMed Central

Porru, Manuela; Zappavigna, Silvia; Salzano, Giuseppina; Luce, Amalia; Stoppacciaro, Antonella; Balestrieri, Maria Luisa; Artuso, Simona; Lusa, Sara; De Rosa, Giuseppe; Leonetti, Carlo; Caraglia, Michele

2014-01-01

Glioblastomas are highly aggressive adult brain tumors with poor clinical outcome. In the central nervous system (CNS) the blood-brain barrier (BBB) is the most important limiting factor for both development of new drugs and drug delivery. Here, we propose a new strategy to treat glioblastoma based on transferrin (Tf)-targeted self-assembled nanoparticles (NPs) incorporating zoledronic acid (ZOL) (NPs-ZOL-Tf). NPs-ZOL-Tf have been assessed on the glioblastoma cell line U373MG-LUC that showed a refractoriness in vitro to temozolomide (TMZ) and fotemustine (FTM). NPs-ZOL-Tf treatment resulted in higher in vitro cytotoxic activity than free ZOL. However, the potentiation of anti-proliferative activity of NPs-ZOL-Tf was superimposable to that one induced by NPs-ZOL (not armed with Tf). On the other hand, NPs-ZOL-Tf showed a higher antitumor efficacy if compared with that one caused by NPs-ZOL in immunosuppressed mice intramuscularly bearing U373MG-LUC xenografts, inducing a significant tumor weight inhibition (TWI). The experiments performed on mice with intracranial U373MG-LUC xenografts confirmed the efficacy of NPs-ZOL-Tf. These effects were paralleled by a higher intratumour localization of fluorescently-labeled-NPs-Tf both in intramuscular and intracranial xenografts. In conclusion, our results demonstrate that the encapsulation of ZOL increases the antitumor efficacy of this drug in glioblastoma through the acquisition of ability to cross the BBB. PMID:25431953

A microfluidic method for synthesis of transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

PubMed Central

Yang, Zhaogang; Yu, Bo; Zhu, Jing; Huang, Xiaomeng; Xie, Jing; Xu, Songlin; Yang, Xiaojuan; Wang, Xinmei; Yung, Bryant C.; Lee, L. James; Lee, Robert J.; Teng, Lesheng

2015-01-01

siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for targeted delivery of LOR-1284 siRNA to acute myeloid leukemia (AML) cells. In vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4–11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than free LOR-1284 in reducing the R2 mRNA and protein levels. Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific thereapeutic delivery of LOR-1284 to AML. PMID:25003978

Thiophenone Attenuates Enteropathogenic Escherichia coli O103:H2 Virulence by Interfering with AI-2 Signaling.

PubMed

Witsø, Ingun Lund; Valen Rukke, Håkon; Benneche, Tore; Aamdal Scheie, Anne

2016-01-01

Interference with bacterial quorum sensing communication provides an anti-virulence strategy to control pathogenic bacteria. Here, using the Enteropathogenic E. coli (EPEC) O103:H2, we showed for the first time that thiophenone TF101 reduced expression of lsrB; the gene encoding the AI-2 receptor. Combined results of transcriptional and phenotypic analyses suggested that TF101 interfere with AI-2 signalling, possibly by competing with AI-2 for binding to LsrB. This is supported by in silico docking prediction of thiophenone TF101 in the LsrB pocket. Transcriptional analyses furthermore showed that thiophenone TF101 interfered with expression of the virulence genes eae and fimH. In addition, TF101 reduced AI-2 induced E. coli adhesion to colorectal adenocarcinoma cells. TF101, on the other hand, did not affect epinephrine or norepinephrine enhanced E. coli adhesion. Overall, our results showed that thiophenone TF101 interfered with virulence expression in E. coli O103:H2, suggestedly by interfering with AI-2 mediated quorum sensing. We thus conclude that thiophenone TF101 might represent a promising future anti-virulence agent in the fight against pathogenic E. coli.

Thiophenone Attenuates Enteropathogenic Escherichia coli O103:H2 Virulence by Interfering with AI-2 Signaling

PubMed Central

Valen Rukke, Håkon; Benneche, Tore; Aamdal Scheie, Anne

2016-01-01

Interference with bacterial quorum sensing communication provides an anti-virulence strategy to control pathogenic bacteria. Here, using the Enteropathogenic E. coli (EPEC) O103:H2, we showed for the first time that thiophenone TF101 reduced expression of lsrB; the gene encoding the AI-2 receptor. Combined results of transcriptional and phenotypic analyses suggested that TF101 interfere with AI-2 signalling, possibly by competing with AI-2 for binding to LsrB. This is supported by in silico docking prediction of thiophenone TF101 in the LsrB pocket. Transcriptional analyses furthermore showed that thiophenone TF101 interfered with expression of the virulence genes eae and fimH. In addition, TF101 reduced AI-2 induced E. coli adhesion to colorectal adenocarcinoma cells. TF101, on the other hand, did not affect epinephrine or norepinephrine enhanced E. coli adhesion. Overall, our results showed that thiophenone TF101 interfered with virulence expression in E. coli O103:H2, suggestedly by interfering with AI-2 mediated quorum sensing. We thus conclude that thiophenone TF101 might represent a promising future anti-virulence agent in the fight against pathogenic E. coli. PMID:27309855

Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.

PubMed

Couch, Jessica A; Yu, Y Joy; Zhang, Yin; Tarrant, Jacqueline M; Fuji, Reina N; Meilandt, William J; Solanoy, Hilda; Tong, Raymond K; Hoyte, Kwame; Luk, Wilman; Lu, Yanmei; Gadkar, Kapil; Prabhu, Saileta; Ordonia, Benjamin A; Nguyen, Quyen; Lin, Yuwen; Lin, Zhonghua; Balazs, Mercedesz; Scearce-Levie, Kimberly; Ernst, James A; Dennis, Mark S; Watts, Ryan J

2013-05-01

Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier.

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

PubMed

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

TF1, the bacteriophage SPO1-encoded type II DNA-binding protein, is essential for viral multiplication.

PubMed

Sayre, M H; Geiduschek, E P

1988-09-01

The lytic Bacillus subtilis bacteriophage SPO1 encodes an abundant, 99-amino-acid type II DNA-binding protein, transcription factor 1 (TF1). TF1 is special in this family of procaryotic chromatin-forming proteins in its preference for hydroxymethyluracil-containing DNA, such as SPO1 DNA, and in binding with high affinity to specific sites in the SPO1 chromosome. We constructed recessive null alleles of the TF1 gene and introduced them into SPO1 chromosomes. Segregation analysis with partially diploid phage heterozygous for TF1 showed that phage bearing only these null alleles was inviable. Deletion of the nine C-proximal amino acids of TF1 prohibited phage multiplication in vivo and abolished its site-specific DNA-binding activity in vitro.

How reliable are ligand-centric methods for Target Fishing?

NASA Astrophysics Data System (ADS)

Peon, Antonio; Dang, Cuong; Ballester, Pedro

2016-04-01

Computational methods for Target Fishing (TF), also known as Target Prediction or Polypharmacology Prediction, can be used to discover new targets for small-molecule drugs. This may result in repositioning the drug in a new indication or improving our current understanding of its efficacy and side effects. While there is a substantial body of research on TF methods, there is still a need to improve their validation, which is often limited to a small part of the available targets and not easily interpretable by the user. Here we discuss how target-centric TF methods are inherently limited by the number of targets that can possibly predict (this number is by construction much larger in ligand-centric techniques). We also propose a new benchmark to validate TF methods, which is particularly suited to analyse how predictive performance varies with the query molecule. On average over approved drugs, we estimate that only five predicted targets will have to be tested to find two true targets with submicromolar potency (a strong variability in performance is however observed). In addition, we find that an approved drug has currently an average of eight known targets, which reinforces the notion that polypharmacology is a common and strong event. Furthermore, with the assistance of a control group of randomly-selected molecules, we show that the targets of approved drugs are generally harder to predict.

Uptake of 137Cs by Leafy Vegetables and Grains from Calcareous Soils

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

Robison, W; Hamilton, T; Conrado, C

2004-04-19

Cesium-137 was deposited on Bikini Island at Bikini Atoll in 1954 as a result of nuclear testing and has been transported and cycled in the ecosystem ever since. Atoll soils are of marine origin and are almost pure CaCO{sub 3} with high concentrations of organic matter in the top 40 cm. Data from previous experiments with mature fruit trees show very high transfer factors (TF's), [Bq g{sup -1} plant/ Bq g{sup -1} soil, both in dry weight] into fruits from atoll calcareous soil. These TF's are much higher than reported for continental, silica-based soils. In this report TF's for 5more » types of leafy vegetable crops and 2 types of grain crops are provided for use in predictive dose assessments and for comparison with other data from other investigators working with other types of soil in the IAEA CRP ''The Classification of Soil Systems on the Basis of Transfer Factors of Radionuclides from Soil to Reference Plants''. Transfer factors for plants grown on calcareous soil are again very high relative to clay-containing soils and range from 23 to 39 for grain crops and 21 to 113 for leafy vegetables. Results from these experiments, in this unique, high pH, high organic content, low potassium (K) soil, provide a boundary condition for models relating soil properties to TF.« less

footprintDB: a database of transcription factors with annotated cis elements and binding interfaces.

PubMed

Sebastian, Alvaro; Contreras-Moreira, Bruno

2014-01-15

Traditional and high-throughput techniques for determining transcription factor (TF) binding specificities are generating large volumes of data of uneven quality, which are scattered across individual databases. FootprintDB integrates some of the most comprehensive freely available libraries of curated DNA binding sites and systematically annotates the binding interfaces of the corresponding TFs. The first release contains 2422 unique TF sequences, 10 112 DNA binding sites and 3662 DNA motifs. A survey of the included data sources, organisms and TF families was performed together with proprietary database TRANSFAC, finding that footprintDB has a similar coverage of multicellular organisms, while also containing bacterial regulatory data. A search engine has been designed that drives the prediction of DNA motifs for input TFs, or conversely of TF sequences that might recognize input regulatory sequences, by comparison with database entries. Such predictions can also be extended to a single proteome chosen by the user, and results are ranked in terms of interface similarity. Benchmark experiments with bacterial, plant and human data were performed to measure the predictive power of footprintDB searches, which were able to correctly recover 10, 55 and 90% of the tested sequences, respectively. Correctly predicted TFs had a higher interface similarity than the average, confirming its diagnostic value. Web site implemented in PHP,Perl, MySQL and Apache. Freely available from http://floresta.eead.csic.es/footprintdb.

Genome-wide transcriptional responses of Alteromonas naphthalenivorans SN2 to contaminated seawater and marine tidal flat sediment.

PubMed

Jin, Hyun Mi; Jeong, Hye Im; Kim, Kyung Hyun; Hahn, Yoonsoo; Madsen, Eugene L; Jeon, Che Ok

2016-02-18

A genome-wide transcriptional analysis of Alteromonas naphthalenivorans SN2 was performed to investigate its ecophysiological behavior in contaminated tidal flats and seawater. The experimental design mimicked these habitats that either added naphthalene or pyruvate; tidal flat-naphthalene (TF-N), tidal flat-pyruvate (TF-P), seawater-naphthalene (SW-N), and seawater-pyruvate (SW-P). The transcriptional profiles clustered by habitat (TF-N/TF-P and SW-N/SW-P), rather than carbon source, suggesting that the former may exert a greater influence on genome-wide expression in strain SN2 than the latter. Metabolic mapping of cDNA reads from strain SN2 based on KEGG pathway showed that metabolic and regulatory genes associated with energy metabolism, translation, and cell motility were highly expressed in all four test conditions, probably highlighting the copiotrophic properties of strain SN2 as an opportunistic marine r-strategist. Differential gene expression analysis revealed that strain SN2 displayed specific cellular responses to environmental variables (tidal flat, seawater, naphthalene, and pyruvate) and exhibited certain ecological fitness traits -- its notable PAH degradation capability in seasonally cold tidal flat might be reflected in elevated expression of stress response and chaperone proteins, while fast growth in nitrogen-deficient and aerobic seawater probably correlated with high expression of glutamine synthetase, enzymes utilizing nitrite/nitrate, and those involved in the removal of reactive oxygen species.

Genome-wide transcriptional responses of Alteromonas naphthalenivorans SN2 to contaminated seawater and marine tidal flat sediment

PubMed Central

Jin, Hyun Mi; Jeong, Hye Im; Kim, Kyung Hyun; Hahn, Yoonsoo; Madsen, Eugene L.; Jeon, Che Ok

2016-01-01

A genome-wide transcriptional analysis of Alteromonas naphthalenivorans SN2 was performed to investigate its ecophysiological behavior in contaminated tidal flats and seawater. The experimental design mimicked these habitats that either added naphthalene or pyruvate; tidal flat-naphthalene (TF-N), tidal flat-pyruvate (TF-P), seawater-naphthalene (SW-N), and seawater-pyruvate (SW-P). The transcriptional profiles clustered by habitat (TF-N/TF-P and SW-N/SW-P), rather than carbon source, suggesting that the former may exert a greater influence on genome-wide expression in strain SN2 than the latter. Metabolic mapping of cDNA reads from strain SN2 based on KEGG pathway showed that metabolic and regulatory genes associated with energy metabolism, translation, and cell motility were highly expressed in all four test conditions, probably highlighting the copiotrophic properties of strain SN2 as an opportunistic marine r-strategist. Differential gene expression analysis revealed that strain SN2 displayed specific cellular responses to environmental variables (tidal flat, seawater, naphthalene, and pyruvate) and exhibited certain ecological fitness traits –– its notable PAH degradation capability in seasonally cold tidal flat might be reflected in elevated expression of stress response and chaperone proteins, while fast growth in nitrogen-deficient and aerobic seawater probably correlated with high expression of glutamine synthetase, enzymes utilizing nitrite/nitrate, and those involved in the removal of reactive oxygen species. PMID:26887987

Stellar oxygen abundances. I - A resolution to the 7774 A O I abundance discrepancy

NASA Astrophysics Data System (ADS)

King, Jeremy R.

1993-09-01

We investigate the discrepancy between O/Fe abundance ratios of metal-poor stars derived from the 7774 A O I triplet and O/Fe ratios determined from other oxygen lines. We propose a possible resolution to this discrepancy which also eliminates the correlation of O/Fe and T(eff) found in a recent 7774 A O I analysis. The equivalent widths of Abia & Rebolo (1989) are found to be systematically too high by 25 percent. Arguments are presented that current temperature estimates for halo stars are 150-200 K too low. Using the guidance of both model atmospheres and other empirical color-T(eff) relations, we construct new color temperature relations for metal-poor stars. These relations are tied to the temperature scale of Saxner & Hammarback (1985) for metal-rich stars. We use (b-y) and (V-K) indices to redetermine values of T(eff) for a handful of halo stars. (B-V)-T(eff) relations which do not take into account the effects of metallicity are found to be inadequate. Revised O/Fe ratios are determined using the new temperature scale. The mean abundance ratio of the reanalyzed halo dwarfs is about +0.52. There is no trend of O/Fe with Fe/H or T(eff).

Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling

PubMed Central

2012-01-01

Background Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. Results We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (P<0.05). Among the 442 TF genes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2–4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. Conclusions We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice. PMID:23228240

Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling.

PubMed

Wang, Yubing; Guo, Huimin; Li, Haichao; Zhang, Hao; Miao, Xuexia

2012-12-10

Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (P<0.05). Among the 442 TF genes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2-4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice.

Conservation of ectomycorrhizal fungi: green-tree retention preserves species diversity

Treesearch

Joyce L. Eberhart; Daniel L. Luoma

2013-01-01

Th e Demonstration of Ecosystem Management Options (DEMO) project is a large, interdisciplinary study designed to test the biological and silvicultural eff ects of green-tree retention in Douglas-fi r (Pseudotsuga menziesii) forests. Six treatments were replicated on six blocks in Washington and Oregon, USA: no harvest, 75 percent aggregated, 40 percent (dispersed and...

Utilization of data estimation via existing models, within a tiered data quality system, for populating species sensitivity distributions

EPA Science Inventory

The acquisition toxicity test data of sufficient quality from open literature to fulfill taxonomic diversity requirements can be a limiting factor in the creation of new 304(a) Aquatic Life Criteria. The use of existing models (WebICE and ACE) that estimate acute and chronic eff...

Slavery in America: A Thematic Unit Appropriate for Adult Literacy Classrooms. Teacher to Teacher.

ERIC Educational Resources Information Center

White, Lisa

This thematic unit is designed for adult literacy students with at least a third grade reading level. Objectives are tied closely to skills needed for the General Educational Development tests and include computer and workplace skills. Equipped for the Future (EFF) roles and skills are also integrated into the plans. Best practice teaching…

Transfrontal and Transsphenoidal Approaches to Pediatric Craniopharyngioma: A National Perspective.

PubMed

Lin, Yimo; Hansen, Daniel; Sayama, Christina M; Pan, I-Wen; Lam, Sandi

2017-01-01

This study compared transsphenoidal (TS) and transfrontal (TF) approaches to craniopharyngioma utilizing a national database. The Kids' Inpatient Database (2003, 2006, and 2009) was surveyed for patients with a diagnosis of craniopharyngioma who underwent a subset of surgical interventions to compare TS and TF surgery. Demographics, hospital variables, and complications/comorbidities were analyzed with multivariate regression. 314 admissions (TS = 104, TF = 210) were identified. The mean age was 14.8 (TS) versus 9.8 (TF) years (p < 0.001). The mean number of diagnoses was 4.6 (TS) versus 6.2 (TF) (p < 0.001). Diabetes insipidus was associated with 38% (TS) and 69% (TF). Cerebrospinal fluid (CSF) leak affected 19% TS and 4% TF resections. Other complications and comorbidities included postoperative stroke (2% TS vs. 5% TF), panhypopituitarism (5 vs. 8%), death (0 vs. 1%), cranial nerve deficits (1 vs. 6%), thrombotic events (7 vs. 17%), and seizures (0 vs. 12%). 98% of patients were discharged home after a mean 6-day length of stay (LOS) after TS, whereas 90% of TF patients had a LOS of 12 days. TS cases were more likely to be privately insured (68%) and from higher income brackets (61%) than TF ones (56 and 2%, respectively) (p < 0.05). In multivariate regression models adjusting for age, sex, race, number of diagnoses, surgical approach, hospital volume, and insurance type, the TS approach was associated with an increased incidence of CSF leak (OR 10, p < 0.001). More documented diagnoses (OR 16-60, p < 0.01) and TF approach (OR 2.6, p < 0.01) were associated with an increased incidence of other complications and comorbidities. Age younger than 10 (β-coefficient 2.3, p = 0.01), more diagnoses (β-coefficient 1.2, p < 0.001), and TF approach (β- coefficient 3.0, p < 0.01) were associated with increased LOS. A higher number of diagnoses were associated with nonhome discharge destinations (β-coefficient 1.29, p < 0.001). TS surgery was associated with an increased incidence of CSF leak but shorter LOS; TF surgery was associated with an increased incidence of other complications. Patients undergoing TS surgery were more likely to have private insurance and a higher family income bracket. © 2017 S. Karger AG, Basel.

Tissue factor and Toll-like receptor (TLR)4 in hyperglycaemia-hyperinsulinaemia. Effects in healthy subjects, and type 1 and type 2 diabetes mellitus.

PubMed

Singh, Anamika; Boden, Guenther; Rao, A Koneti

2015-04-01

Diabetes mellitus (DM) patients have an increased incidence of cardiovascular events. Blood tissue factor-procoagulant activity (TF-PCA), the initiating mechanism for blood coagulation, is elevated in DM. We have shown that hyperglycaemia (HG), hyperinsulinaemia (HI) and combined HG+HI (induced using 24-hour infusion clamps) increases TF-PCA in healthy and type 2 DM (T2DM) subjects, but not in type 1 DM (T1DM) subjects. The mechanisms for this are unknown. DM patients have elevated plasma lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. We postulated that TLR4 plays a role in modulating TF levels. We studied the effect of HG+HI on TLR4 and TF-PCA in vivo during 24-hour HG+HI infusion clamps in healthy subjects, and T1DM and T2DM subjects, and in vitro in blood. In vivo, in healthy subjects, 24-hour HG + HI infusion increased TLR4 six-fold, which correlated with TF-PCA (r= 0.91, p<0.0001). T2DM patients showed smaller increases in both. In T1DM subjects, TLR4 declined (50%, p<0.05) and correlated with TF-PCA (r=0.55; p<0.05). In vitro, HG (200 mg/dl added glucose) and HI (1-100 nM added insulin) increased TF-PCA in healthy subjects (~2-fold, 2-4 hours). Insulin inhibited by ~30% LPS-induced increase in TF-PCA and high glucose reversed it. TLR4 levels paralleled TF-PCA (r=0.71, p<0.0001); HG and HI increased TLR4 and insulin inhibited LPS-induced TLR4 increase. This is first evidence that even in healthy subjects, HG of short duration increases TLR4 and TF-PCA, key players in inflammation and thrombosis. TLR4-TF interplay is strikingly different in non-diabetic, T1DM and T2DM subjects.

Disruption of sex-hormone levels and steroidogenic-related gene expression on Mongolia Racerunner (Eremias argus) after exposure to triadimefon and its enantiomers.

PubMed

Li, Jitong; Chang, Jing; Li, Wei; Guo, Baoyuan; Li, Jianzhong; Wang, Huili

2017-03-01

Triadimefon (TF) is a widely used chiral fungicide with one chiral centre and two enantiomers (TF 1 and TF 2 ). However, little is reported about the ecological toxicity of reptiles on an enantioselective level. TF is a potential endocrine disruptor that may interfere with sex steroid hormones, such as testosterone (T) and 17beta-estradiol (E 2 ). In our study, the lizards Mongolia Racerunner (Eremias argus) were orally exposed to TF and its enantiomers for 21 days. Plasma sex steroid hormones and steroidogenic-related genes, including 17-beta-hydroxysteroid (hsd17β), cytochrome P450 enzymes (cyp19 and cyp17), and steroid hormone receptors (erα and Ar) were evaluated. After exposure, the plasma testosterone level in the 100 mg/kg bw group was elevated, while the oestradiol level was reduced. This phenomenon may be caused by the transformation of cyp19, which may inhibit the conversion of testosterone to oestradiol and affect sexual behaviour. In addition, the two enantiomers have different effects on hormone levels, which testified to the previously reported biotoxic dissimilarity between TF 1 and TF 2 in organisms. Furthermore, the cyp19 mRNA level in liver and gonad of the TF 2 and TF group (100 mg/kg bw ) were significantly down-regulated, while the cyp17 and hsd17β mRNA levels were up-regulated. The expression of erα and Ar mRNA levels were up-regulated in males but not in females, which may indicate that TF has sex differences on these two genes. As seen from the above results, TF and its enantiomers may have endocrine-disrupting effects on lizards (E. argus) by acting sensitively on sex steroid hormones and steroidogenic-related genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase.

PubMed

Chitambar, Christopher R; Al-Gizawiy, Mona M; Alhajala, Hisham S; Pechman, Kimberly R; Wereley, Janine P; Wujek, Robert; Clark, Paul A; Kuo, John S; Antholine, William E; Schmainda, Kathleen M

2018-06-01

Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMEC) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSC) lines express TfRs, and that their growth is inhibited by gallium maltolate (GaM) in vitro After 24 hours of incubation with GaM, cells displayed a loss of mitochondrial reserve capacity followed by a dose-dependent decrease in oxygen consumption and a decrease in the activity of the iron-dependent M2 subunit of ribonucleotide reductase (RRM2). IHC staining of rat and human tumor-bearing brains showed that glioblastoma, but not normal glial cells, expressed TfR1 and RRM2, and that glioblastoma expressed greater levels of H- and L-ferritin than normal brain. In an orthotopic U-87 MG glioblastoma xenograft rat model, GaM retarded the growth of brain tumors relative to untreated control ( P = 0.0159) and reduced tumor mitotic figures ( P = 0.045). Tumors in GaM-treated animals displayed an upregulation of TfR1 expression relative to control animals, thus indicating that gallium produced tumor iron deprivation. GaM also inhibited iron uptake and upregulated TfR1 expression in U-87 MG and D54 cells in vitro We conclude that GaM enters the brain via TfR1 on BMECs and targets iron metabolism in glioblastoma in vivo, thus inhibiting tumor growth. Further development of novel gallium compounds for brain tumor treatment is warranted. Mol Cancer Ther; 17(6); 1240-50. ©2018 AACR . ©2018 American Association for Cancer Research.

Tissue Factor and Toll Like Receptor (TLR)4 in Hyperglycemia-Hyperinsulinemia: Effects in Healthy Subjects, and Type 1 and Type 2 Diabetes Mellitus

PubMed Central

Singh, Anamika; Boden, Guenther; Rao, A. Koneti

2015-01-01

SUMMARY Background Diabetes mellitus (DM) patients have increased cardiovascular events. Blood tissue factor-procoagulant activity (TF-PCA), the initiating mechanism for blood coagulation, is elevated in DM. We have shown that hyperglycemia (HG), hyperinsulinemia (HI) and combined HG+HI (induced using 24 hr infusion clamps) increases TF-PCA in healthy and T2DM subjects, but not in T1DM subjects. The mechanisms for this are unknown. DM patients have elevated plasma lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. We postulated that TLR4 plays a role in modulating TF levels. Objectives and Methods We studied the effect of HG+HI on TLR4 and TF-PCA in vivo during 24 hr HG+HI infusion clamps in healthy subjects, and T1DM and T2DM subjects, and in vitro in blood. Results In vivo, in healthy subjects, 24 hr HG + HI infusion increased TLR4 6-fold, which correlated with TF-PCA (r= 0.91, p<0.0001). T2DM patients showed smaller increases in both. In T1DM subjects, TLR4 declined (50%, p<0.05) and correlated with TF-PCA (r=0.55; p<0.05). In vitro, HG (200 mg/dl added glucose) and HI (1-100 nM added insulin) increased TF-PCA in healthy subjects (~2-fold, 2-4 hr). Insulin inhibited by ~30% LPS-induced increase in TF-PCA and high glucose reversed it. TLR4 levels paralleled TF-PCA (r=0.71, p<0.0001); HG and HI increased TLR4 and insulin inhibited LPS-induced TLR4 increase. Conclusions This is first evidence that even in healthy subjects, HG of short duration increases TLR4 and TF-PCA, key players in inflammation and thrombosis. TLR4-TF interplay is strikingly different in non-diabetic, T1DM and T2DM subjects. PMID:25653143

Twenty-four hour intraocular pressure monitoring with the SENSIMED Triggerfish contact lens: effect of body posture during sleep.

PubMed

Beltran-Agulló, Laura; Buys, Yvonne M; Jahan, Farzana; Shapiro, Colin M; Flanagan, John G; Cheng, Jason; Trope, Graham E

2017-10-01

To determine the difference in relative intraocular pressure (IOP) measured by the SENSIMED Triggerfish (TF) contact lens in flat compared with 30° head-up sleeping positions in patients with progressive primary open-angle glaucoma or normotensive glaucoma, based on recent or recurrent disc haemorrhage. Prospective, randomised, cross-over, open-label comparative study. IOP was monitored for 24 hours using TF on two separate sessions. Patients were randomly assigned to sleep flat one night and 30° head-up the other. Outputs in arbitrary units were obtained. Sleep and wake periods were defined as 22:00-6:00 and 8:00-22:00, respectively. Mean TF values during sleep and wake periods and wake-sleep and sleep-wake slopes were calculated for each session. TF output signals were compared between positions. Twelve subjects completed the study. Significant mean positive slopes were noted during the sleep period for both positions (p<0.01). No significant differences in the TF mean values were observed between positions (p=0.51). Six (54%) subjects had mean TF values significantly higher during the flat supine session, while four (36%) subjects had higher values during the head-up session. A significant increase in Goldmann IOP (p=0.001) and TF (p=0.02) measurements were observed after 24 hours of TF wear ('drift phenomenon'). Sleep position affects IOP as measured by TF in some patients with progressive glaucoma. The upward drift in TF output detected in >50% of the subjects requires further investigation to establish whether the increased output values over time are an artefact induced by the TF or a real change in IOP. NCT01351779. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

PubMed

Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

2018-06-01

 Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

The role of serum transferrin receptor in the diagnosis of iron deficiency.

PubMed

Remacha, A F; Sarda, M P; Parellada, M; Ubeda, J; Manteiga, R

1998-11-01

Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.

A single-nucleotide polymorphism in transferrin is associated with soluble transferrin receptor in Chinese adolescents.

PubMed

Piao, Wei; Wang, Li; Zhang, Ting; Wang, Zhen; Shangguan, Shaofang; Sun, Jing; Huo, Junsheng

2017-01-01

Associations between genetic variants in the hepcidin regulation pathway and iron status have been reported in previous studies. Most of these studies were conducted in populations of European descent and relatively few studies have been conducted in Chinese populations. In this study, we evaluated associations between single-nucleotide polymorphisms (SNPs) in the hepcidin regulation pathway, serum ferritin (SF) and soluble transferrin receptor (sTfR) in Chinese adolescents. In total, 692 students from rural boarding schools were selected from six cities in China. The participants were divided into case and control groups according to criteria for SF and sTfR. Furthermore, 33 SNPs in TMPRSS6, TF, TFR2, BMP2, BMP4, HJV, CYBRD1, HFE, IL6, PCSK7, HAMP, KIAA1468, and SRPRB were selected. Associations between the genetic variants and SF or sTfR were detected. For SF, rs4820268 in TMPRSS6 was associated with an SF <25 ng/mL status. Carriers of the G/G genotype of rs4820268 exhibited significantly lower SF levels than A allele carriers did (p=0.047). For sTfR, rs1880669 in TF, rs4901474 in BMP4, and rs7536827 in HJV were significantly associated with an sTfR >=4.4 mg/L status. However, in general linear model analysis, after adjustment for age, sex, and location, only rs1880669 exhibited a stable association with higher sTfR levels (p=0.032). We found rs4820268, in TMPRSS6 that was associated with a low SF level, as previously reported, and a new association between 1880669 in TF and sTfR.

The Application of a Homologous Recombination Assay Revealed Amino Acid Residues in an LTR-Retrotransposon That Were Critical for Integration

PubMed Central

Atwood, Angela; Choi, Jeannie; Levin, Henry L.

1998-01-01

Retroviruses and their relatives, the LTR-retrotransposons, possess an integrase protein (IN) that is required for the insertion of reverse transcripts into the genome of host cells. Schizosaccharomyces pombe is the host of Tf1, an LTR-retrotransposon with integration activity that can be studied by using techniques of yeast genetics. In this study, we sought to identify amino acid substitutions in Tf1 that specifically affected the integration step of transposition. In addition to seeking amino acid substitutions in IN, we also explored the possibility that other Tf1 proteins contributed to integration. By comparing the results of genetic assays that monitored both transposition and reverse transcription, we were able to seek point mutations throughout Tf1 that blocked transposition but not the synthesis of reverse transcripts. These mutant versions of Tf1 were candidates of elements that possessed defects in the integration step of transposition. Five mutations in Tf1 that resulted in low levels of integration were found to be located in the IN protein: two substitutions in the N-terminal Zn domain, two in the catalytic core, and one in the C-terminal domain. These results suggested that each of the three IN domains was required for Tf1 transposition. The potential role of these five amino acid residues in the function of IN is discussed. Two of the mutations that reduced integration mapped to the RNase H (RH) domain of Tf1 reverse transcriptase. The Tf1 elements with the RH mutations produced high levels of reverse transcripts, as determined by recombination and DNA blot analysis. These results indicated that the RH of Tf1 possesses a function critical for transposition that is independent of the accumulation of reverse transcripts. PMID:9445033

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

PubMed

Kılıç, Sefa; Sagitova, Dinara M; Wolfish, Shoshannah; Bely, Benoit; Courtot, Mélanie; Ciufo, Stacy; Tatusova, Tatiana; O'Donovan, Claire; Chibucos, Marcus C; Martin, Maria J; Erill, Ivan

2016-01-01

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/. © The Author(s) 2016. Published by Oxford University Press.

Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

PubMed Central

Greene, Christopher J.; Attwood, Kristopher; Sharma, Nitika J.; Gross, Kenneth W.; Smith, Gary J.; Xu, Bo; Kauffman, Eric C.

2017-01-01

The central dysregulated pathway of clear cell (cc) renal cell carcinoma (RCC), the von Hippel Lindau/hypoxia inducible factor-α axis, is a key regulator of intracellular iron levels, however the role of iron uptake in human RCC tumorigenesis and progression remains unknown. We conducted a thorough, large-scale investigation of the expression and prognostic significance of the primary iron uptake protein, transferrin receptor 1 (TfR1/CD71/TFRC), in RCC patients. TfR1 immunohistochemistry was performed in over 1500 cores from 574 renal cell tumor patient tissues (primary tumors, matched benign kidneys, metastases) and non-neoplastic tissues from 36 different body sites. TfR1 levels in RCC tumors, particularly ccRCC, were significantly associated with adverse clinical prognostic features (anemia, lower body mass index, smoking), worse tumor pathology (size, stage, grade, multifocality, sarcomatoid dedifferentiation) and worse survival outcomes, including after adjustments for tumor pathology. Highest TfR1 tissue levels in the non-gravid body were detected in benign renal tubule epithelium. Opposite to TfR1 changes in the primary tumor, TfR1 levels in benign kidney dropped during tumor progression and were inversely associated with worse survival outcomes, independent of tumor pathology. Quantitative measurement of TfR1 subcellular localization in cell lines demonstrated mixed cytoplasmic and membranous expression with increased TfR1 in clusters in ccRCC versus benign renal cell lines. Results of this study support an important role for TfR1 in RCC progression and identify TfR1 as a novel RCC biomarker and therapeutic target. PMID:29291011

Overexpression of OsTF1L, a rice HD-Zip transcription factor, promotes lignin biosynthesis and stomatal closure that improves drought tolerance.

PubMed

Bang, Seung Woon; Lee, Dong-Keun; Jung, Harin; Chung, Pil Joong; Kim, Youn Shic; Choi, Yang Do; Suh, Joo-Won; Kim, Ju-Kon

2018-05-21

Drought stress seriously impacts on plant development and productivity. Improvement of drought tolerance without yield penalty is a great challenge in crop biotechnology. Here, we report that the rice (Oryza sativa) homeodomain-leucine zipper transcription factor gene, OsTF1L (Oryza sativa transcription factor 1-like), is a key regulator of drought tolerance mechanisms. Overexpression of the OsTF1L in rice significantly increased drought tolerance at the vegetative stages of growth and promoted both effective photosynthesis and a reduction in the water loss rate under drought conditions. Importantly, the OsTF1L overexpressing plants showed a higher drought tolerance at the reproductive stage of growth with a higher grain yield than non-transgenic controls under field-drought conditions. Genome-wide analysis of OsTF1L overexpression plants revealed up-regulation of drought-inducible, stomatal movement and lignin biosynthetic genes. Overexpression of OsTF1L promoted accumulation of lignin in shoots, whereas the RNAi lines showed opposite patterns of lignin accumulation. OsTF1L is mainly expressed in outer cell layers including the epidermis, and the vasculature of the shoots, which coincides with areas of lignification. In addition, OsTF1L overexpression enhances stomatal closure under drought conditions resulted in drought tolerance. More importantly, OsTF1L directly bound to the promoters of lignin biosynthesis and drought-related genes involving poxN/PRX38, Nodulin protein, DHHC4, CASPL5B1 and AAA-type ATPase. Collectively, our results provide a new insight into the role of OsTF1L in enhancing drought tolerance through lignin biosynthesis and stomatal closure in rice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Follow-Up Study from a Multisite, Randomized Controlled Trial for Traumatized Children Receiving TF-CBT.

PubMed

Jensen, Tine K; Holt, Tonje; Ormhaug, Silje M

2017-11-01

Trauma-focused cognitive behavioral therapy (TF-CBT) is the treatment of choice for traumatized youth, however, follow-up studies are scarce, and treatment effects for co-occurring depression show mixed findings. The aims of this study were to examine whether treatment effects of TF-CBT are maintained at 18 month follow-up and whether degree of co-occurring depression influences treatment effects. As rapid improvement in psychological functioning is warranted for youth, we also investigated whether the symptom trajectory was different for TF-CBT compared to therapy as usual (TAU). The sample consisted of 156 youth (M age = 15.05, 79.50% girls) randomly assigned to TF-CBT or TAU. The youth were assessed for posttraumatic stress symptoms (PTSS), depression, anxiety and general mental health symptoms. Mixed effects analyses followed the symptom courses over 5 time points. Youth receiving TF-CBT maintained their symptom improvement at 18 months follow-up with scores below clinical cut-of on all symptom measures. The most depressed youth had also a significant decline in symptoms that were maintained at follow-up. Symptom trajectories differed as the TF-CBT group reported a more rapid symptom reduction compared to the TAU condition. In the TAU condition, participants received 1.5 times the number of treatment sessions compared to the TF-CBT participants. After 18 months the groups were significantly different on general mental health symptoms only. In conclusion, youth receiving TF-CBT experienced more efficient improvement in trauma related symptoms than youth receiving TAU and these improvements were maintained after 18 months. Also youth experiencing serious co-occurring depression benefitted from TF-CBT.

The impact of theaflavins on systemic-and microcirculation alterations: The murine and randomized feasibility trials.

PubMed

Saito, Akiko; Nakazato, Risa; Suhara, Yoshitomo; Shibata, Masahiro; Fukui, Toshiki; Ishii, Takeshi; Asanuma, Toshimichi; Mochizuki, Kazuo; Nakayama, Tsutomu; Osakabe, Naomi

2016-06-01

Theaflavins are polyphenols found in black tea; their physiological activities were not well investigated. The present study in rats evaluated the influence of theaflavins on circulation. In addition, an intervention pilot study examined the influence of a theaflavin drink on postprandial hemodynamic change. In an animal study, a single oral dose of theaflavin rich fraction (TF, 10mg/kg) caused transient increase in mean blood pressure (MBP) and heart rate (HR). TF also elevated cremastric blood flow significantly, and the magnitude of this effect was in this order: theaflavin 3'-O-gallate (TF2B) >theaflavin-3-O-gallate (TF2A) >theaflavin (TF1)=theaflavin-3, 3'-di-O-gallate (TF3). In addition, these hemodynamic alterations in mammals totally disappeared when pretreated with carvedilol as an adrenaline blocker. We also treated 10-mg/kg/day TF to the rats for 2 weeks. At the end of the ingestion period, MBP was reduced significantly, and aortic eNOS level was elevated by the repeated ingestion of TF compared with distilled water. In the intervention trial, blood pressure of the volunteers was increased significantly 2 and 4h after ingestion of the TF drink (45mg/drink) compared with before treatment. A significant difference was observed in FMD between the placebo and theaflavin groups 4h after ingestion. These results suggested that theaflavin has potent activity to alter hemodynamics in both murine and healthy subjects. Further studies is needed to elucidate the details; however, the results of animal study suggested that the possible involvement of sympathetic nervous system in the hemodynamic changes caused by TF. Copyright © 2016 Elsevier Inc. All rights reserved.

Criticality Safety Evaluation Report CSER-96-019 for Spent Nuclear Fuel (SNF) Processing and Storage Facilities Multi Canister Overpack (MCO)

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

KESSLER, S.F.

This criticality evaluation is for Spent N Reactor fuel unloaded from the existing canisters in both KE and KW Basins, and loaded into multiple canister overpack (MCO) containers with specially built baskets containing a maximum of either 54 Mark IV or 48 Mark IA fuel assemblies. The criticality evaluations include loading baskets into the cask-MCO, operation at the Cold Vacuum Drying Facility,a nd storage in the Canister Storage Building. Many conservatisms have been built into this analysis, the primary one being the selection of the K{sub eff} = 0.95 criticality safety limit. This revision incorporates the analyses for the sampling/weldmore » station in the Canister Storage Building and additional analysis of the MCO during the draining at CVDF. Additional discussion of the scrap basket model was added to show why the addition of copper divider plates was not included in the models.« less

WISE TF: A MID-INFRARED, 3.4 {mu}m EXTENSION OF THE TULLY-FISHER RELATION USING WISE PHOTOMETRY

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

Lagattuta, David J.; Mould, Jeremy R.; Staveley-Smith, Lister

2013-07-10

We present a mid-infrared Tully-Fisher (TF) relation using photometry from the 3.4 {mu}m W1 band of the Wide-field Infrared Survey Explorer (WISE) satellite. The WISE TF relation is formed from 568 galaxies taken from the all-sky 2MASS Tully-Fisher (2MTF) galaxy catalog, spanning a range of environments including field, group, and cluster galaxies. This constitutes the largest mid-infrared TF relation constructed to date. After applying a number of corrections to galaxy magnitudes and line widths, we measure a master TF relation given by M{sub corr} = -22.24 - 10.05[log (W{sub corr}) - 2.5], with an average dispersion of {sigma}{sub WISE} =more » 0.686 mag. There is some tension between WISE TF and a preliminary 3.6 {mu}m relation, which has a shallower slope and almost no intrinsic dispersion. However, our results agree well with a more recent relation constructed from a large sample of cluster galaxies. We additionally compare WISE TF to the near-infrared 2MTF template relations, finding a good agreement between the TF parameters and total dispersions of WISE TF and the 2MTF K-band template. This fact, coupled with typical galaxy colors of (K - W1) {approx} 0, suggests that these two bands are tracing similar stellar populations, including the older, centrally-located stars in the galactic bulge which can (for galaxies with a prominent bulge) dominate the light profile.« less

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction.

PubMed

Schmidt, Florian; Gasparoni, Nina; Gasparoni, Gilles; Gianmoena, Kathrin; Cadenas, Cristina; Polansky, Julia K; Ebert, Peter; Nordström, Karl; Barann, Matthias; Sinha, Anupam; Fröhler, Sebastian; Xiong, Jieyi; Dehghani Amirabad, Azim; Behjati Ardakani, Fatemeh; Hutter, Barbara; Zipprich, Gideon; Felder, Bärbel; Eils, Jürgen; Brors, Benedikt; Chen, Wei; Hengstler, Jan G; Hamann, Alf; Lengauer, Thomas; Rosenstiel, Philip; Walter, Jörn; Schulz, Marcel H

2017-01-09

The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid costly TF ChIP-seq assays. Thus, it is important to develop computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices. TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq. Additionally, Histone-Marks (HMs) can be used to identify candidate TF binding sites. TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength. Using machine learning, we find low affinity binding sites to improve our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites. Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance. In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq data sets. Finally, these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Molecular dynamics shows that ion pairing and counterion anchoring control the properties of triflate micelles: a comparison with triflate at the air/water interface.

PubMed

Lima, Filipe S; Chaimovich, Hernan; Cuccovia, Iolanda M; Horinek, Dominik

2014-02-11

Micellar properties of dodecyltrimethylammonium triflate (DTA-triflate, DTATf) are very different from those of DTA-bromide (DTAB). DTATf aggregates show high aggregation numbers (Nagg), low degree of counterion dissociation (α), disk-like shape, high packing, ordering, and low hydration. These micellar properties and the low surface tension of NaTf aqueous solutions point to a high affinity of Tf(-) to the micellar and air/water interfaces. Although the micellar properties of DTATf are well defined, the source of the Tf(-) effect upon the DTA aggregates is unclear. Molecular dynamics (MD) simulations of Tf(-) (and Br(-)) at the air/water interface and as counterion of a DTA aggregate were performed to clarify the nature of Tf(-) preferences for these interfaces. The effect of NaTf or NaBr on surface tension calculated from MD simulations agreed with the reported experimental values. From the MD simulations a high affinity of Tf(-) toward the interface, which occurred in a specific orientation, was calculated. The micellar properties calculated from the MD simulations for DTATf and DTAB were consistent with experimental data: in MD simulations, the DTATf aggregate was more ordered, packed, and dehydrated than the DTAB aggregate. The Tf(-)/alkyltrimethylammonium interaction energies, calculated from the MD simulations, suggested ion pair formation at the micellar interface, stabilized by the preferential orientation of the adsorbed Tf(-) at the micellar interface.

The functionally conserved nucleoporins Nup124p from fission yeast and the human Nup153 mediate nuclear import and activity of the Tf1 retrotransposon and HIV-1 Vpr.

PubMed

Varadarajan, Padmapriya; Mahalingam, Sundarasamy; Liu, Peiyun; Ng, Sarah Boon Hsi; Gandotra, Sheetal; Dorairajoo, Desmond Suresh Kumar; Balasundaram, David

2005-04-01

We report that the fission yeast nucleoporin Nup124p is required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr. Failure to import Tf1-Gag into the nucleus in a nup124 null mutant resulted in complete loss of Tf1 transposition. Similarly, nuclear import of HIV-1 Vpr was impaired in nup124 null mutant strains and cells became resistant to Vpr's cell-killing activity. On the basis of protein domain similarity, the human nucleoporin Nup153 was identified as a putative homolog of Nup124p. We demonstrate that in vitro-translated Nup124p and Nup153 coimmunoprecipitate Tf1-Gag or HIV-1 Vpr. Though full-length Nup153 was unable to complement the Tf1 transposition defect in a nup124 null mutant, we provide evidence that both nucleoporins share a unique N-terminal domain, Nup124p(AA264-454) and Nup153(AA448-634) that is absolutely essential for Tf1 transposition. Epigenetic overexpression of this domain in a wild-type (nup124(+)) background blocked Tf1 activity implying that sequences from Nup124p and the human Nup153 challenged the same pathway affecting Tf1 transposition. Our results establish a unique relationship between two analogous nucleoporins Nup124p and Nup153 wherein the function of a common domain in retrotransposition is conserved.

Photoaffinity labeling of the TF1-ATPase from the thermophilic bacterium PS3 with 3'-O-(4-benzoyl)benzoyl ADP.

PubMed

Bar-Zvi, D; Yoshida, M; Shavit, N

1985-05-31

3'-O-(4-Benzoyl)benzoyl ADP (BzADP) was used as a photoaffinity label for covalent binding of adenine nucleotide analogs to the nucleotide binding site(s) of the thermophilic bacterium PS3 ATPase (TF1). As with the CF1-ATPase (Bar-Zvi, D. and Shavit, N. (1984) Biochim. Biophys. Acta 765, 340-356) noncovalently bound BzADP is a reversible inhibitor of the TF1-ATPase. BzADP changes the kinetics of ATP hydrolysis from noncooperative to cooperative in the same way as ADP does, but, in contrast to the effect on the CF1-ATPase, it has no effect on the Vmax. In the absence of Mg2+ 1 mol BzADP binds noncovalently to TF1, while with Mg2+ 3 mol are bound. Photoactivation of BzADP results in the covalent binding of the analog to the nucleotide binding site(s) on TF1 and correlates with the inactivation of the ATPase. Complete inactivation of the TF1-ATPase occurs after covalent binding of 2 mol BzADP/mol TF1. Photoinactivation of TF1 by BzADP is prevented if excess of either ADP or ATP is present during irradiation. Analysis by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate of the Bz[3H]ADP-labeled TF1-ATPase shows that all the radioactivity is incorporated into the beta subunit.

Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling.

PubMed

Naito, Yoshiro; Hosokawa, Manami; Sawada, Hisashi; Oboshi, Makiko; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Tsujino, Takeshi; Masuyama, Tohru

2016-06-01

Iron is associated with the pathophysiology of several cardiovascular diseases, including pulmonary hypertension (PH). In addition, disrupted pulmonary iron homeostasis has been reported in several chronic lung diseases. Transferrin receptor 1 (TfR1) plays a key role in cellular iron transport. However, the role of TfR1 in the pathophysiology of PH has not been well characterized. In this study, we investigate the role of TfR1 in the development of hypoxia-induced pulmonary vascular remodeling. PH was induced by exposing wild-type (WT) mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via assessment of pulmonary vascular remodeling, right ventricular (RV) systolic pressure, and RV hypertrophy. In addition, we assessed the functional role of TfR1 in pulmonary artery smooth muscle cells in vitro. The morphology of pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4 weeks hypoxia showed attenuated pulmonary vascular remodeling, RV systolic pressure, and RV hypertrophy compared with WT mice. In addition, the depletion of TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of toroidal field ripple on plasma rotation in JET

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

De Vries, P.; Salmi, A.; Parail, V.

Dedicated experiments on TF ripple effects on the performance of tokamak plasmas have been carried out at JET. The TF ripple was found to have a profound effect on the plasma rotation. The central Mach number, M, defined as the ratio of the rotation velocity and the thermal velocity, was found to drop as a function of TF ripple amplitude ( ) from an average value of M = 0.40 0.55 for operations at the standard JET ripple of = 0.08% to M = 0.25 0.40 for = 0.5% and M = 0.1 0.3 for = 1%. TF ripple effectsmore » should be considered when estimating the plasma rotation in ITER. With standard co-current injection of neutral beam injection (NBI), plasmas were found to rotate in the co-current direction. However, for higher TF ripple amplitudes ( ~ 1%) an area of counter rotation developed at the edge of the plasma, while the core kept its co-rotation. The edge counter rotation was found to depend, besides on the TF ripple amplitude, on the edge temperature. The observed reduction of toroidal plasma rotation with increasing TF ripple could partly be explained by TF ripple induced losses of energetic ions, injected by NBI. However, the calculated torque due to these losses was insufficient to explain the observed counter rotation and its scaling with edge parameters. It is suggested that additional TF ripple induced losses of thermal ions contribute to this effect.« less

Enhanced washout of 99mTc-tetrofosmin in hypertrophic cardiomyopathy: quantitative comparisons with regional 123I-BMIPP uptake and wall thickness determined by MRI.

PubMed

Thet-Thet-Lwin; Takeda, Tohoru; Wu, Jin; Fumikura, Yuko; Iida, Keiji; Kawano, Satoru; Yamaguchi, Iwao; Itai, Yuji

2003-07-01

The diagnostic value of technetium-99m tetrofosmin (TF) washout in hypertrophic cardiomyopathy (HCM) was examined by investigating its relation to the metabolic abnormality depicted by iodine-123 beta-methyl- p-iodophenylpentadecanoic acid (BMIPP) uptake and the left ventricular (LV) myocardial wall thickness as measured by magnetic resonance imaging (MRI). TF washout was evaluated in 31 patients with HCM and 23 normal control subjects using 30-min (early) and 3-h (delayed) TF single-photon emission tomography images. The LV myocardial wall was divided into 19 segments and the percentage TF washout, regional BMIPP uptake and LV wall thickness were measured in each segment. Mean TF washout in the patients with HCM was significantly faster than that in normal control subjects (23.7+/-5.7 vs 13.4+/-4.1, P<0.0001). In the patients with HCM, TF washout showed an excellent correlation with MRI wall thickness ( r=0.82, P<0.0001) and a good inverse correlation with regional BMIPP uptake ( r=-0.72, P<0.0001). In addition, a good linear correlation was observed between TF uptake and MRI wall thickness in the 19 regional segments. In conclusion, the degree of TF washout corresponds well with the severity of myocardial wall thickness and the degree of metabolic abnormality in patients with HCM. These results suggest that enhanced TF washout might provide additional clinical information regarding metabolic alterations in HCM.

Medical Surveillance Monthly Report (MSMR). Volume 19, Number 1, January 2012

DTIC Science & Technology

2012-01-01

malaria ; or (b) Hospitalization in Iraq/Afghanistan with a malaria diagnosis in any diagnostic position; or (c) Two or more outpatient primary (fi rst...e most common diagnostic test for malaria is the examination under the micro- scope of thin and thick fi lm blood smears. Aft er the blood on the...improve compliance with personal protective measures. Future eff orts will focus on rapid diagnostic tests , creating an inventory and archive of DoD

Retrieval of Ice Cloud Properties Using an Optimal Estimation Algorithm and MODIS Infrared Observations: 2. Retrieval Evaluation

NASA Technical Reports Server (NTRS)

Wang, Chenxi; Platnick, Steven; Zhang, Zhibo; Meyer, Kerry; Wind, Galina; Yang, Ping

2016-01-01

An infrared-based optimal estimation (OE-IR) algorithm for retrieving ice cloud properties is evaluated. Specifically, the implementation of the algorithm with MODerate resolution Imaging Spectroradiometer (MODIS) observations is assessed in comparison with the operational retrieval products from MODIS on the Aqua satellite (MYD06), Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP), and the Imaging Infrared Radiometer (IIR); the latter two instruments fly on the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite in the Afternoon Constellation (A-Train) with Aqua. The results show that OE-IR cloud optical thickness (tau) and effective radius (r(sub eff)) retrievals perform best for ice clouds having 0.5 < tau< 7 and r(sub eff) < 50microns. For global ice clouds, the averaged retrieval uncertainties of tau and r(sub eff) are 19% and 33%, respectively. For optically thick ice clouds with tau larger than 10, however, the tau and r(sub eff) retrieval uncertainties can exceed 30% and 50%, respectively. For ice cloud top height (h), the averaged global uncertainty is 0.48km. Relatively large h uncertainty (e.g., > 1km) occurs for tau < 0.5. Analysis of 1month of the OE-IR retrievals shows large tau and r(sub eff) uncertainties in storm track regions and the southern oceans where convective clouds are frequently observed, as well as in high-latitude regions where temperature differences between the surface and cloud top are more ambiguous. Generally, comparisons between the OE-IR and the operational products show consistent tau and h retrievals. However, obvious differences between the OE-IR and the MODIS Collection 6 r(sub eff) are found.

Concentration and mobility of charge carriers in thin polymers at high temperature determined by electrode polarization modeling

NASA Astrophysics Data System (ADS)

Diaham, Sombel; Locatelli, Marie-Laure

2012-07-01

Charge carrier concentration (n0) and effective mobility (μeff) are reported in two polymer films (<10 μm) and in a very high temperature range (from 200 to 400 °C). This was possible thanks to an electrode polarization modeling of broadband dielectric spectroscopy data. It is shown that the glass transition temperature (Tg) occurrence has a strong influence on the temperature dependence of n0 and μeff. We carry out that n0 presents two distinct Arrhenius-like behaviors below and above Tg, while μeff exhibits a Vogel-Fulcher-Tamman behavior only above Tg whatever the polymer under study. For polyimide films, n0 varies from 1 × 1014 to 4 × 1016 cm-3 and μeff from 1 × 10-8 to 2 × 10-6 cm2 V-1 s-1 between 200 °C to 400 °C. Poly(amide-imide) films show n0 values between 6 × 1016 and 4 × 1018 cm-3 from 270 °C to 400 °C, while μeff varies between 1 × 10-10 and 2 × 10-7 cm2 V-1 s-1. Considering the activation energies of these physical parameters in the temperature range of investigation, n0 and μeff values appear as coherent with those reported in the literature at lower temperature (<80 °C). Surface charge carrier concentrations (nS) are reported and discussed for potential passivation (i.e., surface electrical insulation) applications. Polyimide films appear as good candidates due to nS values less than 1011 cm-2 up to 300 °C.

Serum transferrin receptor status of healthy adult Arabs.

PubMed

Knox-Macaulay, Huxley; Gravell, David; Elender, Frances

2007-01-01

Several studies have provided reference ranges for the concentration of serum transferrin receptor (sTfR) in various white populations, but there is a dearth of relevant reference sTfR data in non-whites. The aim of this investigation was to establish sTfR reference ranges and mean values for a healthy non-white Arab population that could be used also for Arabs worldwide. sTfR and serum ferritin concentrations were estimated by immunoassays and blood counts were determined by conventional methods. Analysis of the data of 114 volunteer Arab blood donors (91 male, 23 female) revealed a higher mean sTfR concentration in males of 22.6+/-8.1 nmol/L (range 10.9-38.7 nmol/L) compared to that in females of 18.7+/-4.4 nmol/L (range 10.7-25.8 nmol/L, p=0.001). There was no significant correlation of sTfR concentration with age, serum ferritin level, or blood haemoglobin level, but a strong inverse correlation was demonstrated with mean cell volume and mean cell haemoglobin of red cells. Iron-replete volunteer subjects with alpha-thalassaemia trait appear to have relatively high mean sTfR concentration. We recommend the use of gender-dependent sTfR reference values for Arabs.

Expression of Tissue Factor by Melanoma Cells Promotes Efficient Hematogenous Metastasis

NASA Astrophysics Data System (ADS)

Mueller, Barbara M.; Reisfeld, Ralph A.; Edgington, Thomas S.; Ruf, Wolfram

1992-12-01

Metastasis is a multistep process which requires highly adapted interactions of tumor cells with host target organs. Compared with nonmetastatic cells, metastatic human melanoma cells express 1000-fold higher levels of tissue factor (TF), the major cellular initiator of the plasma coagulation protease cascades. To explore whether TF may contribute to metastatic tumor dissemination, we analyzed the effect of specific inhibition of TF function on human melanoma metastasis in severe combined immunodeficient (SCID) mice. Using species-specific antibodies to TF, we demonstrate that initial adherence is insufficient for successful tumor cell implantation in a target organ. Rapid arrest of human tumor cells in the lungs of mice was not diminished by inhibition of TF. However, inhibition of TF receptor function and consequent reduction in local protease generation abolished prolonged adherence of tumor cells, resulting in significantly reduced numbers of tumor cells retained in the vasculature of the lungs. The growth of pulmonary metastases was also significantly inhibited by a blocking anti-TF monoclonal antibody and Fab fragments thereof, whereas a noninhibitory antibody lacked antimetastatic effects. Cell surface expression of functional TF thus contributes to melanoma progression by allowing metastatic cells to provide requisite signals for prolonged adhesive interactions and/or transmigration of tumor cells across the endothelium, resulting in successful metastatic tumor implantation.

A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

NASA Astrophysics Data System (ADS)

Yang, Zhaogang; Yu, Bo; Zhu, Jing; Huang, Xiaomeng; Xie, Jing; Xu, Songlin; Yang, Xiaojuan; Wang, Xinmei; Yung, Bryant C.; Lee, L. James; Lee, Robert J.; Teng, Lesheng

2014-07-01

The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.

Trigger Factor and DnaK possess overlapping substrate pools and binding specificities.

PubMed

Deuerling, Elke; Patzelt, Holger; Vorderwülbecke, Sonja; Rauch, Thomas; Kramer, Günter; Schaffitzel, Elke; Mogk, Axel; Schulze-Specking, Agnes; Langen, Hanno; Bukau, Bernd

2003-03-01

Ribosome-associated Trigger Factor (TF) and the DnaK chaperone system assist the folding of newly synthesized proteins in Escherichia coli. Here, we show that DnaK and TF share a common substrate pool in vivo. In TF-deficient cells, deltatig, depleted for DnaK and DnaJ the amount of aggregated proteins increases with increasing temperature, amounting to 10% of total soluble protein (approximately 340 protein species) at 37 degrees C. A similar population of proteins aggregated in DnaK depleted tig+ cells, albeit to a much lower extent. Ninety-four aggregated proteins isolated from DnaK- and DnaJ-depleted deltatig cells were identified by mass spectrometry and found to include essential cytosolic proteins. Four potential in vivo substrates were screened for chaperone binding sites using peptide libraries. Although TF and DnaK recognize different binding motifs, 77% of TF binding peptides also associated with DnaK. In the case of the nascent polypeptides TF and DnaK competed for binding, however, with competitive advantage for TF. In vivo, the loss of TF is compensated by the induction of the heat shock response and thus enhanced levels of DnaK. In summary, our results demonstrate that the co-operation of the two mechanistically distinct chaperones in protein folding is based on their overlap in substrate specificities.

Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands

PubMed Central

Butcher, Robert M. R.; Sokana, Oliver; Jack, Kelvin; Macleod, Colin K.; Marks, Michael E.; Kalae, Eric; Sui, Leslie; Russell, Charles; Tutill, Helena J.; Williams, Rachel J.; Breuer, Judith; Willis, Rebecca; Le Mesurier, Richard T.; Mabey, David C. W.; Solomon, Anthony W.; Roberts, Chrissy h.

2016-01-01

Background Trachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation—follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population. Methods We conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1–9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis. Results We observed a moderate prevalence of TF in children aged 1–9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation—intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1–9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains. Discussion The low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study. PMID:27603015

Transfer-function modelling between environmental variation and mesozooplankton in the Baltic Sea [review article

NASA Astrophysics Data System (ADS)

Vuorinen, I.; Hänninen, J.; Kornilovs, G.

2003-12-01

Time series of freshwater runoff, seawater salinity, temperature and oxygen were used in transfer functions (TF) to model changes of mesozooplankton taxa in the Baltic Sea from the 1960’s to the 1990’s. The models were then compared with long term zooplankton monitoring data from the same period. The TF models for all taxa over the whole Baltic proper and at different depth layers showed statistically significant estimates in t-tests. TF models were further compared using parsimony as a criterion. We present models showing 1) r2 > 0.4, 2) the smallest residual standard error with the combination of exploratory variables, 3) the lowest number of parameters and 4) the highest proportional decrease in error term when the TF model residual standard error was compared with those of the univariate ARIMA model of the same response variable. Most often (7 taxa out of a total of 8), zooplankton taxa were dependent on freshwater runoff and/or seawater salinity. Cladocerans and estuarine copepods were more conveniently modelled through the inclusion of seawater temperature and oxygen data as independent variables. Our modelling, however, explains neither the overall increase in zooplankton abundance nor a simultaneous decrease found in the neritic copepod, Temora longicornis. Therefore, biotic controlling agents (e.g. nutrients, primary production and planktivore diets) are suggested as independent variables for further TF modelling. TF modelling enabled us to put the controlling factors in a time frame. It was then possible, despite the inherent multiple correlation among parameters studied to deduce a chain-of-events from the environmental controls and biotic feedback mechanisms to changes in zooplankton species. We suggest that the documented long-term changes in zooplankton could have been driven by climatic regulation only. The control by climate could be mediated to zooplankton through marine chemical and physical factors, as well as biotic factors if all of these were responding to the same external control, such as changes in the freshwater runoff. Increased runoff would explain both the increasing eutrophication, causing the overall increase of zooplankton, and the changes in selective predation, contributing to decline of Temora.

Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands.

PubMed

Butcher, Robert M R; Sokana, Oliver; Jack, Kelvin; Macleod, Colin K; Marks, Michael E; Kalae, Eric; Sui, Leslie; Russell, Charles; Tutill, Helena J; Williams, Rachel J; Breuer, Judith; Willis, Rebecca; Le Mesurier, Richard T; Mabey, David C W; Solomon, Anthony W; Roberts, Chrissy H

2016-09-01

Trachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation-follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population. We conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1-9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis. We observed a moderate prevalence of TF in children aged 1-9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation-intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1-9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains. The low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study.

[siRNA-mediated tissue factor knockdown in porcine neonatal islet cell clusters in vitro].

PubMed

Ji, Ming; Yi, Shounan; Yu, Deling; Wang, Wei

2011-12-01

To determine the genetic modification on neonatal porcine islet cell clusters (NICC) by small interfering RNA (siRNA)-mediated tissue factor (TF) knockdown in vitro. Porcine NICC were transfected with 5 pairs of designed siRNA respectively or in different combinations with lipofectamine 2000. Transfected NICC were analyzed for TF gene by real-time PCR to select the siRNA which worked best. Meanwhile, the viability of NICC after the TF siRNA transfection was examined by FACS. The efficiency of TF gene and protein suppression was measured by real-time PCR and and FACS respectively. Real-time PCR and FACS showed that a 60% reduction in the TF gene expression and a 50% reduction in the protien level of TF on NICC were achieved by transfecting 3 pairs of selected siRNA. The siRNA transfection had no significant effect on the viability of NICC which was analyzed by FACS. The expression of TF on porcine NICC is efficiently suppressed by 3 pairs of designed siRNA in vitro.